Anal High-Grade Squamous Intraepithelial Lesions (HSIL): BJS | March 2026

Introduction:

Anal squamous cell carcinoma is an increasingly common but largely preventable cancer. Most cases arise from persistent high-risk human papillomavirus (HPV) infection, progressing through high-grade squamous intraepithelial lesions (HSIL). This comprehensive review summarizes the current approach to screening, diagnosis, classification, and management of anal HSIL.

Why was this review needed?

• The incidence of anal cancer is steadily increasing worldwide.
• High-risk groups can now be clearly identified for targeted screening.
• Classification and management of anal dysplasia have evolved considerably.
• High-resolution anoscopy (HRA) has become the cornerstone for diagnosis and treatment.
• Recent evidence supports active treatment of HSIL to prevent anal cancer.

Key Takeaways:

• Persistent high-risk HPV (especially HPV-16 and HPV-18) is the principal cause of anal HSIL and anal squamous cell carcinoma.
• High-risk populations include people living with HIV, immunosuppressed patients, men who have sex with men, and transplant recipients.
• Low-grade squamous intraepithelial lesions (LSIL) often regress spontaneously, whereas HSIL carries a substantial risk of progression and warrants treatment.
• Screening high-risk individuals enables early detection and significantly reduces the risk of invasive anal cancer.
• High-resolution anoscopy (HRA) is the preferred diagnostic technique, allowing accurate identification, biopsy, and treatment of precancerous lesions.
• Treatment of HSIL is now recommended because it has been shown to reduce progression to invasive anal cancer.
• HPV vaccination is expected to substantially reduce the future burden of anal cancer but will not eliminate disease in currently at-risk adults.
• Artificial intelligence has the potential to improve HRA interpretation, increase diagnostic accuracy, and shorten the learning curve for clinicians.

Clinical Impact:

Anal cancer is increasingly viewed as a preventable malignancy. Targeted screening of high-risk populations, timely treatment of HSIL, wider HPV vaccination, and expanding access to high-resolution anoscopy have the potential to dramatically reduce anal cancer incidence over the coming decades.

Bottom Line:

Anal HSIL is a treatable precancerous condition. Early identification using high-resolution anoscopy, combined with timely treatment and HPV vaccination, represents the most effective strategy for preventing anal squamous cell carcinoma.