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.

Authors

Isabelle Etienney, Deependra Singh, Emmanuelle Ressiot, Jean-Michel Didelot, Sylvie Radenne, Olivia Zaegel-Faucher, Anne-Carole Lesage, Laurent Siproudhis, Cedric Arvieux, Lionel Piroth, Isabelle Heard, Gilles Pialoux, Fatoumata Coulibaly, Nadia Hoyeau, Sebastien Henno, Catharina J Alberts, Timo J Ter Braak, Renske D M Steenbergen, Jean-Damien Combes, Gary M Clifford, ANRS-EP57-APACHES study group

Published in

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. Aug 14, 2026. Epub Aug 14, 2026.

Abstract

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.
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.
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.
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.

PMID:
42600099
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.