Abstract Background/Objectives: There has been a 225% increase in the incidence of oropharyngeal cancer, a sub-site of head and neck cancer, in the United States in the last three decades. This massive increase is largely associated with HPV, a sexually transmitted infection that peaks in prevalence among adolescents and young adults of college age. This study aimed at assessing sexual risk-taking behavior among university students, analyzing predictors of HPV vaccine initiation, as well as assessing levels of knowledge of the association between HPV and head and neck cancer. Methods: An anonymous online cross-sectional survey was distributed to 921 university students between the ages of 19-26 years. The survey elicited sociodemographic characteristics, HPV and HPV vaccine knowledge, and barriers and facilitators for vaccine initiation and completion. Results: Seven-hundred and forty-six students completed the survey; primarily female (68%), White (78%), and non-smokers (96%). Among participants, 61.7% have had vaginal sex and 70.7% oral sex. A greater number of participants have had multiple (4 or more) oral sexual partners than vaginal sexual partners (25.5% vs. 20.3%). Average age at first vaginal and oral sex onset were similar (18.41 vs. 17.80 years). Almost half of participants (49%) had completed all 3-doses of the HPV vaccine, and 60% had received at least one dose. Only 38% had a high knowledge of association between HPV and head and neck cancer. After adjusting for covariables, it was found that HPV knowledge was the main predictor of HPV vaccine initiation. Those with a higher level of knowledge of HPV were more likely to have initiated the vaccine (aOR = 1.04, 95% CI 1.00-1.08). Additionally, there were decreased odds of initiating HPV vaccine as age increased (aOR = 0.83, 95% CI 0.75-0.90); and participant single or dating (aOR 1.72, 95% CI 1.12-2.65) and not currently dating (aOR 1.91, 95% CI 1.22-2.99) had higher odds of initiating the vaccine than those in committed relationships, including marriage. Race was a significant predictor of knowledge of association between HPV and head and neck cancer. Non-White students were 2.25 times (95% CI: 1.14 – 4.45) more likely to have low knowledge compared to White students. Conclusions: Sexual risk-taking behavior associated with HPV infection is high among university students, while knowledge of the association between HPV and head and neck cancer is low. These findings provide impetus for developing specifically targeted interventions that serve to increase head and neck cancer knowledge, improve HPV vaccine education and uptake, and mitigate sexual risk-taking behaviors among college-aged students. Citation Format: Nosayaba Osazuwa-Peters, Kara M. Christopher, Christian Geneus, Rebecca Rohde, Ronald J. Walker, Mark A. Varvares. Assessing university students' sexual risk behavior, knowledge of the human papillomavirus, (HPV), HPV vaccine, and association between HPV and head and neck cancer. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B58.