{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T01:56:23Z","timestamp":1755222983754,"version":"3.43.0"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Anal squamous cell carcinoma is commonly associated with human papillomavirus (HPV) infection and preceded by low\u2010 and high\u2010grade anal lesions (LSIL; HSIL). We performed a molecular comparison on paired LSIL\u2010 and HSIL\u2010lesions collected in a longitudinal fashion to assess their relationship. Fifty biopsies from 22 men diagnosed with LSIL at baseline (T0) who developed HSIL during follow\u2010up (T1) were subjected to a comprehensive molecular analysis: HPV\u2010typing and HPV16 variant, cellular DNA methylation levels, and copy number aberrations (CNA). After histopathological revision, 23 biopsies were classified as LSIL and 27 as HSIL. Both methylation levels and CNA were significantly increased in HSIL compared to LSIL. In 15 out of 22 patients, LSIL at T0 was associated with HSIL at T1. Among them, six showed HPV\u2010type persistence with similar or increased methylation levels and CNA in the HSIL at follow\u2010up. Six patients harbored a different HPV\u2010type in the follow\u2010up biopsy, while in three patients, HPV was not detected or not\u2010typable in one or both lesions. A subset of HSIL preceded by LSIL displayed both HPV\u2010type persistence and an increase in molecular alterations, suggesting that some LSIL may progress to HSIL. In contrast, the HPV\u2010type switch in another subset of HSIL preceded by LSIL, may suggest an alternative pathway of anal carcinogenesis, where HSIL develop directly.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmv.70397","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T02:53:12Z","timestamp":1747882392000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Insights Into the Natural History of Anal HSIL"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1952-6729","authenticated-orcid":false,"given":"Aude","family":"Jary","sequence":"first","affiliation":[{"name":"Pathology Amsterdam UMC Location VU University Amsterdam The Netherlands"},{"name":"Cancer Center Amsterdam, Imaging and Biomarkers Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1325-1901","authenticated-orcid":false,"given":"Ramon P.","family":"van der Zee","sequence":"additional","affiliation":[{"name":"Pathology Amsterdam UMC Location VU University Amsterdam The Netherlands"},{"name":"Cancer Center Amsterdam, Imaging and Biomarkers Amsterdam The Netherlands"},{"name":"Internal Medicine Amsterdam UMC Location University of Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vita","family":"Jongen","sequence":"additional","affiliation":[{"name":"Amsterdam Institute for Immunology and Infectious Diseases (AII) Amsterdam The Netherlands"},{"name":"Department of Infectious Diseases Public Health Service Amsterdam Amsterdam The Netherlands"},{"name":"Stichting HIV Monitoring Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timo J.","family":"Ter Braak","sequence":"additional","affiliation":[{"name":"Pathology Amsterdam UMC Location VU University Amsterdam The Netherlands"},{"name":"Cancer Center Amsterdam, Imaging and Biomarkers Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongsoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Pathology Amsterdam UMC Location VU University Amsterdam The Netherlands"},{"name":"Cancer Center Amsterdam, Imaging and Biomarkers Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2758-9463","authenticated-orcid":false,"given":"Chris J. 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