Abstract 6414: Epigenetic signatures of oral HPV-related cancer risk in HIV-positive subjects from Puerto Rico

Abstract Background: Advances in antiretroviral therapy (ART) have not reduced the disproportional incidence and prevalence of oral Human Papillomavirus (HPV) and oropharyngeal cancers in people with HIV (PWH), suggesting ART alone may not fully restore immunity. While DNA methylation is an epigenetic marker strongly linked with aging and cancer, the putative role of epigenetic regulation in HPV-related cancers, particularly in PWH, remains scarce. Methods: We evaluated the methylation profiles from saliva of 16 sexually active PWH (9 HPV-, and 7 HPV+). Oral rinse samples were collected and analyzed for HPV infection and genotyped using the DNA ELISA kit HPV SPF10 and RHA kit HPV SPF10-LiPA25. We measured the genome-wide methylation levels using the Illumina Infinium Methylation BeadChip arrays. We performed enrichment and functional analyses of differentially methylated loci and genes with differential methylation using GREAT and Metascape, respectively. Physical and functional protein-protein interaction networks were constructed using STRINGdatabase. Results: We identified 521 loci with significant differences in the levels of DNA methylation (p<0.1). There was genome-wide hypermethylation in HPV+ participants. Differential methylation analysis associated to cis-regulatory elements showed that 136 loci were associated to one gene, and 381 loci were associated to two or more genes, while four loci were not associated to any genes. Functional analysis of gene-associated loci with differential methylation illustrated significantly impacted biological processes and pathways, including: regulation of G1/S transition of mitotic cell cycle, RAC1 GTPase cycle, oxidative stress response, MAPK cascade, among others (adjusted p<0.05). Additionally, physical and functional interaction networks showed H3C12 as a major hub with 8 interactions with other genes including EGF, RBFOX3, NTRK3, and SIN3B. Conclusion: We found a distinct methylation profile by HPV status associated with cancer-related genes, which may represent novel biomarkers of early identification for HPV-related cancers in PWH in Puerto Rico. Reprogramming DNA methylation patterns may be a safe way to identify, prevent, or treat HPV persistence. Citation Format: Jurelis Torres-Reyes, Mayra S. Haedo-Cruz, Juliana M. Serrano-Rodríguez, Jeannette L. Salgado-Montilla, Maria M. Sánchez-Vázquez, Magaly Martínez-Ferrer, Gabriel Borges-Velez, Josué Pérez-Santiago. Epigenetic signatures of oral HPV-related cancer risk in HIV-positive subjects from Puerto Rico [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 6414.