Introduction: Anal cancer is increasing in the general population of Puerto Rico. Anal cytology is currently the standardized method for screening among populations at higher risk for developing anal high-grade squamous intraepithelial lesions (HSIL), the precursor lesion of anal cancer. However, studies have shown that anal cytology alone underestimates the anal lesion grade compared to the gold standard test, high-resolution anoscopy (HRA). While studies with both anal histology and cytology confirmed results are limited, the validity of cytology as a screening test seems to improve with more extensive HSILs. We evaluated the validity of anal cytology in detecting HSIL overall and by anal HSIL extension in a clinic-based Hispanic population. Methods: Data from baseline visits and examination from October 2014 to April 2021 of the Anal Neoplasia Clinic at the University of Puerto Rico Comprehensive Cancer Center were analyzed. Individuals who attended the clinic were eligible if they had completed anal cytology testing, HR-HPV typing, and HRA with biopsy. During the baseline visit basic demographic and clinical characteristics were collected. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were estimated by comparing anal cytology results with biopsy results from HRA, overall and by extent of histologically confirmed HSIL, defined as number of octants in the anal canal affected by HSIL (1 vs 2+). Results: Among 431 patients, 67.5% were male and the mean age was 43.57 +/- 13.27 years. Overall, 75.2% were living with HIV and 76.8% tested positive for HR-HPV. Persons diagnosed with any type of squamous intraepithelial lesion (SIL) via anal cytology and histology were 71.46% and 84.22%, respectively. In contrast, while anal HSIL was detected in only 2.09% of individuals through anal cytology, it was detected in 40.37% through biopsy-confirmed histology samples. The overall sensitivity of anal cytology compared to histology was 83.9% (95% CI: 77.6%-89%), whereas the specificity was 37% (95% CI: 31%-43.2%). Among persons with biopsy-confirmed HSIL, when comparing anal cytology to histology by HSIL extension (1 vs. 2+ octants affected) the sensitivity remained similar for both groups (83.7% vs. 84.1%), while specificity was the same with 37%. While the PPV decreased with HSIL extension (32.2% vs. 29.9%) and the NPV increased (86.4% vs. 88.0%), these indicators act as poor predictors of disease status in both groups. Conclusion: In this Hispanic population, anal cytology underestimates biopsy-confirmed HSIL and its performance in detected anal HSIL did not improve with HSIL extension. While future studies with larger sample sizes are needed to further validate research findings, this study emphasizes the need to continue to optimize anal cancer screening methods in high-risk populations. Determining the best way to detect and treat cellular abnormalities will help prevent further disease progression and anal cancer development. AMC-NCI Grant #'s: UM1CA121947, 2U54CA096297-17, R25CA240120.

Citation Format: Kandyce G. Keller, Jeslie M. Ramos-Cartagena, MS, Humberto M. Guiot, Cristina Munoz, Yolanda Rodriguez, Vivian Colon-Lopez, Ashish A. Deshmukh, Maribel Tirado-Gomez, Ana Patricia Ortiz. Assessment of the performance of anal cytology as a screening tool for anal high-grade squamous intraepithelial lesions by extent of disease in a clinic-based sample in Puerto Rico [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-254.