e18214 Background: HPV association remains one of the most important predictors of clinical outcome in SCCHN. We aimed to determine whether the relationship between HPV status and overall survival (OS) varied by certain socioeconomic factors. Methods: Data were obtained from the National Cancer Database (NCDB). We examined the relationship between OS and HPV status, controlling for demographics and socioeconomic variables (insurance, income, education, urban/rural, great circle distance, and/or distance to treatment facility of 0-10, 10-50, and > 50 miles). Results: HPV status modified the relationship between insurance status (p = 0.011), urban/rural residence (p = 0.041), and overall survival, controlling for age, race, sex, and clinical stage. Whereas for HPV- patients, government insurance conferred a lower risk of death compared to no insurance (HR: 0.86, 95% CI: 0.75-0.99, p = 0.038); this finding did not hold for patients with HPV related disease (HR: 0.97, 95% CI: 0.80-1.18, p = 0.781). For patients with HPV related SCCHN, those living in rural areas have significantly higher risk of death compared to those living in metro areas (HR: 1.55, 95% CI: 1.17-2.05, p = 0.002), which did not hold for patients with HPV unrelated SCCHN (HR: 0.94, 95% CI: 0.68-1.30, p = 0.703). Conclusions: Despite HPV’s prospective prognostication, patients with HPV + SCCHN who live in rural environments have a higher risk of death likely from lack of physical access to care. This finding did not hold for HPV negative population, presumably because of their worse outcomes at baseline, and their struggle for access to care regardless of physical location.