Adverse Events Associated With Treatment for Anal High-Grade Squamous Intraepithelial Lesions: A Systematic Review

To systematically review the type, severity, frequency, and reporting quality of adverse events (AEs) associated with treatment of anal high-grade squamous intraepithelial lesions (HSIL) to inform guideline development, clinical decision-making, and future research priorities, and improve patient-centered outcome assessment.

We searched Medline, Embase, Cochrane Library, and CINAHL databases for publications to October 11, 2024. Studies were included if reporting data on AEs relating to anal HSIL treatment. Study quality was assessed using an adapted Newcastle-Ottawa Scale. Data were extracted on study characteristics, treatment protocols, and AEs.

Forty-two studies were included, of which 8 were high quality, 24 moderate quality, and 10 low quality. Most studies were conducted in men living with HIV and evaluated single-treatment modalities. There was considerable heterogeneity in AE definitions and data collection, precluding meta-analysis. Pain and bleeding were the most commonly reported AEs across all modalities. Ablative treatments were most frequently associated with pain (reported in 80% of studies), with radiofrequency ablation showing particularly high reported rates of bleeding (>80%). Topical treatments universally caused anal discomfort, with marked variation in terminology. Only 14 studies used a structured AE collection tool, and only 2 used validated instruments. The ANCHOR study reported fewer AEs than other studies.

AE reporting in anal HSIL treatment studies is inconsistent and poorly standardized. Validated definitions, structured reporting tools, and core outcome sets are urgently needed. Future studies should standardize treatment protocols, improve AE monitoring, and prioritize large comparative randomized controlled trials to guide clinical practice and shared decision-making.