Madeleine, Margaret MMcWhorter, Mary Elizabeth2019-02-222019-02-222018McWhorter_washington_0250O_19504.pdfhttp://hdl.handle.net/1773/43396Thesis (Master's)--University of Washington, 2018HPV is related to ~70% of in situ and invasive vulvar cancers, ~80% of those HPV positive cases of associated with HPV16. Numerous studies in cervical cancer have shown that the major histocompatibility complex (MHC) genes influence the risk of disease, specifically human leukocyte antigen genes on chromosome 6. We examined associations between single and multiple co-occurring class I A, B, and C genes and class II DRB1 and DQB1 genes relative risk of HPV16-related in situ and invasive vulvar cancer (VSCC16). Cases and controls were self-identified white women residing in the greater Seattle, WA, area. We performed high-resolution HLA typing on peripheral blood samples from 238 VSCC16 women and 637 population-based control women, and HPV genotyping on FFPE biopsies from tumor tissue. Using logistic regression, we first assessed the relative risk of VSCC16 associated with HLA, then compared the results with our previously published associations between HPV16 cervical cancer cases (CXSCC16). Among 352 co-occurring allele combinations present in ≥ 5% in the case or control groups, 178 were significantly associated with VSCC16 risk. Three very strong trends stood out: 1) B*44:02 and B*44:03 were noted in various combinations to have significantly increased relative risk of VSCC16 results, particularly seen with B*44:02, DRB1*11:01, and DQB1*03:01 (OR 5.0, 95% CI 2.0-12.7). 2) When B*07:02, C*07:02 co-occur with DQB1*03:01 there was significantly increased risk of VSCC16, such as A*02:01, B*07:02, C*07:02, DRB1*11:01, DQB1*03:01 (OR 6.4, 95% CI 2.2-18.4). 3) A*01:01, B*08:01, C*07:01, DRB1*03:01, DQB1*02:01 showed significant decreased risk among VSCC16 samples (OR 0.6, 95% CI 0.4-1.0). Interestingly, there was a much larger number of significant associations with VSCC16 results than with CXSCC16, suggesting that the immune response is more important in the etiology of VSCC16. Overall, the data suggests that CD4 and CD8 T cell responses are important cofactors with HPV in HPV-related cancers. Significant co-occurring HLA alleles shared between vulvar and cervical case samples may be markers for disease risk and have future clinical value for targeted screening or new therapies.application/pdfen-USnonePublic healthHealth servicesThesis