Risk of Anal Cancer Following Benign Anal Disease and Anal Cancer Precursor Lesions: A Danish Nationwide Cohort Study

Background: Human papillomavirus (HPV) is associated with the majority of anal high-grade intraepithelial neoplasia (AIN) and anal cancers. Little is known about the risk of anal cancer following a diagnosis of benign anal disease and AIN. Methods: Using data from nationwide, population-based Danish registries, a cohort of 126,174 individuals with either non-neoplastic anal disease or AIN 1 to 3 during 1970 to 2016 was followed until first occasion of anal cancer. Information on HIV status was obtained from the Danish HIV Cohort Study. The absolute risk of anal cancer was estimated using the Aalen-Johansen estimator taking into account censoring at emigration and end of follow-up and competing risk at time of death. Standardized incidence ratios (SIR) for anal cancer among individuals with non-neoplastic anal disease, including inflammatory lesions, hemorrhoids, and polyps, were estimated in Poisson models. Sex-, age-, and calendar period-specific national population rates were estimated using the Danish National Pathology Registry. Results: Anal cancer risk increased with increasing severity of lesions, reaching 4% 5 years after diagnosis of AIN3. Even among those with non-neoplastic anal lesions, particularly inflammatory lesions, anal cancer risk was significantly higher than expected from Danish national anal cancer rates (SIR = 2.8; 95% confidence intervals, 2.3-3.2). The absolute 5-year risk of anal cancer following AIN3 was considerably higher among HIV-positive (14.1%) than HIV-negative (3.2%) individuals. Conclusions: Anal cancer risk increases with increasing severity of lesions and is especially high among HIV-positive individuals. Impact: Vaccination against HPV is important in the prevention of both high-grade AIN and anal cancer.