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Karachalios C, Petousis S, Margioula-Siarkou C, Dinas K. Human papillomaviruses and breast cancer: A systematic review and meta‑analysis. Oncol Lett 2024; 27:75. [PMID: 38192655 PMCID: PMC10773228 DOI: 10.3892/ol.2023.14208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 10/12/2023] [Indexed: 01/10/2024] Open
Abstract
Breast cancer (BC) is the leading malignancy worldwide. The association between human papillomavirus (HPV) and BC is debatable. The present systematic review and meta-analysis aimed to assess the prevalence of HPV DNA in malignant breast tumors. An extensive search of the PubMed and SCOPUS databases was carried out for case-control studies published between January 1, 2003 and January 7, 2023, which compared HPV DNA detection in breast tissue specimens of female patients with BC and women with absent or benign breast disorders. Once the initial title/abstract screening was completed by two independent investigators, the full texts of the included studies from that stage were reviewed by the aforementioned investigators to determine if they should be included in the present study. Data extraction was independently conducted by two investigators. A third investigator was consulted to resolve disagreements through free discussion. MedCalc was used for quantitative synthesis. The significance of association was estimated by pooled odds ratios (ORs) with 95% confidence intervals (CIs) calculated using the random-effects model. A total of 23 primary studies, including 3,243 subjects (2,027 patients and 1,216 controls), were eligible for quantitative analysis. HPV prevalence in patients with BC and controls was 21.95 and 8.96%, respectively. The prevalence of HPV differed significantly between the two groups (OR 3.83; 95% CI 2.03-7.25; P<0.01). Heterogeneity among studies was quantified using the I2 index which was 69.57% (95% CI 51.89-80.75). The risk of bias was assessed using an appropriate tool contributed by the CLARITY Group at McMaster University. Seven studies had a low risk of bias, 15 studies had a moderate risk of bias and only one study had a serious risk of bias. These results reinforce the hypothesis that HPV is involved in BC development and progression, indicating a possible role of HPV vaccination in BC prevention.
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Affiliation(s)
- Charalampos Karachalios
- Second Academic Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Thessaloniki 54624, Greece
| | - Stamatios Petousis
- Second Academic Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Thessaloniki 54624, Greece
| | - Chrysoula Margioula-Siarkou
- Second Academic Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Thessaloniki 54624, Greece
| | - Konstantinos Dinas
- Second Academic Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Thessaloniki 54624, Greece
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Awan UA, Khattak AA, Ahmed N, Guo X, Akhtar S, Kamran S, Yongjing Z, Liu J, Khan S. An updated systemic review and meta-analysis on human papillomavirus in breast carcinogenesis. Front Oncol 2023; 13:1219161. [PMID: 37711194 PMCID: PMC10498127 DOI: 10.3389/fonc.2023.1219161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 07/17/2023] [Indexed: 09/16/2023] Open
Abstract
Background Breast Cancer (BC) stands out as the widely prevalent malignancy among all the types of cancer affecting women worldwide. There is significant evidence that the pathogenicity of BC may be altered by Human Papillomavirus (HPV) infection; however, conclusive data are not yet available. Methods By searching five databases, including EMBASE, IBECS, PubMed, Scopus, Science Direct, Google Scholar, and Web of Science, a thorough systematic analysis was conducted on the prevalence of HPV in BC patients from 1990 to June 30, 2022. After applying extensive eligibility criteria, we selected 74 publications for further analysis based on the prevalence of HPV infections in breast tissues. All of the data were analyzed using a random-effects meta-analysis, Cochran Q test and I2 statistic were used to calculate the heterogeneity of the prevalence among these studies using subgroup analysis. Variations in the HPV prevalence estimates in different subgroups were evaluated by subgroup meta-analysis. Results In total, 3156 studies were initially screened, resulting in 93 full-text studies reviewed, with 74 meeting inclusion criteria. Among a total of 7156 BC biopsies, the pool prevalence of HPV was 25.6% (95% CI= 0.24-0.33, τ2 = 0.0369 with significant heterogeneity between estimates (I 2 = 97% and p< 0.01). Consequently, 45 studies with available controls were further studied, and the prevalence of HPV in case-control studies was 26.2% with overall odds 5.55 (95% CI= 3.67-8.41, I 2 = 38%, τ2 = 1.4878, p< 0.01). Further subgroup analysis of HPV revealed HPV-16 had a maximum prevalence of 9.6% (95% CI= 3.06-11.86, I 2 = 0%, τ2 = 0.6111, p< 0.01). Among different geographical regions, Europe reported the maximum prevalence of HPV, i.e., 39.2% (95% CI=1.29-7.91, I 2 = 18%, τ2 = 1.2911, p< 0.01). Overall distribution showed HPV-18 was a frequent HPV subtype reported in Australia. Conclusion Current study provides a global estimate of HPV prevalence in BC patients and demonstrates a significant association between this virus and BC etiology. Nevertheless, we recommend further investigation into the underlying mechanism is essential to validate this hypothesis.
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Affiliation(s)
- Usman Ayub Awan
- Medical Research Center, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Medical Laboratory Technology, The University of Haripur, Haripur, Khyber Pakhtunkhwa, Pakistan
| | - Aamer Ali Khattak
- Department of Medical Laboratory Technology, The University of Haripur, Haripur, Khyber Pakhtunkhwa, Pakistan
| | - Noman Ahmed
- Department of Medical Laboratory Technology, The University of Haripur, Haripur, Khyber Pakhtunkhwa, Pakistan
| | - Xingyi Guo
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, United States
- Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, United States
| | - Sohail Akhtar
- Department of Mathematics and Statistics, The University of Haripur, Haripur, Khyber Pakhtunkhwa, Pakistan
| | - Shehrish Kamran
- Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH&RC), Lahore, Pakistan
| | - Zhao Yongjing
- Zhengzhou Key Laboratory of Children’s Infection and Immunity, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou, China
| | - Jianbo Liu
- Henan Key Laboratory of Precision Diagnosis of Respiratory Infectious Diseases, Zhengzhou Key Laboratory of Precision Diagnosis of Respiratory Infectious Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Suliman Khan
- Medical Research Center, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Medical Laboratory Technology, The University of Haripur, Haripur, Khyber Pakhtunkhwa, Pakistan
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HPV-Associated Breast Cancer: Myth or Fact? Pathogens 2022; 11:pathogens11121510. [PMID: 36558844 PMCID: PMC9786769 DOI: 10.3390/pathogens11121510] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 12/01/2022] [Accepted: 12/08/2022] [Indexed: 12/14/2022] Open
Abstract
Some estimates place the proportion of human malignancies attributable to viruses at between 15 and 20 percent. Viruses including the human papillomavirus are considered an interesting but controversial etiological risk factor for breast cancer. HPV infection is anticipated to be an early trigger in breast cancer carcinogenesis, followed by cumulative alterations over time ("hit and run" mechanism) through synergy with other environmental factors. The association between HPV and breast cancer has not yet been verified. There are very conflicting data on the presence of HPV DNA in breast cancer samples, and we lack a clarified, exact mode of HPV transmission to the breast. In our review article we analyzed the up-to-date knowledge about the association of HPV and breast cancer. Furthermore, we summarized the available original research published since 2010. In conclusion, the complexity and inconsistency of the available results together with the relatively low prevalence of HPV infection requires extensive research with much larger studies and exact and unified diagnostic methods are required to better understand the role of the HPV in breast carcinogenesis.
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Usman M, Hameed Y, Ahmad M, Jalil Ur Rehman, Ahmed H, Hussain MS, Asif R, Murtaza MG, Jawad MT, Iqbal MJ. Breast Cancer Risk and Human Papillomavirus Infection: A Bradford Hill Criteria Based Evaluation. Infect Disord Drug Targets 2022; 22:e200122200389. [PMID: 35048811 DOI: 10.2174/1573401318666220120105931] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 10/20/2021] [Accepted: 11/17/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND The association between human papillomavirus (HPV) and human breast cancer (BC) has already been thoroughly studied worldwide with contradictory findings. Although the researchers have tried to minimize the conflict using statistical meta-analysis, because of its shortcomings, there is still a need to evaluate the correlation between HPV and BC using any additional method. OBJECTIVES This study was launched to investigate the correlation between HPV and BC through the application of Bradford Hill criteria postulates. METHODS Population-wide studies associating HPV with BC were searched using the PubMed database. Then, the information of HPV burden in BC, normal/benign samples was analyzed, and ultimately Bradford Hill criteria postulates were applied on the collected evidence to explore the relationship between HPV and BC. In addition, to make the outcomes more authentic, we also reviewed the methodologies of previous studies to address the propensity of false results. RESULTS After a careful evaluation of the obtained data against major Bradford Hill criteria postulates, it was noted that all these postulates including strength, consistency, biological gradient, temporality, plausibility, experiment, specificity, and analogy were not fulfilled. CONCLUSION The results of the present study have failed to establish a casual association between HPV and BC rather suggested HPV as a cause-effective agent or at least a co-participant in the pathogenesis of BC. The weakness of association especially the low level of consistency across studies, and the lack of specificity of effect, there is a need for more experiments concerning Bradford Hill criteria postulates.
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Affiliation(s)
- Muhammad Usman
- Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Yasir Hameed
- Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Mukhtiar Ahmad
- Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Jalil Ur Rehman
- Department of Eastern Medicine, Qarshi University, Lahore, Pakistan
| | - Hamad Ahmed
- Department of Eastern Medicine, Government College University Faisalabad, Pakistan
| | - Muhammad Safdar Hussain
- Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Rizwan Asif
- Department of Microbiology, Government College University Faisalabad, Pakistan
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Guo H, Idrovo JP, Cao J, Roychoudhury S, Navale P, Auguste LJ, Bhuiya T, Sheikh-Fayyaz S. Human Papillomavirus (HPV) Detection by Chromogenic In Situ Hybridization (CISH) and p16 Immunohistochemistry (IHC) in Breast Intraductal Papilloma and Breast Carcinoma. Clin Breast Cancer 2021; 21:e638-e646. [PMID: 34059433 DOI: 10.1016/j.clbc.2021.04.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 04/02/2021] [Accepted: 04/13/2021] [Indexed: 12/14/2022]
Abstract
PURPOSE This study explored human papillomavirus (HPV) amplification in breast benign and malignant lesions by chromogenic in situ hybridization (CISH) and the concordance of p16 expression by immunohistochemistry. PATIENTS AND METHODS The presence of HPV6/11 and HPV16/18 in 33 cases of intraductal papilloma, 34 cases of ductal carcinoma in situ (DCIS), and 56 cases of invasive breast carcinoma (IBC) was evaluated using matched-background breast parenchyma and breast reduction as control groups. Association with clinicopathologic factors including prognosis was assessed. RESULTS HPV 6/11 was observed in 0 cases (0%) of breast reduction, one case (3%) of intraductal papilloma, 11 cases (32.4%) of DCIS, and eight cases (14.3%) of IBC. HPV 16/18 was detected in three cases of (9.1%) breast reduction, six cases (18.8%) of intraductal papillomas, 14 cases (41.2%) of DCIS, and 25 cases (44.6%) of IBC. There was no difference in the HPV status between intraductal papilloma and breast reduction. HPV amplification in intraductal papilloma did not associate with developing atypia or carcinoma after long-term follow-up. However, HPV 6/11 and HPV 16/18 amplification was significantly higher in both DCIS and IBC when compared with breast reduction (P < .05). Compared with background breast parenchyma, HPV 16/18 amplification was significantly higher in both DCIS and IBC (P = .003 and P = .013, respectively). No correlation between p16 immunohistochemical staining and either of the HPV CISH testing was found (P > .05). CONCLUSION HPV infection was detected in both breast lesions and background parenchyma. HPV infection may play a role in the pathogenesis of breast cancer but is not associated with intraductal papilloma. Immunohistochemical stain for p16 is not a good surrogate marker for HPV infection in breast lesions.
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Affiliation(s)
- Hua Guo
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY
| | - Juan P Idrovo
- Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY
| | - Jin Cao
- Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY
| | - Sudarshana Roychoudhury
- Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY
| | - Pooja Navale
- Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY
| | - Louis J Auguste
- Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY
| | - Tawfiqul Bhuiya
- Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY
| | - Silvat Sheikh-Fayyaz
- Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY.
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Martins SF, Mariano V, Rodrigues M, Longatto-Filho A. Human papillomavirus (HPV) 16 infection is not detected in rectal carcinoma. Infect Agent Cancer 2020; 15:17. [PMID: 32165915 PMCID: PMC7059378 DOI: 10.1186/s13027-020-00281-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 02/19/2020] [Indexed: 12/18/2022] Open
Abstract
Introduction Persistence of human papillomavirus (HPV) infections is associated with squamous cell carcinomas of different human anatomic sites. Several studies have suggested a potential role for HPV infection, particularly HPV16 genotype, in rectal cancer carcinogenesis.. The aim of this study was to assess the frequency of oncogenic HPV 16 viral DNA sequences in rectal carcinomas cases retrieved from the pathology archive of Braga Hospital, North Portuga. Methods TaqMan-based type-specific real-time PCR for HPV 16 was performed using primers and probe targeting HPV16 E7 region. Results Most of the rectal cancer patients (88.5%, n = 206 patients), were symptomatic at diagnosis. The majority of the lesions (55.3%, n = 129) presented malignancies of polypoid/vegetant phenotype. 26.8% (n = 63) had synchronic metastasis at diagnosis. 26.2% (n = 61) patients had clinical indication for neoadjuvant therapy. Most patients with rectal cancer were stage IV (19.7% patients), followed by stage IIA (19.3%) and stage I (18.5%). All cases of the present series tested negative for HPV16. Conclusion The total of negative tests for HPV 16 infection is a robust argument to support the assumption that HPV 16 infection, despite of previous evidences, is not involved in rectal cancer carcinogenesis and progression.
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Affiliation(s)
- Sandra F Martins
- 1Life and Health Science Research Institute (ICVS), School of Health Sciences, School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.,ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Braga, Portugal.,Coloproctology Unit, Braga Hospital, Braga, Portugal
| | - Vânia Mariano
- Molecular Oncology Research Center, Barretos, São Paulo, Brazil
| | | | - Adhemar Longatto-Filho
- 1Life and Health Science Research Institute (ICVS), School of Health Sciences, School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.,ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Braga, Portugal.,Molecular Oncology Research Center, Barretos, São Paulo, Brazil.,5Laboratory of Medical Investigation (LIM) 14, Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil
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An aptasensor for the detection of Mycobacterium tuberculosis secreted immunogenic protein MPT64 in clinical samples towards tuberculosis detection. Sci Rep 2019; 9:16273. [PMID: 31700125 PMCID: PMC6838340 DOI: 10.1038/s41598-019-52685-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 10/18/2019] [Indexed: 12/21/2022] Open
Abstract
This work presents experimental results on detection of Mycobacterium tuberculosis secreted protein MPT64 using an interdigitated electrode (IDE) which acts as a platform for capturing an immunogenic protein and an electrochemical impedance spectroscopy (EIS) as a detection technique. The assay involves a special receptor, single stranded DNA (ssDNA) aptamer, which specifically recognizes MPT64 protein. The ssDNA immobilization on IDE was based on a co-adsorbent immobilization at an optimized ratio of a 1/100 HS-(CH6)6-OP(O)2O-(CH2CH2O)6-5′-TTTTT-aptamer-3′/6-mercaptohexanol. The optimal sample incubation time required for a signal generation on an aptamer modified IDE was found to be at a range of 15–20 min. Atomic Force Microscopy (AFM) results confirmed a possible formation of an aptamer - MPT64 complex with a 20 nm roughness on the IDE surface vs. 4.5 nm roughness for the IDE modified with the aptamer only. A limit of detection for the EIS aptasensor based on an IDE for the detection of MPT64 in measurement buffer was 4.1 fM. The developed EIS aptasensor was evaluated on both serum and sputum clinical samples from the same TB (−) and TB (+) patients having a specificity and sensitivity for the sputum sample analysis 100% and 76.47%, respectively, and for the serum sample analysis 100% and 88.24%, respectively. The developed aptasensor presents a sensitive method for the TB diagnosis with the fast detection time.
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Tumban E. A Current Update on Human Papillomavirus-Associated Head and Neck Cancers. Viruses 2019; 11:v11100922. [PMID: 31600915 PMCID: PMC6833051 DOI: 10.3390/v11100922] [Citation(s) in RCA: 148] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 10/03/2019] [Accepted: 10/04/2019] [Indexed: 02/07/2023] Open
Abstract
Human papillomavirus (HPV) infection is the cause of a growing percentage of head and neck cancers (HNC); primarily, a subset of oral squamous cell carcinoma, oropharyngeal squamous cell carcinoma, and laryngeal squamous cell carcinoma. The majority of HPV-associated head and neck cancers (HPV + HNC) are caused by HPV16; additionally, co-factors such as smoking and immunosuppression contribute to the progression of HPV + HNC by interfering with tumor suppressor miRNA and impairing mediators of the immune system. This review summarizes current studies on HPV + HNC, ranging from potential modes of oral transmission of HPV (sexual, self-inoculation, vertical and horizontal transmissions), discrepancy in the distribution of HPV + HNC between anatomical sites in the head and neck region, and to studies showing that HPV vaccines have the potential to protect against oral HPV infection (especially against the HPV types included in the vaccines). The review concludes with a discussion of major challenges in the field and prospects for the future: challenges in diagnosing HPV + HNC at early stages of the disease, measures to reduce discrepancy in the prevalence of HPV + HNC cases between anatomical sites, and suggestions to assess whether fomites/breast milk can transmit HPV to the oral cavity.
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Affiliation(s)
- Ebenezer Tumban
- Department of Biological Sciences, Michigan Technological University, 1400 Townsend Dr, Houghton, MI 49931, USA.
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Balci FL, Uras C, Feldman SM. Is human papillomavirus associated with breast cancer or papilloma presenting with pathologic nipple discharge? Cancer Treat Res Commun 2019; 19:100122. [PMID: 30785026 DOI: 10.1016/j.ctarc.2019.100122] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 01/31/2019] [Accepted: 02/05/2019] [Indexed: 12/15/2022]
Abstract
PURPOSE There are little data on the presence or interaction of human papillomavirus (HPV) in intraductal papilloma or Breast cancer (BC) presenting with pathologic nipple discharge (PND). The study aimed to determine whether the HPV-genotypes are identifiable in papilloma or carcinoma of the breast by real-time PCR with broad-spectrum genotyping. METHODS Formalin-fixed-paraffin-blocks obtained from the patients who were suffering from PND and underwent ductoscopic papilloma extraction (n = 27) or segmental/total mastectomy for cancer diagnosis (n = 18). HPV-DNAs were identified by PCR with broad-spectrum genotyping. Mc Nemar test was used to compare cancer-involved cases to normal-adjacent tissue concerning HPV positivity. Chi-Square test was used to analyze the association for receptor status in HPV positive cancer-involved cases. RESULTS The mean age (±SD) was 49 ± 16 in papilloma and 52 ± 14 in BC patients, respectively. We found high prevalence of HPV in papilloma and carcinoma: 29.6% (n = 8) and 44.4% (n = 8), respectively. The most common type identified in breast lesions was HPV-11, and the others were HPV- 6, -11, -39, and -82. Cancer-involved samples were more contaminated by HPV in comparison to normal-adjacent tissues (p = 0.016). In HPV positive cancer-involved cases, hormone receptors were found to be more positive than HER2-Neu (p = 0.035). CONCLUSIONS Our data suggest that HPV might be a causative agent for the development of papilloma and carcinoma of the breast in some cases presenting with PND. HPV positive breast cancers are more likely to be hormone positive. Further studies needed for validation regarding the integration of HPV-DNAs into the human genome that causes BC.
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Affiliation(s)
- Fatih Levent Balci
- Department of General Surgery, Bahcesehir University Faculty of Medicine, Medical Park Hospitals, Istanbul, Turkey.
| | - Cihan Uras
- Department of General Surgery, Acibadem Research Institute of Senology, Istanbul, Turkey
| | - Sheldon Marc Feldman
- Breast Surgery, Montefiore Medical Center, The University Hospital for the Albert Einstein College of Medicine, New York, NY, USA
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Human Papilloma Virus Vaccination and Incidence of Ocular Surface Squamous Neoplasia. Int Ophthalmol Clin 2018; 57:57-74. [PMID: 27898614 DOI: 10.1097/iio.0000000000000157] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Bønløkke S, Blaakær J, Steiniche T, Høgdall E, Jensen SG, Hammer A, Balslev E, Strube ML, Knakkergaard H, Lenz S. Evidence of No Association Between Human Papillomavirus and Breast Cancer. Front Oncol 2018; 8:209. [PMID: 29938198 PMCID: PMC6002490 DOI: 10.3389/fonc.2018.00209] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 05/23/2018] [Indexed: 01/02/2023] Open
Abstract
Background Globally, breast cancer is the most frequent cancer among women. Studies reported an increased risk of breast cancer among women with prior cervical dysplasia. This study aimed to describe the prevalence of human papillomavirus (HPV) in breast cancer and explore if women with prior cervical neoplasia carry an increased risk of HPV-positive breast cancer compared to women without. Methods This case–control study identified 193 Danish women diagnosed with breast cancer (1998–2012) at Aarhus University Hospital or Copenhagen University Hospital Herlev. Cases were 93 women with cervical intraepithelial neoplasia grade 3 or worse (CIN3+) prior to breast cancer. Controls were 100 women without prior cervical dysplasia. HPV testing and genotyping were done using SPF10 PCR-DEIA-LiPA25 and an in-house semi-Q-PCR assay. Results Overall HPV prevalence in breast cancer for the assays was 1.55% (95% CI 0.32–4.48) and 0.52% (95% CI 0.01–2.85). There was no difference in HPV prevalence between cases and controls (2.15 vs. 1.00%, p = 0.61 and 1.08 vs. 0.00%, p = 0.48). HPV prevalence in CIN3+ was 94.62% (95% CI 0.88–0.98). Concordance between the assays was 98.60%. Conclusion HPV prevalence in breast cancer is very low suggesting no etiological correlation between HPV and breast cancer.
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Affiliation(s)
- Sara Bønløkke
- Department of Pathology, Aarhus University Hospital, Aarhus, Denmark
| | - Jan Blaakær
- Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark
| | - Torben Steiniche
- Department of Pathology, Aarhus University Hospital, Aarhus, Denmark
| | - Estrid Høgdall
- Department of Pathology, Copenhagen University Hospital, Herlev, Denmark
| | | | - Anne Hammer
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Department of Obstetrics and Gynecology, Herning Hospital, Herning, Denmark
| | - Eva Balslev
- Department of Pathology, Copenhagen University Hospital, Herlev, Denmark
| | - Mikael Lenz Strube
- DTU Bioengineering, Technical University of Denmark, Kongens Lyngby, Denmark
| | | | - Suzan Lenz
- Private Gynecological Clinic "Suzan Lenz Gynækolog", Copenhagen, Denmark
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Malhone C, Longatto-Filho A, Filassi JR. Is Human Papilloma Virus Associated with Breast Cancer? A Review of the Molecular Evidence. Acta Cytol 2018; 62:166-177. [PMID: 29694946 DOI: 10.1159/000487700] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Accepted: 02/15/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Although the association of human papillomavirus (HPV) with many cancers is well established, the involvement of HPV in breast cancer remains controversial. The purpose of this study is to perform a comprehensive review of the results and methods used to demonstrate that HPV markers are present in human breast cancer, and how well these studies fulfil the criteria for proving the viral etiology of a cancer. STUDY DESIGN We conducted a search for molecular studies published until November 2016 that relate human breast cancer to HPV. RESULTS Forty-three original molecular studies were found, some of which compared cases to nonneoplastic controls. Some investigations did not identify HPV in mammary tissue, but others identified it with different frequencies of positivity, varying between 1.2 and 86%. In most case-control studies (21/24 studies), positivity in cases was found to be higher than in controls, but odds ratios and confidence intervals were not reported. CONCLUSION The results are controversial. However, they arouse a great interest in the potential participation of HPV in breast carcinogenesis, but rather as an essential cause-effect participant, at least as a co-participant in some cases. The circumstance of HPV positivity in breast cancer can be criticized, but the elements that clearly demonstrate it in a number of cases are also relevant.
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Affiliation(s)
- Carolina Malhone
- Breast Division, Cancer Institute of São Paulo, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Adhemar Longatto-Filho
- Laboratory of Medical Investigation (LIM) 14, Department of Pathology, University of São Paulo School of Medicine, São Paulo, Brazil
- Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil
| | - José Roberto Filassi
- Breast Division, Cancer Institute of São Paulo, University of São Paulo School of Medicine, São Paulo, Brazil
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Gannon OM, Antonsson A, Bennett IC, Saunders NA. Viral infections and breast cancer - A current perspective. Cancer Lett 2018; 420:182-189. [PMID: 29410005 DOI: 10.1016/j.canlet.2018.01.076] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Revised: 01/08/2018] [Accepted: 01/31/2018] [Indexed: 01/25/2023]
Abstract
Sporadic human breast cancer is the most common cancer to afflict women. Since the discovery, decades ago, of the oncogenic mouse mammary tumour virus, there has been significant interest in the potential aetiologic role of infectious agents in sporadic human breast cancer. To address this, many studies have examined the presence of viruses (e.g. papillomaviruses, herpes viruses and retroviruses), endogenous retroviruses and more recently, microbes, as a means of implicating them in the aetiology of human breast cancer. Such studies have generated conflicting experimental and clinical reports of the role of infection in breast cancer. This review evaluates the current evidence for a productive oncogenic viral infection in human breast cancer, with a focus on the integration of sensitive and specific next generation sequencing technologies with pathogen discovery. Collectively, the majority of the recent literature using the more powerful next generation sequencing technologies fail to support an oncogenic viral infection being involved in disease causality in breast cancer. In balance, the weight of the current experimental evidence supports the conclusion that viral infection is unlikely to play a significant role in the aetiology of breast cancer.
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Affiliation(s)
- O M Gannon
- University of Queensland Diamantina Institute, The Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - A Antonsson
- Department of Population Health, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland 4006, Australia; School of Medicine, The University of Queensland, Herston Road, Herston, Queensland 4006, Australia
| | - I C Bennett
- School of Medicine, The University of Queensland, Herston Road, Herston, Queensland 4006, Australia; Private Practice, The Wesley and St Andrews Hospital, Auchenflower 4066, Australia
| | - N A Saunders
- University of Queensland Diamantina Institute, The Faculty of Medicine, The University of Queensland, Brisbane, Australia.
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Baltzell KA, Shen HM, Krishnamurthy S, Sison JD, Nuovo GJ, Buehring GC. Bovine leukemia virus linked to breast cancer but not coinfection with human papillomavirus: Case-control study of women in Texas. Cancer 2017; 124:1342-1349. [PMID: 29266207 DOI: 10.1002/cncr.31169] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Revised: 09/11/2017] [Accepted: 10/24/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND Bovine leukemia virus (BLV) and human papillomavirus (HPV) were previously identified in human breast tissue and have been associated with breast cancer in independent studies. The objective of the current study was to test for the presence of BLV and HPV in the same breast tissue specimens to determine whether the viruses were associated with breast cancer either singly or together. METHODS Archival formalin-fixed paraffin-embedded breast tissue sections from 216 women were received from The University of Texas MD Anderson Cancer Center along with patient diagnosis. In situ polymerase chain reaction and/or DNA hybridization methods were used to detect targeted DNA segments of BLV and HPV. Standard statistical methods were used to calculate age-adjusted odds ratios, attributable risk, and P values for the trend related to the association between presence of a virus and a diagnosis of breast disease. RESULTS Women diagnosed with breast cancer were significantly more likely to have BLV DNA in their breast tissue compared with women with benign diagnoses and no history of breast cancer. Women with breast pathology classified as premalignant and no history of breast cancer also were found to have an elevated risk of harboring BLV DNA in their breast tissue. HPV status was not associated with malignancy, premalignant breast disease, or the presence of BLV in the breast tissues. CONCLUSIONS The data from the current study supported previous findings of a significant association between BLV DNA in breast tissue and a diagnosis of breast cancer, but did not demonstrate oncogenic strains of HPV associated with breast cancer or the presence of BLV DNA in breast tissue. The authors believe the findings of the current study contribute to overall knowledge regarding a possible causal role for viruses in human breast cancer. Cancer 2018;124:1342-9. © 2017 American Cancer Society.
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Affiliation(s)
- Kimberly A Baltzell
- Department of Family Health Care Nursing, University of California at San Francisco, San Francisco, California
| | - Hua Min Shen
- School of Public Health, University of California at Berkeley, Berkeley, California
| | - Savitri Krishnamurthy
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jennette D Sison
- Department of Neurological Surgery, School of Medicine, University of California at San Francisco, San Francisco, California
| | - Gerard J Nuovo
- Department of Pathology, Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Gertrude C Buehring
- School of Public Health, University of California at Berkeley, Berkeley, California
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Delgado-García S, Martínez-Escoriza JC, Alba A, Martín-Bayón TA, Ballester-Galiana H, Peiró G, Caballero P, Ponce-Lorenzo J. Presence of human papillomavirus DNA in breast cancer: a Spanish case-control study. BMC Cancer 2017; 17:320. [PMID: 28482874 PMCID: PMC5423011 DOI: 10.1186/s12885-017-3308-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Accepted: 05/01/2017] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Breast cancer is one of the most important neoplasia among women. It was recently suggested that biological agents could be the etiological cause, particularly Human Papilloma Virus (HPV). The aim of this study was to explore the presence of HPV DNA in a case-control study. METHODS We performed our study including 251 cases (breast cancer) and 186 controls (benign breast tumors), using three different molecular techniques with PCR (GP5/GP6, CLART® and DIRECT FLOW CHIP®). RESULTS HPV DNA was evidenced in 51.8% of the cases and in 26.3% of the controls (p < 0.001). HPV-16 was the most prevalent serotype. The odds ratio (OR) of HPV within a multivariate model, taking into account age and breastfeeding, was 4.034. CONCLUSIONS Our study, with methodological rigour and a sample size not previously found in the literature, demonstrate a significant presence of HPV DNA in breast cancer samples. A possible causal relationship, or mediation or not as a cofactor, remains to be established by future studies.
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Affiliation(s)
- Silvia Delgado-García
- Department of Obstetrics and Gynecology, University General Hospital of Alicante, c/ Pintor Baeza, 11, 03010 Alicante, Spain
| | - Juan-Carlos Martínez-Escoriza
- Department of Obstetrics and Gynecology, University General Hospital of Alicante, c/ Pintor Baeza, 11, 03010 Alicante, Spain
| | - Alfonso Alba
- Department of Genetics, Institute of Cellular and Molecular Studies, Lugo, Spain
| | - Tina-Aurora Martín-Bayón
- Department of Obstetrics and Gynecology, University General Hospital of Alicante, c/ Pintor Baeza, 11, 03010 Alicante, Spain
| | - Hortensia Ballester-Galiana
- Department of Obstetrics and Gynecology, University General Hospital of Alicante, c/ Pintor Baeza, 11, 03010 Alicante, Spain
| | - Gloria Peiró
- Department of Pathology, University General Hospital of Alicante, Institute of Sanitary and Biomedical Research of Alicante (ISABIAL), Alicante, Spain
| | - Pablo Caballero
- Department of Community Nursing, Preventive Medicine and Public Health and History of Science, University of Alicante, Alicante, Spain
| | - Jose Ponce-Lorenzo
- Department of Medical Oncology, University General Hospital of Alicante, Alicante, Spain
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16
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Wu YL, Hsu NY, Cheau-Feng Lin F, Lee H, Cheng YW. MiR-30c-2* negative regulated MTA-1 expression involved in metastasis and drug resistance of HPV-infected non-small cell lung cancer. Surgery 2016; 160:1591-1598. [PMID: 27506865 DOI: 10.1016/j.surg.2016.06.025] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Revised: 05/26/2016] [Accepted: 06/08/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND MiR-30c-2* is considered to be a tumor suppressor microRNA in various cancers and is associated with gemcitabine sensitivity of lung cancer cells. Downregulation of miR-30c-2* promotes tumor invasion via increased expression of metastasis-associated protein-1. We hypothesized that downregulated expression of miR-30c-2* was involved in human papillomavirus-associated lung tumorigenesis and drug resistance. METHODS We examined whether expression of human papillomavirus 16/18 oncoprotein and miR-30c-2*-associated genes could be linked to patient outcome by collecting 319 lung tumors from patients with non-small cell lung cancer to determine expression of human papillomavirus 16/18 E6 protein, miR-30c-2*, and miR-30c-2* downstream metastasis-associated protein-1 mRNA by immunohistochemical and real-time polymerase chain reaction analysis. RESULTS Our results showed that miR-30C-2* levels were increased 45-fold in the E6-knockdown TL-1 cells when compared with levels in the parental cells. More interestingly, metastasis-associated protein-1 expression correlated negatively with miR-30C-2* and positively with human papillomavirus 16 E6 protein expression in lung tumors from lung cancer patients. Metastasis-associated protein-1 expression levels in the tumor tissues correlated positively with tumor stage and nodal metastasis. Patients with high metastasis-associated protein-1 expression, and especially patients infected with human papillomavirus, experienced a poor clinical outcome, tumor recurrence, and a poor therapeutic response compared with those with low metastasis-associated protein-1 expression. CONCLUSION These results showed that miR-30C-2* and levels of downstream metastasis-associated protein-1 gene expression in the tumor tissues of patients could be useful in predicting clinical outcome and therapeutic response and in selecting useful therapeutic drugs for lung cancer patients, especially patients with human papillomavirus infection.
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Affiliation(s)
- Yi-Liang Wu
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Nan-Yung Hsu
- Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan; Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan; Division of Thoracic Surgery, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, China
| | - Frank Cheau-Feng Lin
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Huei Lee
- Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
| | - Ya-Wen Cheng
- Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
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17
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Karimi M, Khodabandehloo M, Nikkhoo B, Ghaderi E. No Significant Association between Human Papillomavirus
and Breast Cancer, Sanandaj, Iran. Asian Pac J Cancer Prev 2016; 17:4741-4745. [PMID: 27893206 PMCID: PMC5454626 DOI: 10.22034/apjcp.2016.17.10.4741] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Background and Objective: Any role of human papillomavirus (HPV) in the development of breast cancer is conjectural. The aim of this study was to investigate possible links between HPV and breast cancer in women, Sanandaj, Iran. Methods: In this case-control study, 70 formalin fixed and paraffin embedded blocks of breast malignant tumors as a case group and 70 blocks of lesions without malignancy were selected as controls. Sections about 10 µm thick were prepared. After removing the paraffin, DNA was extracted. Samples were tested by PCR using general and high-risk specific HPV primers. Results: All 70 malignant breast tumors (cases) were invasive ductal carcinomas, and of the 70 controls, 17 (24.3%) were fibrocystic tumors and 53 (75.7%) fibroadenomas. The age range of women in the case group was 25-72 years old and in the control group It was13-66 years. Using HPV general primers two samples were positive in the case group, confirmed to be HPV-18 using high-risk specific primers. Conclusion: No statistically significant association was found between breast cancer and HPV. It is necessary to confirm this result by further investigations in other populations.
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Affiliation(s)
- Maryam Karimi
- Student of Research Committee, Department of Microbiology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
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Wang D, Fu L, Shah W, Zhang J, Yan Y, Ge X, He J, Wang Y, Li X. Presence of high risk HPV DNA but indolent transcription of E6/E7 oncogenes in invasive ductal carcinoma of breast. Pathol Res Pract 2016; 212:1151-1156. [PMID: 27688086 DOI: 10.1016/j.prp.2016.09.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2016] [Revised: 09/12/2016] [Accepted: 09/15/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS The causative role of high risk human papillomavirus (HR-HPV) in breast cancer development is controversial, though a number of reports have identified HR-HPV DNA in breast cancer specimens. Nevertheless, most studies to date have focused primarily on viral DNA rather than the viral transcription. The aim of this study was to investigate the presence of HR-HPV in breast cancer tissues at HPV DNA level and HPV oncogenes mRNA level by in situ hybridization (ISH). METHODS One hundred and forty six (146) cases of breast invasive ductal carcinoma(IDC) and 83 cases of benign breast lesions were included in the study. Type specific oligonucleotide probes were used for the DNA detection of HPV 16,18 and 58 by ISH. HR-HPV oncogenes mRNA was assayed by novel RNAscope HR-HPV HR7 assay ISH. p16 protein expression was evaluated by immunohistochemistry (IHC). RESULTS HR-HPV 16,18 and 58 DNA were detected in 52 out of 146 (35.6%) IDC and in 3 out of 83 (3.6%) benign breast lesions by ISH. The HR-HPV mRNAs was detected only in a few specimens with strong HPV DNA positivity(4/25) in a few scattered cancer cells with very weak punctate nuclear and/or cytoplasmic staining. p16 over-expression did not correlate with the HPV DNA positive breast cancer samples(17/52 HPVDNA+ vs 28/94 HPV DNA-, p=0.731). CONCLUSIONS HR-HPVs certainly exist in breast cancer tissue with less active transcription, which implies that the causal role of HPV in breast cancer development need further study.
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Affiliation(s)
- Depu Wang
- Center of Translational Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, #227 YanTaXiLu, Xi'an, 710061, China
| | - Ling Fu
- Institute of Cancer Research, School of Basic Medical Science, Xi'an Jiaotong University, #76 YanTaXiLu, Xi'an, 710061, China
| | - Walayat Shah
- Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, 25000, Pakistan
| | - Jingwen Zhang
- Institute of Cancer Research, School of Basic Medical Science, Xi'an Jiaotong University, #76 YanTaXiLu, Xi'an, 710061, China
| | - Yan Yan
- Institute of Cancer Research, School of Basic Medical Science, Xi'an Jiaotong University, #76 YanTaXiLu, Xi'an, 710061, China
| | - Xinhong Ge
- Institute of Cancer Research, School of Basic Medical Science, Xi'an Jiaotong University, #76 YanTaXiLu, Xi'an, 710061, China
| | - Jianjun He
- Cancer Center of the First Affiliated Hospital, Xi'an Jiaotong University, #227 YanTaXiLu, Xi'an, 710061, China
| | - Yili Wang
- Institute of Cancer Research, School of Basic Medical Science, Xi'an Jiaotong University, #76 YanTaXiLu, Xi'an, 710061, China.
| | - Xu Li
- Center of Translational Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, #227 YanTaXiLu, Xi'an, 710061, China.
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19
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Cheng YW, Lin FCF, Chen CY, Hsu NY. Environmental exposure and HPV infection may act synergistically to induce lung tumorigenesis in nonsmokers. Oncotarget 2016; 7:19850-62. [PMID: 26918347 PMCID: PMC4991423 DOI: 10.18632/oncotarget.7628] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Accepted: 02/16/2016] [Indexed: 11/25/2022] Open
Abstract
Most studies of lung tumorigenesis have focused on smokers rather than nonsmokers. In this study, we used human papillomavirus (HPV)-positive and HPV-negative lung cancer cells to test the hypothesis that HPV infection synergistically increases DNA damage induced by exposure to the carcinogen benzo[a]pyrene (B[a]P), and contributes to lung tumorigenesis in nonsmokers. DNA adduct levels induced by B[a]P in HPV-positive cells were significantly higher than in HPV-negative cells. The DNA adduct formation was dependent on HPV E6 oncoprotein expression. Gene and protein expression of two DNA repair genes, XRCC3 and XRCC5, were lower in B[a]P-treated E6-positive cells than in E6-negative lung cancer cells. The reduced expression was also detected immunohistochemically and was caused by increased promoter hypermethylation. Moreover, mutations of p53 and epidermal growth factor receptor (EGFR) genes in lung cancer patients were associated with XRCC5 inactivation. In sum, our study indicates that HPV E6-induced promoter hypermethylation of the XRCC3 and XRCC5 DNA repair genes and the resultant decrease in their expression increases B[a]P-induced DNA adducts and contributes to lung tumorigenesis in nonsmokers.
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Affiliation(s)
- Ya-Wen Cheng
- Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
- Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
| | - Frank Cheau-Feng Lin
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Chih-Yi Chen
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Nan-Yung Hsu
- Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
- Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
- Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan
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20
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Zhou Y, Li J, Ji Y, Ren M, Pang B, Chu M, Wei L. Inconclusive role of human papillomavirus infection in breast cancer. Infect Agent Cancer 2015; 10:36. [PMID: 26504492 PMCID: PMC4620698 DOI: 10.1186/s13027-015-0029-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2015] [Accepted: 08/27/2015] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Epidemiological studies have examined the association between human papillomavirus (HPV) and breast cancer, but the findings are inconclusive. This study aimed to detect the prevalence of HPV in breast cancer tissue in patients from northeastern China and define the association between HPV and breast cancer using meta-analysis. METHODS Polymerase chain reaction (PCR) was used to test cutaneous or mucosal HPV DNA sequence in 77 breast cancer samples and 77 corresponding adjacent normal tissues. The prevalence of HPV in breast cancer was estimated by pooling data from 38 studies. A meta-analysis of 16 case-control studies was conducted to investigate the association between HPV and breast cancer. RESULTS We did not find HPV DNA sequence in any of the 154 tissue specimens we tested. However, our meta-analysis revealed a HPV prevalence of 30.30 % (95 % confidence interval [CI] = 22.30-38.40 %) among breast cancer cases; most of these involved high-risk HPV types (35.50 %, 95 % CI = 25.00-46.10 %). HPV prevalence in breast cancer varied by geographic region, publication period, and PCR detection method. An increased risk of breast cancer was observed in association with exposure to HPV (odds ratio [OR] = 3.24, 95 % CI = 1.59-6.57), which was influenced by geographic region, HPV DNA source, PCR primer used, and publication period. CONCLUSIONS HPV, especially high-risk HPV types, may be associated with an increased risk of breast cancer, and this association varies dramatically among geographic regions.
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Affiliation(s)
- Yi Zhou
- />Department of Thyroid and Breast Diseases, The Central Laboratory in The First Affiliated Hospital of Harbin Medical University, Harbin, 150001 Heilongjiang China
| | - Jinyuan Li
- />Department of Microbiology, Harbin Medical University, Immunity and Infection, Pathogenic Biology Key Laboratory in Heilongjiang Province, Harbin, 150081 Heilongjiang China
| | - Yuting Ji
- />Department of Microbiology, Harbin Medical University, Immunity and Infection, Pathogenic Biology Key Laboratory in Heilongjiang Province, Harbin, 150081 Heilongjiang China
| | - Ming Ren
- />Department of Thyroid and Breast Diseases, The Central Laboratory in The First Affiliated Hospital of Harbin Medical University, Harbin, 150001 Heilongjiang China
| | - Bo Pang
- />Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, 150001 Heilongjiang China
| | - Ming Chu
- />Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, 150001 Heilongjiang China
| | - Lanlan Wei
- />Department of Microbiology, Harbin Medical University, Immunity and Infection, Pathogenic Biology Key Laboratory in Heilongjiang Province, Harbin, 150081 Heilongjiang China
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Fimereli D, Gacquer D, Fumagalli D, Salgado R, Rothé F, Larsimont D, Sotiriou C, Detours V. No significant viral transcription detected in whole breast cancer transcriptomes. BMC Cancer 2015; 15:147. [PMID: 25884932 PMCID: PMC4374178 DOI: 10.1186/s12885-015-1176-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2014] [Accepted: 03/06/2015] [Indexed: 02/07/2023] Open
Abstract
Background Studies evaluating the presence of viral sequences in breast cancer (BC), including various strains of human papillomavirus and human herpes virus, have yielded conflicting results. Most were based on RT-PCR and in situ hybridization. Methods In this report we searched for expressed viral sequences in 58 BC transcriptomes using five distinct in silico methods. In addition, we complemented our RNA sequencing results with exome sequencing, PCR and immunohistochemistry (IHC) analyses. A control sample was used to test our in silico methods. Results All of the computational methods correctly detected viral sequences in the control sample. We identified a small number of viral sequences belonging to human herpesvirus 4 and 6 and Merkel cell polyomavirus. The extremely low expression levels—two orders of magnitude lower than in a typical hepatitis B virus infection in hepatocellular carcinoma—did not suggest active infections. The presence of viral elements was confirmed in sample-matched exome sequences, but could not be confirmed by PCR or IHC. Conclusions Our results show that no viral sequences are expressed in significant amounts in the BC investigated. The presence of non-transcribed viral DNA cannot be excluded.
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Affiliation(s)
- Danai Fimereli
- IRIBHM - Université Libre de Bruxelles, ULB, Campus Erasme CP602, 808 route de Lennik, 1070, Brussels, Belgium.
| | - David Gacquer
- IRIBHM - Université Libre de Bruxelles, ULB, Campus Erasme CP602, 808 route de Lennik, 1070, Brussels, Belgium.
| | - Debora Fumagalli
- Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Bld de Waterloo, 125-1000, Brussels, Belgium.
| | - Roberto Salgado
- Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Bld de Waterloo, 125-1000, Brussels, Belgium. .,Department of Pathology, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Bld de Waterloo, 125-1000, Brussels, Belgium.
| | - Françoise Rothé
- Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Bld de Waterloo, 125-1000, Brussels, Belgium.
| | - Denis Larsimont
- Department of Pathology, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Bld de Waterloo, 125-1000, Brussels, Belgium.
| | - Christos Sotiriou
- Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Bld de Waterloo, 125-1000, Brussels, Belgium.
| | - Vincent Detours
- IRIBHM - Université Libre de Bruxelles, ULB, Campus Erasme CP602, 808 route de Lennik, 1070, Brussels, Belgium. .,WELBIO, 808 route de Lennik, 1070, Brussels, Belgium.
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22
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Piana AF, Sotgiu G, Muroni MR, Cossu-Rocca P, Castiglia P, De Miglio MR. HPV infection and triple-negative breast cancers: an Italian case-control study. Virol J 2014; 11:190. [PMID: 25413873 PMCID: PMC4243283 DOI: 10.1186/s12985-014-0190-3] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Accepted: 10/26/2014] [Indexed: 12/13/2022] Open
Abstract
Background Breast cancer is one of the most important neoplasia among women. To reduce its incidence and mortality impact it would be desirable to early identify risk factors associated with its development. It was recently suggested that biological agents could be the etiological cause, particularly Human Papilloma Virus (HPV). No specific relationship with different breast cancer types has been demonstrated until now. In particular, the triple-negative breast cancer (TNBC), characterized by a receptor negative pattern (ER/PgR/HER2–negative) and poor prognosis, can represent one of the most relevant clinical and public health priority in terms of observational research. Findings Aim of the study was to evaluate the HPV-positivity prevalence in two breast cancer series (TNBC vs. non-TNBC) in Northern Sardinia, Italy. The sample size of each group was represented by 40 formalin-fixed and paraffin-embedded specimens. The mean age was 60.3 years. The majority of the cancers were ductal (84%). The grading distribution was different: G2 was the most prevalent grade in the non-TNBC series, whereas G3 was the most frequent in the TNBC series (70% and 72%, respectively). Six biological samples were HPV-positive (7.5%): the positivity was assessed only in the TNBC group (15%; p-value: 0.026). The isolated genotypes were: 16, 31, 45, 52, 6, and 66. Only one co-infection was found (i.e., HPV-6 and -66). Conclusions The prevalence of HPV-positivity in TNBC specimens was 15%. On the basis of its carcinogenetic ability, an etiological role in the pathogenesis of the cancer could be supposed. This association should be confirmed with longitudinal studies to better assess the role of the HPV infection in TNBC and non-TNBC tumors.
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Affiliation(s)
- Andrea Fausto Piana
- Hygiene and Preventive Medicine, Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
| | - Giovanni Sotgiu
- Hygiene and Preventive Medicine, Department of Biomedical Sciences, University of Sassari, Sassari, Italy. .,Epidemiology and Medical Statistics Unit, Department of Biomedical Sciences, University of Sassari - Research, Medical Education and Professional Development Unit, AOU Sassari, Sassari, Italy.
| | - Maria Rosaria Muroni
- Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
| | - Paolo Cossu-Rocca
- Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy. .,Surgical Pathology Unit, Department of Diagnostic Services, ASL Olbia, Olbia, Italy.
| | - Paolo Castiglia
- Hygiene and Preventive Medicine, Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
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Abstract
Viruses are known to be etiologically related to several types of human cancer. In several published studies, viruses such as human mammary tumor virus, human papillomaviruses, Epstein-Barr virus, human cytomegalovirus, herpes simplex virus, and measles virus have been implicated in the pathogenesis of a subset of breast cancers (BC). However, these studies have produced conflicting results, causing considerable controversy. In this context, recent demonstration of elevated levels of mutagenic antiviral enzyme APOBEC3B in a majority of BCs is a highly significant development, as it provides a possible mechanism for development of large numbers of mutations (kataegis) that characterize many of the BCs. It has also provided further impetus for revaluating the role of viruses in the pathogenesis of BC.
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Cobos C, Figueroa JA, Mirandola L, Colombo M, Summers G, Figueroa A, Aulakh A, Konala V, Verma R, Riaz J, Wade R, Saadeh C, Rahman RL, Pandey A, Radhi S, Nguyen DD, Jenkins M, Chiriva-Internati M, Cobos E. The role of human papilloma virus (HPV) infection in non-anogenital cancer and the promise of immunotherapy: a review. Int Rev Immunol 2014; 33:383-401. [PMID: 24811210 DOI: 10.3109/08830185.2014.911857] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Over the past 30 years, human papilloma virus (HPV) has been shown to play a role in the development of various cancers. Most notably, HPV has been linked to malignant progression in neoplasms of the anogenital region. However, high-risk HPV has also been suggested to play a significant role in the development of cancers in other anatomic locations, such as the head and neck, lung, breast and bladder. In 2006, the first vaccine for HPV, Gardasil, was approved for the prevention of subtypes 6, 11, 16 and 18. A few years later, Cevarix was approved for the prevention of subtypes 16 and 18, the HPV subtypes most frequently implicated in malignant progression. Although increased awareness and vaccination could drastically decrease the incidence of HPV-positive cancers, these approaches do not benefit patients who have already contracted HPV and developed cancer as a result. For this reason, researchers need to continue developing treatment modalities, such as targeted immunotherapies, for HPV-positive lesions. Here, we review the potential evidence linking HPV infection with the development of non-anogenital cancers and the potential role of immunotherapy in the prevention and eradication of HPV infection and its oncogenic sequela.
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Affiliation(s)
- Chris Cobos
- 1Department of Internal Medicine at the Division of Hematology & Oncology, Texas Tech University Health Sciences Center and Southwest Cancer Treatment and Research Center, Lubbock, TX, USA
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25
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Sugianto J, Sarode V, Peng Y. Ki-67 expression is increased in p16-expressing triple-negative breast carcinoma and correlates with p16 only in p53-negative tumors. Hum Pathol 2014; 45:802-9. [DOI: 10.1016/j.humpath.2013.11.013] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2013] [Revised: 11/14/2013] [Accepted: 11/22/2013] [Indexed: 10/26/2022]
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Francis IM, Al-Ayadhy B, Al-Awadhi S, Kapila K, Al-Mulla F. Prevalence and correlation of human papilloma virus and its types with prognostic markers in patients with invasive ductal carcinoma of the breast in kuwait. Sultan Qaboos Univ Med J 2013; 13:527-33. [PMID: 24273662 DOI: 10.12816/0003311] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2013] [Revised: 06/10/2013] [Accepted: 07/04/2013] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVES This study aimed to document the association of human papilloma virus (HPV) and its types in breast carcinoma tissues in Kuwaiti women, and correlate this with known prognostic markers. METHODS The clinicopathological data of archived tissue from 144 cases of invasive ductal breast carcinoma were studied (age, histological grade, size of tumour, lymph node metastases, oestrogen/progesterone receptors and human epidermal growth factor receptor 2 status). HPV frequency was documented using immunohistochemistry (IHC) and chromogenic in-situ hybridisation (CISH). HPV types were documented by CISH using HPV probes. CISH and IHC techniques were compared and HPV correlated with prognostic parameters. RESULTS The HPV prevalence as determined by CISH and IHC was 51 (35.4%) and 24 (16.7%) cases, respectively. The sensitivity of HPV by IHC was 37.3% and specificity was 94.6%. The sensitivity and specificity of HPV-CISH compared to HPVIHC was statistically significant (P <0.001). HPV-CISH was seen in 51 cases. A combination of HPV 6 and 11, and 16 and 18 was seen in 2 (3.9%) cases, and a combination of HPV 6, 11, 31 and 33 was seen in 7 (13.7%) cases. All three HPV probes: 6 and 11, 16 and 18, as well as 31 and 33 were present in 2 (3.9%) cases. The prevalence of HPVCISH in the Kuwaiti and non-Kuwaiti populations was 27 (52.9%) and 19 (37.2%), respectively. No correlation was observed with the prognostic parameters. CONCLUSION The frequency of HPV in breast carcinoma cases in Kuwait was 35.4% (CISH). Of those, 52.9% were Kuwaitis in whom both low- and high-risk HPV types were detected.
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Affiliation(s)
- Issam M Francis
- Department of Pathology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait
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De Paoli P, Carbone A. Carcinogenic viruses and solid cancers without sufficient evidence of causal association. Int J Cancer 2013; 133:1517-29. [PMID: 23280523 DOI: 10.1002/ijc.27995] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2012] [Accepted: 12/07/2012] [Indexed: 01/01/2023]
Abstract
Viral infections are important risk factors for tumor development in humans. Selected types of cancers, either lymphomas or carcinomas, for which there is sufficient evidence in humans of a causal association with specific viruses, have been identified. Experimental and clinical data on the possible association of other tumor types and carcinogenic viruses are presently controversial. In this article, we review the current evidence on the relationship between breast, colorectal and lung cancers and carcinogenic viruses. The majority of the publications reviewed do not provide definitive evidence that the viruses studied are associated with breast, colon and lung cancers. However, since this association may be clinically relevant for some tumor subtypes (i.e., lung cancer and papillomaviruses), there is an urgent need for further investigation on this topic. Using innovative laboratory techniques for viral detection on well-defined tumor types, National and International networks against cancer should encourage and organize concerted research programs on viruses and solid cancer association.
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Affiliation(s)
- Paolo De Paoli
- Scientific Directorate, Centro di Riferimento Oncologico, IRCCS, Istituto Nazionale Tumori, Via Franco Gallini 2, Aviano, Italy.
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Liang W, Wang J, Wang C, Lv Y, Gao H, Zhang K, Liu H, Feng J, Wang L, Ma R. Detection of high-risk human papillomaviruses in fresh breast cancer samples using the hybrid capture 2 assay. J Med Virol 2013; 85:2087-92. [PMID: 23959946 DOI: 10.1002/jmv.23703] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/17/2013] [Indexed: 11/10/2022]
Abstract
The etiology of breast cancer remains unknown and the role of human papillomavirus (HPV) in breast carcinogenesis is controversial. This study investigated the prevalence of high-risk HPV infections in Chinese women with breast cancer and the possible relationship between high-risk HPV infection and the clinicopathological characteristics of breast cancer. Tumor cells from 224 fresh breast cancer samples and 37 fresh breast fibroadenomas were collected for hybrid capture 2 (HC2) assay. HC2 was the only technique approved by the United States Food and Drug Administration for screening for high-risk HPV infection in 2008. The prevalence of high-risk HPV infection in breast cancer samples was 21.4%, which was slightly higher than the 16.2% observed in breast fibroadenomas. Age and menopausal status were not risk factors for high-risk HPV infection among breast cancer patients. The clinical and pathological characteristics of breast cancer showed no significant correlation with high-risk HPV infection. Although the prevalence of 13 subtypes of high-risk HPV infections was similar in breast cancer and nonmalignant breast samples, the presence of high-risk HPVs in both malignant and benign breast samples implies that a possible causal role in breast cancer carcinogenesis could not be ruled out. Clarifying the possible link between high-risk HPVs and breast cancer might benefit women vaccinated against HPV and could decrease the incidence of HPV-related breast cancer.
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Affiliation(s)
- Weili Liang
- Department of Breast Surgery, Qilu Hospital of Shandong University, Shandong, P.R., China
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Association of p53 Codon 72 Genotypes and Clinical Outcome in Human Papillomavirus-Infected Lung Cancer Patients. Ann Thorac Surg 2013; 95:1196-203. [DOI: 10.1016/j.athoracsur.2012.12.059] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2012] [Revised: 12/25/2012] [Accepted: 12/28/2012] [Indexed: 01/22/2023]
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Chen TH, Huang CC, Yeh KT, Chang SH, Chang SW, Sung WW, Cheng YW, Lee H. Human papilloma virus 16 E6 oncoprotein associated with p53 inactivation in colorectal cancer. World J Gastroenterol 2012; 18:4051-4058. [PMID: 22912557 PMCID: PMC3420003 DOI: 10.3748/wjg.v18.i30.4051] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2012] [Revised: 03/31/2012] [Accepted: 04/09/2012] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the association between human papilloma virus (HPV) infection and colorectal cancer. METHODS Sixty-nine patients with pathologically confirmed primary colorectal cancer including 6 stage I, 24 stage II, 21 stage III, and 18 stage IV patients were enrolled in this study to investigate whether HPV 16 could be involved in colorectal tumorigenesis. Nested-polymerase chain reaction (nested-PCR) was used to detect HPV16 DNA in colorectal tumor tissues and further confirmed by in situ hybridization (ISH). In addition, immunohistochemistry analysis was performed to examine the E6 oncoprotein in colorectal tumors. To verify whether E6 could inactivate the p53 transcriptional function, the levels of p21 and Mdm2 mRNA expression were evaluated by real-time reverse transcription (RT)-PCR. RESULTS Of the 69 colorectal tumors, HPV16 DNA was detected in 11 (16%) by nested-PCR, and HPV16 DNA was present in 8 of the 11 (73%) tumors which was confirmed by ISH. The presence of HPV16 DNA in colorectal tumors was not associated with patients' clinical parameters including age, gender, smoking status, tumor site; however, HPV16 infection was more common in stage I patients than in late-stages patients (II, III and IV). We next asked whether HPV16 infection could be linked with colorectal cancer development. Immunohistochemical data indicated that 8 of the 11 HPV16 DNA-positive tumors had E6 oncoprotein expression. Moreover, we also observed that the adjacent normal tissues including endothelial cells, lymphocytes, fibroblasts, and gland cells in E6-positive tumors had E6 oncoprotein expression. In addition, 3 of the 4 (75%) E6-positive tumors carrying p53 wild-type had negative immunostaining, but one tumor had less p53 immunostaining. We further examined whether E6-positive and/or p53 mutated tumors reduce p53 transcriptional activity. Real-time RT-PCR analysis indicated that p21 and mdm2 mRNA expression levels in E6/p53-wildtype tumors were significantly lower than in their adjacent normal tissues; as expected, E6-positive/p53-mutated tumors had lower p21 and mdm2 mRNA expression levels compared with their adjacent normal tissues. These results clearly indicate that the E6 oncoprotein expressed in p53 wildtype tumors may reduce p21 and mdm2 expression via p53 inactivation. CONCLUSION These results suggest that HPV16 infection may be involved in a subset of colorectal cancer, and we suggest that the transmission of HPV to the colon and rectum might occur through peripheral blood lymphocytes.
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Yu ACH, Vatcher G, Yue X, Dong Y, Li MH, Tam PHK, Tsang PYL, Wong AKY, Hui MHK, Yang B, Tang H, Lau LT. Nucleic acid-based diagnostics for infectious diseases in public health affairs. Front Med 2012; 6:173-86. [PMID: 22660977 PMCID: PMC7088663 DOI: 10.1007/s11684-012-0195-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2011] [Accepted: 03/03/2012] [Indexed: 11/29/2022]
Abstract
Infectious diseases, mostly caused by bacteria and viruses but also a result of fungal and parasitic infection, have been one of the most important public health concerns throughout human history. The first step in combating these pathogens is to get a timely and accurate diagnosis at an affordable cost. Many kinds of diagnostics have been developed, such as pathogen culture, biochemical tests and serological tests, to help detect and fight against the causative agents of diseases. However, these diagnostic tests are generally unsatisfactory because they are not particularly sensitive and specific and are unable to deliver speedy results. Nucleic acid-based diagnostics, detecting pathogens through the identification of their genomic sequences, have shown promise to overcome the above limitations and become more widely adopted in clinical tests. Here we review some of the most popular nucleic acid-based diagnostics and focus on their adaptability and applicability to routine clinical usage. We also compare and contrast the characteristics of different types of nucleic acid-based diagnostics.
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Affiliation(s)
- Albert Cheung-Hoi Yu
- Neuroscience Research Institute, Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience, Peking University, Beijing, 100191, China.
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Joshi D, Buehring GC. Are viruses associated with human breast cancer? Scrutinizing the molecular evidence. Breast Cancer Res Treat 2012; 135:1-15. [PMID: 22274134 DOI: 10.1007/s10549-011-1921-4] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2011] [Accepted: 12/09/2011] [Indexed: 01/29/2023]
Abstract
The three viruses most studied as possible causes of human breast cancer are mouse mammary tumor virus-like sequences (MMTV-LS), Epstein-Barr virus (EBV), and oncogenic (high risk) types of human papilloma virus (HPV). The first step in fulfilling traditional criteria for inferring that a cancer is caused by a virus is to demonstrate the virus in the affected tissue. Molecular techniques, compared to host antibody assessment and immunohistochemistry, are the most definitive in establishing viral presence. Results of 85 original molecular research investigations to detect one or more of the three viruses have been extremely divergent with no consensus reached. We evaluated the methodology of these studies for the following: type of molecular assay, DNA/RNA quality control, positive and negative assay controls, type of fixation, genome targets, methods for preventing and detecting molecular contamination, pathology of specimens processed, sample size, and proportion of specimens positive for the viral genome region targeted. Only seven of the studies convincingly demonstrated the presence of an oncogenic virus biomarker (EBV: 4/30 studies (13%); HPV 3/29 studies (10%), whereas 25 convincingly demonstrated absence of the virus studied (MMTV-LS: 4/25 (16%); EBV: 15/30 (50%); 6/29 (21%). The remainder of the studies suffered shortcomings, which, in our opinion, prevented a definitive conclusion. Only one of the studies compared frequency of the virus in breast tissue of breast cancer patients versus appropriate normal control subjects with no history of breast cancer. None of the studies were designed as epidemiologic studies to determine if the presence of the virus was significantly associated with breast cancer. Based on our evaluation, the data in the publications reviewed here remain preliminary, and do not justify a conclusion that MMTV-LS, HPV, or EBV are causally associated with breast cancer. However, they form a valuable basis for redirecting future studies.
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Affiliation(s)
- Deepti Joshi
- Department of Pathology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, District Wardha, Maharashtra, India.
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