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1
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Fulton NE, Horn TD, Demerhi S. Inciting commensal human papillomavirus immunity to combat cancer. Trends Cancer 2025:S2405-8033(25)00098-6. [PMID: 40316467 DOI: 10.1016/j.trecan.2025.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 04/06/2025] [Accepted: 04/08/2025] [Indexed: 05/04/2025]
Abstract
The incidence of squamous cell carcinoma (SCC) is rising, especially in immunosuppressed individuals, highlighting the need for new prevention strategies. Commensal human papillomaviruses (cHPVs) are associated with cutaneous SCC (cSCC) in immunosuppressed patients. Because of the intricate interactions between T cell immunity and cHPVs in virus-colonized tissues, we propose that enhancing T cell immunity against cHPVs through vaccination could suppress SCC.
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Affiliation(s)
- Natalie E Fulton
- Center for Cancer Immunology, Krantz Family Center for Cancer Research, Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Thomas D Horn
- Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
| | - Shadmehr Demerhi
- Center for Cancer Immunology, Krantz Family Center for Cancer Research, Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
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2
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Munabi IG, Kamulegeya A, Kateete DP, Semitala F, Kalungi S, Cameron JE, Patton LL, Divaris K, Buwembo W. Changes in Oral Papilloma Virus Infections Over Six Months in People Living with HIV. RESEARCH SQUARE 2025:rs.3.rs-6495161. [PMID: 40313758 PMCID: PMC12045371 DOI: 10.21203/rs.3.rs-6495161/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/03/2025]
Abstract
There is a paucity of data on changes in oral papilloma virus (PV) infection in people living with HIV (PLHIV) especially in low resource settings. The objective of this study was to determine the changes in oral PV infections in PLHIV from a low resource setting over a six-month follow-up period. This was a cohort study in which data was derived from a sub-sample of a parent study that examined oral human papilloma viruses, microbiota, and cancer in PLWHIV. This as a six-month follow up and a 2 mls saliva sample was collected from 541 participants on both visits. The saliva sample was used for DNA extraction, PV screening and typing using PCR methods. The DNA was subjected to Nanopore PV sequencing and subsequently analyzed using the phyloseq object, followed by a series of comparisons using the Phyloseq and Vegan packages in R to generate the alpha and beta diversity indices of the sequencing data from the sampled participants PV OTUs at the two visits. We found that 60% of participants had no detectable PVs at six-month follow-up, with a significant clearance rate of 84.47%. Oncogenic PVs were less likely to be detected as new infections compared to non-oncogenic PVs (Rate Ratio (RR) 0.42, 95% CI 0.31 to 0.56, P < 0.01). Oncogenic PV types were more likely cleared than non-oncogenic strains (RR 1.16, 95% CI 1.03 to 1.31, P = 0.02), but persistence rates did not significantly differ. This study highlights important trends in the natural course of oral PV infections, demonstrating that while most infections clear over time, there are distinct differences in the behavior of oncogenic versus non-oncogenic strains. These findings have important implications for the understanding of PV epidemiology and may guide future preventive and therapeutic strategies, particularly in the context of Human PV-related cancer prevention.
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Affiliation(s)
- Ian G Munabi
- Department of Dentistry, School of Dentistry, Makerere University College of Health Sciences, Kampala, Uganda
| | - Adriane Kamulegeya
- Department of Oral and Maxillofacial surgery, School of Dentistry, Makerere University College of Health Sciences, Kampala, Uganda
| | - David P Kateete
- Department of Immunology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
| | - Fred Semitala
- Department of Medicine, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - Samuel Kalungi
- Department of Pathology, Mulago National Referral and Teaching Hospital, Kampala, Uganda of Medicine, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | | | - Lauren L Patton
- Department of Craniofacial and Surgical Care, Adams School of Dentistry, University of North Carolina Chapel Hill, North Carolina, USA. f Pediatric Dentistry and Dental Public Health, Adams School of Dentistry, University of North Carolina Chapel Hill, North Carolina, USA
| | - Kimon Divaris
- Department of Pediatric Dentistry and Dental Public Health, Adams School of Dentistry, University of North Carolina Chapel Hill, North Carolina, USA., Department of Pediatric Dentistry and Dental Public Health, Adams School of Dentistry, University of North Carolina Chapel Hill, North Carolina, USA.Gillings School of Global Public Health, University of North Carolina Chapel Hill, North Carolina, USA
| | - William Buwembo
- Department of Anatomy, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
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3
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Xiao R, Yang X, Duan R, Zhang H. Characteristics of HPV Infection in Women Cervical and Anal with HIV-Infected and the Advances in Epidemiological Research. Infect Drug Resist 2025; 18:1785-1791. [PMID: 40225108 PMCID: PMC11992993 DOI: 10.2147/idr.s511440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 03/28/2025] [Indexed: 04/15/2025] Open
Abstract
Antiretroviral therapy (ART) has significantly reduced the incidence and mortality of AIDS-related diseases, bringing the life expectancy of human immunodeficiency virus (HIV)-infected individuals close to that of uninfected individuals. However, the incidence and mortality rates of tumors associated with human papillomavirus (HPV) have not decreased. Persistent infection with high-risk HPV is a major cause of cervical cancer and other related malignancies, and the risk of HPV infection and the incidence of related diseases are higher among HIV-infected individuals. Although the World Health Organization provides screening recommendations for the general population, there is a lack of guidelines for cervical and anal cancer screening specifically in HIV-positive patients. Further research is urgently needed to develop effective preventive measures. This article reviews the epidemiological characteristics and associations of HPV infections and related cancers in HIV-infected women, providing reference for prevention and treatment.
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Affiliation(s)
- Rong Xiao
- Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan, Kunming, Yunnan, People’s Republic of China
- Department of Gynecology, Huize Maternal and Child Health Hospital, Huize, Yunnan, People’s Republic of China
| | - Xue Yang
- Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan, Kunming, Yunnan, People’s Republic of China
| | - Rufei Duan
- Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan, Kunming, Yunnan, People’s Republic of China
| | - Hongping Zhang
- Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan, Kunming, Yunnan, People’s Republic of China
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Li W, Zhang P, Fu H, Yan S, Zhu D. Targeted therapeutic strategy for oral squamous carcinoma using celecoxib-loaded GABA/wheat gluten-alginate nanocarrier hydrogel with glutathione down-regulation and enhanced CCND2-mediated apoptosis. Int J Biol Macromol 2025; 303:140679. [PMID: 39909279 DOI: 10.1016/j.ijbiomac.2025.140679] [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: 10/08/2024] [Revised: 01/20/2025] [Accepted: 02/03/2025] [Indexed: 02/07/2025]
Abstract
The intricate architecture of the oral cavity results in insufficient surgical excision of oral squamous cell carcinoma (OSCC) potentially increasing the risk of metastasis and recurrence during treatment. In situ generating injectable hydrogels, characterized by minimally invasive methods, encapsulating stability, and pH-responsive breakdown have emerged as viable delivery systems. Herein, we aim to explore a particular therapeutic modality involving the use of celecoxib-loaded GABA/wheat gluten‑sodium alginate (SA/WG-GABA+COX(40)) nanocarriers in enhancing apoptosis of OSCC (HSC-3 & SCC-25). Eventually, drug release profiles show that loaded COX and GABA demonstrated 96.04% and 98.1% at 7.2 pH. Interestingly, crucial experimental techniques like MTT assay, AO/EB staining, DAPI labeling for SCC-25, and HSC-3 displayed the highest cell lysis percentages of 86.5% and 93.3%. Notably, OSCC cell proliferation and migration and cell multiplications were limited with formulated WG/SA-GABA+COX(40) which was evident from In vitro ROS assay, flow cytometry, and JC-1 analysis. In vivo histology, blood serum biochemistry, and tumor examination in xenograft nude mice demonstrated that SA/WG-GABA+COX(40) mice reduced HSC-3 tumor cell proliferation. Downregulation of glutathione and activation of CCND2 signaling pathway caused HSC-3 OSCC cell death. Henceforth, present findings offer an advanced drug delivery method for targeted chemotherapy in treating OSCC.
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Affiliation(s)
- Wenlu Li
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450000, China.
| | - Peipei Zhang
- Department of Stomatology, Zhengzhou Central Hospital affiliated to Zhengzhou University, Zhengzhou University, Zhengzhou 450001, China
| | - Hao Fu
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450000, China
| | - Shunchao Yan
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450000, China
| | - Dandan Zhu
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450000, China
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Adans-Dester G, Evrard P, D’Hondt L, Carlier FM. The Need to Enhance Intimacy Care in Immunosuppressed Patients: A Case Report of Neglected Penile Cancer in a Long-term Lung Transplant Recipient. Transplant Direct 2025; 11:e1763. [PMID: 39995962 PMCID: PMC11850037 DOI: 10.1097/txd.0000000000001763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 11/26/2024] [Accepted: 11/27/2024] [Indexed: 02/26/2025] Open
Affiliation(s)
| | | | - Lionel D’Hondt
- Department of Medical Oncology, CHU UCL Namur, Yvoir, Belgium
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Achdiat PA, Larasati R, Hidayah RMN, Avriyanti E, Usman HA, Maharani RH. Atypical HPV Typing: Detection of Genital-Associated HPV Type 6 in Verruca Vulgaris of the Hands and Feet in an HIV-Positive Patient. Int Med Case Rep J 2025; 18:67-74. [PMID: 39817050 PMCID: PMC11734615 DOI: 10.2147/imcrj.s494454] [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: 09/05/2024] [Accepted: 12/25/2024] [Indexed: 01/18/2025] Open
Abstract
Verruca vulgaris is a cutaneous infection predominantly caused by human papillomavirus (HPV) type 1, 2, and 4. In immunocompromised individuals infected with human immunodeficiency virus (HIV) infection, HPV leads to a higher prevalence of infections and also has a greater likelihood of being infected with atypical types such as genital-associated HPV in extragenital sites. This case report describes a 48-year-old male patient who presented with skin-colored verrucous papules on the hands and feet, with no evidence of genital lesions. Polymerase Chain Reaction (PCR) genotyping identified the presence of HPV types 4, 6, and 16 as an etiology of verruca vulgaris, low-risk HPV with genital-associated lesions, and high-risk HPV. This atypical result may suggest a failure of the immune defense system of the body. Therefore, accurately identifying HPV types through PCR testing in immunocompromised patients is essential for appropriate clinical management and monitoring.
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Affiliation(s)
- Pati Aji Achdiat
- Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Bandung, West Java, Indonesia
| | - Ranisa Larasati
- Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Bandung, West Java, Indonesia
| | - Risa Miliawati Nurul Hidayah
- Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Bandung, West Java, Indonesia
| | - Erda Avriyanti
- Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Bandung, West Java, Indonesia
| | - Hermin Aminah Usman
- Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Bandung, West Java, Indonesia
| | - Retno Hesty Maharani
- Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Bandung, West Java, Indonesia
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Miyaji KT, Infante V, Picone CM, Dillner J, Kann H, Eklund C, Levi JE, de Oliveira ACS, Lara AN, Kawakami LS, Tacla M, Castanheira CP, Mayaud P, Sartori AMC. Quadrivalent HPV (4vHPV) vaccine immunogenicity and safety in women using immunosuppressive drugs due to solid organ transplant. Front Cell Infect Microbiol 2024; 14:1452916. [PMID: 39559707 PMCID: PMC11570996 DOI: 10.3389/fcimb.2024.1452916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 08/19/2024] [Indexed: 11/20/2024] Open
Abstract
Introduction Immunocompromised persons are at high risk of persistent Human Papilloma Virus (HPV) infection and associated diseases. Few studies evaluated HPV vaccines in immunocompromised persons. This study aimed to evaluate the quadrivalent HPV vaccine (4vHPV) immunogenicity and safety in solid organ transplant (SOT) recipients, in comparison to immunocompetent women (IC). Methods Open-label clinical trial that enrolled SOT recipients and immunocompetent women aged 18 to 45 years. All participants received three doses of 4vHPV vaccine. Blood samples were drawn for evaluation of immune responses at baseline and one month after the third vaccination. Seroconversion rates and antibody geometric mean concentration (GMC) against HPV 6, 11, 16, 18, 31, 35, 52 and 58 were measured with in-house multiplexed serology assay (xMAP technology). Follow-up for the local and systemic adverse events (AEs) continued for seven days after each vaccination. Severe AEs were evaluated throughout the study. Results 125 SOT and 132 immunocompetent women were enrolled; 105 (84%) SOT and 119 (90%) immunocompetent women completed the study. At baseline, HPV seropositivity was not significantly different between groups. Seroconversion rates were significantly lower in SOT (HPV18, 57%; HPV6 and 16, 69%; and HPV11, 72%) than in immunocompetent women (100% seroconversion to all vaccine types) (p<0.001). Antibody GMCs of all four HPV vaccine types were also significantly lower in SOT (p<0.001). Pain in the injection site and headache were the most frequent adverse event in both groups. Local pain was more frequent in immunocompetent women than in SOT recipients. Rates of other AEs were comparable in both groups. Conclusion 4vHPV vaccine was well-tolerated by SOT recipients. We found strong evidence of lower humoral immune responses to 4vHPV vaccine in SOT compared to immunocompetent women, which strengthen recommendation of routine cervical cancer screening in SOT recipients regardless of HPV vaccination status.
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MESH Headings
- Humans
- Female
- Adult
- Antibodies, Viral/blood
- Papillomavirus Infections/prevention & control
- Papillomavirus Infections/immunology
- Young Adult
- Immunosuppressive Agents/adverse effects
- Organ Transplantation/adverse effects
- Middle Aged
- Adolescent
- Immunogenicity, Vaccine
- Papillomavirus Vaccines/immunology
- Papillomavirus Vaccines/adverse effects
- Papillomavirus Vaccines/administration & dosage
- Immunocompromised Host
- Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/immunology
- Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/adverse effects
- Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/administration & dosage
- Transplant Recipients
- Seroconversion
- Vaccination
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Affiliation(s)
- Karina Takesaki Miyaji
- Departamento de Infectologia e Medicina Tropical da Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo, Brazil
- Clinica de Molestias Infecciosas e Parasitarias do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Sao Paulo, Brazil
- Centro de Referencia para Imunobiológicos Especiais, HCFMUSP, Sao Paulo, Brazil
| | - Vanessa Infante
- Clinica de Molestias Infecciosas e Parasitarias do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Sao Paulo, Brazil
- Centro de Referencia para Imunobiológicos Especiais, HCFMUSP, Sao Paulo, Brazil
| | - Camila Melo Picone
- Departamento de Infectologia e Medicina Tropical da Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo, Brazil
- Clinica de Molestias Infecciosas e Parasitarias do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Sao Paulo, Brazil
| | - Joakim Dillner
- Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
| | - Hanna Kann
- Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
- Department of Microbiology and Immunology, Gothenburg University, Gothenburg, Sweden
| | - Carina Eklund
- Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
| | - José Eduardo Levi
- Laboratório de Investigação Medica – Virologia, Instituto de Medicina Tropical, Sao Paulo, Brazil
| | | | - Amanda Nazareth Lara
- Clinica de Molestias Infecciosas e Parasitarias do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Sao Paulo, Brazil
- Centro de Referencia para Imunobiológicos Especiais, HCFMUSP, Sao Paulo, Brazil
| | | | - Maricy Tacla
- Clínica de Ginecologia, HC-FMUSP, Sao Paulo, Brazil
| | | | - Philippe Mayaud
- Clinical Research Department, London School of Tropical Medicine and Hygiene (LSHTM), London, United Kingdom
| | - Ana Marli Christovam Sartori
- Departamento de Infectologia e Medicina Tropical da Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo, Brazil
- Clinica de Molestias Infecciosas e Parasitarias do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Sao Paulo, Brazil
- Centro de Referencia para Imunobiológicos Especiais, HCFMUSP, Sao Paulo, Brazil
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Li J, He L, He Q, Xie K, Xie H. Exploring the interaction mechanisms between cervical carcinoma in situ and antibody-mediated immune responses through Mendelian randomization analysis. Discov Oncol 2024; 15:568. [PMID: 39417906 PMCID: PMC11486878 DOI: 10.1007/s12672-024-01456-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Accepted: 10/12/2024] [Indexed: 10/19/2024] Open
Abstract
OBJECTIVE This study aims to investigate the causal relationship between cervical carcinoma in situ and antibody-mediated immune responses, providing a scientific basis for the prevention and treatment of cervical carcinoma in situ. METHODS A bidirectional Mendelian Randomization (MR) approach was utilized, leveraging two Genome-Wide Association Studies (GWAS) related to cervical carcinoma in situ and antibody-mediated immune responses to collect Single Nucleotide Polymorphism (SNP) data. Multiple statistical methods, including the inverse-variance weighted (IVW) method, MR-Egger regression, weighted median, and weighted mode, were utilized. Antibody-mediated immune response-related SNPs were used as instrumental variables (IVs) for a forward MR analysis of cervical carcinoma in situ, while cervical carcinoma in situ-related SNPs served as IVs for a reverse MR analysis of antibody-mediated immune responses. RESULTS The forward MR analysis revealed significant causal associations between two SNPs, GCST90006901 (P = 0.012, OR (95%CI) = 1.167(1.034-1.317)) and GCST90006909 (P < 0.001, OR (95%CI) = 1.805(1.320-2.467)), within antibody-mediated immune responses and the occurrence of cervical carcinoma in situ. The reverse MR analysis demonstrated that cervical carcinoma in situ exerts influence on multiple SNPs associated with antibody-mediated immune responses. Specifically, GCST90006891 (P = 0.018, OR (95%CI) = 1.164(1.027-1.319)) and GCST90006894 (P = 0.048, OR (95%CI) = 1.074 (1.001-1.153)) showed positive effects, while GCST90006899 (P = 0.022, OR (95%CI) = 0.935(0.882-0.990)) and GCST90006911 (P = 0.0193, OR (95%CI) = 1.226(1.034-1.454)) exhibited distinct trends of influence. CONCLUSION The Mendelian Randomization analysis indicates a clear causal relationship between antibody-mediated immune responses and the prevalence of cervical carcinoma in situ, with cervical carcinoma in situ also exerting a certain degree of influence on antibody-mediated immune responses. This finding provides important insights into the interaction mechanism between the two and suggests avenues for developing effective prevention and control strategies.
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Affiliation(s)
- Junfei Li
- Department of Gynecology, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, 423000, People's Republic of China
| | - Lihuang He
- Department of Oncology, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, 423000, People's Republic of China
| | - Qun He
- Department of Supply Room, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, 423000, People's Republic of China
| | - Kaihong Xie
- Department of Oncology, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, 423000, People's Republic of China.
| | - Hui Xie
- Department of Radiation Oncology, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, 423000, People's Republic of China.
- Faulty of Applied Sciences, Macao Polytechnic University, Macao, 999078, People's Republic of China.
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Jin J, Li S, Huang H, Li J, Lyu Y, Ran Y, Chang H, Zhao X. Development of human papillomavirus and its detection methods (Review). Exp Ther Med 2024; 28:382. [PMID: 39161614 PMCID: PMC11332130 DOI: 10.3892/etm.2024.12671] [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: 04/03/2024] [Accepted: 07/04/2024] [Indexed: 08/21/2024] Open
Abstract
Human papillomavirus (HPV) infection plays an important role in cervical cancer. HPV is classified within the Papillomaviridae family and is a non-enveloped, small DNA virus. HPV infection can be classified into two distinct scenarios: i) With or without integration into the host chromosomes. Detection of its infection can be useful in the study of cervical lesions. In the present review, the structural and functional features of HPV, HPV typing, infection and transmission mode, the risk factors for cervical susceptibility to infection and HPV detection methods are described in detail. The development of HPV detection methods may have far-reaching significance in the prevention and treatment of cervical disease. This review summarizes the advantages and limitations of each HPV detection method.
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Affiliation(s)
- Jian Jin
- Medical Research Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
- Tianjian Laboratory of Advanced Biomedical Sciences, School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
| | - Shujuan Li
- Medical Research Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
| | - Hehuan Huang
- Medical Research Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
| | - Junqi Li
- Medical Research Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
- Tianjian Laboratory of Advanced Biomedical Sciences, School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
| | - Yuan Lyu
- Medical Research Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
- Tianjian Laboratory of Advanced Biomedical Sciences, School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
| | - Yunwei Ran
- Medical Research Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
| | - Hui Chang
- Medical Research Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
- Tianjian Laboratory of Advanced Biomedical Sciences, School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
- School of Public Health, Xi'an Jiaotong University, Xi'an, Shanxi 710049, P.R. China
| | - Xin Zhao
- Medical Research Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
- Tianjian Laboratory of Advanced Biomedical Sciences, School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
- Department of Radiology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
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Bruera S, Bowman S, Huang Y, Suarez-Almazor ME, Lo GH, Lopez-Olivo M, Chiao E, Kramer JR, Pereira FA, Agarwal SK. Factors Associated With Adherence of Cervical Cancer Screening in Women With Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken) 2024; 76:1224-1231. [PMID: 38682616 DOI: 10.1002/acr.25355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 03/19/2024] [Accepted: 04/26/2024] [Indexed: 05/01/2024]
Abstract
OBJECTIVE The objective is to determine cervical cancer screening rates and factors associated with decreased cervical cancer screening in women with systemic lupus erythematosus (SLE). METHODS We conducted a cross-sectional study that enrolled consecutive women (age 21-64 years) with SLE. We collected demographics, clinical characteristics, constructs of the Health Beliefs Model (HBM) (ie, susceptibility, severity, barriers, benefits, cues to action, and self-efficacy), and self-reported cervical cancer screening (confirmed with the electronic medical record). The primary outcome was adherence to cervical cancer screening according to current guidelines. Multivariable logistic regression models were used to examine the association between SLE disease activity and cervical cancer screening and explore mediation effects from HBM constructs. RESULTS We enrolled 130 women with SLE. The median age was 42 years (interquartile range 32-52 years). The cervical cancer screening adherence rate was 61.5%. Women with high SLE disease activity were less likely to have cervical cancer screening versus those with low disease activity (odds ratio 0.59, 95% confidence interval [CI] 0.39-0.89; P = 0.01), which remained statistically significant after adjusting for baseline demographics and drug therapy in a multivariable model (odds ratio 0.25, 95% CI 0.08-0.79; P = 0.02). Regarding the HBM constructs, increased perceived barriers to cervical cancer screening (r = -0.30, P < 0.01) and decreased self-efficacy (r = -0.21, P = 0.02) correlated with decreased cervical cancer screening. CONCLUSION Patients with SLE with high disease activity undergo cervical cancer screening less frequently than those with low disease activity. Perceived barriers to cervical cancer screening are moderately correlated with decreased screening. These data highlight the need to develop strategies to increase cervical cancer screening in this high-risk patient population.
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Affiliation(s)
| | | | | | | | - Grace H Lo
- Baylor College of Medicine, Houston, Texas
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11
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Dancy E, Stratton P, Pichard DC, Marciano BE, Cowen EW, McBride AA, Van Doorslaer K, Merideth MA, Salmeri N, Hughes MS, Heller T, Parta M, Hickstein DD, Kong HH, Holland SM, Zerbe CS. Human papillomavirus disease in GATA2 deficiency: a genetic predisposition to HPV-associated female anogenital malignancy. Front Immunol 2024; 15:1445711. [PMID: 39267745 PMCID: PMC11390362 DOI: 10.3389/fimmu.2024.1445711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 08/08/2024] [Indexed: 09/15/2024] Open
Abstract
Objective Patients with pathogenic variants in the GATA Binding Protein 2 (GATA2), a hematopoietic transcription factor, are at risk for human papillomavirus-related (HPV) anogenital cancer at younger than expected ages. A female cohort with GATA2 haploinsufficiency was systematically assessed by two gynecologists to characterize the extent and severity of anogenital HPV disease, which was also compared with affected males. Methods A 17-year retrospective review of medical records, including laboratory, histopathology and cytopathology records was performed for patients diagnosed with GATA2 haploinsufficiency followed at the National Institutes of Health. Student's t-test and Mann-Whitney U test or Fisher's exact test were used to compare differences in continuous or categorical variables, respectively. Spearman's rho coefficient was employed for correlations. Results Of 68 patients with GATA2 haploinsufficiency, HPV disease was the initial manifestation in 27 (40%). HPV occurred at median 18.9 (15.2-26.2) years in females, and 25.6 (23.4-26.9) years in males. Fifty-two (76%), 27 females and 25 males, developed HPV-related squamous intraepithelial lesions (SIL) including two males with oral cancer. Twenty-one patients developed anogenital high-grade SIL (HSIL) or carcinoma (16 females versus 5 males, (59% versus 20%, respectively, p=0.005) at median 27 (18.6-59.3) years for females and 33 (16.5-40.1) years for males. Females were more likely than males to require >2 surgeries to treat recurrent HSIL (p=0.0009). Of 30 patients undergoing hematopoietic stem cell transplant (HSCT) to manage disease arising from GATA2 haploinsufficiency, 12 (nine females, three males) had persistent HSIL/HPV disease. Of these nine females, eight underwent peri-transplant surgical treatment of HSIL. Five of seven who survived post-HSCT received HPV vaccination and had no or minimal evidence of HPV disease 2 years post-HSCT. HPV disease persisted in two receiving immunosuppression. HPV disease/low SIL (LSIL) resolved in all three males. Conclusion Females with GATA2 haploinsufficiency exhibit a heightened risk of recurrent, multifocal anogenital HSIL requiring frequent surveillance and multiple treatments. GATA2 haploinsufficiency must be considered in a female with extensive, multifocal genital HSIL unresponsive to multiple surgeries. This population may benefit from early intervention like HSCT accompanied by continued, enhanced surveillance and treatment by gynecologic oncologists and gynecologists in those with anogenital HPV disease.
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Affiliation(s)
- Ehren Dancy
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
| | - Pamela Stratton
- Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
| | - Dominique C Pichard
- National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, United States
| | - Beatriz E Marciano
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
| | - Edward W Cowen
- Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United States
| | - Alison A McBride
- Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
| | - Koenraad Van Doorslaer
- Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Department of Immunobiology, College of Medicine, BIO5 Institute, Cancer Biology Graduate Interdisciplinary Program, Genetics Graduate Interdisciplinary Program, University of Arizona Cancer Center, University of Arizona, Tucson, AZ, United States
| | - Melissa A Merideth
- Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
| | - Noemi Salmeri
- Gynecology/Obstetrics Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
- Rehabilitation Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, United States
| | - Marybeth S Hughes
- Department of Surgery, Eastern Virginia Medical School, Norfolk, VA, United States
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States
| | | | - Dennis D Hickstein
- Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
| | - Heidi H Kong
- Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United States
| | - Steven M Holland
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
| | - Christa S Zerbe
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
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12
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Lindquist S, Frederiksen K, Petersen LK, Kjær SK. The risk of vaginal, vulvar and anal precancer and cancer according to high-risk HPV status in cervical cytology samples. Int J Cancer 2024; 155:61-70. [PMID: 38418719 DOI: 10.1002/ijc.34896] [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: 11/06/2023] [Revised: 01/26/2024] [Accepted: 02/12/2024] [Indexed: 03/02/2024]
Abstract
High-risk human papillomavirus (hrHPV) is the cause of virtually all cervical cancers, most vaginal and anal cancers, and some vulvar cancer cases. With HPV testing becoming the primary screening method for cervical cancer, understanding the link between cervical hrHPV infection and the risk of other anogenital cancers is crucial. We assessed the risk of vulvar, vaginal and anal cancer and precancer (VIN2+, VaIN2+ and AIN2+) in a prospective cohort study including 455,349 women who underwent cervical hrHPV testing in Denmark from 2005 to 2020. We employed Cox proportional hazard models, adjusting for age, calendar year and HPV vaccination status, and estimated hazard ratios (HRs) and 95% confidence intervals (CI). We used the Aalen Johansen estimator to calculate the absolute risks of VIN2+, VaIN2+ and AIN2+. In total, 15% of the women were hrHPV positive at baseline. A positive cervical hrHPV test was associated with increased incidence of vulvar, vaginal and anal squamous cell carcinoma (SCC). Five-year risk estimates of VIN2+, VaIN2+ and AIN2+ among hrHPV-positive women (0.45%, 0.14% and 0.12%) were higher than among hrHPV-negative women (0.14%, 0.01% and 0.05%). Particularly high risk was observed among the hrHPV-positive women of the oldest age, with a history of anogenital precancer and those not HPV vaccinated. In conclusion, our study confirms the association between cervical hrHPV infection and non-cervical anogenital precancers and cancers. Currently, no established risk threshold or guidelines for follow-up. As HPV testing becomes the primary method for cervical cancer screening, future data will help define high-risk groups and acceptable risk thresholds.
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Affiliation(s)
- Sofie Lindquist
- Unit of Virus, Lifestyle, and Genes, Danish Cancer Institute, Copenhagen, Denmark
| | - Kirsten Frederiksen
- Unit of Statistics, Biostatistics, and Registry, Danish Cancer Institute, Copenhagen, Denmark
| | - Lone Kjeld Petersen
- Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark
- Department of Clinical Medicine, University of Southern Denmark, Odense, Denmark
| | - Susanne K Kjær
- Unit of Virus, Lifestyle, and Genes, Danish Cancer Institute, Copenhagen, Denmark
- Department of Gynecology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark
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13
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Sanchez J, Guevara N, Mekonen Y, Newman A, Chapiolkina V, Perez Rosario EM, Fahim S, Fulger I. Metachronous Human Papillomavirus (HPV)-Related Eye Carcinoma in Previously Metastatic Breast Cancer: A Case Report. Cureus 2024; 16:e64198. [PMID: 38993623 PMCID: PMC11238144 DOI: 10.7759/cureus.64198] [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: 06/21/2024] [Accepted: 07/09/2024] [Indexed: 07/13/2024] Open
Abstract
Multiple primary malignancies (MPMs) occur when an individual develops two or more distinct primary cancers. These are categorized as synchronous or metachronous based on the timing of their diagnosis. Patients previously diagnosed with cancer face increased risks due to exposure to carcinogenic factors and treatments such as chemotherapy and radiotherapy. Individuals with a history of breast cancer are known to have elevated risks for secondary malignancies compared to the general population. However, cases of squamous cell carcinoma (SCC) of the eyelid in this group are exceedingly rare. Here, we present a case report describing a young female patient who sequentially developed metachronous breast cancer, and a human papillomavirus (HPV)-associated SCC of the eyelid. To the best of our knowledge, this case report represents the first documented instance of this specific combination of primary neoplasms in medical literature.
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Affiliation(s)
- Jorge Sanchez
- Internal Medicine, St. Barnabas Hospital Health System, New York, USA
| | - Nehemias Guevara
- Internal Medicine, St. Barnabas Hospital Health System, New York, USA
| | - Yemesrach Mekonen
- Internal Medicine, St. Barnabas Hospital Health System, New York, USA
| | - Azana Newman
- Internal Medicine, St. Barnabas Hospital Health System, New York, USA
| | - Volha Chapiolkina
- Internal Medicine, St. Barnabas Hospital Health System, New York, USA
| | | | - Somayeh Fahim
- Internal Medicine, St. Barnabas Hospital Health System, New York, USA
| | - Ilmana Fulger
- Hematology-Oncology, St. Barnabas Hospital Health System, New York, USA
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14
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Kraus FBT, Sultova E, Heinrich K, Jung A, Westphalen CB, Tauber CV, Kumbrink J, Rudelius M, Klauschen F, Greif PA, König A, Chelariu-Raicu A, Czogalla B, Burges A, Mahner S, Wuerstlein R, Trillsch F. Genetics and beyond: Precision Medicine Real-World Data for Patients with Cervical, Vaginal or Vulvar Cancer in a Tertiary Cancer Center. Int J Mol Sci 2024; 25:2345. [PMID: 38397025 PMCID: PMC10888648 DOI: 10.3390/ijms25042345] [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: 01/14/2024] [Revised: 02/09/2024] [Accepted: 02/09/2024] [Indexed: 02/25/2024] Open
Abstract
Advances in molecular tumor diagnostics have transformed cancer care. However, it remains unclear whether precision oncology has the same impact and transformative nature across all malignancies. We conducted a retrospective analysis of patients with human papillomavirus (HPV)-related gynecologic malignancies who underwent comprehensive molecular profiling and subsequent discussion at the interdisciplinary Molecular Tumor Board (MTB) of the University Hospital, LMU Munich, between 11/2017 and 06/2022. We identified a total cohort of 31 patients diagnosed with cervical (CC), vaginal or vulvar cancer. Twenty-two patients (fraction: 0.71) harbored at least one mutation. Fifteen patients (0.48) had an actionable mutation and fourteen (0.45) received a recommendation for a targeted treatment within the MTB. One CC patient received a biomarker-guided treatment recommended by the MTB and achieved stable disease on the mTOR inhibitor temsirolimus for eight months. Factors leading to non-adherence to MTB recommendations in other patient cases included informed patient refusal, rapid deterioration, stable disease, or use of alternative targeted but biomarker-agnostic treatments such as antibody-drug conjugates or checkpoint inhibitors. Despite a remarkable rate of actionable mutations in HPV-related gynecologic malignancies at our institution, immediate implementation of biomarker-guided targeted treatment recommendations remained low, and access to targeted treatment options after MTB discussion remained a major challenge.
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Affiliation(s)
- Fabian B. T. Kraus
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Munich, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
- Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Elena Sultova
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Munich, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
| | - Kathrin Heinrich
- Department of Medicine III, Comprehensive Cancer Center Munich, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
| | - Andreas Jung
- Institute of Pathology, Comprehensive Cancer Center Munich, LMU University Hospital, Ludwig Maximilians University (LMU), 81377 Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, 81377 Munich, Germany
| | - C. Benedikt Westphalen
- Department of Medicine III, Comprehensive Cancer Center Munich, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, 81377 Munich, Germany
| | - Christina V. Tauber
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Munich, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
| | - Jörg Kumbrink
- Institute of Pathology, Comprehensive Cancer Center Munich, LMU University Hospital, Ludwig Maximilians University (LMU), 81377 Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, 81377 Munich, Germany
| | - Martina Rudelius
- Institute of Pathology, Comprehensive Cancer Center Munich, LMU University Hospital, Ludwig Maximilians University (LMU), 81377 Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, 81377 Munich, Germany
| | - Frederick Klauschen
- Institute of Pathology, Comprehensive Cancer Center Munich, LMU University Hospital, Ludwig Maximilians University (LMU), 81377 Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, 81377 Munich, Germany
| | - Philipp A. Greif
- Department of Medicine III, Comprehensive Cancer Center Munich, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, 81377 Munich, Germany
- German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany
| | - Alexander König
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Munich, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
| | - Anca Chelariu-Raicu
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Munich, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
| | - Bastian Czogalla
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Munich, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
| | - Alexander Burges
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Munich, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
| | - Sven Mahner
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Munich, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
| | - Rachel Wuerstlein
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Munich, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
| | - Fabian Trillsch
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Munich, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
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15
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Conforti C, Retrosi C, Agozzino M, Dianzani C, Nardon E, Oliveri A, Azzalini E, Guida S, Pellacani G, Di Lella G, Rongioletti F, Zalaudek I, Bonin S. Unraveling the Complex Nexus of Human Papillomavirus (HPV) in Extragenital Keratinocyte Skin Tumors: A Comprehensive Analysis of Bowen's Disease and In Situ Squamous-Cell Carcinoma. J Clin Med 2024; 13:1091. [PMID: 38398404 PMCID: PMC10889444 DOI: 10.3390/jcm13041091] [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: 12/29/2023] [Revised: 02/07/2024] [Accepted: 02/09/2024] [Indexed: 02/25/2024] Open
Abstract
This comprehensive study delves into the intricate landscape surrounding the role of human papillomavirus (HPV) in extragenital keratinocyte skin tumors, specifically exploring Bowen's disease (BD) and in situ squamous-cell carcinoma (iSCC). Through a multifaceted examination, this research study elucidates the nuanced interplay of HPV, gender dynamics, anatomical site variations, and potential implications for the etiopathogenesis of these malignancies.
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Affiliation(s)
- Claudio Conforti
- IDI-IRCCS, Dermatological Research Hospital, 00167 Rome, Italy; (C.C.); (C.R.); (G.D.L.)
| | - Chiara Retrosi
- IDI-IRCCS, Dermatological Research Hospital, 00167 Rome, Italy; (C.C.); (C.R.); (G.D.L.)
| | - Marina Agozzino
- Dermatology Clinic, Maggiore Hospital, Piazza Ospitale 1, 34125 Trieste, Italy; (M.A.)
| | - Caterina Dianzani
- Department of Plastic, Reconstructive and Cosmetic Surgery, Dermatology Section, Campus Bio-Medico University Hospital, 00128 Rome, Italy;
| | - Ermanno Nardon
- Department of Medical Sciences (DSM), University of Trieste, 34149 Trieste, Italy (A.O.); (E.A.); (S.B.)
| | - Anselmo Oliveri
- Department of Medical Sciences (DSM), University of Trieste, 34149 Trieste, Italy (A.O.); (E.A.); (S.B.)
| | - Eros Azzalini
- Department of Medical Sciences (DSM), University of Trieste, 34149 Trieste, Italy (A.O.); (E.A.); (S.B.)
| | - Stefania Guida
- Dermatology Clinic, IRCCS San Raffaele Hospital, Vita-Salute University, 20132 Milan, Italy;
| | - Giovanni Pellacani
- Dermatology Clinic, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00196 Rome, Italy;
| | - Giovanni Di Lella
- IDI-IRCCS, Dermatological Research Hospital, 00167 Rome, Italy; (C.C.); (C.R.); (G.D.L.)
| | - Franco Rongioletti
- Dermatology Clinic, IRCCS San Raffaele Hospital, Vita-Salute University, 20132 Milan, Italy;
| | - Iris Zalaudek
- Dermatology Clinic, Maggiore Hospital, Piazza Ospitale 1, 34125 Trieste, Italy; (M.A.)
- Department of Medical Sciences (DSM), University of Trieste, 34149 Trieste, Italy (A.O.); (E.A.); (S.B.)
| | - Serena Bonin
- Department of Medical Sciences (DSM), University of Trieste, 34149 Trieste, Italy (A.O.); (E.A.); (S.B.)
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16
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Bridge F, Brotherton J, Stankovich J, Sanfilippo PG, Skibina OG, Buzzard K, Kalincik T, Nguyen AL, Guo K, Monif M, Wrede CD, Rath L, Taylor L, Butzkueven H, Jokubaitis VG, Van Der Walt A. Risk of Cervical Abnormalities for Women With Multiple Sclerosis Treated With Moderate-Efficacy and High-Efficacy Disease-Modifying Therapies. Neurology 2024; 102:e208059. [PMID: 38306594 DOI: 10.1212/wnl.0000000000208059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 10/27/2023] [Indexed: 02/04/2024] Open
Abstract
BACKGROUND AND OBJECTIVES The impact of immunomodulatory therapies on the risk of cervical pre-cancer and invasive cancer development is important for the health and safety of women with multiple sclerosis (wwMS). We investigate the risk of cervical abnormalities in wwMS treated with disease-modifying therapies (DMTs). METHODS This is a multicenter cohort study with data collected from 1998 to 2019 in Victoria, Australia. Data linkage was performed using matching records from the MSBase Registry, the National Human Papillomavirus (HPV) Vaccination Program Register, and the Victorian Cervical Cytology Register. The primary outcome was the detection of any type of cervical abnormality as determined by cytology or histology. Survival methods were used to assess the time to cervical abnormality detection on cervical screening tests (CSTs). Crude and adjusted Cox proportional hazards models were used to determine time to and magnitude of association of DMTs with the risk of cervical abnormality. In a sensitivity analysis, we constructed standardized survival curves averaged over the same set of covariates to determine the commensurate population-average (marginal) causal effects. RESULTS We included 248 wwMS. The incidence of abnormal CSTs was lower (p < 0.001) for women not exposed to moderate-high-efficacy therapy (10.2 per 1,000 patient-years [95% confidence interval (CI) 5.5-14.9]), compared with those exposed (36.6 per 1,000 patient-years [95% CI 21.7-51.6]). Exposure to higher efficacy treatment was associated with a 3.79-fold increased hazard (95% CI 2.02-7.08, p < 0.001) of developing a cervical abnormality relative to those not exposed. When adjusted for vaccination status, smoking, hormonal contraceptive use, and socioeconomic status, the risk remained elevated at 3.79 (95% CI 1.99-7.21, p < 0.001). Marginal hazard ratios declined over time, ranging from 3.90 (95% CI 2.09-7.27) at 20 years of age to 2.06 (95% CI 1.14-3.73) at 70 years of age. DISCUSSION A greater than three-and-a-half-fold increased risk of cervical abnormalities was found after exposure to moderate-high-efficacy DMTs. This risk persisted despite adjusting for HPV vaccination status, hormonal contraception use, smoking, and socioeconomic status. If confirmed in future studies, we would advocate for wwMS exposed to moderate-high-efficacy DMTs to be treated in line with immune-deficient paradigm in cervical screening and HPV vaccination programs. CLASSIFICATION OF EVIDENCE This study provides Class III evidence that highly active MS therapy compared with less active therapy increases the risk of developing cervical abnormalities among women with MS.
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Affiliation(s)
- Francesca Bridge
- From the Department of Neuroscience (F.B., J.S., P.G.S., O.G.S., M.M., H.B., V.G.J., A.V.D.W.), Central Clinical School, Monash University; Department of Neurology (F.B., O.G.S., M.M., L.R., H.B., V.G.J., A.V.D.W.), Alfred Health, Melbourne; Australian Centre for the Prevention of Cervical Cancer (formerly Victorian Cytology Service) (J.B.), Carlton South; Centre for Epidemiology and Biostatistics (J.B.), Melbourne School of Population and Global Health, University of Melbourne; Department of Neurosciences (O.G.S., K.B.), Eastern Health; MS Centre (K.B., T.K., A.-L.N., K.G., M.M., L.T.), Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School (K.B., A.-L.N.), Monash University, Box Hill; CORe (T.K., A.-L.N.), Department of Medicine, University of Melbourne; Oncology and Dysplasia Unit (C.D.W.), Royal Women's Hospital, Parkville; and Department of Obstetrics and Gynaecology (C.D.W.), University of Melbourne, Australia
| | - Julia Brotherton
- From the Department of Neuroscience (F.B., J.S., P.G.S., O.G.S., M.M., H.B., V.G.J., A.V.D.W.), Central Clinical School, Monash University; Department of Neurology (F.B., O.G.S., M.M., L.R., H.B., V.G.J., A.V.D.W.), Alfred Health, Melbourne; Australian Centre for the Prevention of Cervical Cancer (formerly Victorian Cytology Service) (J.B.), Carlton South; Centre for Epidemiology and Biostatistics (J.B.), Melbourne School of Population and Global Health, University of Melbourne; Department of Neurosciences (O.G.S., K.B.), Eastern Health; MS Centre (K.B., T.K., A.-L.N., K.G., M.M., L.T.), Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School (K.B., A.-L.N.), Monash University, Box Hill; CORe (T.K., A.-L.N.), Department of Medicine, University of Melbourne; Oncology and Dysplasia Unit (C.D.W.), Royal Women's Hospital, Parkville; and Department of Obstetrics and Gynaecology (C.D.W.), University of Melbourne, Australia
| | - Jim Stankovich
- From the Department of Neuroscience (F.B., J.S., P.G.S., O.G.S., M.M., H.B., V.G.J., A.V.D.W.), Central Clinical School, Monash University; Department of Neurology (F.B., O.G.S., M.M., L.R., H.B., V.G.J., A.V.D.W.), Alfred Health, Melbourne; Australian Centre for the Prevention of Cervical Cancer (formerly Victorian Cytology Service) (J.B.), Carlton South; Centre for Epidemiology and Biostatistics (J.B.), Melbourne School of Population and Global Health, University of Melbourne; Department of Neurosciences (O.G.S., K.B.), Eastern Health; MS Centre (K.B., T.K., A.-L.N., K.G., M.M., L.T.), Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School (K.B., A.-L.N.), Monash University, Box Hill; CORe (T.K., A.-L.N.), Department of Medicine, University of Melbourne; Oncology and Dysplasia Unit (C.D.W.), Royal Women's Hospital, Parkville; and Department of Obstetrics and Gynaecology (C.D.W.), University of Melbourne, Australia
| | - Paul G Sanfilippo
- From the Department of Neuroscience (F.B., J.S., P.G.S., O.G.S., M.M., H.B., V.G.J., A.V.D.W.), Central Clinical School, Monash University; Department of Neurology (F.B., O.G.S., M.M., L.R., H.B., V.G.J., A.V.D.W.), Alfred Health, Melbourne; Australian Centre for the Prevention of Cervical Cancer (formerly Victorian Cytology Service) (J.B.), Carlton South; Centre for Epidemiology and Biostatistics (J.B.), Melbourne School of Population and Global Health, University of Melbourne; Department of Neurosciences (O.G.S., K.B.), Eastern Health; MS Centre (K.B., T.K., A.-L.N., K.G., M.M., L.T.), Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School (K.B., A.-L.N.), Monash University, Box Hill; CORe (T.K., A.-L.N.), Department of Medicine, University of Melbourne; Oncology and Dysplasia Unit (C.D.W.), Royal Women's Hospital, Parkville; and Department of Obstetrics and Gynaecology (C.D.W.), University of Melbourne, Australia
| | - Olga G Skibina
- From the Department of Neuroscience (F.B., J.S., P.G.S., O.G.S., M.M., H.B., V.G.J., A.V.D.W.), Central Clinical School, Monash University; Department of Neurology (F.B., O.G.S., M.M., L.R., H.B., V.G.J., A.V.D.W.), Alfred Health, Melbourne; Australian Centre for the Prevention of Cervical Cancer (formerly Victorian Cytology Service) (J.B.), Carlton South; Centre for Epidemiology and Biostatistics (J.B.), Melbourne School of Population and Global Health, University of Melbourne; Department of Neurosciences (O.G.S., K.B.), Eastern Health; MS Centre (K.B., T.K., A.-L.N., K.G., M.M., L.T.), Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School (K.B., A.-L.N.), Monash University, Box Hill; CORe (T.K., A.-L.N.), Department of Medicine, University of Melbourne; Oncology and Dysplasia Unit (C.D.W.), Royal Women's Hospital, Parkville; and Department of Obstetrics and Gynaecology (C.D.W.), University of Melbourne, Australia
| | - Katherine Buzzard
- From the Department of Neuroscience (F.B., J.S., P.G.S., O.G.S., M.M., H.B., V.G.J., A.V.D.W.), Central Clinical School, Monash University; Department of Neurology (F.B., O.G.S., M.M., L.R., H.B., V.G.J., A.V.D.W.), Alfred Health, Melbourne; Australian Centre for the Prevention of Cervical Cancer (formerly Victorian Cytology Service) (J.B.), Carlton South; Centre for Epidemiology and Biostatistics (J.B.), Melbourne School of Population and Global Health, University of Melbourne; Department of Neurosciences (O.G.S., K.B.), Eastern Health; MS Centre (K.B., T.K., A.-L.N., K.G., M.M., L.T.), Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School (K.B., A.-L.N.), Monash University, Box Hill; CORe (T.K., A.-L.N.), Department of Medicine, University of Melbourne; Oncology and Dysplasia Unit (C.D.W.), Royal Women's Hospital, Parkville; and Department of Obstetrics and Gynaecology (C.D.W.), University of Melbourne, Australia
| | - Tomas Kalincik
- From the Department of Neuroscience (F.B., J.S., P.G.S., O.G.S., M.M., H.B., V.G.J., A.V.D.W.), Central Clinical School, Monash University; Department of Neurology (F.B., O.G.S., M.M., L.R., H.B., V.G.J., A.V.D.W.), Alfred Health, Melbourne; Australian Centre for the Prevention of Cervical Cancer (formerly Victorian Cytology Service) (J.B.), Carlton South; Centre for Epidemiology and Biostatistics (J.B.), Melbourne School of Population and Global Health, University of Melbourne; Department of Neurosciences (O.G.S., K.B.), Eastern Health; MS Centre (K.B., T.K., A.-L.N., K.G., M.M., L.T.), Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School (K.B., A.-L.N.), Monash University, Box Hill; CORe (T.K., A.-L.N.), Department of Medicine, University of Melbourne; Oncology and Dysplasia Unit (C.D.W.), Royal Women's Hospital, Parkville; and Department of Obstetrics and Gynaecology (C.D.W.), University of Melbourne, Australia
| | - Ai-Lan Nguyen
- From the Department of Neuroscience (F.B., J.S., P.G.S., O.G.S., M.M., H.B., V.G.J., A.V.D.W.), Central Clinical School, Monash University; Department of Neurology (F.B., O.G.S., M.M., L.R., H.B., V.G.J., A.V.D.W.), Alfred Health, Melbourne; Australian Centre for the Prevention of Cervical Cancer (formerly Victorian Cytology Service) (J.B.), Carlton South; Centre for Epidemiology and Biostatistics (J.B.), Melbourne School of Population and Global Health, University of Melbourne; Department of Neurosciences (O.G.S., K.B.), Eastern Health; MS Centre (K.B., T.K., A.-L.N., K.G., M.M., L.T.), Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School (K.B., A.-L.N.), Monash University, Box Hill; CORe (T.K., A.-L.N.), Department of Medicine, University of Melbourne; Oncology and Dysplasia Unit (C.D.W.), Royal Women's Hospital, Parkville; and Department of Obstetrics and Gynaecology (C.D.W.), University of Melbourne, Australia
| | - Kylie Guo
- From the Department of Neuroscience (F.B., J.S., P.G.S., O.G.S., M.M., H.B., V.G.J., A.V.D.W.), Central Clinical School, Monash University; Department of Neurology (F.B., O.G.S., M.M., L.R., H.B., V.G.J., A.V.D.W.), Alfred Health, Melbourne; Australian Centre for the Prevention of Cervical Cancer (formerly Victorian Cytology Service) (J.B.), Carlton South; Centre for Epidemiology and Biostatistics (J.B.), Melbourne School of Population and Global Health, University of Melbourne; Department of Neurosciences (O.G.S., K.B.), Eastern Health; MS Centre (K.B., T.K., A.-L.N., K.G., M.M., L.T.), Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School (K.B., A.-L.N.), Monash University, Box Hill; CORe (T.K., A.-L.N.), Department of Medicine, University of Melbourne; Oncology and Dysplasia Unit (C.D.W.), Royal Women's Hospital, Parkville; and Department of Obstetrics and Gynaecology (C.D.W.), University of Melbourne, Australia
| | - Mastura Monif
- From the Department of Neuroscience (F.B., J.S., P.G.S., O.G.S., M.M., H.B., V.G.J., A.V.D.W.), Central Clinical School, Monash University; Department of Neurology (F.B., O.G.S., M.M., L.R., H.B., V.G.J., A.V.D.W.), Alfred Health, Melbourne; Australian Centre for the Prevention of Cervical Cancer (formerly Victorian Cytology Service) (J.B.), Carlton South; Centre for Epidemiology and Biostatistics (J.B.), Melbourne School of Population and Global Health, University of Melbourne; Department of Neurosciences (O.G.S., K.B.), Eastern Health; MS Centre (K.B., T.K., A.-L.N., K.G., M.M., L.T.), Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School (K.B., A.-L.N.), Monash University, Box Hill; CORe (T.K., A.-L.N.), Department of Medicine, University of Melbourne; Oncology and Dysplasia Unit (C.D.W.), Royal Women's Hospital, Parkville; and Department of Obstetrics and Gynaecology (C.D.W.), University of Melbourne, Australia
| | - C David Wrede
- From the Department of Neuroscience (F.B., J.S., P.G.S., O.G.S., M.M., H.B., V.G.J., A.V.D.W.), Central Clinical School, Monash University; Department of Neurology (F.B., O.G.S., M.M., L.R., H.B., V.G.J., A.V.D.W.), Alfred Health, Melbourne; Australian Centre for the Prevention of Cervical Cancer (formerly Victorian Cytology Service) (J.B.), Carlton South; Centre for Epidemiology and Biostatistics (J.B.), Melbourne School of Population and Global Health, University of Melbourne; Department of Neurosciences (O.G.S., K.B.), Eastern Health; MS Centre (K.B., T.K., A.-L.N., K.G., M.M., L.T.), Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School (K.B., A.-L.N.), Monash University, Box Hill; CORe (T.K., A.-L.N.), Department of Medicine, University of Melbourne; Oncology and Dysplasia Unit (C.D.W.), Royal Women's Hospital, Parkville; and Department of Obstetrics and Gynaecology (C.D.W.), University of Melbourne, Australia
| | - Louise Rath
- From the Department of Neuroscience (F.B., J.S., P.G.S., O.G.S., M.M., H.B., V.G.J., A.V.D.W.), Central Clinical School, Monash University; Department of Neurology (F.B., O.G.S., M.M., L.R., H.B., V.G.J., A.V.D.W.), Alfred Health, Melbourne; Australian Centre for the Prevention of Cervical Cancer (formerly Victorian Cytology Service) (J.B.), Carlton South; Centre for Epidemiology and Biostatistics (J.B.), Melbourne School of Population and Global Health, University of Melbourne; Department of Neurosciences (O.G.S., K.B.), Eastern Health; MS Centre (K.B., T.K., A.-L.N., K.G., M.M., L.T.), Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School (K.B., A.-L.N.), Monash University, Box Hill; CORe (T.K., A.-L.N.), Department of Medicine, University of Melbourne; Oncology and Dysplasia Unit (C.D.W.), Royal Women's Hospital, Parkville; and Department of Obstetrics and Gynaecology (C.D.W.), University of Melbourne, Australia
| | - Lisa Taylor
- From the Department of Neuroscience (F.B., J.S., P.G.S., O.G.S., M.M., H.B., V.G.J., A.V.D.W.), Central Clinical School, Monash University; Department of Neurology (F.B., O.G.S., M.M., L.R., H.B., V.G.J., A.V.D.W.), Alfred Health, Melbourne; Australian Centre for the Prevention of Cervical Cancer (formerly Victorian Cytology Service) (J.B.), Carlton South; Centre for Epidemiology and Biostatistics (J.B.), Melbourne School of Population and Global Health, University of Melbourne; Department of Neurosciences (O.G.S., K.B.), Eastern Health; MS Centre (K.B., T.K., A.-L.N., K.G., M.M., L.T.), Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School (K.B., A.-L.N.), Monash University, Box Hill; CORe (T.K., A.-L.N.), Department of Medicine, University of Melbourne; Oncology and Dysplasia Unit (C.D.W.), Royal Women's Hospital, Parkville; and Department of Obstetrics and Gynaecology (C.D.W.), University of Melbourne, Australia
| | - Helmut Butzkueven
- From the Department of Neuroscience (F.B., J.S., P.G.S., O.G.S., M.M., H.B., V.G.J., A.V.D.W.), Central Clinical School, Monash University; Department of Neurology (F.B., O.G.S., M.M., L.R., H.B., V.G.J., A.V.D.W.), Alfred Health, Melbourne; Australian Centre for the Prevention of Cervical Cancer (formerly Victorian Cytology Service) (J.B.), Carlton South; Centre for Epidemiology and Biostatistics (J.B.), Melbourne School of Population and Global Health, University of Melbourne; Department of Neurosciences (O.G.S., K.B.), Eastern Health; MS Centre (K.B., T.K., A.-L.N., K.G., M.M., L.T.), Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School (K.B., A.-L.N.), Monash University, Box Hill; CORe (T.K., A.-L.N.), Department of Medicine, University of Melbourne; Oncology and Dysplasia Unit (C.D.W.), Royal Women's Hospital, Parkville; and Department of Obstetrics and Gynaecology (C.D.W.), University of Melbourne, Australia
| | - Vilija G Jokubaitis
- From the Department of Neuroscience (F.B., J.S., P.G.S., O.G.S., M.M., H.B., V.G.J., A.V.D.W.), Central Clinical School, Monash University; Department of Neurology (F.B., O.G.S., M.M., L.R., H.B., V.G.J., A.V.D.W.), Alfred Health, Melbourne; Australian Centre for the Prevention of Cervical Cancer (formerly Victorian Cytology Service) (J.B.), Carlton South; Centre for Epidemiology and Biostatistics (J.B.), Melbourne School of Population and Global Health, University of Melbourne; Department of Neurosciences (O.G.S., K.B.), Eastern Health; MS Centre (K.B., T.K., A.-L.N., K.G., M.M., L.T.), Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School (K.B., A.-L.N.), Monash University, Box Hill; CORe (T.K., A.-L.N.), Department of Medicine, University of Melbourne; Oncology and Dysplasia Unit (C.D.W.), Royal Women's Hospital, Parkville; and Department of Obstetrics and Gynaecology (C.D.W.), University of Melbourne, Australia
| | - Anneke Van Der Walt
- From the Department of Neuroscience (F.B., J.S., P.G.S., O.G.S., M.M., H.B., V.G.J., A.V.D.W.), Central Clinical School, Monash University; Department of Neurology (F.B., O.G.S., M.M., L.R., H.B., V.G.J., A.V.D.W.), Alfred Health, Melbourne; Australian Centre for the Prevention of Cervical Cancer (formerly Victorian Cytology Service) (J.B.), Carlton South; Centre for Epidemiology and Biostatistics (J.B.), Melbourne School of Population and Global Health, University of Melbourne; Department of Neurosciences (O.G.S., K.B.), Eastern Health; MS Centre (K.B., T.K., A.-L.N., K.G., M.M., L.T.), Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School (K.B., A.-L.N.), Monash University, Box Hill; CORe (T.K., A.-L.N.), Department of Medicine, University of Melbourne; Oncology and Dysplasia Unit (C.D.W.), Royal Women's Hospital, Parkville; and Department of Obstetrics and Gynaecology (C.D.W.), University of Melbourne, Australia
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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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18
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Jodry D, Obedin-Maliver J, Flowers L, Jay N, Floyd S, Teoh D, Conageski C, Downs L, Khan MJ. Understanding Sexual and Gender Minority Populations and Organ-Based Screening Recommendations for Human Papillomavirus-Related Cancers. J Low Genit Tract Dis 2023; 27:307-321. [PMID: 37729043 PMCID: PMC10545069 DOI: 10.1097/lgt.0000000000000763] [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] [Indexed: 09/22/2023]
Abstract
OBJECTIVES Sexual gender minority (SGM) populations are at risk for human papillomavirus (HPV)-related cancers of the anogenital tract and oropharynx and often face barriers to health care. The goals of this document are to clarify language to provide inclusive care for SGM populations and to provide recommendations for screening and prevention of HPV-related cancers in SGM populations. MATERIALS AND METHODS An expert committee convened by the American Society for Colposcopy and Cervical Pathology performed a narrative review of the literature through February 2023. A comprehensive MEDLINE database search was performed for relevant studies. The literature review was divided into categories by organ/topic and by SGM population. Given the variability in available data for several of the categories, recommendations were made based on national guidelines where appropriate or expert opinion where there were less data to support risk-based guidelines. RESULTS Definitions and terminology relevant to SGM populations are presented. The authors advocate the adoption of sexual orientation gender identity data collection and an organ-based screening approach, which is possible with knowledge of patient anatomy, sexual behaviors, and clinical history. This includes screening for cervical cancer per national recommendations, as well as screening for anal, vulvar, vaginal, penile, and oral cancers based on risk factors and shared clinical decision making. The authors recommend consideration of HPV vaccination in all SGM individuals up to age 45 years old who are at risk. CONCLUSIONS An organ-based screening approach is part of a global strategy to create an inclusive care environment and mitigate barriers to screening and prevention of HPV-mediated cancers in SGM populations.
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Affiliation(s)
| | | | - Lisa Flowers
- Emory University School of Medicine, Atlanta, GA
| | - Naomi Jay
- University of California, San Francisco School of Medicine, San Francisco, California
| | - Serina Floyd
- Planned Parenthood of Metropolitan Washington, DC, Washington, DC
| | - Deanna Teoh
- Division of Gynecologic Oncology, University of Minnesota, Minneapolis, MN
| | | | - Levi Downs
- Park Nicollet Health Services, Minneapolis, MN
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19
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Bossart S, Daneluzzi C, Moor MB, Hirzel C, Heidemeyer K, Seyed Jafari SM, Hunger RE, Sidler D. HPV Vaccination in Immunosuppressed Patients with Established Skin Warts and Non-Melanoma Skin Cancer: A Single-Institutional Cohort Study. Vaccines (Basel) 2023; 11:1490. [PMID: 37766167 PMCID: PMC10535650 DOI: 10.3390/vaccines11091490] [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: 07/04/2023] [Revised: 09/04/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023] Open
Abstract
cSCC (cutaneous squamous cell carcinoma) and its precursors are a major cause of morbidity, especially in immunosuppressed patients, and are frequently associated with human papillomavirus (HPV) infections. The purpose of this study is to investigate the therapeutic potential of alpha-HPV vaccination for immunosuppressed patients with established cSCC and its precursors. In this retrospective study, all patients who received Gardasil-9®, a nonavalent HPV vaccine, as secondary prophylaxis were examined. Dermatologic interventions in both the pre- and post-vaccination periods were analyzed with zero-inflated Poisson regression and a proportional intensity model for repeated events with consideration of the clinically relevant cofactors. The hazard ratio for major dermatologic interventions was 0.27 (CI 0.14-0.51, p < 0.001) between pre- and post-Gardasil-9® intervention. Gardasil-9® vaccination showed good efficacy in reducing major dermatologic interventions even after correction of relevant cofactors and national COVID-19 caseloads during the observational period. Alpha-HPV vaccination may potentially cause a significant decrease in dermatologic interventions and overall mortality as well as healthcare costs in immunosuppressed patients with high skin tumor burden.
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Affiliation(s)
- Simon Bossart
- Department of Dermatology, Inselspital University Hospital of Bern, University of Bern, 3010 Bern, Switzerland
| | - Cloé Daneluzzi
- Department of Dermatology, Inselspital University Hospital of Bern, University of Bern, 3010 Bern, Switzerland
| | - Matthias B Moor
- Department of Nephrology, Inselspital University Hospital of Bern, University of Bern, 3010 Bern, Switzerland
| | - Cédric Hirzel
- Department of Infectious Diseases, Inselspital University Hospital of Bern, University of Bern, 3010 Bern, Switzerland
| | - Kristine Heidemeyer
- Department of Dermatology, Inselspital University Hospital of Bern, University of Bern, 3010 Bern, Switzerland
| | - S Morteza Seyed Jafari
- Department of Dermatology, Inselspital University Hospital of Bern, University of Bern, 3010 Bern, Switzerland
| | - Robert E Hunger
- Department of Dermatology, Inselspital University Hospital of Bern, University of Bern, 3010 Bern, Switzerland
| | - Daniel Sidler
- Department of Nephrology, Inselspital University Hospital of Bern, University of Bern, 3010 Bern, Switzerland
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Ratan C, Arian AM, Rajendran R, Jayakumar R, Masson M, Mangalathillam S. Nano-based formulations of curcumin: elucidating the potential benefits and future prospects in skin cancer. Biomed Mater 2023; 18:052008. [PMID: 37582394 DOI: 10.1088/1748-605x/acf0af] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 08/15/2023] [Indexed: 08/17/2023]
Abstract
Skin cancer refers to any malignant lesions that occur in the skin and are observed predominantly in populations of European descent. Conventional treatment modalities such as excision biopsy, chemotherapy, radiotherapy, immunotherapy, electrodesiccation, and photodynamic therapy (PDT) induce several unintended side effects which affect a patient's quality of life and physical well-being. Therefore, spice-derived nutraceuticals like curcumin, which are well tolerated, less expensive, and relatively safe, have been considered a promising agent for skin cancer treatment. Curcumin, a chemical constituent extracted from the Indian spice, turmeric, and its analogues has been used in various mammalian cancers including skin cancer. Curcumin has anti-neoplastic activity by triggering the process of apoptosis and preventing the multiplication and infiltration of the cancer cells by inhibiting some signaling pathways and thus subsequently preventing the process of carcinogenesis. Curcumin is also a photosensitizer and has been used in PDT. The major limitations associated with curcumin are poor bioavailability, instability, limited permeation into the skin, and lack of solubility in water. This will constrain the use of curcumin in clinical settings. Hence, developing a proper formulation that can ideally release curcumin to its targeted site is important. So, several nanoformulations based on curcumin have been established such as nanogels, nanoemulsions, nanofibers, nanopatterned films, nanoliposomes and nanoniosomes, nanodisks, and cyclodextrins. The present review mainly focuses on curcumin and its analogues as therapeutic agents for treating different types of skin cancers. The significance of using various nanoformulations as well non-nanoformulations loaded with curcumin as an effective treatment modality for skin cancer is also emphasized.
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Affiliation(s)
- Chameli Ratan
- Amrita School of Pharmacy, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041 Kerala, India
| | - Arya Mangalath Arian
- Amrita School of Pharmacy, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041 Kerala, India
| | - Rajalakshmi Rajendran
- Amrita School of Pharmacy, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041 Kerala, India
| | - Rangasamy Jayakumar
- Polymeric Biomaterials Lab, School of Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, 682041 Kerala, India
| | - Mar Masson
- Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Hofsvallagata 53, IS-107, Reykjavík, Iceland
| | - Sabitha Mangalathillam
- Amrita School of Pharmacy, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041 Kerala, India
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21
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Papastamelos C, Linder M. Human papillomavirus anogenital screening in solid organ transplant recipients: a narrative review. Arch Gynecol Obstet 2023; 307:1277-1283. [PMID: 35476141 DOI: 10.1007/s00404-022-06577-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 04/12/2022] [Indexed: 11/02/2022]
Abstract
PURPOSE To provide a narrative review of anogenital screening for human papillomavirus in solid organ transplant recipients. METHODS Keyword searches of PubMed and Ovid MEDLINE databases were performed. Keywords included human papillomavirus, malignancy, cervical cancer, Pap smear, solid organ transplant, and immunosuppression. Manual searches were also conducted of other relevant journals and reference lists of primary articles. RESULTS Forty-one studies, articles, or clinical practice guidelines across 25 years of literature were included. Eligible literature was written in English or offered an English translation. CONCLUSION Human papillomavirus-related anogenital malignancies disproportionately affect transplant recipients compared to the general population. Evidence-based guidelines for cervical cancer screening and prevention in transplant patients are lacking. Current practice guidelines generally agree on increased Pap screening for transplant recipients compared to the general population. However, recommended screening frequency differs between organizations and amongst medical specialties. Vaccination against HPV remains the most effective strategy to prevent HPV-driven pre-malignant and malignant lesions.
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Affiliation(s)
| | - Mitchell Linder
- University of Rochester Medical Center, Obstetrics and Gynecology, Rochester, NY, USA
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Hewavisenti RV, Arena J, Ahlenstiel CL, Sasson SC. Human papillomavirus in the setting of immunodeficiency: Pathogenesis and the emergence of next-generation therapies to reduce the high associated cancer risk. Front Immunol 2023; 14:1112513. [PMID: 36960048 PMCID: PMC10027931 DOI: 10.3389/fimmu.2023.1112513] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 02/03/2023] [Indexed: 03/09/2023] Open
Abstract
Human papillomavirus (HPV), a common sexually transmitted virus infecting mucosal or cutaneous stratified epithelia, is implicated in the rising of associated cancers worldwide. While HPV infection can be cleared by an adequate immune response, immunocompromised individuals can develop persistent, treatment-refractory, and progressive disease. Primary immunodeficiencies (PIDs) associated with HPV-related disease include inborn errors of GATA, EVER1/2, and CXCR4 mutations, resulting in defective cellular function. People living with secondary immunodeficiency (e.g. solid-organ transplants recipients of immunosuppression) and acquired immunodeficiency (e.g. concurrent human immunodeficiency virus (HIV) infection) are also at significant risk of HPV-related disease. Immunocompromised people are highly susceptible to the development of cutaneous and mucosal warts, and cervical, anogenital and oropharyngeal carcinomas. The specific mechanisms underlying high-risk HPV-driven cancer development in immunocompromised hosts are not well understood. Current treatments for HPV-related cancers include surgery with adjuvant chemotherapy and/or radiotherapy, with clinical trials underway to investigate the use of anti-PD-1 therapy. In the setting of HIV co-infection, persistent high-grade anal intraepithelial neoplasia can occur despite suppressive antiretroviral therapy, resulting in an ongoing risk for transformation to overt malignancy. Although therapeutic vaccines against HPV are under development, the efficacy of these in the setting of PID, secondary- or acquired- immunodeficiencies remains unclear. RNA-based therapeutic targeting of the HPV genome or mRNA transcript has become a promising next-generation therapeutic avenue. In this review, we summarise the current understanding of HPV pathogenesis, immune evasion, and malignant transformation, with a focus on key PIDs, secondary immunodeficiencies, and HIV infection. Current management and vaccine regimes are outlined in relation to HPV-driven cancer, and specifically, the need for more effective therapeutic strategies for immunocompromised hosts. The recent advances in RNA-based gene targeting including CRISPR and short interfering RNA (siRNA), and the potential application to HPV infection are of great interest. An increased understanding of both the dysregulated immune responses in immunocompromised hosts and of viral persistence is essential for the design of next-generation therapies to eliminate HPV persistence and cancer development in the most at-risk populations.
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Affiliation(s)
- Rehana V. Hewavisenti
- Immunovirology and Pathogenesis Program, The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia
| | - Joshua Arena
- Immunovirology and Pathogenesis Program, The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia
- UNSW RNA Institute, The University of New South Wales, Sydney, NSW, Australia
| | - Chantelle L. Ahlenstiel
- Immunovirology and Pathogenesis Program, The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia
- UNSW RNA Institute, The University of New South Wales, Sydney, NSW, Australia
| | - Sarah C. Sasson
- Immunovirology and Pathogenesis Program, The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia
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HPV-Induced Anal and Peri-Anal Neoplasia, a Surgeon's Experience: 5-Year Case Series. Diagnostics (Basel) 2023; 13:diagnostics13040702. [PMID: 36832190 PMCID: PMC9955444 DOI: 10.3390/diagnostics13040702] [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: 12/09/2022] [Revised: 01/30/2023] [Accepted: 02/07/2023] [Indexed: 02/16/2023] Open
Abstract
Purpose: One of the most known sexually transmitted diseases is Condylomata acuminata (CA), a skin lesion occurring due to infection from Human Papilloma Virus (HPV). CA has a typical appearance of raised, skin-colored papules ranging in size from 1 mm to 5 mm. These lesions often form cauliflower-like plaques. Depending on the involved HPV-subtype (either high-risk or low-risk) and its malignant potential, these lesions are likely to lead to malignant transformation when specific HPV subtypes and other risk factors are present. Therefore, high clinical suspicion is required when examining the anal and perianal area. Methods: In this article, the authors aim to present the results of a five-year case series (2016-2021) of anal and perianal cases of CA. Results: A total of 35 patients were included in this study. Patients were categorized based on specific criteria, which included gender, sex preferences, and human immunodeficiency virus infection. All patients underwent proctoscopy and excision biopsies were obtained. Based on dysplasia grade patients were further categorized. The group of patients where high-dysplasia squamous cell carcinoma was present was initially treated with chemoradiotherapy. Abdominoperineal resection was necessary in five cases after local recurrence. Conclusions: CA remains a serious condition where several treatment options are available if detected early. Delay in diagnosis can lead to malignant transformation, often leaving abdominoperineal resection as the only option. Vaccination against HPV poses a key role in eliminating the transmission of the virus, and thus the prevalence of CA.
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Bridge F, Brotherton JML, Foong Y, Butzkueven H, Jokubaitis VG, Van der Walt A. Risk of cervical pre-cancer and cancer in women with multiple sclerosis exposed to high efficacy disease modifying therapies. Front Neurol 2023; 14:1119660. [PMID: 36846149 PMCID: PMC9950275 DOI: 10.3389/fneur.2023.1119660] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 01/24/2023] [Indexed: 02/12/2023] Open
Abstract
There is a growing need to better understand the risk of malignancy in the multiple sclerosis (MS) population, particularly given the relatively recent and widespread introduction of immunomodulating disease modifying therapies (DMTs). Multiple sclerosis disproportionately affects women, and the risk of gynecological malignancies, specifically cervical pre-cancer and cancer, are of particular concern. The causal relationship between persistent human papillomavirus (HPV) infection and cervical cancer has been definitively established. To date, there is limited data on the effect of MS DMTs on the risk of persistent HPV infection and subsequent progression to cervical pre-cancer and cancer. This review evaluates the risk of cervical pre-cancer and cancer in women with MS, including the risk conferred by DMTs. We examine additional factors, specific to the MS population, that alter the risk of developing cervical cancer including participation in HPV vaccination and cervical screening programs.
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Affiliation(s)
- Francesca Bridge
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia
- Department of Neurology, Alfred Health, Melbourne, VIC, Australia
| | - Julia M. L. Brotherton
- Australian Centre for the Prevention of Cervical Cancer (Formerly Victorian Cytology Service), Carlton South, VIC, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia
| | - Yi Foong
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia
- Department of Neurology, Alfred Health, Melbourne, VIC, Australia
- Department of Neurosciences, Eastern Health, Melbourne, VIC, Australia
| | - Helmut Butzkueven
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia
- Department of Neurology, Alfred Health, Melbourne, VIC, Australia
| | - Vilija G. Jokubaitis
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia
- Department of Neurology, Alfred Health, Melbourne, VIC, Australia
| | - Anneke Van der Walt
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia
- Department of Neurology, Alfred Health, Melbourne, VIC, Australia
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Mauri F, Cottler-Casanova S, Cavassini M, Stoeckle M, Wandeler G, Schmid P, Braun DL, Scherrer A, Bernasconi E, Calmy A, Abdulcadir J. Female Genital Mutilation/Cutting in the Swiss HIV Cohort Study: A Cross-Sectional Study. J Immigr Minor Health 2023; 25:136-141. [PMID: 35943681 PMCID: PMC9813055 DOI: 10.1007/s10903-022-01390-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/14/2022] [Indexed: 01/09/2023]
Abstract
FGM/C is a harmful practice that involves injury of the external female genitalia without medical purpose. It is mainly practiced in Africa, Asia, and the Middle East. However, with the migratory flows, women and girls with FGM/C and its consequences live all over the world. The lack of knowledge on how to care for women and girls living with FGM/C extends among all categories of health professionals involved in women's health, including infectious disease specialists. This is a national, exploratory descriptive cross-sectional study aimed to generate descriptive statistics about FGM/C among HIV-infected migrant women included in the Swiss HIV Cohort Study (SHCS). Among the 387 women interviewed about FGM/C and who provided an answer, 80 (20.7%) reported to have undergone FGM/C. Fifty-six of the 80 women (70.0%) who reported having undergone FGM/C, also reported that they had never discussed their cutting with a health professional before. Our study demonstrates how common female genital mutilation is in women living with HIV and who have migrated to Switzerland and suggest how care and prevention could be improved significantly.
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Affiliation(s)
- Fabio Mauri
- grid.150338.c0000 0001 0721 9812Department of Pediatrics, Obstetrics and Gynecology, Geneva University Hospitals, Bld de la Cluse, 1211, 0041-22- 3724049 Geneva, Switzerland
| | - Sara Cottler-Casanova
- grid.150338.c0000 0001 0721 9812Department of Pediatrics, Obstetrics and Gynecology, Geneva University Hospitals, Bld de la Cluse, 1211, 0041-22- 3724049 Geneva, Switzerland ,grid.416786.a0000 0004 0587 0574Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland ,grid.6612.30000 0004 1937 0642University of Basel, Basel, Switzerland
| | - Matthias Cavassini
- grid.8515.90000 0001 0423 4662Division of Infectious Diseases, Lausanne University Hospital, Lausanne, Switzerland
| | - Marcel Stoeckle
- grid.410567.1Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
| | - Gilles Wandeler
- grid.411656.10000 0004 0479 0855Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Patrick Schmid
- grid.413349.80000 0001 2294 4705Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Dominique L Braun
- grid.412004.30000 0004 0478 9977Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, Zurich, Switzerland ,grid.7400.30000 0004 1937 0650Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Alexandra Scherrer
- grid.410567.1Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
| | - Enos Bernasconi
- grid.417053.40000 0004 0514 9998Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland
| | - Alexandra Calmy
- grid.150338.c0000 0001 0721 9812HIV/AIDS Unit, Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland
| | - Jasmine Abdulcadir
- grid.150338.c0000 0001 0721 9812Department of Pediatrics, Obstetrics and Gynecology, Geneva University Hospitals, Bld de la Cluse, 1211, 0041-22- 3724049 Geneva, Switzerland
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26
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Matza Porges S, Shamriz O. Genetics of Immune Dysregulation and Cancer Predisposition: Two Sides of the Same Coin. Clin Exp Immunol 2022; 210:114-127. [PMID: 36165533 PMCID: PMC9750831 DOI: 10.1093/cei/uxac089] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 08/17/2022] [Accepted: 09/23/2022] [Indexed: 01/25/2023] Open
Abstract
Approximately 10% of cancers have a hereditary predisposition. However, no genetic diagnosis is available in 60%-80% of familial cancers. In some of these families, immune dysregulation-mediated disease is frequent. The immune system plays a critical role in identifying and eliminating tumors; thus, dysregulation of the immune system can increase the risk of developing cancer. This review focuses on some of the genes involved in immune dysregulation the promote the risk for cancer. Genetic counseling for patients with cancer currently focuses on known genes that raise the risk of cancer. In missing hereditary familial cases, the history family of immune dysregulation should be recorded, and genes related to the immune system should be analyzed in relevant families. On the other hand, patients with immune disorders diagnosed with a pathogenic mutation in an immune regulatory gene may have an increased risk of cancer. Therefore, those patients need to be under surveillance for cancer. Gene panel and exome sequencing are currently standard methods for genetic diagnosis, providing an excellent opportunity to jointly test cancer and immune genes.
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Affiliation(s)
- Sigal Matza Porges
- Department of Human Genetics, Institute for Medical Research, the Hebrew University of Jerusalem, Jerusalem, Israel
- Department of Biotechnology, Hadassah Academic College, Jerusalem, Israel
| | - Oded Shamriz
- Allergy and Clinical Immunology Unit, Department of Medicine, Hadassah Medical Organization, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
- The Lautenberg Center for Immunology and Cancer Research, Institute of Medical Research Israel-Canada, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
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27
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Barzallo D, Kusari A, Leslie KS. Recalcitrant verruca vulgaris regression following severe SARS-CoV-2 infection. JAAD Case Rep 2022; 28:1-3. [PMID: 35966354 PMCID: PMC9361623 DOI: 10.1016/j.jdcr.2022.07.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Affiliation(s)
- Devin Barzallo
- Department of Dermatology, University of California, San Francisco, San Francisco, California.,School of Medicine, Case Western Reserve University, Cleveland, Ohio
| | - Ayan Kusari
- Department of Dermatology, University of California, San Francisco, San Francisco, California
| | - Kieron S Leslie
- Department of Dermatology, University of California, San Francisco, San Francisco, California
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28
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Fronek L, Giansiracusa D, Nourmohammadi N, Johnson C, Yelich A, Hogan D. A Review of Cutaneous Diseases Observed in Solid Organ Transplant Recipients. THE JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY 2022; 15:21-31. [PMID: 36312823 PMCID: PMC9586525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Solid organ transplant recipients are at increased risk for numerous cutaneous conditions that fall within four categories: pre-neoplastic, neoplastic, infectious, or idiopathic. Many of these diseases can be attributed to immunosuppressive medications, including mycophenolate mofetil, cyclosporine, azathioprine, tacrolimus, or glucocorticoids. Iatrogenic lessening of the immune system places the patient at risk of malignancies, opportunistic infections, immune-mediated dermatoses, and adverse effects of medications. As the life expectancy of patients with solid organ transplants continues to increase, dermatologists and transplant physicians must stay abreast of this spectrum of dermatologic conditions, their respective prognoses, prevention, mitigation, and treatment.
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Affiliation(s)
- Lisa Fronek
- Dr. Fronek is with Bighorn Mohs Surgery and Dermatology Center, Scripps Clinic, La Jolla, California
| | - Derrek Giansiracusa
- Mr. Giansiracusa and Ms. Nourmohammadi are with Lake Erie College of Osteopathic Medicine in Bradenton, Florida
| | - Niki Nourmohammadi
- Mr. Giansiracusa and Ms. Nourmohammadi are with Lake Erie College of Osteopathic Medicine in Bradenton, Florida
| | - Cassandra Johnson
- Drs. Johnson, Yelich, and Hogan are with HCA Healthcare and USF Morsani College of Medicine at Largo Medical Center in Largo, Florida
| | - Allyson Yelich
- Drs. Johnson, Yelich, and Hogan are with HCA Healthcare and USF Morsani College of Medicine at Largo Medical Center in Largo, Florida
| | - Daniel Hogan
- Drs. Johnson, Yelich, and Hogan are with HCA Healthcare and USF Morsani College of Medicine at Largo Medical Center in Largo, Florida
- Dr. Hogan is additionally with the Department of Dermatology at Bay Pines Veterans Affairs Healthcare System in Bay Pines, Florida
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29
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Purzycka-Bohdan D, Nowicki RJ, Herms F, Casanova JL, Fouéré S, Béziat V. The Pathogenesis of Giant Condyloma Acuminatum (Buschke-Lowenstein Tumor): An Overview. Int J Mol Sci 2022; 23:4547. [PMID: 35562936 PMCID: PMC9100137 DOI: 10.3390/ijms23094547] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 04/13/2022] [Accepted: 04/18/2022] [Indexed: 11/18/2022] Open
Abstract
Giant condyloma acuminatum, also known as Buschke-Lowenstein tumor (BLT), is a rare disease of the anogenital region. BLT is considered a locally aggressive tumor of benign histological appearance, but with the potential for destructive growth and high recurrence rates. BLT development is strongly associated with infection with low-risk human papillomaviruses (HPVs), mostly HPV-6 and -11. Immunity to HPVs plays a crucial role in the natural control of various HPV-induced lesions. Large condyloma acuminata are frequently reported in patients with primary (e.g., DOCK8 or SPINK5 deficiencies) and secondary (e.g., AIDS, solid organ transplantation) immune defects. Individuals with extensive anogenital warts, including BLT in particular, should therefore be tested for inherited or acquired immunodeficiency. Research into the genetic basis of unexplained cases is warranted. An understanding of the etiology of BLT would lead to improvements in its management. This review focuses on the role of underlying HPV infections, and human genetic and immunological determinants of BLT.
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Affiliation(s)
- Dorota Purzycka-Bohdan
- Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, 80-214 Gdansk, Poland;
| | - Roman J. Nowicki
- Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, 80-214 Gdansk, Poland;
| | - Florian Herms
- Department of Dermatology, APHP, Saint-Louis Hospital, Université de Paris, 1 Avenue Claude Vellefaux, 75010 Paris, France; (F.H.); (S.F.)
- Centre for Genital and Sexually Transmitted Diseases, APHP, Saint-Louis Hospital, 75010 Paris, France
| | - Jean-Laurent Casanova
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR-1163, Necker Hospital for Sick Children, 75015 Paris, France;
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA
- Imagine Institute, University of Paris Cité, 75015 Paris, France
- Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, 75015 Paris, France
- Howard Hughes Medical Institute, New York, NY 10065, USA
| | - Sébastien Fouéré
- Department of Dermatology, APHP, Saint-Louis Hospital, Université de Paris, 1 Avenue Claude Vellefaux, 75010 Paris, France; (F.H.); (S.F.)
- Centre for Genital and Sexually Transmitted Diseases, APHP, Saint-Louis Hospital, 75010 Paris, France
| | - Vivien Béziat
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR-1163, Necker Hospital for Sick Children, 75015 Paris, France;
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA
- Imagine Institute, University of Paris Cité, 75015 Paris, France
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30
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Carvalho CF, Teixeira JC, Bragança JF, Derchain S, Zeferino LC, Vale DB. Cervical Cancer Screening with HPV Testing: Updates on the Recommendation. REVISTA BRASILEIRA DE GINECOLOGIA E OBSTETRÍCIA 2022; 44:264-271. [PMID: 35170010 PMCID: PMC9948069 DOI: 10.1055/s-0041-1739314] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 10/14/2021] [Indexed: 12/15/2022] Open
Abstract
The present update is a reassessment of the 2018 'Guidelines for HPV-DNA Testing for Cervical Cancer Screening in Brazil' (Zeferino et al.)9, according to the changes observed in new international guidelines and knowledge updates. The most relevant and recent guidelines were assessed. Questions regarding the clinical practice were formulated, and the answers considered the perspective of the public and private sectors of the Brazilian health system. The review addressed risk-based strategies regarding age to start and stop screening, the use of cytology and colposcopy to support management decisions, treatment, follow-up strategies, and screening in specific groups, including vaccinated women. The update aims to improve the prevention of cervical cancer and to reduce overtreatment and the misuse of HPV testing.
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Affiliation(s)
- Carla Fabrine Carvalho
- Department of Obstetrics and Gynecology, Universidade Estadual de Campinas, Campinas, SP, Brazil
| | - Julio Cesar Teixeira
- Department of Obstetrics and Gynecology, Universidade Estadual de Campinas, Campinas, SP, Brazil
| | - Joana Froes Bragança
- Department of Obstetrics and Gynecology, Universidade Estadual de Campinas, Campinas, SP, Brazil
| | - Sophie Derchain
- Department of Obstetrics and Gynecology, Universidade Estadual de Campinas, Campinas, SP, Brazil
| | - Luiz Carlos Zeferino
- Department of Obstetrics and Gynecology, Universidade Estadual de Campinas, Campinas, SP, Brazil
| | - Diama Bhadra Vale
- Department of Obstetrics and Gynecology, Universidade Estadual de Campinas, Campinas, SP, Brazil
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Zampella J, Cohen B. Consideration of underlying immunodeficiency in refractory or recalcitrant warts: A review of the literature. SKIN HEALTH AND DISEASE 2022; 2:e98. [PMID: 35665206 PMCID: PMC9060099 DOI: 10.1002/ski2.98] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 01/12/2022] [Accepted: 01/16/2022] [Indexed: 11/16/2022]
Abstract
Although the exact mechanisms have yet to be elucidated, it is clear that cellular immunity plays a role in clearance of human papillomavirus (HPV) infections as it relates to the development of warts. Patients with extensive, recalcitrant, or treatment‐refractory warts may have an underlying immune system impairment at the root of HPV susceptibility. Early recognition of genetic disorders associated with immunologic defects that allow for recalcitrant HPV infection may expedite appropriate treatment for patients. Early recognition is often pivotal in preventing subsequent morbidity and/or mortality that may arise from inborn errors of immunity, such as WHIM (Warts, Hypogammaglobulinemia, Infections, Myelokathexis) syndrome. Among these, cervical cancer is one of the most common malignancies associated with HPV, can be fatal if not treated early, and is seen more frequently in patients with underlying immune deficiencies. A review of diseases with susceptibility to HPV provides clues to understanding the pathophysiology of warts. We also present diagnostic guidance to facilitate the recognition of inborn errors of immunity in patients with extensive and/or recalcitrant HPV infections.
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Affiliation(s)
- J. Zampella
- Ronald O. Perelman Department of Dermatology NYU Grossman School of Medicine New York New York USA
| | - B. Cohen
- Division of Pediatric Dermatology Johns Hopkins University School of Medicine Baltimore Maryland USA
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Prevalence and Distribution of HPV Genotypes in Immunosuppressed Patients in Lorraine Region. Viruses 2021; 13:v13122454. [PMID: 34960723 PMCID: PMC8707108 DOI: 10.3390/v13122454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 11/11/2021] [Accepted: 12/02/2021] [Indexed: 11/23/2022] Open
Abstract
Background: The primary objective of this work was to assess the prevalence and distribution of HPV genotypes in immunosuppressed patients, and to compare them with the French Monsonego cohort. Secondary objectives were to evaluate whether the risk of HPV infection was correlated with HIV viral load, CD4 cell count in HIV-infected patients and the type, number of immunosuppressive therapies or type of pathology (transplant vs. autoimmune diseases) in patients undergoing long-term immunosuppressive therapy. Methods: An observational, monocentric and historical study was conducted including all immunosuppressed patients having received an HPV testing, in the Laboratory of Virology, Nancy Regional Teaching Hospital Center, between 2014 and 2020. Immunosuppressed patients were either HIV-infected or received long-term immunosuppressive therapy. Results: In our cohort, the prevalence of HPV infection (75.6% vs. 16.1% p < 0.05), the proportion of patients with high-risk HPV infection (48.9% vs. 15.1% p < 0.05) and with multiple HPV infection (41.1% vs. 5.7% p < 0.05) were significantly higher than in the Monsonego cohort. HPV 52 (13%), 53 (13%) and 16 (10%) were the most common in the immunosuppressed population, while it was HPV 16, 42 and 51 in the Monsonego cohort. Conclusions: This study supports that a particular attention must be given to all the immunosuppressed patients for the screening and care of HPV-related diseases because of major modifications of HPV epidemiology compared with the overall population.
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Ortu G, Barret AS, Danis K, Duchesne L, Levy-Bruhl D, Velter A. Low vaccination coverage for human papillomavirus disease among young men who have sex with men, France, 2019. EURO SURVEILLANCE : BULLETIN EUROPEEN SUR LES MALADIES TRANSMISSIBLES = EUROPEAN COMMUNICABLE DISEASE BULLETIN 2021; 26. [PMID: 34915971 PMCID: PMC8728497 DOI: 10.2807/1560-7917.es.2021.26.50.2001965] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Background In France, human papillomavirus (HPV) vaccination has been recommended in 2016 for men who have sex with men (MSM) up to age 26 years. Aim We aimed to estimate HPV vaccine coverage in 18–28 year-old MSM and identify uptake determinants. Methods We collected data on socio-demographic characteristics, sexual behaviour, sexually transmitted diseases (STI) screening and vaccination uptake using a voluntary cross-sectional online survey conducted in 2019 targeting MSM. We calculated coverage of at least one dose of HPV vaccine and prevalence ratios (PR) of determinants with 95% confidence intervals (CI) using Poisson regression. Results Of 9,469 respondents (age range: 18–28 years), 15% (95% CI: 14–16) reported being vaccinated for HPV. Coverage was significantly higher among MSM < 24 years (PR: 1.25; 95% CI: 1.13–1.39), with education level below university degree (PR: 1.12; 95% CI: 1.08–1.32), living in rural areas (PR: 1.21; 95% CI: 1.08–1.36), attending sex parties (PR: 1.12; 95% CI: 1.03–1.33), using HIV-related biomedical prevention methods (PR: 1.31; 95% CI: 1.12–1.54), with STI diagnosis (PR: 1.22; 95% CI: 1.08–1.38) and with hepatitis A or B vaccination (PR: 4.56; 95% CI: 3.63–5.81 vs PR: 3.35; 95% CI: 2.53–4.44). Conclusions The HPV vaccination uptake among MSM in France was not satisfactory. It was higher among MSM benefitting from other vaccinations and biomedical preventive methods against HIV, suggesting a synergistic effect of the national preventive sexual health recommendations for MSM. Further efforts to improve HPV vaccination coverage targeting MSM are warranted.
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Affiliation(s)
- Giuseppina Ortu
- Santé Publique France, Saint Maurice, France.,European Programme for Intervention Epidemiology Training (EPIET), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden
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Venanzi Rullo E, Maimone MG, Fiorica F, Ceccarelli M, Guarneri C, Berretta M, Nunnari G. Non-Melanoma Skin Cancer in People Living With HIV: From Epidemiology to Clinical Management. Front Oncol 2021; 11:689789. [PMID: 34422644 PMCID: PMC8371466 DOI: 10.3389/fonc.2021.689789] [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: 04/01/2021] [Accepted: 07/07/2021] [Indexed: 12/13/2022] Open
Abstract
Skin cancers represent the most common human tumors with a worldwide increasing incidence. They can be divided into melanoma and non-melanoma skin cancers (NMSCs). NMSCs include mainly squamous cell (SCC) and basal cell carcinoma (BCC) with the latest representing the 80% of the diagnosed NMSCs. The pathogenesis of NMSCs is clearly multifactorial. A growing body of literature underlies a crucial correlation between skin cancer, chronic inflammation and immunodeficiency. Intensity and duration of immunodeficiency plays an important role. In immunocompromised patients the incidence of more malignant forms or the development of multiple tumors seems to be higher than among immunocompetent patients. With regards to people living with HIV (PLWH), since the advent of combined antiretroviral therapy (cART), the incidence of non-AIDS-defining cancers (NADCs), such as NMSCs, have been increasing and now these neoplasms represent a leading cause of illness in this particular population. PLWH with NMSCs tend to be younger, to have a higher risk of local recurrence and to have an overall poorer outcome. NMSCs show an indolent clinical course if diagnosed and treated in an early stage. BCC rarely metastasizes, while SCC presents a 4% annual incidence of metastasis. Nevertheless, metastatic forms lead to poor patient outcome. NMSCs are often treated with full thickness treatments (surgical excision, Mohs micro-graphic surgery and radiotherapy) or superficial ablative techniques (such as cryotherapy, electrodesiccation and curettage). Advances in genetic landscape understanding of NMSCs have favored the establishment of novel therapeutic strategies. Concerning the therapeutic evaluation of PLWH, it’s mandatory to evaluate the risk of interactions between cART and other treatments, particularly antiblastic chemotherapy, targeted therapy and immunotherapy. Development of further treatment options for NMSCs in PLWH seems needed. We reviewed the literature after searching for clinical trials, case series, clinical cases and available databases in Embase and Pubmed. We review the incidence of NMSCs among PLWH, focusing our attention on any differences in clinicopathological features of BCC and SCC between PLWH and HIV negative persons, as well as on any differences in efficacy and safety of treatments and response to immunomodulators and finally on any differences in rates of metastatic disease and outcomes.
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Affiliation(s)
- Emmanuele Venanzi Rullo
- Unit of Infectious Disease, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Maria Grazia Maimone
- Unit of Infectious Disease, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Francesco Fiorica
- Department of Radiation Oncology and Nuclear Medicine, State Hospital "Mater Salutis" Azienda Unità Locale Socio Sanitaria (AULSS) 9, Legnago, Italy
| | - Manuela Ceccarelli
- Unit of Infectious Disease, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.,Unit of Infectious Disease, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Claudio Guarneri
- Unit of Dermatology, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy
| | - Massimiliano Berretta
- Unit of Infectious Disease, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Giuseppe Nunnari
- Unit of Infectious Disease, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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Boey L, Curinckx A, Roelants M, Derdelinckx I, Van Wijngaerden E, De Munter P, Vos R, Kuypers D, Van Cleemput J, Vandermeulen C. Immunogenicity and Safety of the 9-Valent Human Papillomavirus Vaccine in Solid Organ Transplant Recipients and Adults Infected With Human Immunodeficiency Virus (HIV). Clin Infect Dis 2021; 73:e661-e671. [PMID: 33373429 DOI: 10.1093/cid/ciaa1897] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The burden of human papillomavirus (HPV) in human immunodeficiency virus (HIV)-infected persons and solid organ transplant (SOT) recipients is high. Clinical trials on HPV vaccines in persons living with HIV and particularly in SOT recipients have been sparse to date, included low numbers of participants, and none of them assessed the 9-valent HPV (9vHPV) vaccine. We investigated the immunogenicity with respect to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 and the safety of the 9vHPV vaccine in persons living with HIV and recipients of a kidney, lung, or heart transplant. METHODS This is a phase III investigator-initiated study in 100 persons living with HIV (age 18-45 years) and 171 SOT recipients (age 18-55 years). The 9vHPV vaccine was administered at day 1, month 2, and month 6. Primary outcome was seroconversion rates to the 9vHPV types at month 7. Secondary outcomes were geometric mean titers (GMTs) and frequency of adverse events (AEs). RESULTS All HIV-infected participants seroconverted for all HPV types, but seroconversion ranged from 46% for HPV45 to 72% for HPV58 in SOT recipients. GMTs ranged from 180 to 2985 mMU/mL in HIV-positive participants and from 17 to 170 mMU/mL in SOT recipients, depending on the HPV type. Injection-site AEs occurred in 62% of participants but were mostly mild or moderate in intensity. None of the reported serious adverse events were deemed vaccine related. No patients died during the study. CONCLUSIONS Immunogenicity of the 9vHPV vaccine is high in persons living with HIV but suboptimal in SOT recipients. The vaccine is safe and well tolerated in both groups.
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Affiliation(s)
- Lise Boey
- Leuven University Vaccinology Centre, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
| | - Ans Curinckx
- Leuven University Vaccinology Centre, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
| | - Mathieu Roelants
- Leuven University Vaccinology Centre, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
| | - Inge Derdelinckx
- Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.,Department of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium
| | - Eric Van Wijngaerden
- Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.,Department of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium
| | - Paul De Munter
- Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.,Department of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium
| | - Robin Vos
- Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium, and Department CHROMETA (Chronic Diseases, Metabolism and Aging), BREATHE (Laboratory of Respiratory Diseases and Thoracic Surgery), KU Leuven, Leuven, Belgium
| | - Dirk Kuypers
- Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.,Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
| | | | - Corinne Vandermeulen
- Leuven University Vaccinology Centre, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
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Svoboda SA, Rush PS, Sharghi KG, Rady PL, Tyring SK, Eikenberg JD. A case report of disseminated verrucosis secondary to ustekinumab in a patient with Crohn's disease. SAGE Open Med Case Rep 2021; 9:2050313X211003056. [PMID: 33796316 PMCID: PMC7975484 DOI: 10.1177/2050313x211003056] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 01/25/2021] [Indexed: 11/18/2022] Open
Abstract
Ustekinumab is a biologic agent with Food and Drug Administration approval for
the treatment of moderate-to-severe plaque psoriasis, psoriatic arthritis,
ulcerative colitis, and Crohn’s disease. It functions to inhibit the p40 subunit
common to both interleukin-12 and interleukin-23. These pro-inflammatory
cytokines are implicated in autoinflammatory and autoimmune disorders, but they
also play an important role in cell-mediated immunity against viral, bacterial,
and fungal pathogens. Therefore, antagonism of interleukin-12 and interleukin-23
by ustekinumab may increase the risk of human papillomavirus infection or
reactivation which can lead to the development of verrucae. To the best of our
knowledge, there is only one published report of disseminated verrucosis
secondary to ustekinumab treatment for psoriasis. Here, we present the first
case report of ustekinumab-induced disseminated verrucosis occurring in the
setting of treatment for Crohn’s disease.
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Affiliation(s)
| | - Patrick S Rush
- Section of Dermatology, School of Medicine, Virginia Tech Carilion, Roanoke, VA, USA.,Department of Basic Science Education, School of Medicine, Virginia Tech Carilion, Roanoke, VA, USA
| | - Kevin G Sharghi
- Department of Dermatology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Peter L Rady
- Department of Dermatology, McGovern Medical School, The University of Texas Health Science Center, Houston, TX, USA
| | - Stephen K Tyring
- Department of Dermatology, McGovern Medical School, The University of Texas Health Science Center, Houston, TX, USA
| | - Joshua D Eikenberg
- Section of Dermatology, School of Medicine, Virginia Tech Carilion, Roanoke, VA, USA
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George JT, Levine H. Implications of Tumor-Immune Coevolution on Cancer Evasion and Optimized Immunotherapy. Trends Cancer 2021; 7:373-383. [PMID: 33446448 DOI: 10.1016/j.trecan.2020.12.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 12/04/2020] [Accepted: 12/07/2020] [Indexed: 02/06/2023]
Abstract
Cancer represents a diverse collection of diseases characterized by heterogeneous cell populations that dynamically evolve in their environment. As painfully evident in cases of treatment failure and recurrence, this general feature makes identifying long-term successful therapies difficult. It is now well-established that the adaptive immune system recognizes and eliminates cancer cells, and various immunotherapeutic strategies have emerged to augment this effect. These therapies, while promising, often fail as a result of immune-specific cancer evasion. Increasingly available empirical evidence details both cancer and immune system populations pre- and post-treatment, providing rich opportunity for mathematical models of the tumor-immune interaction and subsequent co-evolution. Integrated mathematical and experimental efforts bear immediate relevance for optimized therapies and will undoubtedly accelerate our understanding of this emergent field.
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Affiliation(s)
- Jason T George
- Center for Theoretical Biological Physics, Rice University, Houston, TX, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA.
| | - Herbert Levine
- Center for Theoretical Biological Physics, Rice University, Houston, TX, USA; Department of Bioengineering, Northeastern University, Boston, MA, USA; Department of Physics, Northeastern University, Boston, MA, USA.
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Vaccination of immune compromised children-an overview for physicians. Eur J Pediatr 2021; 180:2035-2047. [PMID: 33665677 PMCID: PMC8195953 DOI: 10.1007/s00431-021-03997-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 02/09/2021] [Accepted: 02/17/2021] [Indexed: 01/19/2023]
Abstract
Immune compromised children are threatened by a higher risk of infections; some of these are preventable by vaccination. Primary care physicians play a fundamental role in optimising vaccination status. In this narrative review, we present the evidence on vaccine safety and immunogenicity in immune compromised children and discuss in which conditions live-attenuated vaccines can possibly be used. Vaccination schedules differ in some of these conditions, including the use of vaccines with higher antigenic contents (e.g. high-dose hepatitis B vaccine), additional vaccine doses (e.g. 2-dose schedule meningococcal vaccine), more frequent booster doses (e.g. life-long pneumococcal vaccine booster), supplementary vaccines (e.g. meningococcal B vaccine) and use of vaccines beyond the age of usual recommendation (e.g. Haemophilus influenza type b vaccine after 5 years of age). Serological monitoring is a useful tool for customizing vaccination schedule in immune compromised children, confirming adequate vaccine response and documenting seroprotection (especially against measles and varicella). Finally, verification of vaccination status of all household members can prevent them being vector of transmission of an infection to the immune compromised children. Conclusion: Intensified information strategies are needed to improve trust, rectify perceived risks and improve vaccine acceptability; primary physicians can play a critical role in the latter. What is Known: • Physician's awareness is key to success, since it repeatedly correlates with higher vaccination rates What is New: • The vaccination status of immunocompromised children is rarely up-to-date • Knowing the latest vaccine recommendations is challenging, as they differ for each medical condition and change periodically • This review summarises the vaccine recommendations for children with compromised immune systems and highlights how paediatricians play a key role in coordinating their application.
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Redox-dependent mechanisms of carcinogenesis in human papillomavirus infection. Cancer 2021. [DOI: 10.1016/b978-0-12-819547-5.00009-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Magalhães GM, Vieira ÉC, Garcia LC, De Carvalho-Leite MDLR, Guedes ACM, Araújo MG. Update on human papilloma virus - part I: epidemiology, pathogenesis, and clinical spectrum. An Bras Dermatol 2021; 96:1-16. [PMID: 33341319 PMCID: PMC7838122 DOI: 10.1016/j.abd.2020.11.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 11/17/2020] [Accepted: 11/18/2020] [Indexed: 02/07/2023] Open
Abstract
Infection with human papilloma virus (HPV) is related to a great number of cutaneous and mucosal manifestations. The spectrum of HPV ranges from inapparent infections, through various clinical benign presentations including cutaneous and mucosal disease, to malignant and premalignant conditions. New HPV types are currently described in the literature; many of them are characterized as high-risk types due to their oncogenic potential. Knowledge regarding their epidemiology and pathogenesis is important to understand not only infection and disease processes, but also to formulate the clinical and laboratory basis for diagnosis, therapeutics, and prophylactic measures. This non-systematic review aims to discuss and to update those aspects, with an emphasis on relevant topics for dermatologists. HPV infection and related diseases in the Brazilian scenario are highlighted, including common dermatologic conditions seen at clinics as well as the condition of a public health problem as a sexually transmitted infection. The oncogenicity of the virus and the variety of clinical outcomes - especially in the immunocompromised individuals - are addressed.
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Affiliation(s)
- Geraldo Magela Magalhães
- Department of Internal Medicine, Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Dermatology Service, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Érica Cristina Vieira
- Dermatology Service, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Lucas Campos Garcia
- Dermatology Service, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | | | - Antônio Carlos Martins Guedes
- Department of Internal Medicine, Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Dermatology Service, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Marcelo Grossi Araújo
- Department of Internal Medicine, Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Dermatology Service, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
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High-Risk Human Papillomavirus Identification in Precancerous Cervical Intraepithelial Lesions. J Low Genit Tract Dis 2020; 24:197-201. [PMID: 32068617 DOI: 10.1097/lgt.0000000000000511] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE This review aims to summarize the currently available human papillomavirus (HPV) testing methods for precancerous cervical intraepithelial lesions. MATERIALS AND METHODS A literature search of PubMed using key words "high-risk HPV, precancerous cervical intraepithelial lesions, FDA-approved HPV tests, p16 IHC, Ki 67 IHC, fluorescent in situ hybridization for HPV, Pap smear, HPV vaccines, HPV tests using self-collected samples, and next-generation sequencing" was performed between January 1 and June 14, 2019. The package inserts of the Food and Drug Administration-approved HPV tests were obtained from the companies' Web sites. RESULTS Multiple morphology-based, immunohistochemical staining and nucleic acid HPV tests were reviewed, including the material required, methodologies, result interpretations, as well as their advantages, limitations, and futures. The structure of HPV and its natural history of infection and transmission were touched on as well for a better understanding of these testing methods. CONCLUSIONS Human papillomavirus tests are a critical component for cervical cancer screening, and understanding of these tests helps test results interpretation and patients' triage.
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Paulsen MR, Patel NR, Sulis C, Farraye FA, Bhat S. Human Papillomavirus, Herpes Zoster, and Hepatitis B Vaccinations in Immunocompromised Patients: An Update for Pharmacists. J Pharm Pract 2020; 34:943-951. [PMID: 32938309 DOI: 10.1177/0897190020958261] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE Current evidence regarding efficacy and safety of human papillomavirus 9-valent (9vHPV), recombinant zoster (RZV), and CpG-adjuvanted recombinant hepatitis B (HepB-CpG) vaccines in adults with human immunodeficiency virus, inflammatory bowel disease, solid organ transplant, and allogeneic hematopoietic stem cell transplant is reviewed. SUMMARY Patients immunocompromised due to underlying disease or treatment are at increased risk for infections; however, insufficient understanding of various vaccines' efficacy, safety, indications, and contraindications in this population has led to suboptimal vaccination rates. The Infectious Disease Society of America (IDSA) published guidelines on vaccines in immunocompromised populations in 2013. Since then, several advances have been made including an expanded indication with 9vHPV for use in males and females 9 to 45 years old, and the introduction of new vaccines for herpes zoster (RZV) and hepatitis B (HepB-CpG). Pharmacists are instrumental to vaccination efforts and may benefit from a review of recent vaccine updates. CONCLUSION The 9vHPV can be used in men and women ages 9 to 45 years old regardless of immune status. RZV safety and efficacy in several immunocompromised populations has been demonstrated; however, manufacturers and major societies have yet to update their recommendations. HepB-CpG may be used in most immunocompromised patients yet remains under-utilized.
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Affiliation(s)
| | - Nikitha R Patel
- Department of Clinical Pharmacy, Boston Medical Center, Boston, MA, USA
| | - Carol Sulis
- Department of Infectious Disease, Boston Medical Center, Boston, MA, USA
| | - Francis A Farraye
- Inflammatory Bowel Disease Center, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Shubha Bhat
- Department of Clinical Pharmacy, Boston Medical Center, Boston, MA, USA
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Thistle P, Parpia R, Pain D, Lee H, Manasa J, Schnipper LE. Prevalence and Subtype Distribution of High-Risk Human Papillomavirus Among Women Presenting for Cervical Cancer Screening at Karanda Mission Hospital. JCO Glob Oncol 2020; 6:1276-1281. [PMID: 32783640 PMCID: PMC7456322 DOI: 10.1200/go.20.00286] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE High-risk human papillomaviruses (hrHPV) are the primary cause of cervical cancer. Human papillomavirus (HPV) vaccination is expected to prevent cervical cancers caused by the HPV types included in vaccines and possibly by cross-protection from other types. This study sought to determine the hrHPV type distribution in women at a rural Zimbabwe hospital. METHODS We implemented a cross-sectional study at the Karanda Mission Hospital. Using the Visual Inspection with Acetic Acid Cervicography technique, clinicians collected cervical swabs from 400 women presenting for screening for cervical cancer. Samples were initially analyzed by Cepheid GeneXpert; candidate hrHPV genotypes were further characterized using the Anyplex II HPV28 Detection Kit. RESULTS Twenty-one percent of the 400 women were positive for a high-risk genotype when using the GeneXpert analyzer; 17% were positive when using the multiplex analysis. Almost two thirds of the hrHPV women had a single DNA type identified, whereas one third had multiple genotypes, ranging from 2 to 5. hrHPV was observed more frequently in HIV-positive than in HIV-negative women (27% v 15%). Of the 113 isolates obtained, 77% were hrHPV genotypes not included in the bivalent or quadrivalent vaccines, and 47% represented DNA types not covered in the nonavalent vaccine. Forty-seven percent of the women with hrHPV harbored a single genotype that was not covered by the nonavalent vaccine. CONCLUSION A large fraction of hrHPV isolates from women participating in a cervical cancer screening program in northern Zimbabwe are DNA types not covered by the bivalent, quadrivalent, or nonavalent vaccines. These findings suggest the importance of characterizing the hrHPV DNA types isolated from cervical neoplasia in this population and determining whether cross-immunization against these genotypes develops after administration of the vaccines in current use.
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Affiliation(s)
- Paul Thistle
- Karanda Mission Hospital, Mount Darwin, Zimbabwe
| | | | | | - Hang Lee
- Massachusetts General Hospital, Boston, MA
| | - Justen Manasa
- African Institute of Biomedical Science and Technologies Laboratory, Harare, Zimbabwe
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Hamilton SN, Urban R, Liu A, Chau N, Berthelet E, Tran E, Wu J, Yin Y, Olson R. Population-based outcomes by immunosuppressed status in patients undergoing radiotherapy for oropharyngeal cancer. Radiother Oncol 2020; 151:110-117. [PMID: 32798599 DOI: 10.1016/j.radonc.2020.08.005] [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: 05/25/2020] [Revised: 08/06/2020] [Accepted: 08/08/2020] [Indexed: 12/13/2022]
Abstract
INTRODUCTION The incidence of immunosuppression in patients with oropharynx head & neck squamous cell carcinoma (SCC) is not well studied. This study evaluates disease characteristics and treatment outcomes in oropharynx SCC in patients with and without immunosuppression. METHODS A retrospective review of all patients treated with radiotherapy for oropharynx SCC at BC Cancer from 2011 to 2016 was performed. Survival outcomes were assessed using Kaplan-Meier methods and competing risk analysis. Multivariate analysis and propensity score matching were performed. RESULTS There were 1077 patients, of which 5.8% (n = 62) had an immunosuppressive medical condition or were taking long-term immunosuppressive medication at diagnosis. Median follow-up was 3.3 years. Three year OS for patients without immunosuppression was 79.5% (95% Confidence Interval [CI] 76.8-82.0%) and for those with immunosuppression was 64.6% (95% CI 50.9-75.3%) (hazard ratio [HR] 1.78, 95% CI 1.18-2.68, p = 0.0062). The three year disease recurrence for patients without immunosuppression was 24.9% (95% CI 22.2-27.7%) and 44.4% (95% CI 31.5-56.6%) for those with immunosuppression (HR 2.12, 95% CI 1.45-3.11, p = 0.0001). Multivariate analysis of disease free survival (DFS) found that active smoking, advanced TNM stage, base of tongue subsite, p16 negative and unknown, no concurrent chemotherapy, higher Charlson Comorbidity Index, and lower radiation dose were also associated with worse DFS (all p < 0.05). Immunosuppressed patients had worse DFS relative to patients without immunosuppression, p < 0.001, HR 1.97 (95% CI 1.33-2.91). CONCLUSION Immunosuppression was an independent predictor of worse DFS in this large cohort of patients with oropharynx SCC.
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Affiliation(s)
- Sarah Nicole Hamilton
- BC Cancer - Vancouver Centre, Vancouver, BC, Canada; Univeristy of British Columbia, Vancouver, BC, Canada.
| | - Ryan Urban
- BC Cancer - Vancouver Centre, Vancouver, BC, Canada; Univeristy of British Columbia, Vancouver, BC, Canada
| | - Alvin Liu
- BC Cancer - Vancouver Centre, Vancouver, BC, Canada; Univeristy of British Columbia, Vancouver, BC, Canada
| | - Nicole Chau
- BC Cancer - Vancouver Centre, Vancouver, BC, Canada
| | - Eric Berthelet
- BC Cancer - Vancouver Centre, Vancouver, BC, Canada; Univeristy of British Columbia, Vancouver, BC, Canada
| | - Eric Tran
- BC Cancer - Vancouver Centre, Vancouver, BC, Canada; Univeristy of British Columbia, Vancouver, BC, Canada
| | - Jonn Wu
- BC Cancer - Vancouver Centre, Vancouver, BC, Canada; Univeristy of British Columbia, Vancouver, BC, Canada
| | - Yaling Yin
- BC Cancer - Vancouver Centre, Vancouver, BC, Canada
| | - Robert Olson
- Univeristy of British Columbia, Vancouver, BC, Canada; BC Cancer - Centre for the North, Prince George, BC, Canada; University of Northern British Columbia, BC, Canada
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Fu Y, Cao R, Schäfer M, Stephan S, Braspenning-Wesch I, Schmitt L, Bischoff R, Müller M, Schäfer K, Vinzón SE, Rösl F, Hasche D. Expression of different L1 isoforms of Mastomys natalensis papillomavirus as mechanism to circumvent adaptive immunity. eLife 2020; 9:e57626. [PMID: 32746966 PMCID: PMC7402679 DOI: 10.7554/elife.57626] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 07/03/2020] [Indexed: 12/11/2022] Open
Abstract
Although many high-risk mucosal and cutaneous human papillomaviruses (HPVs) theoretically have the potential to synthesize L1 isoforms differing in length, previous seroepidemiological studies only focused on the short L1 variants, co-assembling with L2 to infectious virions. Using the multimammate mouse Mastomys coucha as preclinical model, this is the first study demonstrating seroconversion against different L1 isoforms during the natural course of papillomavirus infection. Intriguingly, positivity with the cutaneous MnPV was accompanied by a strong seroresponse against a longer L1 isoform, but to our surprise, the raised antibodies were non-neutralizing. Only after a delay of around 4 months, protecting antibodies against the short L1 appeared, enabling the virus to successfully establish an infection. This argues for a novel humoral immune escape mechanism that may also have important implications on the interpretation of epidemiological data in terms of seropositivity and protection of PV infections in general.
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Affiliation(s)
- Yingying Fu
- Division of Viral Transformation Mechanisms, Research Program 'Infection, Inflammation and Cancer', German Cancer Research CenterHeidelbergGermany
| | - Rui Cao
- Division of Viral Transformation Mechanisms, Research Program 'Infection, Inflammation and Cancer', German Cancer Research CenterHeidelbergGermany
| | - Miriam Schäfer
- Division of Viral Transformation Mechanisms, Research Program 'Infection, Inflammation and Cancer', German Cancer Research CenterHeidelbergGermany
| | - Sonja Stephan
- Division of Viral Transformation Mechanisms, Research Program 'Infection, Inflammation and Cancer', German Cancer Research CenterHeidelbergGermany
| | - Ilona Braspenning-Wesch
- Division of Viral Transformation Mechanisms, Research Program 'Infection, Inflammation and Cancer', German Cancer Research CenterHeidelbergGermany
| | - Laura Schmitt
- Division of Viral Transformation Mechanisms, Research Program 'Infection, Inflammation and Cancer', German Cancer Research CenterHeidelbergGermany
| | - Ralf Bischoff
- Division of Functional Genome Analysis, Research Program 'Functional and Structural Genomics', German Cancer Research CenterHeidelbergGermany
| | - Martin Müller
- Research Group Tumorvirus-specific Vaccination Strategies, Research Program 'Infection, Inflammation and Cancer', German Cancer Research CenterHeidelbergGermany
| | - Kai Schäfer
- Division of Viral Transformation Mechanisms, Research Program 'Infection, Inflammation and Cancer', German Cancer Research CenterHeidelbergGermany
| | - Sabrina E Vinzón
- Division of Viral Transformation Mechanisms, Research Program 'Infection, Inflammation and Cancer', German Cancer Research CenterHeidelbergGermany
| | - Frank Rösl
- Division of Viral Transformation Mechanisms, Research Program 'Infection, Inflammation and Cancer', German Cancer Research CenterHeidelbergGermany
| | - Daniel Hasche
- Division of Viral Transformation Mechanisms, Research Program 'Infection, Inflammation and Cancer', German Cancer Research CenterHeidelbergGermany
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Foster E, Malloy MJ, Jokubaitis VG, Wrede CDH, Butzkueven H, Sasadeusz J, Van Doornum S, Macrae F, Unglik G, Brotherton JML, van der Walt A. Increased risk of cervical dysplasia in females with autoimmune conditions-Results from an Australia database linkage study. PLoS One 2020; 15:e0234813. [PMID: 32555638 PMCID: PMC7302686 DOI: 10.1371/journal.pone.0234813] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Accepted: 06/02/2020] [Indexed: 12/29/2022] Open
Abstract
Background Autoimmune conditions (AICs) and/or their treatment may alter risk of human papilloma virus (HPV) infection and females with AICs are therefore at an increased risk of cervical dysplasia. However, inclusion of these at-risk populations in cervical cancer screening and HPV-vaccination guidelines, are mostly lacking. This study aimed to determine the prevalence of cervical dysplasia in a wide range of AICs and compare that to HIV and immunocompetent controls to support the optimisation of cervical cancer preventive health measures. Methods Data linkage was used to match cervical screening episodes to emergency department records of females with AICs or HIV to immunocompetent controls over a 14-year period. The primary outcome was histologically confirmed high-grade cervical disease. Results, measured as rates by cytology and histology classification per 1,000 females screened, were analysed per disease group, and intergroup comparisons were performed. Results Females with inflammatory bowel disease (2,683), psoriatic and enteropathic arthropathies (1,848), multiple sclerosis (MS) (1,426), rheumatoid arthritis (1,246), systemic lupus erythematosus and/or mixed connective tissue disease (SLE/MCTD) (702), HIV (44), and 985,383 immunocompetent controls were included. SLE/MCTD and HIV groups had greater rates of high-grade histological and cytological abnormalities compared to controls. Increased rates of low-grade cytological abnormalities were detected in all females with AICs, with the exception of the MS group. Conclusions Females with SLE/MCTD or HIV have increased rates of high-grade cervical abnormalities. The increased low-grade dysplasia rate seen in most females with AICs is consistent with increased HPV infection. These findings support expansion of cervical cancer preventative programs to include these at-risk females.
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Affiliation(s)
- Emma Foster
- Department of Neurology, MS and Neuroimmunology Service, Alfred Health, Melbourne, Australia
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia
- Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia
| | - Michael J. Malloy
- Victorian Cervical Screening Registry, VCS Population Health, VCS Foundation, Melbourne, Australia
- Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia
| | - Vilija G. Jokubaitis
- Department of Neurology, MS and Neuroimmunology Service, Alfred Health, Melbourne, Australia
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia
| | - C. David H. Wrede
- Department of Oncology and Dysplasia, Royal Women’s Hospital, Melbourne, Australia
- Department of Obstetrics and Gynaecology, The University of Melbourne, Melbourne, Australia
| | - Helmut Butzkueven
- Department of Neurology, MS and Neuroimmunology Service, Alfred Health, Melbourne, Australia
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia
| | - Joe Sasadeusz
- Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Melbourne, Australia
| | - Sharon Van Doornum
- Rheumatology Department, The Royal Melbourne Hospital, Melbourne, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Australia
| | - Finlay Macrae
- Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia
| | - Gary Unglik
- Department of Clinical Immunology and Allergy, The Royal Melbourne Hospital, Melbourne, Australia
| | - Julia M. L. Brotherton
- Victorian Cervical Screening Registry, VCS Population Health, VCS Foundation, Melbourne, Australia
- Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia
- * E-mail: (AVDW); (JMLB)
| | - Anneke van der Walt
- Department of Neurology, MS and Neuroimmunology Service, Alfred Health, Melbourne, Australia
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia
- Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia
- * E-mail: (AVDW); (JMLB)
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Han J, Waller JL, Colombo RE, Spearman V, Young L, Kheda MF, Mohammed A, Bollag WB, Nahman NS, Baer SL. Incidence and risk factors for HPV-associated cancers in women with end-stage renal disease. J Investig Med 2020; 68:1002-1010. [PMID: 32503931 DOI: 10.1136/jim-2019-001262] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/28/2020] [Indexed: 11/04/2022]
Abstract
Human papillomavirus (HPV) causes the majority of cervical, anal/rectal, and oropharyngeal cancers in women. End-stage renal disease (ESRD) is also associated with an increased risk of malignancy, but the incidence of and risk factors for HPV-associated cancers in US dialysis patients are not defined. We queried the US Renal Data System for women with HPV-associated cancers and assessed for incidence of cancer diagnosis and association of risk factors. From 2005 to 2011, a total of 1032 female patients with ESRD had 1040 HPV-associated cancer diagnoses. Patients had a mean age of 65 years, were mostly white (63%), and on hemodialysis (92%). Cervical cancer (54%) was the most common, followed by anal/rectal (34%), and oropharyngeal (12%). The incidence of HPV-associated cancers in patients with ESRD increased yearly, with up to a 16-fold increased incidence compared with the general population. Major risk factors associated with the development of any HPV-associated cancer included smoking (adjusted relative risk=1.89), alcohol use (1.87), HIV (2.21), and herpes infection (2.02). Smoking, HIV, and herpes infection were prominent risk factors for cervical cancer. The incidence of HPV-associated cancers in women with ESRD is rising annually and is overall higher than in women of the general population. Tobacco use is a universal risk factor. For cervical cancer, the presence of HIV and herpes are important comorbidities. Recognizing risk factors associated with these cancers may improve diagnosis and facilitate survival. The role of HPV vaccination in at-risk dialysis patients remains to be defined but warrants further study.
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Affiliation(s)
- Joan Han
- Department of Medicine, Medical College of Georgia, Augusta, Georgia, USA
| | - Jennifer L Waller
- Department of Population Health Sciences, Medical College of Georgia, Augusta, Georgia, USA
| | - Rhonda E Colombo
- Department of Medicine, Medical College of Georgia, Augusta, Georgia, USA
| | - Vanessa Spearman
- Department of Medicine, Medical College of Georgia, Augusta, Georgia, USA
| | - Lufei Young
- Department of Medicine, Medical College of Georgia, Augusta, Georgia, USA
| | - Mufaddal F Kheda
- Department of Medicine, Medical College of Georgia, Augusta, Georgia, USA
| | - Azeem Mohammed
- Department of Medicine, Medical College of Georgia, Augusta, Georgia, USA
| | - Wendy B Bollag
- Department of Dermatology, Medical College of Georgia, Augusta, Georgia, USA
| | | | - Stephanie L Baer
- Department of Medicine, Medical College of Georgia, Augusta, Georgia, USA .,Infection Control and Epidemiology, Augusta VA Medical Center, Augusta, Georgia, USA
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48
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Pevzner AM, Tsyganov MM, Ibragimova MK, Litvyakov NV. [Viral co-infection with head and neck tumors]. Vestn Otorinolaringol 2020; 85:67-72. [PMID: 32476395 DOI: 10.17116/otorino20208502167] [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: 11/17/2022]
Abstract
The review is devoted to assessing the prevalence of human papillomavirus (HPV) in combination with other viral agents for head and neck tumors (HNT). HPV is recognized as an etiological factor in the development of cervical cancer, but there is evidence that it may be involved in carcinogenesis in other locations, in particular the upper respiratory tract. However, HPV is not the most important factor in tumor growth and progression. Recently, many researchers have reported the presence of concomitant co-infection, affecting tumor progression. Of all the studies analyzed, only 3 studies showed the absence or low rates of co-infection in HNT: from the Czech Republic (0%), China (0.6%) and Japan (3%). Most often, HPV infection was detected together with the Epstein-Barr virus (EBV) - from 12.5 to 34.1% of cases. In Russia, the prevailing combination of viral co-infection was a combination of EBV and cytomegalovirus (9.5%) and a combination of EBV and herpes simplex virus (6.7%). Thus, the degree of incidence of HPV in HNT varies greatly, and the mechanisms of coinfection are poorly understood, which raises the question of whether HPV and concomitant infection can be involved in tumor progression. This makes further research in this direction relevant and promising.
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Affiliation(s)
- A M Pevzner
- Tomsk National Research Medical Center of the Russian Academy of Sciences, Oncology Research Institute, Tomsk, Russia
| | - M M Tsyganov
- Tomsk National Research Medical Center of the Russian Academy of Sciences, Oncology Research Institute, Tomsk, Russia
| | - M K Ibragimova
- Tomsk National Research Medical Center of the Russian Academy of Sciences, Oncology Research Institute, Tomsk, Russia
| | - N V Litvyakov
- Tomsk National Research Medical Center of the Russian Academy of Sciences, Oncology Research Institute, Tomsk, Russia
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Anshelevich EE, Barbieri JS, Kovarik CL. Intralesional cidofovir for treatment of recalcitrant warts in both immunocompetent and immunocompromised patients: A retrospective analysis of 58 patients. J Am Acad Dermatol 2020; 84:206-207. [PMID: 32348821 DOI: 10.1016/j.jaad.2020.04.118] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 04/19/2020] [Accepted: 04/23/2020] [Indexed: 10/24/2022]
Affiliation(s)
- Ellen E Anshelevich
- Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - John S Barbieri
- Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Carrie L Kovarik
- Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
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Head and neck squamous cell cancer associated with lymphoproliferative malignancies is aggressive. The Journal of Laryngology & Otology 2020; 134:460-462. [PMID: 32308160 DOI: 10.1017/s0022215120000729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Patients with non-Hodgkin's lymphoma and chronic lymphocytic leukaemia are at an elevated risk of further malignancy. Head and neck squamous cell carcinoma often presents with cervical lymph node metastasis, and can pose a diagnostic challenge in patients with non-Hodgkin's lymphoma or chronic lymphocytic leukaemia who may have pre-existing palpable neck nodes. METHODS A retrospective case review of a health board was conducted to identify patients with head and neck squamous cell carcinoma with a previous diagnosis of non-Hodgkin's lymphoma or chronic lymphocytic leukaemia. RESULTS Four patients with head and neck squamous cell carcinoma that developed after non-Hodgkin's lymphoma or chronic lymphocytic leukaemia were identified. Two patients had a background of non-Hodgkin's lymphoma treated with chemotherapy. The remaining two patients had a background of chronic lymphocytic leukaemia under active surveillance. Three out of the four patients died within 30 months of diagnosis. CONCLUSION Head and neck squamous cell carcinoma following non-Hodgkin's lymphoma or chronic lymphocytic leukaemia is aggressive. A heightened clinical suspicion is essential to facilitate early diagnosis and treatment of head and neck squamous cell carcinoma in patients with dual pathology.
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