National analysis of more than 48,000 Veterans with human immunodeficiency virus demonstrates CD4/CD8 ratio as a risk marker for anal intraepithelial lesions and anal cancer

Abstract: Background: Anal squamous intraepithelial lesions are identifiable and treatable precancerous lesions that lack defined risk factors determining screening necessity. Objective: Assess the prevalence and risk factors associated with low- and high-grade anal squamous intraepithelial lesions and anal squamous-cell carcinoma. Design: Retrospective cohort analysis of veterans with HIV between 1999 and 2023. Settings: National multicenter study of the Department of Veterans Affairs. Patients: Veterans with HIV who had >1 year of follow-up and no anal squamous intraepithelial lesions or anal cancer diagnosis before the study period. Main outcome measures: Primary outcomes include the prevalence, disease-free survival rates, and HRs associated with risk factors for developing anal squamous intraepithelial lesions and/or anal cancer. Results: A total of 48,368 patients were analyzed. The mean age of patients at study initiation was 47.8 years, with a mean follow-up of 12.3 years. Seven thousand five hundred seventy-two patients (16%) had at least 1 anal cytopathology or histopathology result. The prevalence of anal disease was recorded for low-grade disease (n = 1513; 3.1%), high-grade disease (n = 1484; 3.1%), and cancer (n = 664; 1.4%). Mean (SD) times to first incident low-grade disease, high-grade disease, and cancer were 8.5 (6.0), 9.1 (6.0), and 9.7 (6.2) years, respectively. Five-year, 10-year, and 20-year disease-free survival rates for the development of low-grade disease, high-grade disease, or cancer were 97.5%, 94.5%, and 88.4%, respectively. Cox regression modeling demonstrated that CD4/CD8 ratios of <0.5 were associated with an increased risk of anal cancer (HR, 3.93; 95% CI, 3.33-4.63; p < 0.001). Limitations: Retrospective study that focused almost exclusively on male US veterans. Results might not apply to non-male, non-US populations. Conclusions: National analysis of more than 48,000 veterans with HIV demonstrates that 16% had anal cytopathology or histopathology results with an anal cancer prevalence of 1.4%. CD4/CD8 ratios of <0.5 correlate strongly with the severity of anal disease and can help identify patients at the highest risk for anal cancer to prioritize screening efforts.

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