Tian S, et al. - Researchers used a large database approach to assess the impact of high-risk human papillomavirus (HPV) status on overall survival (OS) in patients with non-oropharyngeal (OPX) squamous cell cancer (SCC). They searched the National Cancer Data Base for patients who received their diagnoses of SCC of the OPX, hypopharynx (HPX), larynx, and oral cavity (OC) with known HPV status from 2004 through 2014. A total of 24,740 diagnosed patients were analyzed between 2010 and 2013: 1,085 HPX patients, 4,804 laryngeal patients, 4,018 OC patients, and 14,833 OPX SCC patients. The percentages of HPV-positive cases were 17.7% for HPX, 11% for larynx, 10.6% for OC, and 62.9% for OPX. In multiple unadjusted and propensity-adjusted non-OPX populations, HPV status was found to be prognostic. In multiple populations of patients with non-OPX head and neck disease (HPX, locally advanced larynx, and OC), positive high-risk HPV status seems to be linked to longer OS. These findings may have implications for risk stratification upon prospective validation.