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Huerta-Padilla V, Marrero-Rodríguez D, Taniguchi-Ponciano K, López AE, Candanedo-González F, Salcedo E, Valdivia-Flores A, Rodriguez-Esquivel M, Virgilio LG, López-Romero R, Nambo-Lucio MDJ, Meza-Toledo SE, Bandala C, Meraz MA, Salcedo M. Thymopoietin- α, - β, and - γ Isoforms Increased Expression in Cervical Cancer Cells. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2025; 2025:1668482. [PMID: 40242184 PMCID: PMC12003041 DOI: 10.1155/cjid/1668482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 11/20/2024] [Indexed: 04/18/2025]
Abstract
Cervical cancer (CC) is a public health concern related to the human papillomavirus (HPV) persistent infection. Minichromosome maintenance 2 (MCM2) has been postulated as a surrogate marker for HPV infection. Thymopoietin (TMPO) is a nuclear protein regulated by E2F such as MCM2 or p16. TMPO can give rise to six different isoforms. Herein, both the mRNA and protein levels of TMPO isoforms were analyzed in cervical cells. TMPO expression was selected and analyzed through in silico in several databases from the healthy cervix and cervical lesions. TMPO RNA expression was evaluated in cervical samples and cell lines by RT-PCR and protein expression by Western-blot and immunohistochemistry assays. TMPO and MCM2 immunostaining were evaluated in cervical smears. The clinical-pathological correlation analysis was performed using Kruskal-Wallis or Χ 2 tests. TMPO is overexpressed in 74% of CC cells and all CC cell lines. Moreover, negative immunostaining was observed in normal cervical tissue, compared to strong expression for cervical lesions. Interestingly, TMPO-α, -β, -δ, -ε, and -γ are expressed in all cervical cells and tissues, but a differential expression for α, -β, and -γ isoforms among the cervical cells was observed as overexpressed when HPV is present. Also, the immunostaining of both MCM2 and TMPO was quite similar, but TMPO expression was more sensitive and specific than MCM2 protein. The present study has revealed that TMPO protein expression could be a potential molecular marker for cervical transformed cells, highlighting the TMPO-α, -β, and -γ isoforms as a promising molecular marker of HPV infection.
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Affiliation(s)
- Víctor Huerta-Padilla
- Oncology Genomics Biomedical Research Unit, Gynecology Pediatrics Hospital 3A, North Unity OOAD, Mexican Institute of Social Security, Mexico City, Mexico
- Departamento de Bioquimica, Laboratorio de Quimioterapia Experimental, Escuela Nacional de Ciencias Biológicas, Instituto Politecnico Nacional, Mexico City, Mexico
| | - Daniel Marrero-Rodríguez
- Endocrine Diseases Research Unit, Specialties Hospital, National Medical Center SXXI, Mexican Institute of Social Security, Mexico City, Mexico
| | - Keiko Taniguchi-Ponciano
- Endocrine Diseases Research Unit, Specialties Hospital, National Medical Center SXXI, Mexican Institute of Social Security, Mexico City, Mexico
| | - Ariana E. López
- Oncology Genomics Biomedical Research Unit, Gynecology Pediatrics Hospital 3A, North Unity OOAD, Mexican Institute of Social Security, Mexico City, Mexico
| | - Fernando Candanedo-González
- Anatomo-Pathology Service, Oncology Hospital, National Medical Center SXXI, Mexican Institute of Social Security, Mexico City, Mexico
| | - Emmanuel Salcedo
- Oncology Genomics Biomedical Research Unit, Gynecology Pediatrics Hospital 3A, North Unity OOAD, Mexican Institute of Social Security, Mexico City, Mexico
| | | | - Miriam Rodriguez-Esquivel
- Oncology Genomics Biomedical Research Unit, Gynecology Pediatrics Hospital 3A, North Unity OOAD, Mexican Institute of Social Security, Mexico City, Mexico
| | - Laura Gómez Virgilio
- Centro de Investigación y de Estudios Avanzados, Molecular Biomedicine Department, Instituto Politecnico Nacional, Mexico City, Mexico
| | - Ricardo López-Romero
- Oncology Genomics Biomedical Research Unit, Gynecology Pediatrics Hospital 3A, North Unity OOAD, Mexican Institute of Social Security, Mexico City, Mexico
| | | | - Sergio E. Meza-Toledo
- Departamento de Bioquimica, Laboratorio de Quimioterapia Experimental, Escuela Nacional de Ciencias Biológicas, Instituto Politecnico Nacional, Mexico City, Mexico
| | - Cindy Bandala
- Departamento de Medicina Traslacional aplicada a Neurociencias, Escuela Superior de Medicina, Instituto Politecnico Nacional, Mexico City, Mexico
| | - Marco A. Meraz
- Centro de Investigación y de Estudios Avanzados, Molecular Biomedicine Department, Instituto Politecnico Nacional, Mexico City, Mexico
| | - Mauricio Salcedo
- Oncology Genomics Biomedical Research Unit, Gynecology Pediatrics Hospital 3A, North Unity OOAD, Mexican Institute of Social Security, Mexico City, Mexico
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Kundrod KA, Natoli ME, Smith CA, Coole JB, Chang MM, Novak EN, Chiao E, Stier EA, Montealegre JR, Scheurer ME, Castle PE, Schmeler KM, Richards-Kortum RR. A novel method for semi-quantitative detection of HPV16 and HPV18 mRNA with a low-cost, open-source fluorimeter. Anal Bioanal Chem 2025; 417:1765-1778. [PMID: 39920386 PMCID: PMC11913951 DOI: 10.1007/s00216-025-05765-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 01/02/2025] [Accepted: 01/08/2025] [Indexed: 02/09/2025]
Abstract
Despite global calls to eliminate cervical cancer, rates of cervical cancer incidence and mortality remain high in resource-limited settings, where it is challenging to implement and sustain screening, diagnosis, and treatment programs. The presence of high-risk HPV mRNA in cervical cells is a sensitive and specific biomarker of cervical precancer. Yet, current testing methods are too costly and complex for use in resource-limited settings. Here, we present a novel method for semi-quantitative detection of HPV16 and HPV18 mRNA with minimal infrastructure requirements. The assay relies on isothermal reverse transcription recombinase polymerase amplification (RT-RPA) with real-time fluorescence readout, demonstrated on rugged, portable, and affordable instruments. We demonstrate adapting the assay from DNA detection to RNA detection, characterizing the test with samples of increasing biological complexity, and ultimately establishing a limit of detection of 1000 HPV16 or HPV18 transcripts per reaction with RNA extracted from cell lines. HPV16 and HPV18 mRNA assays were used to test total RNA from 11 patient samples; results for 10 samples (91%) agreed with the gold standard of RT-qPCR. To reduce cost, the assay was demonstrated with multiplexed detection of HPV16 and HPV18 DNA, validated with a reaction volume that was reduced from 50 to 5 µL with DNA and RNA, and performed using a low-cost, portable reader with DNA and RNA. With incorporation of point-of-care-friendly sample preparation and detection of additional genotypes, this test has the potential to expand global access to HPV testing.
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Affiliation(s)
- Kathryn A Kundrod
- Department of Bioengineering, Rice University, Houston, TX, USA
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Mary E Natoli
- Department of Bioengineering, Rice University, Houston, TX, USA
| | - Chelsey A Smith
- Department of Bioengineering, Rice University, Houston, TX, USA
| | - Jackson B Coole
- Department of Bioengineering, Rice University, Houston, TX, USA
| | - Megan M Chang
- Department of Bioengineering, Rice University, Houston, TX, USA
- Department of Bioengineering, University of Washington, Seattle, WA, USA
| | | | - Elizabeth Chiao
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Elizabeth A Stier
- Department of Obstetrics and Gynecology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
| | - Jane R Montealegre
- Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael E Scheurer
- Department of Pediatrics-Hematology/Oncology, Baylor College of Medicine, Houston, TX, USA
| | - Philip E Castle
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA
| | - Kathleen M Schmeler
- Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Pešut E, Šimić I, Kužilkova D, Kalina T, Fureš R, Erceg Ivkošić I, Milutin Gašperov N, Sabol I. Application of mass cytometry in multiparametric characterization of precancerous cervical lesions. CYTOMETRY. PART B, CLINICAL CYTOMETRY 2025; 108:55-66. [PMID: 39462866 DOI: 10.1002/cyto.b.22211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 08/29/2024] [Accepted: 10/15/2024] [Indexed: 10/29/2024]
Abstract
Cervical cancer (CC) is the fourth most common malignant tumor in women worldwide. Detecting different biomarkers together on single cells by novel method mass cytometry could contribute to more precise screening. Liquid-based cytology (LBC) cervical samples were collected (N = 53) from women categorized as normal and precancerous lesions. Human papillomavirus was genotyped by polymerase chain reaction, while simultaneous examination of the expression of 29 proteins was done by mass cytometry (CyTOF). Differences in cluster abundances were assessed with Spearman's rank correlation as well as high dimensional data analysis (t-SNE, FlowSOM). Cytokeratin (ITGA6, Ck5, Ck10/13, Ck14, Ck7) expression patterns allowed determining the presence of different cells in the cervical epithelium. FlowSOM analysis enabled to phenotype cervical cells in five different metaclusters and find new markers that could be important in CC screening. The markers Ck18, Ck18, and CD63 (Metacluster 3) showed significantly increasing associated with severity of the precancerous lesions (Spearman rank correlation rho 0.304, p = 0.0271), while CD71, KLF4, LRIG1, E-cadherin, Nanog and p53 (Metacluster 1) decreased with severity of the precancerous lesions (Spearman rank correlation rho -0.401, p = 0.0029). Other metaclusters did not show significant correlation, but metacluster 2 (Ck17, MCM, MMP7, CD29, E-cadherin, Nanog, p53) showed higher abundance in low- and high-grade intraepithelial lesion cases. CyTOF appears feasible and should be considered when examining novel biomarkers on cervical LBC samples. This study enabled us to characterize different cells in the cervical epithelium and find markers and populations that could distinguish precancerous lesions.
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Affiliation(s)
- Ena Pešut
- Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia
| | - Ivana Šimić
- Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia
| | - Daniela Kužilkova
- CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czechia
| | - Tomáš Kalina
- CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czechia
| | - Rajko Fureš
- General Hospital Zabok and Veterans Affairs Hospital, Department of Gynecology and Obstetrics, Zabok, Croatia
- Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University Osijek, Osijek, Croatia
| | - Ivana Erceg Ivkošić
- Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University Osijek, Osijek, Croatia
- Special Hospital Sveta Katarina, Department of Women's Health, Zagreb, Croatia
| | | | - Ivan Sabol
- Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia
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Liu G, Lin W, Zhang K, Chen K, Niu G, Zhu Y, Liu Y, Li P, Li Z, An Y. Elucidating the prognostic and therapeutic significance of TOP2A in various malignancies. Cancer Genet 2024; 288-289:68-81. [PMID: 39454521 DOI: 10.1016/j.cancergen.2024.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 09/26/2024] [Accepted: 10/17/2024] [Indexed: 10/28/2024]
Abstract
Topoisomerase IIα (TOP2A) is a crucial enzyme that plays a vital role in DNA replication and transcription mechanisms. Dysregulated expression of TOP2A has been associated with various malignancies, including hepatocellular carcinoma, prostate cancer, colon cancer, lung cancer and breast cancer. In this review, we summarized the prognostic relevances of TOP2A in various types of cancer. The increased expression of TOP2A has been linked to resistance to therapy and reduced survival rates. Therefore, evaluating TOP2A levels could assist in identifying patients who may derive advantages from molecular targeted therapy. The amplification of TOP2A has been linked to a positive response to chemotherapy regimens that contain anthracycline. Nevertheless, the overexpression of TOP2A also indicates a heightened likelihood of disease recurrence and unfavorable prognosis. The prognostic significance of TOP2A has been extensively studied in various types of cancer. The increased expression of TOP2A is associated with poor clinical outcomes, indicating its potential as a valuable biomarker for assessing risk and stratifying treatment in these malignancies. However, further investigation is needed to elucidate the underlying mechanisms by which TOP2A influences cancer progression and to explore its potential as a therapeutic target.
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Affiliation(s)
- Guangchao Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Wenlong Lin
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Kaifeng Zhang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Kangxu Chen
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Guanglin Niu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Yonghao Zhu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Yixuan Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key laboratory of cell signal transduction, Henan University, Kaifeng, 475004, China
| | - Pengkun Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key laboratory of cell signal transduction, Henan University, Kaifeng, 475004, China
| | - Zhihao Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key laboratory of cell signal transduction, Henan University, Kaifeng, 475004, China
| | - Yang An
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key laboratory of cell signal transduction, Henan University, Kaifeng, 475004, China.
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Chandra Sekar PK, Thomas SM, Veerabathiran R. The future of cervical cancer prevention: advances in research and technology. EXPLORATION OF MEDICINE 2024:384-400. [DOI: 10.37349/emed.2024.00226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 03/19/2024] [Indexed: 01/12/2025] Open
Abstract
This article provides an informative overview of the current situation and future trends in cervical cancer prevention. Cervical cancer remains a significant public health concern worldwide and is characterized by notable variations in both incidence and mortality rates between developed and developing countries. This underscores the importance of understanding the pathophysiology of cervical cancer, stressing the involvement of high-risk HPV types. The presence of supplementary risk factors facilitates the transition from infection to cancer. This review examines current preventive methods, including the success of HPV vaccines such as Gardasil and Cervarix, and the effectiveness of screening techniques, from cytology to HPV DNA testing. It noted the limitations faced by primary and secondary preventive measures, particularly in low-resource settings, which include access to vaccines and effective screening procedures. Emerging technologies in cervical cancer prevention, such as liquid-based cytology, molecular testing, and AI, promise to improve early detection and diagnosis accuracy and efficiency. The potential of precision medicine to customize treatment based on individual risk factors was discussed. It explores the innovation in genetic editing techniques, such as CRISPR/Cas9, in targeting HPV oncoproteins, the advent of immunotherapy, the role of tumor-infiltrating lymphocytes, and the prospects of biomarkers in improving early detection. Research and technological advancements are leading to transformative changes in cervical cancer prevention. These developments suggest a path toward improved screening, diagnosis, and treatment that could significantly reduce the global burden of the disease. However, realizing the full potential of these advances requires inclusive research and international collaboration to overcome access disparities, particularly in resource-limited settings.
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Affiliation(s)
- Praveen Kumar Chandra Sekar
- Human Cytogenetics and Genomics Laboratory, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Chennai 603103, Tamil Nadu, India
| | - Sheena Mariam Thomas
- Human Cytogenetics and Genomics Laboratory, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Chennai 603103, Tamil Nadu, India
| | - Ramakrishnan Veerabathiran
- Human Cytogenetics and Genomics Laboratory, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Chennai 603103, Tamil Nadu, India
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Bu Q, Luo X, He L, Ma J, He S, Lei W, Zhou W, Deng H, Lin Y, Zhang L, Hong X. Septin9 DNA methylation as a promising biomarker for cervical cancer. J OBSTET GYNAECOL 2023; 43:2151356. [PMID: 36476308 DOI: 10.1080/01443615.2022.2151356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Aberrant Septin9 methylation in cervical cancer has been rarely studied. We aimed to identify its diagnostic value in cervical cancer using cervical scrapings, and its predictive potential in plasma for pelvic nodal metastasis of cervical cancer. The statuses of methylated Septin9 in fresh cervical lesions and cervical scrapings were first evaluated by using quantitative methylation-specific PCR. Subsequently, the relationship between Septin9 methylation in 113 plasma samples and pelvic nodal metastasis of cervical cancer was evaluated. Methylated Septin9 was detected in all cancerous tissues, but not in cervicitis. The degrees of Septin9 methylation increased with growing severity of cervical lesions in cervical scrapings. The sensitivity of methylated Septin9 was lower than that of cytology, while it yielded a high specificity and area under the curve in detecting high-grade squamous intraepithelial lesion or cervical cancer; and when Septin9 methylation combined with HPV16/18 genotyping, the sensitivity would increase from 70.42% to 82.39%. Plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%. In conclusion, we demonstrated methylated Septin9 to be an innovative diagnostic biomarker for cervical cancer and its non-invasive predictive potential in plasma for pelvic nodal metastasis of cervical cancer.Impact statementWhat is already known on this subject? The occurrence of cervical cancer is related to Septin9 methylation. In fresh specimens and cervical scrapings, we found the degrees of methylated Septin9 increased with growing severity of cervical lesions. Compared with HPV16/18 genotyping and cytological detection, Septin9 methylation had a better specificity and AUC in detecting ≥ HSIL. Furthermore, plasma-based Septin9 methylation also had a high specificity for pelvic lymphatic metastasis prediction.What the results of this study add? Methylation analysis of Septin9 indicated a similar sensitivity, specificity and AUC in detecting ≥ HSIL, relative to HPV16/18 genotyping. Compared with cytological method, Septin9 methylation also yielded a higher specificity and AUC in detecting ≥ HSIL. And we also found plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%; additionally an increasing sensitivity from 50% to nearly 80% was found when combined with SCCAg.What the implications are of these findings for clinical practice and/or further research? This study aimed to evaluate the relationship between Septin9 methylation and cervical cancer, and to explore the value of methylated Septin9 in the detection of cervical (pre)cancerous lesions. Moreover, we would explore plasma-based ctDNA biomarkers for pelvic lymphatic metastasis prediction of cervical cancer, to improve non-invasive predictive accuracy of pelvic nodal metastasis and reduce the complications caused by pelvic lymphadenectomy.
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Affiliation(s)
- Qiaowen Bu
- Department of Gynecology, Guangdong Women and Children Hospital, Guangzhou, China
| | - Xiping Luo
- Department of Gynecology, Guangdong Women and Children Hospital, Guangzhou, China
| | - Lulu He
- Department of Gynecology, Guangdong Women and Children Hospital, Guangzhou, China
| | - Jian Ma
- Translational Medicine Center, Guangdong Women and Children Hospital, Guangzhou, China
| | - Shaoyi He
- Department of Gynecology, Guangdong Women and Children Hospital, Guangzhou, China
| | - Wen Lei
- Translational Medicine Center, Guangdong Women and Children Hospital, Guangzhou, China
| | - Weiping Zhou
- Translational Medicine Center, Guangdong Women and Children Hospital, Guangzhou, China
| | - Hua Deng
- Translational Medicine Center, Guangdong Women and Children Hospital, Guangzhou, China
| | - Yu Lin
- Nanfang Hospital, Southern Medical University, Guangzhou, China.,Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Liang Zhang
- Translational Medicine Center, Guangdong Women and Children Hospital, Guangzhou, China
| | - Xiaoshan Hong
- Department of Gynecology, Guangdong Women and Children Hospital, Guangzhou, China
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Gupta S, Nagtode N, Chandra V, Gomase K. From Diagnosis to Treatment: Exploring the Latest Management Trends in Cervical Intraepithelial Neoplasia. Cureus 2023; 15:e50291. [PMID: 38205499 PMCID: PMC10776490 DOI: 10.7759/cureus.50291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 12/10/2023] [Indexed: 01/12/2024] Open
Abstract
Cervical intraepithelial neoplasia (CIN) stands as a precancerous condition with the potential to progress to invasive cervical cancer. This comprehensive review explores the intricacies of CIN management, beginning with its definition, classification, and etiology. It emphasizes the significance of early detection and outlines the latest trends in diagnosis, including Pap smears, human papillomavirus (HPV) testing, and colposcopy. Grading and staging, pivotal in treatment selection, are elucidated. Current management approaches, encompassing watchful waiting, surgical interventions, emerging minimally invasive techniques, and immunotherapy, are detailed. The factors influencing treatment decisions, informed consent, and patient education are discussed. Potential complications following treatment, the importance of long-term follow-up, and the role of HPV vaccination in prevention are underscored. Finally, the review looks to the future, discussing advances in detection, novel treatments, and the promise of precision medicine. In conclusion, early detection and management remain the cornerstone of CIN care, offering hope for a future where cervical cancer is a preventable and treatable condition.
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Affiliation(s)
- Saloni Gupta
- Community Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Nikhilesh Nagtode
- Community Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Vaibhav Chandra
- Community Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Kavita Gomase
- Obstetrics and Gynecology, Smt. Radhikabai Meghe Memorial College of Nursing, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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He L, Luo X, Bu Q, Jin J, Zhou S, He S, Zhang L, Lin Y, Hong X. PAX1 and SEPT9 methylation analyses in cervical exfoliated cells are highly efficient for detecting cervical (pre)cancer in hrHPV-positive women. J OBSTET GYNAECOL 2023; 43:2179916. [PMID: 36799003 DOI: 10.1080/01443615.2023.2179916] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/18/2023]
Abstract
Studies have investigated PAX1 and SEPT methylation were closely associated with cervical cancer. For this study, we verified the expressions of PAX1 and SEPT9 methylation in 236 hrHPV women cervical exfoliated cells by using quantitative methylation-specific PCR and we further explored their diagnostic value in cervical (pre)cancer detection. Our results identified that the methylation rates and levels of PAX1 and SEPT9 increased with cervical lesion severity. For a diagnosis of cervical (pre)cancer, the area under the curve (AUC) of PAX1 methylation was 0.77 (95% CI 0.71-0.83) and the AUC of SEPT9 methylation was 0.86 (95% CI 0.81∼0.90). Analyses of the PAX1 and SEPT9 methylation statuses alone or combined with commonly used tests can efficiently identify cervical (pre)cancer. In particular, SEPT9 methylation might serve as an effective and powerful biomarker for the diagnosis of cervical (pre)cancer and as an alternative triage test in HPV-based cervical (pre)cancer screening programs.Impact StatementWhat is already known on this subject? This subject showed that PAX1 and SEPT9 methylation were closely associated with cervical cancer. The methylation rates and levels of PAX1 and SEPT9 increased with cervical lesion severity and reached a peak in cervical cancer exfoliated cells. We further assessed the diagnostic performances of PAX1 and SEPT9 methylation in cervical cancer screening. In detecting cervical (pre)cancer, the sensitivity values of PAX1 and SEPT9 methylation were up to 61.18% and 82.35%, respectively, and the specificity values of PAX1 and SEPT9 methylation were up to 95.36% and 86.75%, respectively. Moreover, the ROC curve analysis showed AUC values of 0.77 for PAX1 methylation and 0.86 for SEPT9 methylation tests, which were significantly superior to other commonly used tests. These findings suggest that PAX1 and SEPT9 methylation detection may have great clinical potential in cervical cancer screening.What the results of this study add? The rates and levels of PAX1 and SEPT9 methylation increased with the severity of the cervical lesions. For a diagnosis of cervical (pre)cancer, the area under the curve (AUC) of PAX1 methylation was 0.77 (95% CI 0.71-0.83), and the sensitivity and specificity values were 61.18% and 95.36%, respectively. The AUC value of the SEPT9 methylation was 0.86 (95% CI 0.81 ∼ 0.90), and the sensitivity and specificity values were 82.35% and 86.75%, respectively. Compared with the various tests we conducted, the PAX1 methylation showed the highest specificity (95.36%), and the SEPT9 methylation demonstrated the highest accuracy(86.00%).What the implications are of these findings for clinical practice and/or further research? The methylation levels of PAX1 and SEPT9 had a certain predictive effect on the severity of cervical lesions in hrHPV-positive women. In addition, SEPT9 methylation analysis performs better than PAX1 methylation analysis and commonly used tests in cervical exfoliated cells for detecting cervical (pre)cancer in hrHPV-positive women. SEPT9 methylation analysis merits consideration as an effective and objective, alternative triage test in HPV-based cervical (pre)cancer screening programs.
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Affiliation(s)
- Lulu He
- Department of Gynecology, Guangdong Women and Children Hospital, Guangzhou, China
| | - Xiping Luo
- Department of Gynecology, Guangdong Women and Children Hospital, Guangzhou, China
| | - Qiaowen Bu
- Department of Gynecology, Guangdong Women and Children Hospital, Guangzhou, China
| | - Jing Jin
- Department of Gynecology, Guangdong Women and Children Hospital, Guangzhou, China
| | - Shuai Zhou
- Translational Medicine Center, Guangdong Women and Children Hospital, Guangzhou, China
| | - Shaoyi He
- Department of Gynecology, Guangdong Women and Children Hospital, Guangzhou, China
| | - Liang Zhang
- Translational Medicine Center, Guangdong Women and Children Hospital, Guangzhou, China
| | - Yu Lin
- Nanfang Hospital, Southern Medical University, Guangzhou, China.,Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiaoshan Hong
- Department of Gynecology, Guangdong Women and Children Hospital, Guangzhou, China
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Abstract
Importance Each year in the US, approximately 100 000 people are treated for cervical precancer, 14 000 people are diagnosed with cervical cancer, and 4000 die of cervical cancer. Observations Essentially all cervical cancers worldwide are caused by persistent infections with one of 13 carcinogenic human papillomavirus (HPV) genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68. HPV vaccination at ages 9 through 12 years will likely prevent more than 90% of cervical precancers and cancers. In people with a cervix aged 21 through 65 years, cervical cancer is prevented by screening for and treating cervical precancer, defined as high-grade squamous intraepithelial lesions of the cervix. High-grade lesions can progress to cervical cancer if not treated. Cervicovaginal HPV testing is 90% sensitive for detecting precancer. In the general population, the risk of precancer is less than 0.15% over 5 years following a negative HPV test result. Among people with a positive HPV test result, a combination of HPV genotyping and cervical cytology (Papanicolaou testing) can identify the risk of precancer. For people with current precancer risks of less than 4%, repeat HPV testing is recommended in 1, 3, or 5 years depending on 5-year precancer risk. For people with current precancer risks of 4% through 24%, such as those with low-grade cytology test results (atypical squamous cells of undetermined significance [ASC-US] or low-grade squamous intraepithelial lesion [LSIL]) and a positive HPV test of unknown duration, colposcopy is recommended. For patients with precancer risks of less than 25% (eg, cervical intraepithelial neoplasia grade 1 [CIN1] or histologic LSIL), treatment-related adverse effects, including possible association with preterm labor, can be reduced by repeating colposcopy to monitor for precancer and avoiding excisional treatment. For patients with current precancer risks of 25% through 59% (eg, high-grade cytology results of ASC cannot exclude high-grade lesion [ASC-H] or high-grade squamous intraepithelial lesion [HSIL] with positive HPV test results), management consists of colposcopy with biopsy or excisional treatment. For those with current precancer risks of 60% or more, such as patients with HPV-16-positive HSIL, proceeding directly to excisional treatment is preferred, but performing a colposcopy first to confirm the need for excisional treatment is acceptable. Clinical decision support tools can facilitate correct management. Conclusions and Relevance Approximately 100 000 people are treated for cervical precancer each year in the US to prevent cervical cancer. People with a cervix should be screened with HPV testing, and if HPV-positive, genotyping and cytology testing should be performed to assess the risk of cervical precancer and determine the need for colposcopy or treatment. HPV vaccination in adolescence will likely prevent more than 90% of cervical precancers and cancers.
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Affiliation(s)
- Rebecca B Perkins
- Boston University School of Medicine, Chobanian & Avedisian School of Medicine, Boston Medical Center, Massachusetts
| | - Nicolas Wentzensen
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | - Richard S Guido
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania
- UPMC Magee-Women's Hospital, Pittsburgh, Pennsylvania
| | - Mark Schiffman
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
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Causin RL, Sussuchi da Silva L, Leal LF, Possati-Resende JC, Evangelista AF, Matsushita GM, Scapulatempo-Neto C, Tavares Guerreiro Fregnani JH, Antônio de Oliveira M, Musselwhite LW, Chiquitelli Marques MM, Reis RM. The digital expression profile of BMP7, CDKN2C, HIST1H3G, and PKMYT1 genes improves high-grade cervical lesion detection in liquid-based cytology. Cancer Cytopathol 2023; 131:454-464. [PMID: 37069588 DOI: 10.1002/cncy.22704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 03/03/2023] [Accepted: 03/07/2023] [Indexed: 04/19/2023]
Abstract
BACKGROUND Some studies reported that differential gene expression could be used as a biomarker for high-grade cervical lesion identification. The aim was to evaluate the gene expression profile of cervical intraepithelial neoplasia (CIN) to identify a gene expression signature of CIN2+ in liquid-based cytology (LBC) samples. METHODS LBC samples (n = 85) obtained from women who underwent colposcopy were included with benign (n = 13), CIN1 (n = 26), CIN2 (n = 16), and CIN3 (n = 30) diagnoses. After RNA isolation, gene expression profiling was performed using the nCounter PanCancer Pathways, which consists of 730 cancer-related genes. The genes identified were in silico expression evaluated using the UALCAN database. An accurate prediction model to discriminate CIN2+ from RESULTS This study identified a gene expression profile that significantly differentiates CIN2+ cases from CONCLUSION A gene expression profile that may be helpful in the identification of patients with CIN2+ was identified. This approach could be used together with currently used LBC in a clinical setting, allowing the identification of patients with high risk of CIN2+.
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Affiliation(s)
| | | | - Leticia Ferro Leal
- Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil
- Barretos School of Health Sciences, Dr. Paulo Prata-FACISB, Barretos, São Paulo, Brazil
| | | | - Adriane Feijó Evangelista
- Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil
- Sergio Arouca National School of Public Health, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | | | | | | | | | | | | | - Rui Manuel Reis
- Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil
- Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, Braga, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga, Portugal
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11
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Booth BB, Tranberg M, Gustafson LW, Christiansen AG, Lapirtis H, Krogh LM, Hjorth IMD, Hammer A. Risk of cervical intraepithelial neoplasia grade 2 or worse in women aged ≥ 69 referred to colposcopy due to an HPV-positive screening test. BMC Cancer 2023; 23:405. [PMID: 37142959 PMCID: PMC10161414 DOI: 10.1186/s12885-023-10888-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 04/26/2023] [Indexed: 05/06/2023] Open
Abstract
BACKGROUND Cervical cancer incidence and mortality rates are high in older women in many developed countries, including Denmark. Therefore, Danish women aged 69 and older were invited for one additional human papilloma virus (HPV) based screening test in 2017. Here, we describe the clinical management and detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) in screen-positive women referred for colposcopy. METHODS We conducted an observational study in public gynecology departments in Central Denmark Region, Denmark. Women were eligible for enrolment if they were aged 69 + in 2017, HPV positive on a screening test taken between April 20th, 2017, and December 31st, 2017, and had been referred for direct colposcopy. Data on participants' characteristics, colposcopic findings, and histological outcomes were collected from medical records and the Danish Pathology Databank. We estimated the proportion of women with CIN2 + at the first colposcopy visit and at end of follow up including 95% confidence intervals (CIs). RESULTS A total of 191 women were included with a median age of 74 years (IQR: 71-78). Most women (74.9%) did not have a fully visible transformation zone at colposcopy. At the first visit 170 women (89.0%) had a histological sample collected, 34 of whom (20.0%, 95% CI 14.3-26.8%) had CIN2 + diagnosed, 19 had CIN3 + , and two had cervical cancer). During follow-up additional CIN2 + were detected resulting in a total of 42 women (24.4%, 95% CI: 18.2-31.5%) being diagnosed with CIN2 + , 25 with CIN3 + , and three with cervical cancer. When restricting to women with paired histologic results (i.e., biopsies and a loop electrosurgical excision procedure (LEEP) specimen), we found that CIN2 + was missed in 17.9% (95% CI 8.9-30.4%) of biopsies compared to the LEEP. CONCLUSION Our findings suggest a potential risk of underdiagnosis in older postmenopausal women referred to colposcopy. Future studies should explore potential risk-markers for discrimination of women at increased risk of CIN2 + from those at low risk, as this would reduce risk of underdiagnosis and overtreatment.
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Affiliation(s)
- Berit B Booth
- Department of Obstetrics and Gynecology, NIDO - Centre for Research and Education, Gødstrup Hospital, Hospitalsparken 15, Herning, 7400, Denmark.
| | - Mette Tranberg
- University Research Clinic for Cancer Screening, Department of Public Health Programmes, Randers Regional Hospital, Randers, Denmark
| | - Line W Gustafson
- University Research Clinic for Cancer Screening, Department of Public Health Programmes, Randers Regional Hospital, Randers, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Anne G Christiansen
- Department of Obstetrics and Gynecology, NIDO - Centre for Research and Education, Gødstrup Hospital, Hospitalsparken 15, Herning, 7400, Denmark
| | - Helle Lapirtis
- Department of Obstetrics and Gynecology, Randers Regional Hospital, Randers, Denmark
| | - Lisa M Krogh
- Department of Obstetrics and Gynecology, Viborg Regional Hospital, Viborg, Denmark
| | - Ina Marie D Hjorth
- Department of Obstetrics and Gynecology, Horsens Regional Hospital, Horsens, Denmark
| | - Anne Hammer
- Department of Obstetrics and Gynecology, NIDO - Centre for Research and Education, Gødstrup Hospital, Hospitalsparken 15, Herning, 7400, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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12
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Voidăzan TS, Uzun CC, Kovacs Z, Rosznayai FF, Turdean SG, Budianu MA. The Hybrid Capture 2 Results in Correlation with the Pap Test, Sexual Behavior, and Characteristics of Romanian Women. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:3839. [PMID: 36900850 PMCID: PMC10001103 DOI: 10.3390/ijerph20053839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 02/18/2023] [Accepted: 02/20/2023] [Indexed: 06/18/2023]
Abstract
BACKGROUND Human papillomavirus (HPV) infection is the major cause of cervical cancer (CC); hence, it is critical to understand the processes by which HPV infection causes squamous intraepithelial lesions, as well as the proper diagnostic tools. The objective of this study was to establish the correlations between Pap test results and Hybrid Capture 2 (HC2) tests findings. MATERIALS AND METHODS This study included 169 women between the ages of 30 and 64, who presented for consultation in gynecological clinics in both the public and the private sectors. These women reported symptoms, such as abnormal vaginal discharge and genital irritation, as well as early onset of sexual activity, multiple sexual partners, history of other sexually transmitted infections or high-risk sexual partners, immunosuppression, or tobacco smoking. Pap tests and HPV testing, using the HC2 method, were performed for the women enrolled in the study, including data gathered after patients completed questionnaires concerning their sexual behavior. RESULTS The HC2 method revealed that 66 patients (39.1%) tested positive for high-risk HPV types. Of the patients with positive results, 14 (21.2%) presented Atypical Squamous Cells of Undetermined Significance (ASC-US) compared to 10 (9.7%) patients in the negative group (p = 0.042). Atypical Squamous Cells for which a high-grade lesion cannot be excluded (ASC-H) were identified primarily in women with positive HC2 (6.1%). HR-HPV positivity was substantially more associated with low-grade ASC-US or low-grade squamous intraepithelial lesion (LSIL) and high-grade ASC-H cytology (OR = 2.53; 95% CI: 1.10-5.80, respectively, OR = 14.9; 95%CI: 1.006-34.59). Unmarried women (31.8%; p = 0.004) and women with multiple partners (over four partners, 10.6%; p = 0.03) were more likely to have an HPV infection when compared to married women and those with fewer sexual partners. CONCLUSIONS Understanding the epidemiology of HPV genital infections is essential for developing preventive measures against this infection and CC. Identifying the most prevalent HPV types, and determining the incidence of HPV oncogenic infections, in conjunction with Pap test results and sexual behavior information, can constitute part of an algorithm for the efficient management of cervical intraepithelial lesions.
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Affiliation(s)
- Toader Septimiu Voidăzan
- Department of Epidemiology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Cosmina Cristina Uzun
- Department of Biochemistry, Environmental Chemistry, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Zsolt Kovacs
- Department of Biochemistry, Environmental Chemistry, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Florin Francisc Rosznayai
- Department of Obstetrics Gynecology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Sabin Gligore Turdean
- Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Mihaela-Alexandra Budianu
- Department of Epidemiology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania
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Fleider LA, de los Ángeles Tinnirello M, Gómez Cherey F, García MG, Cardinal LH, García Kamermann F, Tatti SA. High sensitivity and specificity rates of cobas® HPV test as a primary screening test for cervical intraepithelial lesions in a real-world setting. PLoS One 2023; 18:e0279728. [PMID: 36745662 PMCID: PMC9901754 DOI: 10.1371/journal.pone.0279728] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 12/14/2022] [Indexed: 02/07/2023] Open
Abstract
Cervical carcinoma (CC) is the fourth most common malignancy among women. Screening with Papanicolau smear is linked to a reduction in CC incidence rates when screening programs have been developed. However, this technique has several limitations, including moderate sensitivity rates for detection of cervical preneoplastic HPV-related lesions. In this real-world study, we proposed to evaluate the sensitivity and specificity rates of cobas® test, which amplifies target DNA fragments by polymerase chain reaction and hybridization of nucleic acids for the detection of 14 HR-HPV types in a single analysis) used as primary screening test for CC and preneoplastic lesions in women aged 25-65 years in a large University Hospital in Buenos Aires. A total of 1044 patients were included in the sample (median age: 46 years); sensitivity and specificity rates for the HR-HPV test used as primary screening test were 98.66% (95% confidence interval [95CI]: 97.67-99.3%) and 87.15% (95CI: 84.93-89.15%), respectively. The positive predictive value was 88.47% (95CI: 86.54%-90.42%) and the negative predictive value was 98.48% (95CI: 97.75%-99.23%). The cobas® HR-HPV testing was highly sensitive and specific for the detection of CC and preneoplastic lesions in real practice.
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Affiliation(s)
- Laura Alicia Fleider
- OBGYN Department, Genital Tract Unit, Hospital de Clínicas “José de San Martín”, Buenos Aires University, Buenos Aires, Argentina
- * E-mail:
| | - María de los Ángeles Tinnirello
- OBGYN Department, Genital Tract Unit, Hospital de Clínicas “José de San Martín”, Buenos Aires University, Buenos Aires, Argentina
| | - Facundo Gómez Cherey
- OBGYN Department, Genital Tract Unit, Hospital de Clínicas “José de San Martín”, Buenos Aires University, Buenos Aires, Argentina
| | - María Gabriela García
- Molecular Infectious Disease Department, ManLab Laboratories, Buenos Aires, Argentina
| | - Lucía Helena Cardinal
- Gynecological Pathology Division, Pathology Department, Hospital de Clínicas “José de San Martín”, Buenos Aires University, Buenos Aires, Argentina
| | - Florencia García Kamermann
- Gynecological Pathology Division, Pathology Department, Hospital de Clínicas “José de San Martín”, Buenos Aires University, Buenos Aires, Argentina
| | - Silvio Alejandro Tatti
- Chief of OBGYN Department, Hospital de Clínicas “José de San Martín”, Buenos Aires University, Buenos Aires, Argentina
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14
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Derbie A, Mekonnen D, Nibret E, Misgan E, Maier M, Woldeamanuel Y, Abebe T. Cervical cancer in Ethiopia: a review of the literature. Cancer Causes Control 2023; 34:1-11. [PMID: 36242682 DOI: 10.1007/s10552-022-01638-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 09/26/2022] [Indexed: 01/10/2023]
Abstract
BACKGROUND Cervical cancer is one of the most common malignancies affecting women worldwide with large geographic variations in prevalence and mortality rates. It is one of the leading causes of cancer-related deaths in Ethiopia, where vaccination and screening are less implemented. However, there is a scarcity of literature in the field. Therefore, the objective of this review was to describe current developments in cervical cancer in the Ethiopian context. The main topics presented were the burden of cervical cancer, knowledge of women about the disease, the genotype distribution of Human papillomavirus (HPV), vaccination, and screening practices in Ethiopia. METHODS Published literature in the English language on the above topics until May 2021 were retrieved from PubMed/Medline, SCOPUS, Google Scholar, and the Google database using relevant searching terms. Combinations of the following terms were considered to retrieve literature; < Cervical cancer, uterine cervical neoplasms, papillomavirus infections, papillomavirus vaccines, knowledge about cervical cancer, genotype distribution of HPV and Ethiopia > . The main findings were described thematically. RESULTS Cervical cancer is the second most common and the second most deadly cancer in Ethiopia, The incidence and prevalence of the disease is increasing from time to time because of the growth and aging of the population, as well as an increasing prevalence of well-established risk factors. Knowledge and awareness about cervical cancer is quite poor among Ethiopian women. According to a recent report (2021), the prevalence of previous screening practices among Ethiopian women was at 14%. Although HPV 16 is constantly reported as the common genotype identified from different grade cervical lesions in Ethiopia, studies reported different HPV genotype distributions across the country. According to a recent finding, the most common HPV types identified from cervical lesions in the country were HPV-16, HPV-52, HPV-35, HPV-18, and HPV-56. Ethiopia started vaccinating school girls using Gardasil-4™ in 2018 although the coverage is insignificant. Recently emerging reports are in favor of gender-neutral vaccination strategies with moderate coverage that was found superior and would rapidly eradicate high-risk HPVs than vaccinating only girls. CONCLUSIONS Cervical cancer continues to be a major public health problem affecting thousands of women in Ethiopia. As the disease is purely preventable, classic cervical cancer prevention strategies that include HPV vaccination using a broad genotype coverage, screening using a high precision test, and treating cervical precancerous lesions in the earliest possible time could prevent most cervical cancer cases in Ethiopia. The provision of a focused health education supported by educational materials would increase the knowledge of women about cervical cancer in general and the uptake of cervical cancer prevention and screening services in particular.
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Affiliation(s)
- Awoke Derbie
- Department of Medical Microbiology, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia.
- Centre for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), Addis Ababa University, Addis Ababa, Ethiopia.
- Department of Health Biotechnology, Biotechnology Research Institute, Bahir Dar University, Bahir Dar, Ethiopia.
- Department of Medical Microbiology, Immunology and Parasitology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
| | - Daniel Mekonnen
- Department of Medical Microbiology, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
- Department of Health Biotechnology, Biotechnology Research Institute, Bahir Dar University, Bahir Dar, Ethiopia
| | - Endalkachew Nibret
- Department of Biology, College of Science, Bahir Dar University, Bahir Dar, Ethiopia
| | - Eyaya Misgan
- Department of Gynecology and Obstetrics, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
| | - Melanie Maier
- Department of Diagnostics, Institute of Virology, Leipzig University Hospital, Leipzig, Germany
| | - Yimtubezinash Woldeamanuel
- Centre for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), Addis Ababa University, Addis Ababa, Ethiopia
- Department of Medical Microbiology, Immunology and Parasitology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Tamrat Abebe
- Department of Medical Microbiology, Immunology and Parasitology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
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Arip M, Tan LF, Jayaraj R, Abdullah M, Rajagopal M, Selvaraja M. Exploration of biomarkers for the diagnosis, treatment and prognosis of cervical cancer: a review. Discov Oncol 2022; 13:91. [PMID: 36152065 PMCID: PMC9509511 DOI: 10.1007/s12672-022-00551-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 06/16/2022] [Indexed: 12/19/2022] Open
Abstract
As the fourth most diagnosed cancer, cervical cancer (CC) is one of the major causes of cancer-related mortality affecting females globally, particularly when diagnosed at advanced stage. Discoveries of CC biomarkers pave the road to precision medicine for better patient outcomes. High throughput omics technologies, characterized by big data production further accelerate the process. To date, various CC biomarkers have been discovered through the advancement in technologies. Despite, very few have successfully translated into clinical practice due to the paucity of validation through large scale clinical studies. While vast amounts of data are generated by the omics technologies, challenges arise in identifying the clinically relevant data for translational research as analyses of single-level omics approaches rarely provide causal relations. Integrative multi-omics approaches across different levels of cellular function enable better comprehension of the fundamental biology of CC by highlighting the interrelationships of the involved biomolecules and their function, aiding in identification of novel integrated biomarker profile for precision medicine. Establishment of a worldwide Early Detection Research Network (EDRN) system helps accelerating the pace of biomarker translation. To fill the research gap, we review the recent research progress on CC biomarker development from the application of high throughput omics technologies with sections covering genomics, transcriptomics, proteomics, and metabolomics.
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Affiliation(s)
- Masita Arip
- Allergy & Immunology Research Centre, Institute for Medical Research, National Institute of Health, Setia Alam, 40170 Shah Alam, Selangor, Malaysia
| | - Lee Fang Tan
- Department of Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, UCSI University, 56000 Cheras, Kuala Lumpur, Malaysia.
| | - Rama Jayaraj
- Charles Darwin University, Darwin, NT, 0909, Australia
| | - Maha Abdullah
- Immunology Unit, Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Jalan Serdang, 43400, Serdang, Selangor, Malaysia
| | - Mogana Rajagopal
- Department of Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, UCSI University, 56000 Cheras, Kuala Lumpur, Malaysia.
| | - Malarvili Selvaraja
- Department of Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, UCSI University, 56000 Cheras, Kuala Lumpur, Malaysia.
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Shukla A, Sachan R, Maurya M, Patel ML, Sankhwar P. ROC-Analysis Derived Immunohistochemical P53 Cut-Off Scores as an Adjunct to Routine Histopathology for Better Diagnostic Compartmentalisation of Cervical Lesions. Int J Appl Basic Med Res 2022; 12:177-184. [PMID: 36131854 PMCID: PMC9484512 DOI: 10.4103/ijabmr.ijabmr_416_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 03/29/2022] [Accepted: 06/01/2022] [Indexed: 12/24/2022] Open
Abstract
Objective The aim of this study was to evaluate the predictive value of Immunohistochemical p53 cut-off scores as an adjunct to routine histopathology for better diagnosis of cervical lesions. Materials and Methods Prospective study carried out for 1 year. After ethical approval and informed consent, a total of 100 cervical tissue samples were analyzed; chronic cervicitis (CC)-15, cervical intraepithelial neoplasia (CIN)-40, and squamous cell carcinoma cervix (SCC)-45 (FIGO 2018 clinical staging). After routine processing of tissue specimen, hematoxylin and eosin (HE) staining was done. Grading of cervical precancerous lesions (CIN) was done as per World Health Organisation criteria as CIN 1,2 or 3. Broder's grading was assigned for every SCC sample. Results Mean p53 scores of CC, CIN, and SCC cases were 0.0, 1.70, and 4.38, respectively, CIN 1, 2, and 3 were 1.07, 1.63, and 2.22, respectively. SCC was differentiated from CIN3 with p53 ≥4.5 as predictor for SCC, sensitivity and specificity were 57.8% and 88.9%, respectively. Overall diagnostic accuracy of the proposed scoring system for differentiating CC, CIN, and SCC was 61%, while the accuracy of previous methods of interpreting p53 immunoreactivity as immunoscore >2 or arbitrary cut-off of >10% cells with nuclear positivity was only 48%. Conclusion ROC-derived immunoscore cut-offs can provide the much-needed objectivity and optimal decision thresholds to immunohistochemistry interpretation.
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Affiliation(s)
- Ayushi Shukla
- Department of Obstetrics and Gynaecology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Rekha Sachan
- Department of Obstetrics and Gynaecology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Malti Maurya
- Pathology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Munna Lal Patel
- Department of Obstetrics and Gynaecology, King George Medical University, Lucknow, Uttar Pradesh, India
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Johnson LG, Saidu R, Svanholm-Barrie C, Boa R, Moodley J, Tergas A, Persing D, Campbell SA, Tsai WY, Wright TC, Denny L, Kuhn L. Clinical utility of reflex testing with cancer biomarkers to improve diagnostic accuracy of primary Human Papillomavirus screening. Cancer Epidemiol Biomarkers Prev 2022; 31:595-603. [PMID: 35027434 DOI: 10.1158/1055-9965.epi-21-0972] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 11/02/2021] [Accepted: 12/14/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND HPV testing is the cornerstone of cervical cancer screening with outstanding sensitivity but only moderate specificity. We evaluated whether reflex testing for cancer biomarkers improves the sensitivity/specificity balance of screening. METHODS Cervical samples from women in Cape Town, South Africa, aged 30-65 years, were collected and tested with Xpert HPV and with real-time PCR to detect mRNA for Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A), Topoisomerase 2 alpha (TOP2A) and Ki67 (MKi67). Women with histologically-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) (85 women without and 166 with HIV) and women with no cervical disease (331 without and 257 with HIV) were included. RESULTS When used as reflex tests after a positive HPV result, biomarkers discriminated well between women with and without CIN2+. The inclusion of both CDKN2A and MKi67 had the best performance with area under the curve (AUC) of 0.9171 and 0.8734 in women without and with HIV, respectively. While excellent, these performance parameters did not improve on an approach utilizing only HPV testing with more stringent cycle threshold cut-offs and HPV genotype selection which achieved AUC of 0.9059 and 0.8705 in women without and with HIV, respectively. CONCLUSION Biomarkers can be used as triage after positive HPV results but do not out-perform an approach utilizing higher viral load cut-offs on selected high-risk genotypes. IMPACT A screening approach using HPV testing alone can be more easily implemented at the point-of-care.
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Affiliation(s)
| | - Rakiya Saidu
- Department of Obstetrics and Gynecology; South African Medical Research Council Gynaecological Cancer Research Centre (SAMRC GCRC), University of Cape Town
| | | | - Rosalind Boa
- Department of Obstetrics and Gynecology, University of Cape Town
| | - Jennifer Moodley
- School of Public Health and Family Medicine; South African Medical Research Council Gynaecological Cancer Research Centre (SAMRC GCRC), University of Cape Town
| | | | | | | | | | | | - Lynette Denny
- Department of Obstetrics and Gynecology, University of Cape Town
| | - Louise Kuhn
- Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center; Department of Epidemiology, Mailman School of Public Health, Columbia University, Columbia University Irving Medical Center
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18
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Kumar GV, Prabhu AJ, Sebastian A, Raghavendran, Abraham P, Peedicayil A. P16INK4a/ki67 Immunocytochemistry in Improving the Predictive Value for High Grade Cervical Intraepithelial (≥CIN2) Neoplasia in Pap Smear. J Cytol 2022; 38:180-185. [PMID: 35002109 PMCID: PMC8670453 DOI: 10.4103/joc.joc_245_20] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 09/19/2021] [Accepted: 10/18/2021] [Indexed: 11/19/2022] Open
Abstract
Introduction: Cervical cytology has limited sensitivity to detect cervical pre-cancerous lesions. High-risk human papillomavirus (hr-HPV) DNA testing has high sensitivity but its specificity is limited. This study was done to assess the utility of p16INK4a/ki-67 dual stained cytology in improving the predictive value for high-grade cervical (CIN2+) lesions. Aim/Objective: To assess the significance of P16/Ki-67 immunocytochemistry in improving the predictive value for high-grade cervical intraepithelial (≥CIN 2+) lesions on Pap smear. Material and Methods: This was a prospective diagnostic study that included 93 patients with ASC-US/LSIL/ASC-H and HSIL on thin prep cervical smears and who also underwent hr-HPV DNA test and colposcopy-guided biopsy. Biopsy was the gold standard against which the performance of P16INK4a/Ki-67 and hr-HPV results were compared. Results: In women of all ages, sensitivity of (96.8%) hr-HPV test and p16/Ki-67 dual immunocytochemistry (≥1 positive cell) were similar and negative predictive value (NPV) was (97.1% vs. 97.9%) but the latter test showed better specificity (69.4% vs. 53.2%) and positive predictive value (PPV, 61.2% vs. 50.8%) for ≥CIN 2 lesions. A higher cut off of at least 10 positive cells gives a higher specificity and PPV, with slightly decreased sensitivity and NPV. Conclusion: Because high-risk HPV test has a high sensitivity and NPV, whereas P16/Ki-67 dual immunocytochemistry (≥10 positive cells) has a high specificity and PPV, the latter can be recommended as an ancillary test in hr-HPV-positive women to reduce the number of women going for colposcopy and biopsies.
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Affiliation(s)
- G Vinoth Kumar
- Department of General Pathology Christian Medical College, Vellore, Tamil Nadu, India
| | - Anne Jennifer Prabhu
- Department of General Pathology Christian Medical College, Vellore, Tamil Nadu, India
| | - Ajit Sebastian
- Department of Gynecological Oncology Christian Medical College, Vellore, Tamil Nadu, India
| | - Raghavendran
- Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Priya Abraham
- Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Abraham Peedicayil
- Department of Gynecological Oncology Christian Medical College, Vellore, Tamil Nadu, India
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19
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Application of p16, p63, cyclin D1 immunostaining and nuclear morphometric analysis for assessment of cervical dysplasia. VOJNOSANIT PREGL 2022. [DOI: 10.2298/vsp200818087v] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Background/Aim. Human papilloma virus (HPV) infection is the main etiological factor for the development of cervical precancerous dysplastic squamous intraepithelial lesions (SIL). The virus oncoproteins affect several proteins included in cell proliferation. The aim of this study was to evaluate application of immunohistochemical markers related to proteins of the cell cycle and, also, application of nuclear morphometric analysis for assessment of cervical dysplasia. Methods. Retrospective study included 78 women with detection of presence of high-risk HPV by polymerase chain reaction (PCR), with histopathology diagnosis low-grade SIL (LSIL) or high-grade SIL (HSIL). Immunohistochemical staining for p16, p63, cyclin D1 and morphometric analysis of the nuclear surface area were performed. The control group consisted of ten women without SIL and without HPV infection. This study was conducted in accordance with the Helsinki Declaration. Results. Comparing immunohistochemical expression of p16 and p63, highly statistically significant differences (p < 0.001) were established among the control, LSIL and HSIL groups, while cyclin D1 showed significant statistical difference (p < 0.05). Great variations were observed in nuclear morphology and nuclear surface area that had highly statistically significant differences (p < 0.001) among the control, LSIL and HSIL groups. Conclusion. This study demonstrated that immunohistochemical analysis of p16, p63 and cyclin D1 are important for diagnosis of dysplastic changes in cervical epithelium. Also, morphometric analysis of the nuclear surface area demonstrated a high significance for diagnosis of cervical dysplasia.
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20
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Vukomanovic-Djurdjevic B, Andrejic-Visnjic B, Peric A, Nenadic D, Baletic N. Application of p16, p63, cyclin D1 immunostaining and nuclear morphometric analysis for assessment of cervical dysplasia. VOJNOSANIT PREGL 2022; 79:162-167. [DOI: https:/doi.org/10.2298/vsp200818087v] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
Abstract
Background/Aim. Human papilloma virus (HPV) infection is the main etiological factor for the development of cervical precancerous dysplastic squamous intraepithelial lesions (SIL). The virus oncoproteins affect several proteins included in cell proliferation. The aim of this study was to evaluate application of immunohistochemical markers related to proteins of the cell cycle and, also, application of nuclear morphometric analysis for assessment of cervical dysplasia. Methods. Retrospective study included 78 women with detection of presence of high-risk HPV by polymerase chain reaction (PCR), with histopathology diagnosis low-grade SIL (LSIL) or high-grade SIL (HSIL). Immunohistochemical staining for p16, p63, cyclin D1 and morphometric analysis of the nuclear surface area were performed. The control group consisted of ten women without SIL and without HPV infection. This study was conducted in accordance with the Helsinki Declaration. Results. Comparing immunohistochemical expression of p16 and p63, highly statistically significant differences (p < 0.001) were established among the control, LSIL and HSIL groups, while cyclin D1 showed significant statistical difference (p < 0.05). Great variations were observed in nuclear morphology and nuclear surface area that had highly statistically significant differences (p < 0.001) among the control, LSIL and HSIL groups. Conclusion. This study demonstrated that immunohistochemical analysis of p16, p63 and cyclin D1 are important for diagnosis of dysplastic changes in cervical epithelium. Also, morphometric analysis of the nuclear surface area demonstrated a high significance for diagnosis of cervical dysplasia.
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Affiliation(s)
- Biserka Vukomanovic-Djurdjevic
- Military Medical Academy, Institute for Pathology, Belgrade, Serbia + University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia
| | - Bojana Andrejic-Visnjic
- University of Novi Sad, Faculty of Medicine, Department of Histology and Embryology, Novi Sad, Serbia
| | - Aleksandar Peric
- University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia + Military Medical Academy, Clinic of Otorhinolaryngology, Belgrade, Serbia
| | - Dane Nenadic
- University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia + Military Medical Academy, Department of Gynecology, Belgrade, Serbia
| | - Nenad Baletic
- University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia + Military Medical Academy, Clinic of Otorhinolaryngology, Belgrade, Serbia
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21
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Giannos P, Kechagias KS, Bowden S, Tabassum N, Paraskevaidi M, Kyrgiou M. PCNA in Cervical Intraepithelial Neoplasia and Cervical Cancer: An Interaction Network Analysis of Differentially Expressed Genes. Front Oncol 2021; 11:779042. [PMID: 34900731 PMCID: PMC8661029 DOI: 10.3389/fonc.2021.779042] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 10/28/2021] [Indexed: 11/30/2022] Open
Abstract
The investigation of differentially expressed genes (DEGs) and their interactome could provide valuable insights for the development of markers to optimize cervical intraepithelial neoplasia (CIN) screening and treatment. This study investigated patients with cervical disease to identify gene markers whose dysregulated expression and protein interaction interface were linked with CIN and cervical cancer (CC). Literature search of microarray datasets containing cervical epithelial samples was conducted in Gene Expression Omnibus and Pubmed/Medline from inception until March 2021. Retrieved DEGs were used to construct two protein-protein interaction (PPI) networks. Module DEGs that overlapped between CIN and CC samples, were ranked based on 11 topological algorithms. The highest-ranked hub gene was retrieved and its correlation with prognosis, tissue expression and tumor purity in patients with CC, was evaluated. Screening of the literature yielded 9 microarray datasets (GSE7803, GSE27678, GSE63514, GSE6791, GSE9750, GSE29570, GSE39001, GSE63678, GSE67522). Two PPI networks from CIN and CC samples were constructed and consisted of 1704 and 3748 DEGs along 21393 and 79828 interactions, respectively. Two gene clusters were retrieved in the CIN network and three in the CC network. Multi-algorithmic topological analysis revealed PCNA as the highest ranked hub gene between the two networks, both in terms of expression and interactions. Further analysis revealed that while PCNA was overexpressed in CC tissues, it was correlated with favorable prognosis (log-rank P=0.022, HR=0.58) and tumor purity (P=9.86 × 10-4, partial rho=0.197) in CC patients. This study identified that cervical PCNA exhibited multi-algorithmic topological significance among DEGs from CIN and CC samples. Overall, PCNA may serve as a potential gene marker of CIN progression. Experimental validation is necessary to examine its value in patients with cervical disease.
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Affiliation(s)
- Panagiotis Giannos
- Society of Meta-Research and Biomedical Innovation, Cancer Research Working Group, London, United Kingdom.,Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London, United Kingdom
| | - Konstantinos S Kechagias
- Society of Meta-Research and Biomedical Innovation, Cancer Research Working Group, London, United Kingdom.,Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom.,Department of Obstetrics and Gynaecology, Chelsea and Westminster Hospital National Health Service (NHS) Foundation Trust, London, United Kingdom
| | - Sarah Bowden
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom.,Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom
| | - Neha Tabassum
- Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London, United Kingdom
| | - Maria Paraskevaidi
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom.,Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom
| | - Maria Kyrgiou
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom.,Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.,Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.,West London Gynaecological Cancer Centre, Imperial College Healthcare National Health Service (NHS) Trust, London, United Kingdom
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22
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Albulescu A, Plesa A, Fudulu A, Iancu IV, Anton G, Botezatu A. Epigenetic approaches for cervical neoplasia screening (Review). Exp Ther Med 2021; 22:1481. [PMID: 34765022 PMCID: PMC8576616 DOI: 10.3892/etm.2021.10916] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 09/27/2021] [Indexed: 02/07/2023] Open
Abstract
Human papillomavirus (HPV) infection is the leading cause of cervical cancer. The Papanicolaou cytology test is the usually employed type of screening for this infection; however, its sensibility is limited. Only a small percentage of women infected with high-risk HPV develop cervical cancer with an array of genetic and epigenetic modifications. Thus, it is necessary to develop rapid, reproducible and minimally invasive technologies for screening. DNA methylation has gained attention as an alternative method for molecular diagnosis and prognosis in HPV infection. The aim of the present review was to highlight the potential of DNA methylation in cervical neoplasia screening for clinical applications. It was observed that the methylation human and viral genes was correlated with high-grade lesions and cancer. Methylation biomarkers have shown a good capacity to discriminate between high-grade lesions with a transformative potential and cervical cancer, being able to detect these modifications at an early stage. With further research, the epigenetic profiles and subtypes of the tumors could be elaborated, which would aid in therapy selection by opening avenues in personalized precision medicine. Response to therapy could also be evaluated through such methods and the accessibility of liquid biopsies would allow a constant monitoring of the patient's status without invasive sampling techniques.
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Affiliation(s)
- Adrian Albulescu
- Department of Molecular Virology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania.,Pharmacology Department, National Institute for Chemical Pharmaceutical Research and Development, Bucharest 031299, Romania
| | - Adriana Plesa
- Department of Molecular Virology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Alina Fudulu
- Department of Molecular Virology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Iulia Virginia Iancu
- Department of Molecular Virology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Gabriela Anton
- Department of Molecular Virology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Anca Botezatu
- Department of Molecular Virology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
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23
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El Khoury C, Haro E, Alves M, O'Dwyer MC, Meixner K, Albiac LC, Capizzano JN, Ramakrishnan M, Salada C, Gorin SS, Jimbo M, Sen A, Harper DM. Patient-Centered Home Cancer Screening Attitudes During COVID-19 Pandemic. J Patient Cent Res Rev 2021; 8:340-346. [PMID: 34722803 DOI: 10.17294/2330-0698.1835] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
The COVID-19 pandemic disrupted health care delivery of cancer screenings. The primary aim of our work was to evaluate the degree to which populations were accepting of home-based screenings for colorectal cancer (CRC) and cervical cancer (ie, primary human papillomavirus [HPV] testing). Three groups of adults having distinct health burdens that may affect acceptance of home-based cancer screening were identified through outpatient electronic medical records: those having survived a COVID-19 hospitalization; those having been positive for a non-COVID-19 respiratory illness; or those having type 2 diabetes. A total of 132 respondents (58% female) completed an online survey with hypothetical cases about their acceptance of home-based CRC or cervical cancer screening. Among women respondents, urine and vaginal screening for primary HPV testing was acceptable to 64% and 59%, respectively. Among both men and women, at-home CRC screening with fecal immunochemical test or Cologuard® was acceptable to 60% of the respondents. When adjusting for education, women with a positive attitude toward home-based urine and vaginal screening were 49 times and 23 times more likely, respectively, to have a positive attitude toward CRC screening. These findings indicate that home-based cancer screens for CRC and primary HPV testing are acceptable to men and women and may allow for greater compliance with screening in the future.
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Affiliation(s)
| | - Elizabeth Haro
- Department of Family Medicine, University of Michigan, Ann Arbor, MI
| | - Martha Alves
- Department of Family Medicine, University of Michigan, Ann Arbor, MI
| | | | - Kate Meixner
- Department of Family Medicine, University of Michigan, Ann Arbor, MI
| | | | | | | | - Cullen Salada
- Department of Family Medicine, University of Michigan, Ann Arbor, MI
| | | | - Masahito Jimbo
- Department of Family Medicine, University of Michigan, Ann Arbor, MI
| | - Ananda Sen
- Department of Family Medicine, University of Michigan, Ann Arbor, MI
| | - Diane M Harper
- Department of Family Medicine, University of Michigan, Ann Arbor, MI
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24
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Alhamlan F, Obeid D, Khayat H, Asma T, Al-Badawi IA, Almutairi A, Almatrrouk S, Fageeh M, Bakhrbh M, Nassar M, Al-Ahdal M. Prognostic impact of human papillomavirus infection on cervical dysplasia, cancer, and patient survival in Saudi Arabia: A 10-year retrospective analysis. Ann Saudi Med 2021; 41:350-360. [PMID: 34873934 PMCID: PMC8650596 DOI: 10.5144/0256-4947.2021.350] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Data on human papillomavirus (HPV) prevalence and survival rates among HPV-infected women are scarce in Saudi Arabia. OBJECTIVE Assess the prevalence of HPV genotypes in cervical biopsy specimens and its effect on survival over a 10-year timeframe. DESIGN Retrospective, cross-sectional. SETTINGS Saudi referral hospital. PATIENTS AND METHODS Cervical biopsy specimens were collected from women aged 23-95 years old who underwent HPV detection, HPV genotyping, p16INK4a expression measurement using immunohistochemistry. Kaplan-Meier plots were constructed to analyze overall survival rates. MAIN OUTCOME MEASURES Survival rate of HPV-positive cervical cancer patients. SAMPLE SIZE 315 cervical biopsy specimens. RESULTS HPV was detected in 96 patients (30.4%): 37.3% had cervical cancer; 14.2% cervical intraepithelial neoplasia (CIN) III, 4.1% CIN II, and 17.0% CIN I. A significant association was found between HPV presence and cervical cancer (χ2=56.78; P<.001). The expression of p16INK4a was a significant predictor of survival: women who had p16INK4a overexpression had poorer survival rates (multivariate Cox regression, hazard ratio, 3.2; 95% CI, 1.1-8.8). In addition, multivariate models with HPV status and cervical cancer diagnosis showed that HPV status was a significant predictor of survival: HPV-positive women had better survival rates than HPV-negative women. CONCLUSION These findings suggest that implementing cervical and HPV screening programs may decrease cervical cancer rates and improve survival rates of women in Saudi Arabia. LIMITATION Single center and small sample size. CONFLICT OF INTEREST None.
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Affiliation(s)
- Fatimah Alhamlan
- From the Department of Infection and Immunity, Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Dalia Obeid
- From the Department of Infection and Immunity, Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Hadeel Khayat
- From the Department of Infection and Immunity, Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Tulbah Asma
- From the Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Ismail A Al-Badawi
- From the Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Areej Almutairi
- From the Department of Infection and Immunity, Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Shihana Almatrrouk
- From the Department of Infection and Immunity, Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Mohammed Fageeh
- From the Infection Diseases Program, National Center for Biotechnology, King Abdulaziz City for Science and Technology. Riyadh, Saudi Arabia
| | - Muhammed Bakhrbh
- From the Infection Diseases Program, National Center for Biotechnology, King Abdulaziz City for Science and Technology. Riyadh, Saudi Arabia
| | - Majed Nassar
- From the Infection Diseases Program, National Center for Biotechnology, King Abdulaziz City for Science and Technology. Riyadh, Saudi Arabia
| | - Mohammed Al-Ahdal
- From the Department of Infection and Immunity, Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
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25
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Zuberi Z, Mremi A, Chilongola JO, Semango G, Sauli E. Expression analysis of p16 and TOP2A protein biomarkers in cervical cancer lesions and their correlation with clinico-histopathological characteristics in a referral hospital, Tanzania. PLoS One 2021; 16:e0259096. [PMID: 34705880 PMCID: PMC8550370 DOI: 10.1371/journal.pone.0259096] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 10/12/2021] [Indexed: 02/03/2023] Open
Abstract
Introduction Biomarkers yield important information for early diagnosis of cervical cancer. However, they are rarely applied for prognosis of cervical cancer in Tanzania, where visual inspection assay with acetic acid or Lugol’s iodine and Pap test are being used as the standard screening/ diagnostic methods. Methods This was a retrospective hospital-based cross-sectional study that was conducted to assess cyclin-dependent kinase inhibitor (p16) and topoisomerase II-alpha (TOP2A) proteins expression among women seeking cervical cancer care at Kilimanjaro Christian Medical Centre, Tanzania between May 1, 2017 and May 10, 2018. Immunohistochemistry technique was used to detect the expressions of p16 and TOP2A proteins from the retrieved formalin-fixed and paraffin-embedded (FFPE) cervical biopsies. Results A total of 145 patients, with a mean age of 52.1 ± 12.9 years, were included in this study. Upon immunohistochemistry staining, 103 (71.0%) and 90 (62.1%) were p16 and TOP2A positive respectively. There was a strong association between histopathological class and p16/TOP2A expression levels (Fisher’s exact test, p<0.001). Moreover, there was a strong positive correlation between p16/TOP2A and cancerous cervical lesions (Spearman’s rank correlation coefficients = 0.833 and 0.687, p = 0.006 and 0.005, respectively). The age-adjusted odds ratio for predicting cervical cancer lesions were independently significant for p16/TOP2A biomarkers in FFPE cervical tissues [p16: OR = 1.142 (95% CI: 1.059–1.232, p<0.001) and TOP2A: OR = 1.046 (95% CI: 1.008–1.085, p = 0.015)]. Importantly, the diagnostic performance of p16 was higher than that of TOP2A in the diagnosis of cancerous lesions from non-cancerous cervical lesions (sensitivity: 97.2% versus 77.6%, accuracy: 92.8% versus 87.8%, respectively). Conclusion Our study has highlighted that over-expression of TOP2A is related to the grade of cervical intraepithelial neoplasia but does not predict prognosis in cervical cancer. Similarly, expression of p16 is related to degree of histological dysplasia and malignancy, suggesting its prognostic and predictive value in the management of cervical cancers. Further bigger studies are needed to validate their applications in the early diagnosis of cervical cancer.
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Affiliation(s)
- Zavuga Zuberi
- Department of Global Health and Biomedical Sciences, Nelson Mandela African Institution of Science and Technology, Arusha, Tanzania
- Department of Science and Laboratory Technology, Dar es Salaam Institute of Technology, Dar es Salaam, Tanzania
- * E-mail:
| | - Alex Mremi
- Department of Pathology, Kilimanjaro Christian Medical Centre, Moshi, Tanzania
- Kilimanjaro Christian Medical University College, Moshi, Tanzania
| | - Jaffu O. Chilongola
- Kilimanjaro Christian Medical University College, Moshi, Tanzania
- Kilimanjaro Clinical Research Institute, Moshi, Tanzania
| | - George Semango
- Department of Global Health and Biomedical Sciences, Nelson Mandela African Institution of Science and Technology, Arusha, Tanzania
| | - Elingarami Sauli
- Department of Global Health and Biomedical Sciences, Nelson Mandela African Institution of Science and Technology, Arusha, Tanzania
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26
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Burchell AN, Grennan T. Advancing anal cancer prevention in men. Lancet HIV 2021; 8:e522-e523. [PMID: 34339629 DOI: 10.1016/s2352-3018(21)00149-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 06/16/2021] [Indexed: 11/28/2022]
Affiliation(s)
- Ann N Burchell
- St Michael's Hospital, Unity Health Toronto and University of Toronto, Toronto, ON M5B 1W8, Canada.
| | - Troy Grennan
- British Columbia Centre for Disease Control, Vancouver, BC, Canada; University of British Columbia, Vancouver, BC, Canada
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27
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Shin MB, Liu G, Mugo N, Garcia PJ, Rao DW, Broshkevitch CJ, Eckert LO, Pinder LF, Wasserheit JN, Barnabas RV. A Framework for Cervical Cancer Elimination in Low-and-Middle-Income Countries: A Scoping Review and Roadmap for Interventions and Research Priorities. Front Public Health 2021; 9:670032. [PMID: 34277540 PMCID: PMC8281011 DOI: 10.3389/fpubh.2021.670032] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 05/19/2021] [Indexed: 12/14/2022] Open
Abstract
The World Health Organization announced an ambitious call for cervical cancer elimination worldwide. With existing prevention and treatment modalities, cervical cancer elimination is now within reach for high-income countries. Despite limited financing and capacity constraints in low-and-middle-income countries (LMICs), prevention and control efforts can be supported through integrated services and new technologies. We conducted this scoping review to outline a roadmap toward cervical cancer elimination in LMICs and highlight evidence-based interventions and research priorities to accelerate cervical cancer elimination. We reviewed and synthesized literature from 2010 to 2020 on primary and secondary cervical cancer prevention strategies. In addition, we conducted expert interviews with gynecologic and infectious disease providers, researchers, and LMIC health officials. Using these data, we developed a logic model to summarize the current state of science and identified evidence gaps and priority research questions for each prevention strategy. The logic model for cervical cancer elimination maps the needs for improved collaboration between policy makers, production and supply, healthcare systems, providers, health workers, and communities. The model articulates responsibilities for stakeholders and visualizes processes to increase access to and coverage of prevention methods. We discuss the challenges of contextual factors and highlight innovation needs. Effective prevention methods include HPV vaccination, screening using visual inspection and HPV testing, and thermocoagulation. However, vaccine coverage remains low in LMICs. New strategies, including single-dose vaccination could enhance impact. Loss to follow-up and treatment delays could be addressed by improved same-day screen-and-treat technologies. We provide a practical framework to guide cervical cancer elimination in LMICs. The scoping review highlights existing and innovative strategies, unmet needs, and collaborations required to achieve elimination across implementation contexts.
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Affiliation(s)
- Michelle B. Shin
- School of Nursing, University of Washington, Seattle, WA, United States
| | - Gui Liu
- Department of Epidemiology, University of Washington, Seattle, WA, United States
| | - Nelly Mugo
- Department of Global Health, University of Washington, Seattle, WA, United States
- Center for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya
| | - Patricia J. Garcia
- Department of Global Health, University of Washington, Seattle, WA, United States
- School of Public Health, Cayetano Heredia University, Lima, Peru
| | - Darcy W. Rao
- Department of Epidemiology, University of Washington, Seattle, WA, United States
- Department of Global Health, University of Washington, Seattle, WA, United States
| | - Cara J. Broshkevitch
- Department of Global Health, University of Washington, Seattle, WA, United States
| | - Linda O. Eckert
- Department of Global Health, University of Washington, Seattle, WA, United States
- Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, United States
| | - Leeya F. Pinder
- Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, United States
- Department of Obstetrics and Gynecology, University of Zambia, Lusaka, Zambia
| | - Judith N. Wasserheit
- Department of Epidemiology, University of Washington, Seattle, WA, United States
- Department of Global Health, University of Washington, Seattle, WA, United States
- Department of Medicine, University of Washington, Seattle, WA, United States
| | - Ruanne V. Barnabas
- Department of Epidemiology, University of Washington, Seattle, WA, United States
- Department of Global Health, University of Washington, Seattle, WA, United States
- Department of Medicine, University of Washington, Seattle, WA, United States
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
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28
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Harper DM, Plegue M, Sen A, Gorin SS, Jimbo M, Patel MR, Resnicow K. Predictors of screening for cervical and colorectal cancer in women 50-65 years old in a multi-ethnic population. Prev Med Rep 2021; 22:101375. [PMID: 33996388 PMCID: PMC8086134 DOI: 10.1016/j.pmedr.2021.101375] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 02/21/2021] [Accepted: 04/08/2021] [Indexed: 01/05/2023] Open
Abstract
Middle Eastern/North Africa (MENA) women are often not identified in cancer screening studies. The aim of this study was to determine the rates and predictors of cervical and colorectal cancer (CRC) screening for women 50-65 years of three race/ethnicities. White, black and MENA women of Southeast Michigan were surveyed once in 2019 for demographics, health care barriers, chronic diseases, and cancer screening updates using in-person, telephone, and online methods. Descriptive statistics and multivariate multinomial logistic regression were used to predict up-to-date colorectal cancer and cervical cancer screening. All analyses were adjusted by local population weights for comparability and generalizability. 394 women participated with 54% up-to-date on both screenings, 21% for cervical cancer screening alone, and 12% for CRC alone. Women more likely to be up-to-date for only cervical cancer screening compared to both cancer screens are younger (aOR 0.83 (95% CI 0.76, 0.92), are of MENA descent (7.97 (2.46, 25.76) and have no insurance (9.41 (1.07, 82.92). There are no predictors for women being up-to-date for CRC screening alone compared to both screens. Among women 50-65 years old, being up-to-date in cervical cancer screening is unrelated to being up-to-date for CRC screening. Compared to Healthy People 2020, there are significant gaps in cervical and CRC screening among women 50-65 years old of all races, but particularly among women of MENA descent who are even less likely to have CRC screening than cervical cancer screening.
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Key Words
- 50–65 years old
- BMI, body mass index
- COVID-19, coronavirus -19 or SARS-CoV-2 – severe acute respiratory syndrome coronavirus 2
- CRC, colorectal cancer
- Cervical cancer screening
- Colorectal cancer screening
- FDA, Food and Drug Administration of the United States
- FIT DNA, multitarget stool DNA test
- FIT, fecal immunochemical test
- FOBT, fecal occult blood test
- Females
- MENA, Middle Eastern/North African
- MT, sDNA test – multitarget stool DNA test - Cologuard®
- Middle Eastern-North American (MENA) ethnicity
- OR, odds ratio
- SE, standard error
- USPSTF, United States Preventive Services Task Force
- aOR, adjusted odds ratio
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Affiliation(s)
- Diane M. Harper
- Department of Family Medicine, University of Michigan, Ann Arbor, MI, USA
- Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA
- Department of Women’s and Gender Studies, University of Michigan, Ann Arbor, MI, USA
| | - Melissa Plegue
- Department of Family Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Ananda Sen
- Department of Family Medicine, University of Michigan, Ann Arbor, MI, USA
- Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA
| | | | - Mas Jimbo
- Department of Family Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Minal R. Patel
- Department of Health Behavior and Health Education, University of Michigan, Ann Arbor, MI, USA
| | - Ken Resnicow
- Department of Health Behavior and Health Education, University of Michigan, Ann Arbor, MI, USA
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Tavakoli F, Khatami SS, Momeni F, Azadbakht J, Ghasemi F. Cervical Cancer Diagnosis: Insights into Biochemical Biomarkers and Imaging Techniques. Comb Chem High Throughput Screen 2021; 24:605-623. [PMID: 32875976 DOI: 10.2174/1386207323666200901101955] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 07/14/2020] [Accepted: 08/06/2020] [Indexed: 11/22/2022]
Abstract
Cervical malignancy is known as one of the important cancers which is originated from cervix. This malignancy has been observed in women infected with papillomavirus who had regular oral contraceptives, multiple pregnancies, and sexual relations. Early and fast cervical cancer diagnosis is known as two important aspects of cervical cancer therapy. Several investigations indicated that early and fast detection of cervical cancer could be associated with better treatment process and increasing survival rate of patients with this malignancy. Imaging techniques are very important diagnosis tools that could be employed for diagnosis and following responses to therapy in various cervical cancer stages. Multiple lines of evidence indicated that utilization of imaging techniques is related to some limitations (i.e. high cost, and invasive effects). Hence, it seems that along with using imaging techniques, finding and developing new biomarkers could be useful in the diagnosis and treatment of subjects with cervical cancer. Taken together, many studies showed that a variety of biomarkers including, several proteins, mRNAs, microRNAs, exosomes and polymorphisms might be introduced as prognostic, diagnostic and therapeutic biomarkers in cervical cancer therapy. In this review article, we highlighted imaging techniques as well as novel biomarkers for the diagnosis of cervical cancer.
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Affiliation(s)
- Fatemeh Tavakoli
- Department of Biotechnology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sara Sadat Khatami
- Department of Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - Fatemeh Momeni
- Isfahan Research Committee of Multiple Sclerosis, Alzahra Research Institute, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Javid Azadbakht
- Department of Radiology and Imaging, Kashan University of Medical Science, Kashan, Iran
| | - Faezeh Ghasemi
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
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30
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Medda A, Duca D, Chiocca S. Human Papillomavirus and Cellular Pathways: Hits and Targets. Pathogens 2021; 10:262. [PMID: 33668730 PMCID: PMC7996217 DOI: 10.3390/pathogens10030262] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 02/08/2021] [Accepted: 02/19/2021] [Indexed: 12/18/2022] Open
Abstract
The Human Papillomavirus (HPV) is the causative agent of different kinds of tumors, including cervical cancers, non-melanoma skin cancers, anogenital cancers, and head and neck cancers. Despite the vaccination campaigns implemented over the last decades, we are far from eradicating HPV-driven malignancies. Moreover, the lack of targeted therapies to tackle HPV-related tumors exacerbates this problem. Biomarkers for early detection of the pathology and more tailored therapeutic approaches are needed, and a complete understanding of HPV-driven tumorigenesis is essential to reach this goal. In this review, we overview the molecular pathways implicated in HPV infection and carcinogenesis, emphasizing the potential targets for new therapeutic strategies as well as new biomarkers.
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Affiliation(s)
| | | | - Susanna Chiocca
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy; (A.M.); (D.D.)
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31
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Splicing Genomics Events in Cervical Cancer: Insights for Phenotypic Stratification and Biomarker Potency. Genes (Basel) 2021; 12:genes12020130. [PMID: 33498485 PMCID: PMC7909518 DOI: 10.3390/genes12020130] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 01/09/2021] [Accepted: 01/12/2021] [Indexed: 12/24/2022] Open
Abstract
Gynaecological cancers are attributed to the second most diagnosed cancers in women after breast cancer. On a global scale, cervical cancer is the fourth most common cancer and the most common cancer in developing countries with rapidly increasing mortality rates. Human papillomavirus (HPV) infection is a major contributor to the disease. HPV infections cause prominent cellular changes including alternative splicing to drive malignant transformation. A fundamental characteristic attributed to cancer is the dysregulation of cellular transcription. Alternative splicing is regulated by several splicing factors and molecular changes in these factors lead to cancer mechanisms such as tumour development and progression and drug resistance. The serine/arginine-rich (SR) proteins and heterogeneous ribonucleoproteins (hnRNPs) have prominent roles in modulating alternative splicing. Evidence shows molecular alteration and expression levels in these splicing factors in cervical cancer. Furthermore, aberrant splicing events in cancer-related genes lead to chemo- and radioresistance. Identifying clinically relevant modifications in alternative splicing events and splicing variants, in cervical cancer, as potential biomarkers for their role in cancer progression and therapy resistance is scrutinised. This review will focus on the molecular mechanisms underlying the aberrant splicing events in cervical cancer that may serve as potential biomarkers for diagnosis, prognosis, and novel drug targets.
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32
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Sharma P, Gupta P, Gupta N, Suri V, Rajwanshi A. Evaluation of the Performance of CinTec® PLUS in SurePathTM Liquid-Based Cervico-Vaginal Samples. Turk Patoloji Derg 2021; 37:32-38. [PMID: 33372263 PMCID: PMC10508926 DOI: 10.5146/tjpath.2020.01505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 08/24/2020] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVE Cervical cytology and Human papillomavirus (HPV) testing are effective screening techniques but both have limitations. A few recent studies in the literature have highlighted the role of co-expression of p16INK4a and Ki-67 for cervical cancer screening. The present study was undertaken to evaluate the diagnostic performance of the CINtec® PLUS kit (dual immunostaining for p16 and Ki-67) in SurePathTM liquid-based (LBC) cervico-vaginal samples. MATERIALS AND METHODS This was a prospective study performed on 52 cervico-vaginal SurePath™ LBC samples reported as having squamous epithelial cell abnormality (ECA). All the samples were stained using CINtec® PLUS kits. Additionally, HPV-DNA testing was also done and the results were compared. RESULTS The age range was 34-74 years. ECA included 18 (34.6%) cases of ASC-US, 9 (17.3%) cases of low-grade squamous intraepithelial lesion (LSIL), 11 (21.2%) cases of high-grade squamous intraepithelial lesion (HSIL), and 14 (26.9%) cases of squamous cell carcinoma (SCC). Cervical biopsies were available in 19 (36.5%) cases. A total of 34/52 (65.4%) cases were positive for HPV-DNA (5/18-ASC-US; 6/9-LSIL; 10/11-HSIL; 13/14-SCC). The CINtec® PLUS test was positive in 41/52 (78.8%) cases (11/18-ASC-US; 6/9-LSIL; 11/11-HSIL; 13/14-SCC). On comparing CINtec® PLUS positivity (78.8%) with HPV positivity (65.4%), dual positivity was seen in 3/18 cases of ASC-US, 6/9 cases of LSIL, 10/11 cases of HSIL, and 12/14 cases of SCC. One case each of HSIL and SCC was negative on the HPV test and was positive on CINtec® PLUS. CONCLUSIONS CINtec® PLUS test helps to improve the detection of pre-cancerous cervical lesions as compared to cervical cytology or HPV testing alone and hence can serve as a potentially useful diagnostic and triage tool, especially for indeterminate cases.
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Affiliation(s)
- Pooja Sharma
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Parikshaa Gupta
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Nalini Gupta
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vanita Suri
- Obstetrics and Gynecology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Arvind Rajwanshi
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Adiga D, Eswaran S, Pandey D, Sharan K, Kabekkodu SP. Molecular landscape of recurrent cervical cancer. Crit Rev Oncol Hematol 2021; 157:103178. [PMID: 33279812 DOI: 10.1016/j.critrevonc.2020.103178] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 11/06/2020] [Accepted: 11/11/2020] [Indexed: 02/07/2023] Open
Abstract
Cervical cancer (CC) is a major gynecological problem in developing and underdeveloped countries. Despite the significant advancement in early detection and treatment modalities, several patients recur. Moreover, the molecular mechanisms responsible for CC recurrence remains obscure. The patients with CC recurrence often show poor prognosis and significantly high mortality rates. The clinical management of recurrent CC depends on treatment history, site, and extent of the recurrence. Owing to poor prognosis and limited treatment options, recurrent CC often presents a challenge to the clinicians. Several in vitro, in vivo, and patient studies have led to the identification of the critical molecular changes responsible for CC recurrence. Both aberrant genetic and epigenetic modifications leading to altered cell signaling pathways have been reported to impact CC recurrence. Researchers are currently trying to dissect the molecular pathways in CC and translate these findings for better management of disease. This article attempts to review the existing knowledge of disease relapse, accompanying challenges, and associated molecular players in CC.
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Affiliation(s)
- Divya Adiga
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Sangavi Eswaran
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Deeksha Pandey
- Department of OBGYN, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Krishna Sharan
- Department of Radiotherapy and Oncology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Shama Prasada Kabekkodu
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
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34
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Role of PAP Smear Cytology and p16 Immunocytochemistry for Detection of Cervical Lesions of Cervix: A Hospital-Based Study. INDIAN JOURNAL OF GYNECOLOGIC ONCOLOGY 2020. [DOI: 10.1007/s40944-020-00479-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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35
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Molina MA, Carosi Diatricch L, Castany Quintana M, Melchers WJ, Andralojc KM. Cervical cancer risk profiling: molecular biomarkers predicting the outcome of hrHPV infection. Expert Rev Mol Diagn 2020; 20:1099-1120. [PMID: 33044104 DOI: 10.1080/14737159.2020.1835472] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Cervical cancer affects half a million women worldwide annually. Given the association between high-risk human papillomavirus (hrHPV) infection and carcinogenesis, hrHPV DNA testing became an essential diagnostic tool. However, hrHPV alone does not cause the disease, and, most importantly, many cervical lesions regress to normal in a year because of the host immune system. Hence, the low specificity of hrHPV DNA tests and their inability to predict the outcome of infections have triggered a further search for biomarkers. AREAS COVERED We evaluated the latest viral and cellular biomarkers validated for clinical use as primary screening or triage for cervical cancer and assessed their promise for prevention as well as potential use in the future. The literature search focused on effective biomarkers for different stages of the disease, aiming to determine their significance in predicting the outcome of hrHPV infections. EXPERT OPINION Biomarkers such as p16/Ki-67, hrHPV genotyping, hrHPV transcriptional status, and methylation patterns have demonstrated promising results. Their eventual implementation in the screening programs may support the prompt diagnosis of hrHPV infection and its progression to cancer. These biomarkers will help in making clinical management decisions on time, thus, saving the lives of hrHPV-infected women, particularly in developing countries.
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Affiliation(s)
- Mariano A Molina
- Department of Microbiology, Faculty of Science, Radboud University , Nijmegen, The Netherlands.,Department of Medical Microbiology, Radboud university medical center , Nijmegen, The Netherlands
| | | | - Marina Castany Quintana
- Department of Medical Microbiology, Radboud university medical center , Nijmegen, The Netherlands
| | - Willem Jg Melchers
- Department of Medical Microbiology, Radboud university medical center , Nijmegen, The Netherlands
| | - Karolina M Andralojc
- Department of Medical Microbiology, Radboud university medical center , Nijmegen, The Netherlands.,Department of Biochemistry, Radboud Institute for Molecular Life Sciences , Nijmegen, The Netherlands
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36
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Low-Cost Molecular Biomarker HPV-16/18 E6 Oncoprotein Expression in Cervical Intraepithelial Neoplasia (CIN) and Cervical Cancer with Its Relation with Severity of Neoplastic State. INDIAN JOURNAL OF GYNECOLOGIC ONCOLOGY 2020. [DOI: 10.1007/s40944-020-00416-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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37
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Ara R, Khatun S, Pervin S, Jahan M, Shahera U, Ferdous J, Begum SA, Fatema S, Begum M, Nazneen S, Goodman A. Role of molecular biomarker human papilloma virus (HPV) E6 oncoprotein in cervical cancer screening. Gynecol Oncol 2020; 158:590-596. [PMID: 32680634 DOI: 10.1016/j.ygyno.2020.06.496] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 06/19/2020] [Indexed: 11/19/2022]
Abstract
OBJECTIVE The Onco E6™ Cervical Test, based on detection of the E6 oncoprotein of HPV 16 and 18 genotypes is evaluated as a screen for the early detection cervical neoplasia in resource-limited countries. METHODS This prospective study from June 2018 to June 2019 evaluated 235 women aged 21-65 years, who came to Gynaecological Oncology Outpatient Department by VIA, cytology, E6 oncoprotein test and by colposcopy. Screen-positive women by any of the tests or women with suspicious findings were further evaluated by biopsy at colposcopy. The McNemar test was used to compare the performance of E6 oncoprotein test with other screening tests. RESULTS The E6 oncoprotein positivity rate was 6.8% (n = 16) with 81.25% HPV 16 positive and 18.75% HPV 18 positive. Among VIA positive cases (n = 100), E6 oncoprotein was positive in 9% (p < .001). In histopathology confirmed chronic cervicitis, CIN I, CIN II, CIN III and invasive cervical cancer, E6 test was positive for 2.8%, 4.7%, 25%, 50% and 100% respectively. E6 oncoprotein test had the highest specificity and Positive Predictive Value (PPV; 97% and 75%) compared to VIA (42% and 18%), cytology (95% and 46%) and colposcopy (94% and 59%). Sensitivity of the E6 oncoprotein test for detection of CIN3+ was significantly higher than that of cytology (52% VS 25%) but lower than that of VIA (52% VS 74%). CONCLUSIONS The HPV E6 oncoprotein test is highly specific and is an effective triage test to reduce colposcopy referrals for the large number of false positive test outcomes seen with VIA.
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Affiliation(s)
- Rifat Ara
- Gynecologic Oncology Department, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Sabera Khatun
- Gynecologic Oncology Department, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Shahana Pervin
- Gynecologic Oncology Department, National Institute of Cancer Research and Hospital, Dhaka, Bangladesh
| | - Munira Jahan
- Virology Department, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Umme Shahera
- Virology Department, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Jannatul Ferdous
- Gynecologic Oncology Department, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Shirin Akter Begum
- Gynecologic Oncology Department, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Sayada Fatema
- Gynecologic Oncology Department, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Monowara Begum
- Gynecologic Oncology Department, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Shahana Nazneen
- Gynecology and Obstetric Department, Shaheed Tajuddin Ahmad Medical College Hospital, Gazipur, Bangladesh
| | - A Goodman
- Massachusetts General Hospital, USA.
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Castle PE, Adcock R, Cuzick J, Wentzensen N, Torrez-Martinez NE, Torres SM, Stoler MH, Ronnett BM, Joste NE, Darragh TM, Gravitt PE, Schiffman M, Hunt WC, Kinney WK, Wheeler CM. Relationships of p16 Immunohistochemistry and Other Biomarkers With Diagnoses of Cervical Abnormalities: Implications for LAST Terminology. Arch Pathol Lab Med 2020; 144:725-734. [PMID: 31718233 PMCID: PMC8575174 DOI: 10.5858/arpa.2019-0241-oa] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Abstract
CONTEXT.— Lower Anogenital Squamous Terminology (LAST) standardization recommended p16INK4a immunohistochemistry (p16 IHC) for biopsies diagnosed morphologically as cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) to classify them as low-grade or high-grade squamous intraepithelial lesions (HSILs). OBJECTIVE.— To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses. DESIGN.— A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available. RESULTS.— Biopsies were more likely to test p16 IHC positive with increasing severity of CP diagnoses, overall (Ptrend ≤ .001) and within each HPV risk group (Ptrend ≤ .001 except for low-risk HPV [Ptrend < .010]). All abnormal grades of CP-diagnosed biopsies were more likely to test p16 IHC positive with a higher HPV risk group (Ptrend < .001), and testing p16 IHC positive was associated with higher HPV risk group than testing p16 IHC negative for each grade of CP-diagnosed biopsies (P < .001). p16 IHC-positive, CP-diagnosed CIN2 biopsies were less likely than CP-diagnosed CIN3 biopsies to test HPV16 positive, have an antecedent HSIL+ cytology, or to be diagnosed as CIN3+ by the EP (P < .001 for all). p16 IHC-positive, CP-diagnosed CIN1 biopsies had lower HPV risk groups than p16 IHC-negative, CP-diagnosed CIN2 biopsies (P < .001). CONCLUSIONS.— p16 IHC-positive, CP-diagnosed CIN2 appears to be lower cancer risk than CP-diagnosed CIN3. LAST classification of "HSIL" diagnosis, which includes p16 IHC-positive CIN2, should annotate the morphologic diagnosis (CIN2 or CIN3) to inform all management decisions, which is especially important for young (<30 years) women diagnosed with CIN2 for whom surveillance rather than treatment is recommended.
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Affiliation(s)
- Philip E Castle
- From Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Castle); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Ms Adcock and Dr Cuzick); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Drs Wentzensen and Schiffman); the Department of Pathology, University of New Mexico Cancer Center, Albuquerque (Ms Torrez-Martinez, Dr Torres, Dr Joste, Dr Gravitt, Mr Hunt, and Dr Wheeler); the Department of Pathology, University of Virginia Health System, Charlottesville (Dr Stoler); the Department of Pathology, Johns Hopkins University, Baltimore, Maryland (Dr Ronnett); the Department of Pathology, University of California, San Francisco (Dr Darragh); and Sacramento, California (Dr Kinney)
| | - Rachael Adcock
- From Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Castle); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Ms Adcock and Dr Cuzick); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Drs Wentzensen and Schiffman); the Department of Pathology, University of New Mexico Cancer Center, Albuquerque (Ms Torrez-Martinez, Dr Torres, Dr Joste, Dr Gravitt, Mr Hunt, and Dr Wheeler); the Department of Pathology, University of Virginia Health System, Charlottesville (Dr Stoler); the Department of Pathology, Johns Hopkins University, Baltimore, Maryland (Dr Ronnett); the Department of Pathology, University of California, San Francisco (Dr Darragh); and Sacramento, California (Dr Kinney)
| | - Jack Cuzick
- From Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Castle); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Ms Adcock and Dr Cuzick); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Drs Wentzensen and Schiffman); the Department of Pathology, University of New Mexico Cancer Center, Albuquerque (Ms Torrez-Martinez, Dr Torres, Dr Joste, Dr Gravitt, Mr Hunt, and Dr Wheeler); the Department of Pathology, University of Virginia Health System, Charlottesville (Dr Stoler); the Department of Pathology, Johns Hopkins University, Baltimore, Maryland (Dr Ronnett); the Department of Pathology, University of California, San Francisco (Dr Darragh); and Sacramento, California (Dr Kinney)
| | - Nicolas Wentzensen
- From Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Castle); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Ms Adcock and Dr Cuzick); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Drs Wentzensen and Schiffman); the Department of Pathology, University of New Mexico Cancer Center, Albuquerque (Ms Torrez-Martinez, Dr Torres, Dr Joste, Dr Gravitt, Mr Hunt, and Dr Wheeler); the Department of Pathology, University of Virginia Health System, Charlottesville (Dr Stoler); the Department of Pathology, Johns Hopkins University, Baltimore, Maryland (Dr Ronnett); the Department of Pathology, University of California, San Francisco (Dr Darragh); and Sacramento, California (Dr Kinney)
| | - Norah E Torrez-Martinez
- From Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Castle); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Ms Adcock and Dr Cuzick); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Drs Wentzensen and Schiffman); the Department of Pathology, University of New Mexico Cancer Center, Albuquerque (Ms Torrez-Martinez, Dr Torres, Dr Joste, Dr Gravitt, Mr Hunt, and Dr Wheeler); the Department of Pathology, University of Virginia Health System, Charlottesville (Dr Stoler); the Department of Pathology, Johns Hopkins University, Baltimore, Maryland (Dr Ronnett); the Department of Pathology, University of California, San Francisco (Dr Darragh); and Sacramento, California (Dr Kinney)
| | - Salina M Torres
- From Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Castle); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Ms Adcock and Dr Cuzick); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Drs Wentzensen and Schiffman); the Department of Pathology, University of New Mexico Cancer Center, Albuquerque (Ms Torrez-Martinez, Dr Torres, Dr Joste, Dr Gravitt, Mr Hunt, and Dr Wheeler); the Department of Pathology, University of Virginia Health System, Charlottesville (Dr Stoler); the Department of Pathology, Johns Hopkins University, Baltimore, Maryland (Dr Ronnett); the Department of Pathology, University of California, San Francisco (Dr Darragh); and Sacramento, California (Dr Kinney)
| | - Mark H Stoler
- From Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Castle); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Ms Adcock and Dr Cuzick); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Drs Wentzensen and Schiffman); the Department of Pathology, University of New Mexico Cancer Center, Albuquerque (Ms Torrez-Martinez, Dr Torres, Dr Joste, Dr Gravitt, Mr Hunt, and Dr Wheeler); the Department of Pathology, University of Virginia Health System, Charlottesville (Dr Stoler); the Department of Pathology, Johns Hopkins University, Baltimore, Maryland (Dr Ronnett); the Department of Pathology, University of California, San Francisco (Dr Darragh); and Sacramento, California (Dr Kinney)
| | - Brigitte M Ronnett
- From Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Castle); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Ms Adcock and Dr Cuzick); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Drs Wentzensen and Schiffman); the Department of Pathology, University of New Mexico Cancer Center, Albuquerque (Ms Torrez-Martinez, Dr Torres, Dr Joste, Dr Gravitt, Mr Hunt, and Dr Wheeler); the Department of Pathology, University of Virginia Health System, Charlottesville (Dr Stoler); the Department of Pathology, Johns Hopkins University, Baltimore, Maryland (Dr Ronnett); the Department of Pathology, University of California, San Francisco (Dr Darragh); and Sacramento, California (Dr Kinney)
| | - Nancy E Joste
- From Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Castle); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Ms Adcock and Dr Cuzick); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Drs Wentzensen and Schiffman); the Department of Pathology, University of New Mexico Cancer Center, Albuquerque (Ms Torrez-Martinez, Dr Torres, Dr Joste, Dr Gravitt, Mr Hunt, and Dr Wheeler); the Department of Pathology, University of Virginia Health System, Charlottesville (Dr Stoler); the Department of Pathology, Johns Hopkins University, Baltimore, Maryland (Dr Ronnett); the Department of Pathology, University of California, San Francisco (Dr Darragh); and Sacramento, California (Dr Kinney)
| | - Teresa M Darragh
- From Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Castle); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Ms Adcock and Dr Cuzick); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Drs Wentzensen and Schiffman); the Department of Pathology, University of New Mexico Cancer Center, Albuquerque (Ms Torrez-Martinez, Dr Torres, Dr Joste, Dr Gravitt, Mr Hunt, and Dr Wheeler); the Department of Pathology, University of Virginia Health System, Charlottesville (Dr Stoler); the Department of Pathology, Johns Hopkins University, Baltimore, Maryland (Dr Ronnett); the Department of Pathology, University of California, San Francisco (Dr Darragh); and Sacramento, California (Dr Kinney)
| | - Patti E Gravitt
- From Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Castle); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Ms Adcock and Dr Cuzick); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Drs Wentzensen and Schiffman); the Department of Pathology, University of New Mexico Cancer Center, Albuquerque (Ms Torrez-Martinez, Dr Torres, Dr Joste, Dr Gravitt, Mr Hunt, and Dr Wheeler); the Department of Pathology, University of Virginia Health System, Charlottesville (Dr Stoler); the Department of Pathology, Johns Hopkins University, Baltimore, Maryland (Dr Ronnett); the Department of Pathology, University of California, San Francisco (Dr Darragh); and Sacramento, California (Dr Kinney)
| | - Mark Schiffman
- From Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Castle); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Ms Adcock and Dr Cuzick); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Drs Wentzensen and Schiffman); the Department of Pathology, University of New Mexico Cancer Center, Albuquerque (Ms Torrez-Martinez, Dr Torres, Dr Joste, Dr Gravitt, Mr Hunt, and Dr Wheeler); the Department of Pathology, University of Virginia Health System, Charlottesville (Dr Stoler); the Department of Pathology, Johns Hopkins University, Baltimore, Maryland (Dr Ronnett); the Department of Pathology, University of California, San Francisco (Dr Darragh); and Sacramento, California (Dr Kinney)
| | - William C Hunt
- From Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Castle); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Ms Adcock and Dr Cuzick); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Drs Wentzensen and Schiffman); the Department of Pathology, University of New Mexico Cancer Center, Albuquerque (Ms Torrez-Martinez, Dr Torres, Dr Joste, Dr Gravitt, Mr Hunt, and Dr Wheeler); the Department of Pathology, University of Virginia Health System, Charlottesville (Dr Stoler); the Department of Pathology, Johns Hopkins University, Baltimore, Maryland (Dr Ronnett); the Department of Pathology, University of California, San Francisco (Dr Darragh); and Sacramento, California (Dr Kinney)
| | - Walter K Kinney
- From Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Castle); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Ms Adcock and Dr Cuzick); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Drs Wentzensen and Schiffman); the Department of Pathology, University of New Mexico Cancer Center, Albuquerque (Ms Torrez-Martinez, Dr Torres, Dr Joste, Dr Gravitt, Mr Hunt, and Dr Wheeler); the Department of Pathology, University of Virginia Health System, Charlottesville (Dr Stoler); the Department of Pathology, Johns Hopkins University, Baltimore, Maryland (Dr Ronnett); the Department of Pathology, University of California, San Francisco (Dr Darragh); and Sacramento, California (Dr Kinney)
| | - Cosette M Wheeler
- From Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Castle); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Ms Adcock and Dr Cuzick); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Drs Wentzensen and Schiffman); the Department of Pathology, University of New Mexico Cancer Center, Albuquerque (Ms Torrez-Martinez, Dr Torres, Dr Joste, Dr Gravitt, Mr Hunt, and Dr Wheeler); the Department of Pathology, University of Virginia Health System, Charlottesville (Dr Stoler); the Department of Pathology, Johns Hopkins University, Baltimore, Maryland (Dr Ronnett); the Department of Pathology, University of California, San Francisco (Dr Darragh); and Sacramento, California (Dr Kinney)
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Almonte M, Murillo R, Sánchez GI, González P, Ferrera A, Picconi MA, Wiesner C, Cruz-Valdez A, Lazcano-Ponce E, Jerónimo J, Ferreccio C, Kasamatsu E, Mendoza L, Rodríguez G, Calderón A, Venegas G, Villagra V, Tatti S, Fleider L, Terán C, Baena A, Hernández MDLL, Rol ML, Lucas E, Barbier S, Ramírez AT, Arrossi S, Rodríguez MI, González E, Celis M, Martínez S, Salgado Y, Ortega M, Beracochea AV, Pérez N, Rodríguez de la Peña M, Ramón M, Hernández-Nevarez P, Arboleda-Naranjo M, Cabrera Y, Salgado B, García L, Retana MA, Colucci MC, Arias-Stella J, Bellido-Fuentes Y, Bobadilla ML, Olmedo G, Brito-García I, Méndez-Herrera A, Cardinal L, Flores B, Peñaranda J, Martínez-Better J, Soilán A, Figueroa J, Caserta B, Sosa C, Moreno A, Mural J, Doimi F, Giménez D, Rodríguez H, Lora O, Luciani S, Broutet N, Darragh T, Herrero R. Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America: the ESTAMPA screening study protocol. BMJ Open 2020; 10:e035796. [PMID: 32448795 PMCID: PMC7252979 DOI: 10.1136/bmjopen-2019-035796] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 03/18/2020] [Accepted: 04/03/2020] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION Human papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC. METHODS AND ANALYSIS Women aged 30-64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre. ETHICS AND DISSEMINATION The study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER NCT01881659.
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Affiliation(s)
- Maribel Almonte
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France
| | - Raúl Murillo
- Pontificia Universidad Javeriana, Bogotá, Colombia
| | | | - Paula González
- Agencia Costarricense de Investigaciones Biomédicas (ACIB), Fundación Inciensa, Guanacaste, Costa Rica
| | - Annabelle Ferrera
- Instituto de Investigaciones en Microbiología, Universidad Nacional Autónoma de Honduras (UNAH), Tegucigalpa, Honduras
| | | | | | | | | | | | - Catterina Ferreccio
- Advanced Center for Chronic Diseases, ACCDiS, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Elena Kasamatsu
- Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, San Lorenzo, Paraguay
| | - Laura Mendoza
- Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, San Lorenzo, Paraguay
| | | | - Alejandro Calderón
- Caja Costarricense de Seguro Social (CCSS), Región Pacífico Central, San José, Costa Rica
| | - Gino Venegas
- Clínica Angloamericana, Lima, Perú
- Escuela de Medicina Humana, Universidad de Piura, Lima, Perú
| | | | - Silvio Tatti
- Hospital de Clínicas José de San Martín, Buenos Aires, Argentina
| | - Laura Fleider
- Hospital de Clínicas José de San Martín, Buenos Aires, Argentina
| | - Carolina Terán
- Facultad de Medicina, Universidad Mayor, Real y Pontificia de San Francisco Xavier de Chuquisaca, Sucre, Bolivia
| | - Armando Baena
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France
| | - María de la Luz Hernández
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France
- SMS-Oncology, Amsterdam, The Netherlands
| | - Mary Luz Rol
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France
| | - Eric Lucas
- Screening Group, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France
| | - Sylvaine Barbier
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France
| | - Arianis Tatiana Ramírez
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France
| | - Silvina Arrossi
- Centro de Estudios de Estado y Sociedad/Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
| | - María Isabel Rodríguez
- Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, San Lorenzo, Paraguay
| | | | - Marcela Celis
- Instituto Nacional de Cancerología, Bogotá, Colombia
| | | | - Yuly Salgado
- Instituto Nacional de Cancerología, Bogotá, Colombia
| | - Marina Ortega
- Hospital Nacional, Ministerio de Salud Pública y Bienestar Social, Itauguá, Paraguay
- Instituto Nacional del Cáncer, Ministerio de Salud Pública y Bienestar Social, Capiatá, Paraguay
| | - Andrea Verónica Beracochea
- Centro de Salud Ciudad de la Costa, ASSE, Ciudad de la Costa, Uruguay
- Hospital Policial, DNASS, Montevideo, Uruguay
| | - Natalia Pérez
- Hospital de Clínicas, Facultad de Medicina, UDELAR, Montevideo, Uruguay
| | | | | | | | | | - Yessy Cabrera
- Instituto de Investigaciones en Microbiología, Universidad Nacional Autónoma de Honduras (UNAH), Tegucigalpa, Honduras
| | | | - Laura García
- Laboratorio de Biología Molecular, Departamento de Patología Clínica, Centro Hospitalario Pereira Rossell, Montevideo, Uruguay
| | | | - María Celeste Colucci
- Instituto Nacional de Enfermedades Infecciosas - ANLIS Malbrán, Buenos Aires, Argentina
| | | | | | | | - Gladys Olmedo
- Laboratorio Central de Salud Pública, Asunción, Paraguay
| | | | | | - Lucía Cardinal
- Hospital de Clínicas José de San Martín, Buenos Aires, Argentina
| | - Betsy Flores
- Facultad de Medicina, Universidad Mayor, Real y Pontificia de San Francisco Xavier de Chuquisaca, Sucre, Bolivia
| | - Jhacquelin Peñaranda
- Facultad de Medicina, Universidad Mayor, Real y Pontificia de San Francisco Xavier de Chuquisaca, Sucre, Bolivia
| | | | - Ana Soilán
- Hospital Nacional, Ministerio de Salud Pública y Bienestar Social, Itauguá, Paraguay
- Hospital Materno Infantil de San Lorenzo, Ministerio de Salud Pública y Bienestar Social, San Lorenzo, Paraguay
| | | | - Benedicta Caserta
- Departamento de Anatomía Patológica y Citología, Hospital de la Mujer, Centro Hospitalario Pereira Rossell, Montevideo, Uruguay
| | - Carlos Sosa
- Hospital Monseñor Víctor Manuel Sanabria Martínez, CCSS, Puntarenas, Costa Rica
| | - Adrián Moreno
- Hospital Nacional Profesor Alejandro Posadas, Buenos Aires, Argentina
| | - Juan Mural
- Hospital Nacional Profesor Alejandro Posadas, Buenos Aires, Argentina
| | | | - Diana Giménez
- Hospital Materno Infantil de Trinidad, Ministerio de Salud Pública y Bienestar Social, Asunción, Paraguay
| | - Hernando Rodríguez
- Hospital Materno Infantil de Trinidad, Ministerio de Salud Pública y Bienestar Social, Asunción, Paraguay
| | - Oscar Lora
- Facultad de Medicina, Universidad Mayor, Real y Pontificia de San Francisco Xavier de Chuquisaca, Sucre, Bolivia
- Hospital Gineco-Obstétrico y Neonatal "Dr Jaime Sánchez Porcel", Sucre, Bolivia
| | - Silvana Luciani
- Pan American Health Organization (PAHO), Washington, District of Columbia, USA
| | - Nathalie Broutet
- Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland
| | - Teresa Darragh
- Department of Pathology, University of California, San Francisco, California, USA
| | - Rolando Herrero
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France
- Agencia Costarricense de Investigaciones Biomédicas (ACIB), Fundación Inciensa, Guanacaste, Costa Rica
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Shah UJ, Nasiruddin M, Dar SA, Khan MKA, Akhter MR, Singh N, Rabaan AA, Haque S. Emerging biomarkers and clinical significance of HPV genotyping in prevention and management of cervical cancer. Microb Pathog 2020; 143:104131. [PMID: 32169490 DOI: 10.1016/j.micpath.2020.104131] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 02/10/2020] [Accepted: 03/06/2020] [Indexed: 12/15/2022]
Abstract
Cervical cancer is a growing and serious problem world-wide in women, but more acute in developing countries especially in Indian subcontinent. The main causative agent for the disease is Human Papilloma Virus (HPV). The history of the cervical cancer goes back to eighteenth century as the HPV infection is reported since 1800s. Presently, the genetic structure of HPV is well defined. Several screening tests including cytology and visual based screening and high risk HPV testing are available. Also available are various clinical and commercial diagnostic tests. However due to the lack of awareness and population-based screening programs, the morbidity and mortality rate is alarmingly high. There are new emerging biomarkers including E6/E7 mRNA, p16ink4a, markers of aberrant S-phase induction, chromosomal abnormalities and miRNAs along with advanced genotyping methods. These markers have clinical significance and are helpful in disease prevention and management. Further, recent advancement in the field of metagenomics has increased the prospects of identifying newer microbes, viruses hitherto reported thus far in the context of HPV infection. Analysis of HPV cases using modern tools including genotyping using more powerful biomarkers is envisaged to enhance the prospects of early diagnosis, better prognosis, more reliable treatment and eventual management of the disease.
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Affiliation(s)
- Ushma Jaykamal Shah
- MedGenome Labs Ltd., Kailash Cancer Hospital and Research Center, Muni Seva Ashram, P.O. Goraj, Tal. Waghodia, Dist. Vadodara, 391760, Gujarat, India
| | - Mohammad Nasiruddin
- Anand Diagnostic Laboratory (A Neuberg Associate), Neuberg Anand Reference Laboratory, Anand Tower, 54, Bowring Hospital Road, Shivajinagar, Bangalore - 560001, India.
| | - Sajad Ahmad Dar
- Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, 45142, Saudi Arabia
| | - Md Khurshid Alam Khan
- School of Life Sciences, BS Abdur Rahman Crescent Institute of Science and Technology, Chennai, 600048, Tamil Nadu, India
| | - Mohammad Riyaz Akhter
- MedGenome Labs Ltd., 3rd Floor, Narayana Nethralaya Building, Narayana Health City, # 258/A, Bommasandra, Hosur Road, Bangalore, 560099, Karnataka, India
| | - Nidhi Singh
- Department of Obstetrics and Gynecology, Prasad Institute of Medical Sciences, Lucknow, 226401, Uttar Pradesh, India
| | - Ali A Rabaan
- Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Saudi Aramco, Dhahran, 31311, Saudi Arabia
| | - Shafiul Haque
- Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, 45142, Saudi Arabia.
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Obeid DA, Almatrrouk SA, Khayat HH, Al-Muammer TA, Tulbah AM, Albadawi IA, Al-Ahdal MN, Alhamlan FS. Human papillomavirus type 16 and 18 viral loads as predictors associated with abnormal cervical cytology among women in Saudi Arabia. Heliyon 2020; 6:e03473. [PMID: 32140590 PMCID: PMC7047185 DOI: 10.1016/j.heliyon.2020.e03473] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2019] [Revised: 09/08/2019] [Accepted: 02/10/2020] [Indexed: 01/05/2023] Open
Abstract
The detection of HPV viral DNA is regularly conducted with cervical screening. However, using a molecular marker such as the viral load may serve as a predictor associated with disease detection and progression. The present study aimed to screen for and genotype HPV among women in Saudi Arabia, develop and validate sensitive quantitative polymerase chain reaction (qPCR) assays to detect viral load for the two most common HPV types, namely 16 and 18, and assess whether HPV viral load could be used as a marker for cervical abnormality and disease progression. This study examined 733 specimens (both formalin-fixed paraffin embedded specimens and PAP smear samples) from women who underwent cervical screening. The specimens and samples were processed for DNA extraction and then tested for HPV DNA using nested PCR. Approximately 165 specimens (18%) were positive for HPV. Those specimens were genotyped using a reverse line blotting hybridization assay. The results indicated that the most common HPV types detected were a single infection with HPV 16 (51%) or with HPV 18 (28%) followed by infections with multiple HPV types (~7%). A qPCR TaqMan assay developed and validated in-house was used to determine viral load for HPV genotypes 16 (n = 80) and 18 (n = 45). Viral loads for both HPV types were significantly associated with cervical cytology grade (P < 0.05). The odds ratio (OR) for the HPV 16 viral load was high for specimens with cervical cancer (OR, 18.8; 95% CI, 4.3–82.9) or for those with high-grade squamous intraepithelial lesions (OR, 14.7; 95% Cl, 2.43–88.49). For the HPV 18 viral load, the OR was significant only for specimens with cervical cancer (OR, 11.1; 95% Cl, 2.2–54.9). Logistic regression models for HPV 16 and for HPV 18 viral load levels were significant, with higher viral load associated with cervical abnormalities. These findings indicate that viral load is a predictor significantly associated with cytology abnormality in women who are positive for high-risk HPVs and suggest that integrating a viral load test into current clinical screening practices for HPV-positive women is warranted in Saudi Arabia.
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Affiliation(s)
- D A Obeid
- Department of Infection and Immunity, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - S A Almatrrouk
- Department of Infection and Immunity, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - H H Khayat
- Department of Infection and Immunity, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - T A Al-Muammer
- Department of Family Medicine and Polyclinic, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - A M Tulbah
- Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.,College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - I A Albadawi
- Department of Obstetrics and Gynecology, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.,College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - M N Al-Ahdal
- Department of Infection and Immunity, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.,College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - F S Alhamlan
- Department of Infection and Immunity, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.,College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
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Derbie A, Mekonnen D, Woldeamanuel Y, Van Ostade X, Abebe T. HPV E6/E7 mRNA test for the detection of high grade cervical intraepithelial neoplasia (CIN2+): a systematic review. Infect Agent Cancer 2020; 15:9. [PMID: 32047531 PMCID: PMC7006188 DOI: 10.1186/s13027-020-0278-x] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 02/03/2020] [Indexed: 01/31/2023] Open
Abstract
Background Genital infection with certain types of Human papillomavirus (HPV) is a major cause of cervical cancer globally. For early detection of premalignant dysplasia, evidences are coming out on the usefulness of HPV E6/E7 mRNA test as a potential tool compared with cytology and HPV DNA testing. Taking into account shortage of compiled data on this field, the aim of this systematic review was to describe the latest diagnostic performance of HPV E6/E7 mRNA testing to detect high grade cervical lesions (CIN2+) where by histology was taken as a gold standard. Methods Articles published in English were systematically searched using key words from PubMed/Medline and SCOPUS. In addition, Google Scholar and the Google database were searched manually for grey literature. Two reviewers independently assessed study eligibility, risk of bias and extracted the data. We performed a descriptive presentation of the performance of E6/E7 mRNA test (in terms of sensitivity, specificity, negative and positive predictive values) for the detection of CIN2 + . Results Out of 231 applicable citations, we have included 29 articles that included a total of 23,576 study participants (age range, 15–84 years) who had different cervical pathologies. Among the participants who had cervical histology, the proportion of CIN2+ was between 10.6 and 90.6%. Using histology as a gold standard, 11 studies evaluated the PreTect HPV Proofer, 7 studies evaluated the APTIMA HPV assay (Gen-Probe) and 6 studies evaluated the Quantivirus® HPV assay. The diagnostic performance of these three most common mRNA testing tools to detect CIN2+ was; 1) PreTect Proofer; median sensitivity 83%, specificity 73%, PPV 70 and NPV 88.9%. 2) APTIMA assay; median sensitivity 91.4%, specificity 46.2%, PPV 34.3% and NPV 96.3%. 3) Quantivirus®: median sensitivity 86.1%, specificity 54.6%, PPV 54.3% and NPV was at 89.3%. Further, the area under the receiver operating characteristics (AU-ROC) curve varied between 63.8 and 90.9%. Conclusions The reported diagnostic accuracy implies that HPV mRNA based tests possess diagnostic relevance to detect CIN2+ and could potentially be considered in areas where there is no histology facility. Further studies including its cost should be considered.
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Affiliation(s)
- Awoke Derbie
- 1Department of Medical Microbiology, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia.,2Centre for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), Addis Ababa University, Addis Ababa, Ethiopia
| | - Daniel Mekonnen
- 1Department of Medical Microbiology, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia.,3Department of Health Biotechnology, Biotechnology Research Institute, Bahir Dar University, Bahir Dar, Ethiopia
| | - Yimtubezinash Woldeamanuel
- 2Centre for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), Addis Ababa University, Addis Ababa, Ethiopia.,4Department of Medical Microbiology, Immunology and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Xaveer Van Ostade
- 5Laboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
| | - Tamrat Abebe
- 4Department of Medical Microbiology, Immunology and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
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Zhang X, Bai J, Yuan C, Long L, Zheng Z, Wang Q, Chen F, Zhou Y. Bioinformatics analysis and identification of potential genes related to pathogenesis of cervical intraepithelial neoplasia. J Cancer 2020; 11:2150-2157. [PMID: 32127942 PMCID: PMC7052918 DOI: 10.7150/jca.38211] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Accepted: 01/05/2020] [Indexed: 12/16/2022] Open
Abstract
The aim of this study was to explore and identify the key genes and signal pathways contributing to cervical intraepithelial neoplasia (CIN). The gene expression profiles of GSE63514 were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened performing with packages in software R. After Gene ontology terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyzing, and Gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA) was used to analyze these genes. Then sub-modules were subsequently analyzed base CIN grade, and protein-protein interaction (PPI) network of DEGs were constructed. 537 DEGs were screened in total, consisting 331 up-regulated genes and 206 down-regulated genes in CIN samples compared to normal samples. The most DEGs were enriched in chromosomal region in cellular component (CC), organelle fission inbiological process (BP) and ATPase activity in molecular function (MF). KEGG pathway enrichment analyzing found the DEGs were mainly concentrated in 10 pathways. The results of GSEA mainly enriched in 4 functional sets: E2F-Targets, G2M-Checkpoint, Mitotic-Spindle and Spermatogenesis. A total of 6 modules were identified by WCGNA. Subsequently, grey module was the highest correlation (Cor=0.78, P=5e-22) and 31 genes were taken as candidate hub genes for CIN high grade risk (weighted correlation coefficients >0.80). Finally, diagnostic analysis showed that in addition to CCDC7, the expression levels of the remaining 13 DEGs have a high diagnostic value (AUC>0.8 and P<0.05). These findings provided a new sight into the understanding of molecular functions for CIN.
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Affiliation(s)
- Xue Zhang
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Jian Bai
- Department of Gastrointestinal Surgery and Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Cheng Yuan
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Long Long
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Zhewen Zheng
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Qingqing Wang
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Fengxia Chen
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Yunfeng Zhou
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China
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Na Rangsee N, Yanatatsaneejit P, Pisitkun T, Somparn P, Jintaridth P, Topanurak S. Host proteome linked to HPV E7-mediated specific gene hypermethylation in cancer pathways. Infect Agent Cancer 2020; 15:7. [PMID: 32025240 PMCID: PMC6998090 DOI: 10.1186/s13027-020-0271-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Accepted: 01/08/2020] [Indexed: 12/13/2022] Open
Abstract
Background Human papillomavirus (HPV) infection causes around 90% of cervical cancer cases, and cervical cancer is a leading cause of female mortality worldwide. HPV-derived oncoprotein E7 participates in cervical carcinogenesis by inducing aberrant host DNA methylation. However, the targeting specificity of E7 methylation of host genes is not fully understood but is important in the down-regulation of crucial proteins of the hallmark cancer pathways. In this study, we aim to link E7-driven aberrations in the host proteome to corresponding gene promoter hypermethylation events in the hope of providing novel therapeutic targets and biomarkers to indicate the progression of cervical cancer. Methods HEK293 cells were transfected with pcDNA3.1-E7 plasmid and empty vector and subjected to mass spectrometry-based proteomic analysis. Down-regulated proteins (where relative abundance was determined significant by paired T-test) relevant to cancer pathways were selected as gene candidates for mRNA transcript abundance measurement by qPCR and expression compared with that in SiHa cells (HPV type 16 positive). Methylation Specific PCR was used to determine promoter hypermethylation in genes downregulated in both SiHa and transfected HEK293 cell lines. The FunRich and STRING databases were used for identification of potential regulatory transcription factors and the proteins interacting with transcription factor gene candidates, respectively. Results Approximately 400 proteins totally were identified in proteomics analysis. The transcripts of six genes involved in the host immune response and cell proliferation (PTMS, C1QBP, BCAP31, CDKN2A, ZMYM6 and HIST1H1D) were down-regulated, corresponding to proteomic results. Methylation assays showed four gene promoters (PTMS, C1QBP, BCAP31 and CDKN2A) were hypermethylated with 61, 55.5, 70 and 78% increased methylation, respectively. Those four genes can be regulated by the GA-binding protein alpha chain, specificity protein 1 and ETS-like protein-1 transcription factors, as identified from FunRich database predictions. Conclusions HPV E7 altered the HEK293 proteome, particularly with respect to proteins involved in cell proliferation and host immunity. Down-regulation of these proteins appears to be partly mediated via host DNA methylation. E7 possibly complexes with the transcription factors of its targeting genes and DNMT1, allowing methylation of specific target gene promoters.
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Affiliation(s)
- Nopphamon Na Rangsee
- 1Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400 Thailand
| | | | - Trairak Pisitkun
- 3Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330 Thailand
| | - Poorichaya Somparn
- 3Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330 Thailand.,4Center of Excellence in Immunology and Immune-mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330 Thailand
| | - Pornrutsami Jintaridth
- 5Department of Tropical Nutrition and Food Science, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400 Thailand
| | - Supachai Topanurak
- 1Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400 Thailand
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Zhang L, Hu D, Wang S, Zhang Y, Pang L, Tao L, Jia W. Association between dense PAX1 promoter methylation and HPV16 infection in cervical squamous epithelial neoplasms of Xin Jiang Uyghur and Han women. Gene 2020; 723:144142. [PMID: 31589957 DOI: 10.1016/j.gene.2019.144142] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 09/21/2019] [Accepted: 09/23/2019] [Indexed: 12/15/2022]
Abstract
DNA methylation is an epigenetic alteration that may lead to carcinogenesis by silencing key tumor suppressor genes. Hypermethylation of the paired box gene 1 (PAX1) promoter is important in cervical cancer development. Here, PAX1 methylation levels were compared between Uyghur and Han patients with cervical lesions. Data on PAX1 methylation in different cervical lesions were obtained from the Gene Expression Omnibus (GEO) database, whereas data on survival and PAX1 mRNA expression in invasive cervical cancer (ICC) were retrieved from the Cancer Genome Atlas (TCGA) database. MassARRAY spectrometry was used to detect methylation of 19 CpG sites in the promoter region of PAX1, whereas gene mass spectrograms were drawn by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Human papillomavirus (HPV) 16 infection was detected by polymerase chain reaction. PAX1 methylation in high-grade squamous intraepithelial lesion (HSIL) and ICC was significantly higher than in normal tissues. PAX1 hypermethylation was associated with poor prognosis and reduced transcription. ICC-specific PAX1 promoter methylation involved distinct CpG sites in Uyghur and Han patients HPV16 infection in HSIL and ICC patient was significantly higher than in normal women (p < 0.05). Our study revealed a strong association between PAX1 methylation and the development of cervical cancer. Moreover, hypermethylation of distinct CpG sites may induce HSIL transformation into ICC in both Uyghur and Han patients. Our results suggest the existence of ethnic differences in the genetic susceptibility to cervical cancer. Finally, PAX1 methylation and HPV infection exhibited synergistic effects on cervical carcinogenesis.
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Affiliation(s)
- Lu Zhang
- Department of Pathology, The First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, China; Department of Pathology, Shihezi University School of Medicine, Shihezi, China
| | - Danni Hu
- Department of Pathology, The First People's Hospital of Changde City, Changde 415003, China
| | - Shasha Wang
- Department of Pathology, The First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, China; Department of Pathology, Shihezi University School of Medicine, Shihezi, China
| | - Ying Zhang
- Department of Pathology, The First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, China; Department of Pathology, Shihezi University School of Medicine, Shihezi, China
| | - Lijuan Pang
- Department of Pathology, The First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, China; Department of Pathology, Shihezi University School of Medicine, Shihezi, China
| | - Lin Tao
- Department of Pathology, The First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, China; Department of Pathology, Shihezi University School of Medicine, Shihezi, China
| | - Wei Jia
- Department of Pathology, The First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, China; Department of Pathology, Shihezi University School of Medicine, Shihezi, China.
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Curty G, de Carvalho PS, Soares MA. The Role of the Cervicovaginal Microbiome on the Genesis and as a Biomarker of Premalignant Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer. Int J Mol Sci 2019; 21:ijms21010222. [PMID: 31905652 PMCID: PMC6981542 DOI: 10.3390/ijms21010222] [Citation(s) in RCA: 92] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 12/24/2019] [Accepted: 12/25/2019] [Indexed: 12/24/2022] Open
Abstract
The microbiome is able to modulate immune responses, alter the physiology of the human organism, and increase the risk of viral infections and development of diseases such as cancer. In this review, we address changes in the cervical microbiota as potential biomarkers to identify the risk of cervical intraepithelial neoplasia (CIN) development and invasive cervical cancer in the context of human papillomavirus (HPV) infection. Current approaches for clinical diagnostics and the manipulation of microbiota with the use of probiotics and through microbiota transplantation are also discussed.
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Ren C, Zhu Y, Yang L, Zhang X, Liu L, Wang Z, Jiang D. Prognostic and diagnostic validity of p16/Ki-67, HPV E6/E7 mRNA, and HPV DNA in women with ASCUS: a follow-up study. Virol J 2019; 16:143. [PMID: 31752941 PMCID: PMC6873508 DOI: 10.1186/s12985-019-1251-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 11/11/2019] [Indexed: 12/15/2022] Open
Abstract
Background We evaluated the prognostic and diagnostic ability of p16/Ki-67 immunocytochemistry, HPV E6/E7 mRNA testing and HPV DNA assay in triaging ASCUS to find a way to manage cervical lesions more effectively. Methods We conducted a prospective study through follow-up. The detection methods of the three factors: p16/Ki-67 immunocytochemistry conducted by using the CINtec® Plus Kit, E6/E7 mRNA testing by QuantiVirus®HPV E6/E7 mRNA assay and DNA by Hybrid Capture 2 assay. Results One hundred three women with ASCUS satisfied requirements and completed the entire follow-up process. All CIN2+ occurred in women who were mRNA positive at baseline, none in mRNA negative. 100% (6/6) patients with CIN2+ were HPV DNA assay positive, 100% (6/6) were HPV E6/E7 mRNA testing positive and 50.0% (3/6) were p16/Ki-67 immunocytochemistry positive. The risk ratio of E6/E7 mRNA test was 57.306 (95% CI 0.077–42,400.545). For endpoint of CIN2+, the sensitivity between HPV DNA assay and HPV E6/E7 mRNA testing is no statistical difference, but statistical difference exists between HPV E6/E7 mRNA testing vs. p16/Ki-67 immunocytochemistry (χ2 = 5.718, P = 0.023) and HPV DNA assay vs. p16/Ki-67 immunocytochemistry (χ2 = 5.718, P = 0.023). The specificity of E6/E7 mRNA testing, p16/Ki-67 and DNA assay in triaging ASCUS was 44.33, 75.26 and 11.34% respectively and is all statistical difference (χ2 = 26.277, P < 0.001(HPV DNA assay vs. HPV E6/E7 mRNA testing), χ2 = 19.297, P < 0.001(HPV E6/E7 mRNA testing vs. p16/Ki-67 immunocytochemistry), χ2 = 80.707, P < 0.001(HPV DNA assay vs. p16/Ki-67 immunocytochemistry). The expression level of 2097.09 copies/ml was the optimal cut-off value for HPV E6/E7 mRNA testing to diagnose CIN2+, the sensitivity and specificity was 61.1 and 68.2%. Conclusions High expression of HPV E6/E7 mRNA could be a good candidate as a diagnostic biomarker to triage ASCUS superseding HPV DNA. p16/Ki-67 immunocytochemistry is suggested to be a good tool to triage ASCUS, but it reduced the sensitivity of diagnosis when improves the diagnostic specificity.
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Affiliation(s)
- Chenchen Ren
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, No. 7, Front Kangfu Street, Zhengzhou, 450052, Henan Province, People's Republic of China.
| | - Yuanhang Zhu
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, No. 7, Front Kangfu Street, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Li Yang
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, No. 7, Front Kangfu Street, Zhengzhou, 450052, Henan Province, People's Republic of China.
| | - Xiaoan Zhang
- Department of Imaging, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China
| | - Ling Liu
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, No. 7, Front Kangfu Street, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Zhaoxin Wang
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, No. 7, Front Kangfu Street, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Dongyuan Jiang
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, No. 7, Front Kangfu Street, Zhengzhou, 450052, Henan Province, People's Republic of China
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Mendoza-Almanza G, Ortíz-Sánchez E, Rocha-Zavaleta L, Rivas-Santiago C, Esparza-Ibarra E, Olmos J. Cervical cancer stem cells and other leading factors associated with cervical cancer development. Oncol Lett 2019; 18:3423-3432. [PMID: 31516560 PMCID: PMC6733009 DOI: 10.3892/ol.2019.10718] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Accepted: 06/06/2019] [Indexed: 02/07/2023] Open
Abstract
Cervical cancer (CC) is one of the leading causes of cancer-associated mortalities in women from developing countries. Similar to other types of cancer, CC is considered to be a multifactorial disease, involving socioeconomic, cultural, immunological and epigenetic factors, as well as persistent human papilloma virus (HPV) infection. It has been well established that cancer stem cells (CSCs) play an important role in defining tumor size, the speed of development and the level of regression following treatment; therefore, CSCs are associated with a poor prognosis. CSCs have been detected in many types of cancer, including leukemia, pancreatic, colon, esophagus, liver, prostate, breast, gastric and lung cancer. In cervical cancer, CSCs have been associated with resistance to normally used drugs such as cisplatin. The present review summarizes the strategies that high-risk HPV viruses (HPV-16 and HPV-18) have developed to transform normal epithelial cells into cancer cells, as well as the cellular pathways and studies associated with the identification of cervical cancer stem cell biomarkers. In this sense, the present review provides state of the art information regarding CC development.
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Affiliation(s)
- Gretel Mendoza-Almanza
- National Council for Science and Technology, Autonomous University of Zacatecas, Zacatecas 98060, Mexico
| | | | - Leticia Rocha-Zavaleta
- Institute of Biomedical Research, National Autonomous University of Mexico, Mexico City 04510, Mexico
| | - César Rivas-Santiago
- National Council for Science and Technology, Autonomous University of Zacatecas, Zacatecas 98060, Mexico
| | - Edgar Esparza-Ibarra
- Academic Unit of Biological Sciences, Autonomous University of Zacatecas, Zacatecas 98060, Mexico
| | - Jorge Olmos
- Department of Marine Biotechnology, Center for Scientific Research and Higher Education, Ensenada 22860, Mexico
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Knowledge, attitudes, and practices of Saudi physicians regarding cervical cancer and the human papilloma virus vaccine. J Infect Public Health 2019; 13:584-590. [PMID: 31570271 DOI: 10.1016/j.jiph.2019.09.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Revised: 05/23/2019] [Accepted: 09/03/2019] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Cervical cancer is considered the second most common type of cancer in women worldwide, with a reported 570,000 incident cases documented each year. Infection with certain types of the Human Papillomavirus (HPV) has been found to be associated with more than 99% of cervical cancers. The HPV vaccine can prevent HPV infection and most cases of cervical cancers; however the uptake of this vaccine remains low in Saudi Arabia. Physicians can play a vital role in providing their patients with objective information regarding the HPV vaccine, yet little is known about their knowledge, attitudes, and practices in this area. MATERIALS AND METHODS We conducted a cross-sectional study in King Abdul-Aziz Medical City (KAMC), Central Region, Saudi Arabia where data were collected through an online questionnaire to assess the knowledge, attitudes, and practices of physicians. RESULTS Most physicians (61%) displayed a good level of knowledge about cervical cancer; 94% were knowledgeable of the causative link between (HPV) infection and cervical cancer. Family medicine physicians had better knowledge regarding cervical cancer, HPV, and HPV vaccination than pediatricians (p=0.023). Physicians with >10 years of practice had better knowledge of cervical cancer than other respondents (p=0.041). 80% of the sample thought it was important for women to receive the HPV vaccine and 82% stated they would allow their daughters to be given the HPV vaccine. Lack of parental knowledge of the vaccine was significantly (p=0.034) associated with a lack of knowledge about HPV, and this was one of the most common barriers preventing recommendation of the HPV vaccine. CONCLUSION With the increasing prevalence of HPV infections, better knowledge of HPV infection, HPV-related diseases, and the availability of HPV vaccinations from health professionals will assist with the implementation of effective prevention and treatment programmes.
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Kundrod KA, Smith CA, Hunt B, Schwarz RA, Schmeler K, Richards-Kortum R. Advances in technologies for cervical cancer detection in low-resource settings. Expert Rev Mol Diagn 2019; 19:695-714. [PMID: 31368827 DOI: 10.1080/14737159.2019.1648213] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Introduction: Cervical cancer mortality rates remain high in low- and middle-income countries (LMICs) and other medically underserved areas due to challenges with implementation and sustainability of routine screening, accurate diagnosis, and early treatment of preinvasive lesions. Areas covered: In this review, we first discuss the standard of care for cervical cancer screening and diagnosis in high- and low-resource settings, biomarkers that correlate to cervical precancer and cancer, and needs for new tests. We review technologies for screening and diagnosis with a focus on tests that are already in use in LMICs or have the potential to be adapted for use in LMICs. Finally, we provide perspectives on the next five years of technology development for improved cervical cancer screening and diagnosis in LMICs. Expert opinion: Innovation toward improved molecular and imaging tests is needed to enable effective, affordable see-and-treat approaches to detect and treat cervical precancer in a single visit. Current molecular tests remain too complex and/or costly for widespread use. Especially with imaging tests, decision support may improve performance of new technologies.
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Affiliation(s)
| | - Chelsey A Smith
- Department of Bioengineering, Rice University , Houston , TX , USA
| | - Brady Hunt
- Department of Bioengineering, Rice University , Houston , TX , USA
| | | | - Kathleen Schmeler
- Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center , Houston , TX , USA
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