Efficacy and Safety of Anal High-Grade Squamous Intraepithelial Lesion Treatment Modalities: A Systematic Review

There is compelling evidence that treating high-grade squamous intraepithelial lesions (HSIL), the anal squamous cell cancer (ASCC) precursor, reduces the risk of developing ASCC. Using high-resolution anoscopy (HRA), surgical excision, ablative and topical therapies are widely used to treat HSIL.

With ASCC incidence increasing and new guidelines on screening high-risk patients, we sought to evaluate the efficacy and safety of HSIL treatment modalities.

EMBASE, MEDLINE, and Cochrane databases were searched for English-language, original studies specifically on HSIL or anal intraepithelial neoplasia (AIN) treatment from inception until December 31, 2025.

Two reviewers independently reviewed abstracts and full-text articles with a third reviewer for discrepancies. Studies were evaluated for efficacy, recurrence and safety.

Sixty-four original papers were evaluated, of which five were randomised controlled trials (two directly comparing different modalities). Numbers in each study and overall quality were low, and extensive heterogeneity existed in methodology. Side effects were common, but significant complications only occurred with surgical excision and photodynamic therapy.

There is insufficient evidence to clearly identify any gold standard HSIL treatment modality. Regardless of the modality, treatment overall is safe, but recurrence is high. Studies directly comparing modalities with standardisation of methodologies and outcome measures are required, especially in light of increasing incidence of ASCC and up-take of HRA.