ArticleInternational journal of cancer2021
Characterisation of anal intraepithelial neoplasia and anal cancer in HIV-positive men by immunohistochemical markers p16, Ki-67, HPV-E4 and DNA methylation markers.
Article in International journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- German-Austrian guideline on screening for anal dysplasia and anal carcinoma in people living with HIV.Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG · 2025Guideline
- Anal High-Grade Squamous Intraepithelial Lesions in People Living with HIV: A Systematic Review of Treatment Outcomes.Cancers · 2026Review
- The Role of Human Papillomavirus E6 Oncoprotein as a Biomarker in Anal Cancer Screening in Persons Living with HIV.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025Article
- A Case of a Longstanding Perianal Lesion Presenting as Advanced Squamous Cell Carcinoma of the Anus.Cureus · 2025Article
- Molecular Insights Into the Natural History of Anal HSIL.Journal of medical virology · 2025Article
- Diagnostic Performance of Host and Viral DNA Methylation Analysis in the Identification of Anal Intraepithelial Neoplasia and Cancer: Systematic Review and Meta-Analysis.Healthcare (Basel, Switzerland) · 2024Review
- Anal carcinoma - exploring the epidemiology, risk factors, pathophysiology, diagnosis, and treatment.World journal of experimental medicine · 2024Review
- Methylation markers for anal cancer screening: A repeated cross-sectional analysis of people living with HIV, 2015-2016.International journal of cancer · 2024Article
- Two-Year Incidence and Cumulative Risk and Predictors of Anal High-Grade Squamous Intraepithelial Lesions (Anal Precancer) Among Women With Human Immunodeficiency Virus.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Article
- State of the science and future directions for research on HIV and cancer: Summary of a joint workshop sponsored by IARC and NCI.International journal of cancer · 2024Review
- HPV-related diseases in male patients: an underestimated conundrum.Journal of endocrinological investigation · 2024Review
- Article
- Characterisation of anal intraepithelial neoplasia and anal cancer in HIV-positive men by immunohistochemical markers p16, Ki-67, HPV-E4 and DNA methylation markers.International journal of cancer · 2021Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human papillomavirus (HPV)-induced anal intraepithelial neoplasia (AIN, graded 1-3) is highly prevalent in HIV-positive (HIV+) men who have sex with men (MSM), but only a minority of lesions progresses to cancer. Our study aimed to characterise comprehensively anal tissue samples from a cross-sectional series (n = 104) of HIV+ MSM and longitudinal series (n = 40) of AIN2/3 progressing to cancer using different biomarkers. The cross-sectional series consisted of 8 normal, 26 AIN1, 45 AIN2, 15 AIN3 and 10 anal squamous cell carcinoma. Tissue sections were immunohistochemically (IHC) stained for p16 (viral transformation marker), Ki-67 (cellular proliferation marker) and HPV-E4 (viral production marker). We evaluated the expression of IHC markers and compared it with DNA methylation, a marker for malignant transformation. E4 positivity decreased, whereas p16 and Ki-67 scores and methylation marker positivity increased (P values < .001) with increasing severity of anal lesions. Within AIN2, a heterogeneous biomarker pattern was observed concerning E4, p16 and methylation status, reflecting the biological heterogeneity of these lesions. In the longitudinal series, all AIN2/3 and carcinomas showed high p16 and Ki-67 expression, strong methylation positivity and occasional E4 positivity. We earlier showed that high methylation levels are associated with progression to cancer. The observed E4 expression in some AIN2/3 during the course of progression to cancer and absence of E4 in a considerable number of AIN1 lesions make the potential clinical significance of E4 expression difficult to interpret. Our data show that IHC biomarkers can help to characterise AIN; however, their prognostic value for cancer risk stratification, next to objective methylation analysis, appears to be limited.
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