QS208 - A Comparison of Anal Cancer Risk Among Veterans with HIV Who Undergo Initial Anal Evaluations With Screening Versus Diagnostic Assessments

Purpose/Background: Anal squamous cell carcinoma (ASCC) disproportionately affects specific populations, such as people with HIV (PWH). As the largest integrated healthcare system in the U.S. and a national leader in HIV care, the Department of Veterans Affairs (VA) is an ideal setting for studying ASCC in PWH. Detection of ASCC can occur in different ways, including as part of a routine screening algorithm or after a symptomatic clinical presentation. Initial pathologic assessment performed in these situations typically differs wherein screening protocols generally involve cytologic evaluations (anal Pap smears) while patients with symptomatic complaints often receive histologic evaluations without a preceding Pap test. The primary objective of this study is to compare the risk of ASCC development between PWH who undergo initial anal pathologic evaluations via screening assessments with cytopathology versus diagnostic assessments with histopathology.

Methods/Interventions: This is a national retrospective cohort analysis of veterans with HIV between 1999-2023. We divided patients into two groups based on their first-ever VA anal pathology evaluation: 1) assessment with cytopathology and 2) assessment with histopathology. We identified ASCC cases by analyzing anal cytopathology and histopathology reports. Kaplan-Meier methods were used to estimate rates of ASCC-free survival from time of first-ever anal pathology result, censoring on loss to follow-up and death. ASCC-free survival rates were determined at 5, 10, and 15 years and compared using the log-rank test. We evaluated factors associated with ASCC development using Cox proportional hazards models. As a sensitivity analysis, we repeated our survival analyses after removing patients with ASCC within 6 months of their first-ever anal pathology result.

Results/Outcomes: 7,127 veterans with HIV that had at least one anal pathology result were included for analysis. The majority were male (98%) with a mean age of 52 years and follow-up of 8 years. First-ever anal pathologic assessments were cytopathology in 4,477 (63%) and histopathology in 2,650 (37%). We identified 455 patients with ASCC, and the average time to ASCC from initial pathology result was 1.7 years. 5-, 10-, and 15-year ASCC-free survival rates for the cytopathology and histopathology groups were 98.9%, 98.1%, 97.3%, and 86.6%, 84.6%, 83.2% (p < 0.001), respectively. Cox regression showed an increased risk of ASCC in the histopathology group (HR 8.74, 95% CI; 6.66-11.47, p< 0.001) (Fig 1). After removing patients (n=311, 68% of all ASCC) for the sensitivity analysis, 6,816 patients remained. The average time to ASCC was 5.4 years and initial pathologic evaluations were cytopathology in 4,456 (65%) and histopathology in 2,360 (35%). ASCC free-survival rates for the cytopathology and histopathology groups were 99.4%, 98.6%, 97.8%, and 97.2%, 95.0%, 93.4% (p < 0.001), respectively. Cox regression showed an increased risk of ASCC in the histopathology group (HR 2.0, 95% CI: 1.38-3.12, p< 0.001) (Fig 2).

Conclusion/Discussion: In this national analysis of veterans with HIV, 6.4% of veterans with anal pathology results were diagnosed with ASCC. About two-thirds (68%) of ASCC diagnoses were made < 6 months after first-ever anal pathology evaluations. There was an increased risk of ASCC among patients whose initial anal evaluation was histology rather than screening cytology. In patients diagnosed with ASCC >6 months after their initial anal pathology result, those whose initial test was a screening Pap had a longer ASCC-free survival.

Figure 1.
A) Kaplan-Meier curve of time to development of anal cancer. B) Multivariable Cox regression model for risk factors associated with development of anal cancer.

Figure 2.
A) Kaplan-Meier curve of time to development of anal cancer (patients with cancer <6 months after their first anal pathology evaluation removed). B) Multivariable Cox regression model for risk factors associated with development of anal cancer (patients with cancer <6 months after their first anal pathology evaluation removed).