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Objectives The aim of the study was to estimate the cumulative incidence of, and rates of progression to, invasive anal cancer ( IAC) according to baseline anal cytology screening category in an unselected HIV clinical care cohort in the antiretroviral era. Methods A retrospective cohort analysis of HIV-infected patients under care at the University of California at San Diego Owen Clinic was carried out. Patients were eligible for this analysis if they had at least two anal cytohistological results available for longitudinal analysis. Kaplan− Meier analysis was used to estimate the cumulative incidence of IAC over time according to baseline cytology category [less than high-grade intraepithelial lesion ( HSIL) versus HSIL]. Cox regression analysis was used to adjust for the following covariates: antiretroviral use, level of HIV viraemia, smoking status and infrared photocoagulation ( IRC) ablation therapy. Results Between 2000 and 2012, we followed 2804 HIV-infected patients for a median of 4 years under a clinic protocol requiring baseline anal cytology screening. Incident IAC was diagnosed in 23 patients. Patients with a baseline HSIL anal cytology had an estimated 5-year probability of progression to IAC of 1.7% and an estimated annual progression risk of 1 in 263. None of the examined covariates was significantly associated with IAC incidence when examined in separate unadjusted Cox models. Conclusions HIV-infected patients with a baseline HSIL anal cytology had a 5-year cumulative incidence of IAC of 1.65%, with an upper 95% confidence bound of 4.5%. This population-based study provides quantitative risk estimates that may be used for counselling patients regarding management options for abnormal cytology results. [ABSTRACT FROM AUTHOR]