National Analysis of Over 48,000 Veterans With HIV Demonstrates CD4/CD8 Ratio as a Risk Marker for Anal Intraepithelial Lesions and Anal Cancer

Austin Hewitt; Matthew J Freeman; Glen Leverson; Howard H Bailey; Evie Carchman; Rob Striker; Cristina B Sanger

doi:10.1097/DCR.0000000000003611

National Analysis of Over 48,000 Veterans With HIV Demonstrates CD4/CD8 Ratio as a Risk Marker for Anal Intraepithelial Lesions and Anal Cancer

Dis Colon Rectum. 2025 Jan 2. doi: 10.1097/DCR.0000000000003611. Online ahead of print.

Authors

Austin Hewitt¹, Matthew J Freeman¹, Glen Leverson¹, Howard H Bailey^{2

3}, Evie Carchman^{1

3

4}, Rob Striker², Cristina B Sanger^{1

4}

Affiliations

¹ Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
² Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
³ University of Wisconsin Carbone Cancer Center, Madison, Wisconsin.
⁴ Department of Surgery, William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin.

PMID: 39745282
DOI: 10.1097/DCR.0000000000003611

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 1999-2023.

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 prior to the study period.

Main outcomes and measures: Primary outcomes include the prevalence, disease-free survival rates, and hazard ratios associated with risk factors for developing anal squamous intraepithelial lesions and/or anal cancer.

Results: 48,368 patients were analyzed. The average age of patients at study initiation was 47.8 years with a mean follow-up of 12.3 years. 7,572 (16%) patients had at least one anal cytopathology or histopathology result. Prevalence of anal disease was recorded for low-grade disease (n = 1,513, 3.1%), high-grade disease (n = 1,484, 3.1%), and cancer (n = 664, 1.4%). Mean times to first incident low-grade disease, high-grade disease, and cancer were 8.5 (SD = 6.0), 9.1 (SD = 6.0), and 9.7 (SD = 6.2) years, respectively. 5-year, 10-year, and 20-year disease-free survival rates for development of low-grade disease, high-grade disease, or cancer were 97.5%, 94.5%, and 88.4%, respectively. Cox regression modeling demonstrated CD4/CD8 ratios <0.5 were associated with increased risk of anal cancer (HR: 3.93, 95% CI: 3.33-4.63, p < 0.001).

Limitations: Retrospective study that focuses almost exclusively on male U.S. veterans. Results might not apply to non-male, non-U.S. populations.

Conclusions: National analysis of over 48,000 veterans with HIV demonstrates 16% had anal cytopathology or histopathology results with an anal cancer prevalence of 1.4%. CD4/CD8 ratios <0.5 correlate strongly with severity of anal disease and can help identify patients at highest risk for anal cancer to prioritize screening efforts. See Video Abstract.