Background: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States, with nearly 80% of the population infected at some point in their lifetime. HPV is the cause of approximately 70% of oropharyngeal cancers (OPC). Methods: Chapter 1 utilized data from the Health Information National Trends Survey 5, cycles 1-3; logistic regression analyses examined differences in HPV-related oral cancer knowledge between sexual minorities and their heterosexual counterparts. Chapter 2 utilized electronic health record data of patients without prior history of HPV vaccination. Logistic regression modeling, guided by the Andersen Behavioral Model, examined associations between predisposing, enabling, and need factors with HPV vaccine initiation. Chapter 3 utilized survey data from medical and dental providers that assessed attitudes regarding HPV-related OPC patient engagement. Guided by the Theory of Planned Behavior, HPV- related OPC responses were compared between medical and dental providers using chi- square tests and linear regression analyses. Results: In Chapter 1, HPV-related oral cancer knowledge overall was low and there were no significant differences in knowledge for sexual minority men or women compared to heterosexual counterparts. In Chapter 2, HPV vaccine initiation rates overall, were relatively low (20%). For males, minority sexual orientation (OR:1.75; 95% CI:1.20-2.55) and HIV+ status (OR:2.63; 95% CI:1.16-5.97) were associated with greater odds of HPV vaccine initiation; as age increased, odds of HPV vaccine initiation decreased (OR:0.74; 95% CI:0.66-0.84). For females, non-White race (OR:1.26; 95% CI:1.04-1.53), having a nurse practitioner/physician assistant as a provider (OR:1.33; 95% CI:1.08-1.65), and more frequent utilization (OR:1.54; 95% CI:1.31-1.80) were associated with greater odds of HPV vaccine initiation. In Chapter 3, regression analysis indicated dental providers had higher levels of agreement related to perceived behavioral control (greater confidence/feeling adequately trained to engage patients) compared to medical providers (p<0.001). Conclusion: Findings showed HPV-related OPC knowledge and HPV vaccine initiation were low and providers reported lack of adequate training/confidence in HPV-related OPC patient engagement. Action should be taken to increase HPV-related OPC knowledge for vulnerable populations, promote HPV vaccination while considering behavioral risk profiles, and provide continuing education opportunities for providers to improve confidence regarding HPV-related OPC patient engagement.