Anal High-Grade Squamous Intraepithelial Lesions in People Living with HIV: A Systematic Review of Treatment Outcomes

Background/Objectives: People living with HIV (PLWH) are at substantially increased risk of anal high-grade squamous intraepithelial lesions (HSIL), a recognized precursor of anal cancer. Although the ANCHOR trial demonstrated that treatment reduces progression to invasive disease, important uncertainties remain regarding durability of response, recurrence patterns, and treatment-related toxicity across available therapeutic strategies. Methods: We conducted a systematic review of studies evaluating treatment outcomes for anal HSIL published between 2000 and 2026. PubMed, Embase, and the Cochrane Library were searched according to PRISMA guidelines, with a particular focus on studies involving PLWH. Results: A total of 45 studies comprising 6093 patients, including five randomized controlled trials, met the inclusion criteria. Definitions of treatment response, recurrence, and adverse events varied considerably across studies, together with differences in assessment methods and follow-up, limiting direct comparisons between treatment modalities. Ablative, topical, and surgical approaches achieved variable short-term clearance; however, no modality demonstrated consistent durable disease control. Recurrence rates were high, frequently exceeding 50% in PLWH, consistent with the chronic and relapsing nature of HPV-driven disease in this population. Serious adverse events were uncommon, although treatment-related morbidity was frequent and varied across modalities. Conclusions: Randomized evidence supports treatment of biopsy-confirmed anal HSIL in PLWH for prevention of squamous cell carcinoma of the anus. However, comparative evidence remains limited by few randomized trials, heterogeneous study designs, and inconsistent outcome reporting. High recurrence rates and limited durability of response support the need for improved therapeutic strategies, biomarker-driven risk stratification, and longitudinal management approaches.