P-436. Anal Pap Cytology for Anal Intraepithelial Neoplasia in Individuals under 45 Years of Age

Abstract Background Human Papilloma Virus (HPV)-related high-grade anal intraepithelial neoplasia (AIN) is the precursor of anal cancer. There are limited data identifying factors that influence AIN progression in adults eligible to HPV vaccines.Figure 1.Distribution of anal cytology and reference test results (n=488). (A) Anal cytology. (B) Reference testASCUS, atypical squamous cells of undetermined significance; LSIL, low grade squamous intraepithelial lesions; ASC-H, atypical squamous cells cannot exclude high-grade squamous intraepithelial lesions; HSIL, high-grade squamous intraepithelial lesions; SCCIS, squamous cell carcinoma in situ. Methods This retrospective study includes individuals followed at University of Pittsburgh Anal Dysplasia Clinic from 2020-2024. Inclusion criteria were ages 18-45 years as of 2020, all sexes/genders, people with HIV (PWH) or without, and at least one anal cytology paired with pathology (reference standard) or high-resolution anoscopy (HRA) appearance (reference standard if pathology unavailable). We used Logistic regression to evaluate factors associated with high-grade squamous intraepithelial lesion (HSIL) or squamous cell carcinoma in situ (SCCIS) on reference tests (designated as ref-HSIL here). The University of Pittsburgh IRB approved this study.Table 1.Baseline demographics. Results We included 239 individuals, with median age 37 years, 16% female, and 95 (40%) received at least one dose of HPV vaccine at initial median age of 26 years (Table 1). Of 191 PWH, 93% were virologically suppressed, with median CD4 count 748 cells/µl at initial visits (2020 or after), and median nadir CD4 count 360 cells/µl. Distribution of cytology and reference tests (149 from pathology and 339 from HRA) was shown in Figure 1. Anal cytology had low-moderate sensitivity (55%) and specificity (82%), but an acceptable negative predictive value of 96% for ref-HSIL. In full cohort, risk factors for ref-HSIL were ASC-H (atypical squamous cells, cannot exclude HSIL) or HSIL on cytology (adjusted odds ratio [aOR] 6.19, P< 0.001). In PWH, nadir CD4 count <200 cells/µl (aOR 4.08, P=0.008) was associated with ref-HSIL while viral suppression tended to be protective (Table 2). Seven individuals with initial non-ref-HSIL progressed to ref-HSIL. Nadir CD4 < 100 cells/µl (aOR 25.0, P=0.010) and current smoking (aOR 6.2, P=0.095, Table 3) showed a trend in association with progression.Table 2.Factors associated with HSIL or SCCIS on reference tests in PWH.Table 3.Factors associated with progression to HSIL/SCCIS. Conclusion In this cohort of adults ≤45 years, cytologic ASC-H or HSIL predicts ref-HSIL. In PWH, low nadir CD4 count is a risk factor for ref-HSIL, while viral suppression is protective. Low nadir CD4 count is also a risk factor for AIN progression to ref-HIL. Our study helps prioritize target individuals who need HRA the most. Disclosures All Authors: No reported disclosures