AbstractBackground:People with HIV (PWH) are disproportionately affected by Human papillomavirus (HPV), a major risk factor for oropharyngeal cancers. Additionally, PWH are more susceptible to acquiring opportunistic infections, such as Epstein-Barr Virus (EBV). EBV may lead to the development and progression of Burkitt’s and Hodgkin’s lymphoma and other types of cancers. HPV-related malignancies coupled with EBV infection have been associated with an increased risk of cervical cancer, however the relationship between EBV and HPV in in the oral cavity, particularly in PWH has not been investigated. In this study, we evaluated the prevalence of EBV in PWH and assessed their relationship with oral HPV infection due to their potential impact in immune suppression and oropharyngeal cancer development.Methods:Saliva samples, sociodemographic, and clinical data from 91 sexually active subjects (68 PWH and 23 people without HIV [PWOH]) from a community clinic in San Juan, Puerto Rico. We analyzed for oral HPV infection (34 HPV+ and 57 HPV-) and genotyped HPV using the DNA ELISA kit HPV SPF10 and RHA kit HPV SPF10-LiPA25 that detects 40 HPV subtypes. We quantified EBV levels in saliva using qPCR. Statistical analyses of levels of EBV were assessed in relation to HPV status using R-statistical software.Results:PWH had a median CD4 count of 791 cells/µL. The prevalences of EBV in PWH was 88% (60/68) vs in PWOH was 74% (17/23). In addition, the prevalence of EBV was higher in males than females (90% vs 63%). PWH with HPV had a 62% (21/34) of high-risk HPV genotypes, with HPV-18 being the most prevalent subtype 38% (8/21). Furthermore, EBV detectability had a trend with HPV status (p=0.07), especially in males with HPV showed higher detectability of EBV (p=0.002). In a multivariate model, EBV detectability was associated with biological sex after adjusting for HIV status and HPV status (p=0.004).Conclusions:Higher prevalence of EBV were observed in males than females. The trend observed between EBV detectability and HPV status, suggest a potential association between these viral infections, which could have implications for immune regulation in PWH. The high prevalence of HPV in PWH, and the association with EBV, particularly in males may indicated a need to underline the importance of HPV vaccination and regular screening in this population. We aim to increase the sample size to further validate the association of EBV and HPV in Puerto Rican PWH and include sociodemographic and lifestyle variable to investigate how socio-cultural characteristics may influence this association.Citation Format:Jurelis Torres-Reyes, Oscar A. Loperena-González, Jeyra L. Pérez-Lozada, Juliana M. Serrano-Rodríguez, Gabriel Borges-Vélez, María M. Sánchez-Vázquez, Magaly Martínez-Ferrer, Josué Pérez-Santiago. HPV and EBV coinfection in Puerto Rican people with HIV: insights into oropharyngeal cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7418.