6565 Background: The sinonasal tract is a lesser known “hot spot” for the human papillomavirus (HPV), compared with the oropharynx. Additionally, unlike the oropharynx, the role of HPV tumor status in the survival and overall prognosis of the sinonasal tract and other non-oropharyngeal head and neck cancer sites remains inconclusive. Understanding differences in survival based on HPV status could be useful clinically, as it has been for HPV-positive oropharyngeal disease. This study examined whether there are survival differences in sinonasal cancer based on HPV status. Methods: This study included adult sinonasal cancer cases diagnosed between 2010 and 2015 in the National Cancer Database. A multivariable Cox proportional hazards model estimated the association between sinonasal cancer HPV status (HPV-positive, HPV-negative) and all-cause mortality while controlling for covariates (sex, age, race/ethnicity, insurance status, urban/rural, county-level household income, county-level percentage without high school diploma, comorbidity score, stage, histology, facility type, and treatment). A second multivariable proportional hazards model stratified HPV-positive tumor status by high-risk HPV (16, 18, 26, 31, 33, 35, 36, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 70, 73, 82, and 85) vs. low-risk HPV (6, 11, 32, 34, 40, 42, 44, 54, 61, 62, 64, 71, 72, 74, 81, 83, 84, 87, and 89) and compared their all-cause mortality to HPV-negative patients. Results: There were 1,750 sinonasal cancer patients included in this study, and 484 (27.7%) had HPV-positive disease. Among patients with HPV-positive disease, 75.6% had high-risk types. Mortality risk among all HPV-positive patients combined was 23% lower than HPV-negative patients (aHR = 0.77; 95% CI 0.64, 0.93). After stratifying by high-risk vs. low-risk HPV, high-risk HPV positive patients had 30% lower mortality risk than HPV-negative patients (aHR = 0.70; 95% CI 0.57, 0.88) while risk of mortality did not significantly differ between low-risk HPV-positive patients and HPV-negative sinonasal cancer patients. Conclusions: Sinonasal cancer shows differential survival based on HPV status, and sinonasal cancer patients positive for high-risk HPV had a significantly greater survival advantage than low-risk strains and those with HPV negative disease. HPV status might yet play a role in prognostication of sinonasal cancer, if future studies confirm these findings.