Abstract 4110: Non-classical HLA epigenetic biomarkers associated with concordant cervical and oral HPV infection

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Background: Human papillomavirus (HPV) is prevalent in mucocutaneous surfaces, with the persistence of infections causing approximately 5% of human cancers. While HPV presence at one site increases the risk at others and, possibly, increases the risk of cancer(s) in other anatomical sites, this risk varies among individuals despite similar sexual behaviors. Identifying women with high-risk cervical HPV who are also at risk for high-risk oral HPV could help reduce HPV-associated cancers. This study aims to identify methylation biomarkers explaining the risk of concordant high-risk oral HPV in women with cervical high-risk HPV infections. Methods: As part of the Sexual Behavior and HPV Infections in Nigerians in Ibadan study, we conducted a cross-sectional analysis of sexually active women aged 18-45 years in Ibadan, Nigeria. Participants had interviews and clinical examinations and provided oral rinse and cervical swab samples. DNA was extracted and genotyped for HPV using the Anyplex™ II HPV28 assay. An epigenome-wide association study compared DNA methylation patterns between women with high-risk HPV types 16, 18, or 35 detected in both oral and cervical samples (concordant group) and those with high-risk HPV only in cervical samples (control group), matched by age, sexual behaviors, and lifestyle factors. Genome-wide DNA methylation profiling was performed on both sample types (total n=32) using the Infinium Methylation EPIC v2.0 BeadChip. Results: We identified 61 differentially methylated CpG sites in the concordant group, with consistent associations in both cervical and oral samples (Pearson's r = 0.91, p<0.001). Notably, cg11201654 in the promoter region of a non-classical human leukocyte antigen (HLA) gene, HLA-F, was one of the top significant CpGs and showed approximately two-fold hypermethylation in the concordant group in cervical (p = 0.00080) and oral samples (p = 0.00005). Similarly, cg27020253 in the promoter of another non-classical HLA gene, HLA-L, exhibited ∼1.7-fold hypermethylation in both cervical (p = 0.00039) and oral samples (p = 0.00025). These epigenetic modifications suggest that HPV may facilitate immune evasion and persistent infection by suppressing non-classical HLA genes, which are known for modulating immune responses through interactions with natural killer cells. Conclusion: Hypermethylation of non-classical HLA genes may serve as novel biomarkers for identifying women at elevated risk for persistent high-risk HPV infections and related malignancies, offering insights into HPV-mediated immune evasion mechanisms. The consistent methylation patterns across oral and cervical tissues highlight the capacity of HPV to broadly influence host gene regulation. These epigenetic biomarkers could have applications in broader contexts of immunogenetics and cancer risk prediction, potentially refining the stratification of high-risk women. Citation Format: Yinan Zheng, Imran Morhason-Bello, Yishu Qu, Jun Wang, Adeola Fowotade, Adekunle Daniel, Akinyele Adisa, Olutosin Awolude, John Ogunbiyi, Miquel Pavon, Robert Murphy, Isaac Adewole, Deborah Watson-Jones, Lifang Hou. Non-classical HLA epigenetic biomarkers associated with concordant cervical and oral HPV infection [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 4110.

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