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

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ID: 325072
2026
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Ranked #261 of 635 articles by views in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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Abstract
Abstract Background Histologically-confirmed anal high-grade squamous intraepithelial lesions (hHSIL) are targets for diagnosis and treatment in anal cancer screening programmes. However, long-term natural history of untreated hHSIL remains poorly understood. Methods In the APACHES study, 513 HIV-positive men who have sex with men aged ≥35 years underwent three annual visits for anal cytology, HPV testing, and high-resolution anoscopy with biopsies to detect hHSIL. hHSIL were not treated but monitored every six months for up to five years. Methylation markers, ASCL1 and ZNF582, were assessed in biopsies at hHSIL diagnosis. hHSIL regression probability was estimated using Cox proportional hazards models, adjusted hazard ratios (aHR) and Kaplan-Meier survival curves. Results Of 127 untreated hHSIL, 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 hHSIL with concurrent high-grade anal cytology (aHR = 0.41; 95% CI: 0.19–0.88), 12-month persistent HPV16 infection in anal swabs (aHR = 0.46; 95% CI: 0.21–0.97), or positivity for both ASCL1 and ZNF582 (aHR = 0.39; 95% CI: 0.18–0.82). 5-year regression probability ranged from ∼30% for ASCL1/ZNF582-positive hHSIL with high-grade cytology, to ∼90% for ASCL1/ZNF582-negative hHSIL without high-grade cytology. hHSIL regression was not influenced by age, smoking, or HIV-related markers. Conclusions Only one quarter of untreated hHSIL persisted at 5 years, representing lesions with the highest anal cancer risk. Methylation markers ASCL1/ZNF582 were the strongest predictors of persistent hHSIL and, combined with HPV testing and cytology, may inform prioritisation for diagnosis and treatment in anal cancer screening programmes.
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Authors Isabelle Etienney, Deependra Singh, E. Ressiot, Jean‐Michel Didelot, Sylvie Radenne, Olivia Zaegel‐Faucher, Anne-Carole Lesage, Laurent Siproudhis, C. Arvieux, Lionel Piroth, Isabelle Heard, Gilles Pialoux, Fatoumata Coulibaly, Nadia Hoyeau, Sébastien Henno, Catharina J. Alberts, Timo J Ter Braak, Renske D.M. Steenbergen, Jean‐Damien Combes, Gary M. Clifford, for the ANRS-EP57-APACHES study group, Ana Canestri, Valérie Costes-Martineau, Jean Del Grande, Michaël Falguières, Tristan Ferry, H Fischer, Jean–François Fléjou, Marine Landon, Hélène Laude, F. Le Breton, Annie Lion, Gilles Maincent, Haingo Njatonirina Andrianiaina, Olivier Patey, Ventzislava Petrov Sanchez, G P Marion Pirel, L P Isabelle Poizot-Martin, Jacques Reynes, Laurent Siproudhis Catherine Tamalet, Pierre Tattevin
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Journal Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Year 2026
DOI
10.1093/cid/ciag477
URL
https://doi.org/10.1093/cid/ciag477
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