Adverse Effects of Treatments for Anogenital Warts in Non-immunocompromised Adults: A Network Meta-analysis of...

International guidelines for the management of anogenital warts (AGWs) propose multiple first-line options but do not prioritize treatments based on safety or tolerability. This study aimed to compare the safety profiles of topical, systemic, and ablative treatments used for external AGWs in immunocompetent adults.

A systematic review and frequentist network meta-analysis of randomized controlled trials published through August 2025 was performed. Adverse events (AEs) were classified as low-, moderate-, or high-grade local AEs (LGL, MGL, HGL) and low-grade general AEs (LGG). Relative risks were estimated using random-effects models with placebo as the reference.

We included 107 RCTs involving 12,423 participants. Ablative procedures were associated with higher rates of moderate-to-severe local AEs compared with topical therapies. Among topical treatments, imiquimod 5% and cidofovir cream were associated with lower rates of severe AEs, whereas podophyllotoxin was more often associated with LGL. SUCRA rankings placed topical treatments above ablative therapies in terms of tolerability. Cidofovir cream demonstrated the best safety profile, followed by imiquimod 5%.

This network meta-analysis highlights significant differences in tolerability across AGW treatments and offers a comparative framework for patient-centered therapeutic decision-making. It also emphasizes the need for standardized AE reporting in future trials.