{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T09:19:18Z","timestamp":1787649558866,"version":"build-2736575974"},"reference-count":28,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"ANRS-MIE"},{"name":"APACHES"},{"name":"APACHES-HSIL"},{"name":"APACHES-methylation"},{"name":"Soci\u00e9t\u00e9 Nationale Fran\u00e7aise d'H\u00e9pato-gastro-ent\u00e9rologie"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Histologically confirmed anal high-grade squamous intraepithelial lesions (hHSILs) are targets for diagnosis and treatment in anal cancer screening programs. However, the long-term natural history of untreated hHSILs remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In the APACHES study, 513 human immunodeficiency virus (HIV)\u2013positive men who have sex with men and were aged \u226535 years underwent 3 annual visits for anal cytology, human papillomavirus (HPV) testing, and high-resolution anoscopy with biopsies to detect hHSILs. hHSILs were not treated but were monitored every 6 months for up to 5 years. Methylation markers, ASCL1 and ZNF582, were assessed in biopsy specimens at hHSIL diagnosis. The hHSIL regression probability was estimated using Cox proportional hazards models, adjusted hazard ratios, and Kaplan-Meier survival curves.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 127 untreated hHSILs, 21% regressed within 1 year, 41% within 2 years, and 75% within 5 years. None progressed to cancer during follow-up. Regression was significantly less likely for hHSILs with concurrent high-grade findings at anal cytology (adjusted hazard ratio, 0.41 [95% confidence interval, .19\u2013.88]), 12-month persistent HPV-16 infection in anal swab samples (0.46 [.21\u2013.97]), or positivity for both ASCL1 and ZNF582 (0.39 [.18\u2013.82). The 5-year regression probabilities ranged from approximately 30% for ASCL1\/ZNF582-positive hHSILs with high-grade cytology, to approximately 90% for ASCL1\/ZNF582-negative hHSILs without high-grade cytology. hHSIL regression was not influenced by age, smoking, or HIV-related markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Only one-quarter of untreated hHSILs persisted at 5 years, representing lesions with the highest anal cancer risk. The methylation markers ASCL1\/ZNF582 were the strongest predictors of persistent hHSIL and, combined with HPV testing and cytology, may inform prioritization for diagnosis and treatment in anal cancer screening programs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciag477","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:21:17Z","timestamp":1786360877000},"source":"Crossref","is-referenced-by-count":0,"title":["Evolution of Untreated Anal High-Grade Squamous Intraepithelial Lesions in High-Risk Men: A Prospective 5-Year Clinical Follow-up in the ANRS-EP57-APACHES Study"],"prefix":"10.1093","author":[{"given":"Isabelle","family":"Etienney","sequence":"first","affiliation":[{"name":"Service de Proctologie M\u00e9dico-Interventionnelle, Groupe Hospitalier Diaconesses Croix-Saint-Simon , Paris 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