Background: Oropharyngeal cancer patients with Human Papillomavirus (HPV)-associated disease have more favorable outcomes. HPV16 is the primary genotype in this population. Our knowledge of the impact of high-risk non-16 HPV (HRN16) subtypes on survival is limited. The objective of this study is to investigate the incidence, demographics, and survival outcomes of HRN16 genotypes in patients with HPV-positive head and neck squamous cell carcinoma (HNSCC). Methods: This is a retrospective chart review of patients diagnosed with HPV+ HNSCC from 2012-2021 at the Mount Sinai Health System. Genotyping was performed with polymerase chain reaction (PCR). Demographic, clinical and tumor data was extracted from electronic medical records.The primary outcomes are overall survival (OS) and event-free survival (EFS) for patients with non-metastatic disease at presentation, treated with curative-intent, with > 6 months follow-up.Survival analysis was performed by Kaplan-Meier method. Results: 733 patients had HPV+ HNSCC, and 109 (14.9%) are HRN16 subtypes. Mean age at diagnosis is 62.4 years. Most individuals are non-Hispanic white males, non-active smokers, social drinkers, and have good performance status (Table). A majority has non-metastatic oropharyngeal cancer treated with standard of care (SOC) definitive therapy. The predominate genotypes are HPV35 (39.4%, n = 41), HPV33 (27.9%, n = 29), and HPV18 (14.4%, n = 15). Survival analysis demonstrated no significant differences in OS (log-rank p = 0.90) and EFS (log-rank p = 0.19) among the different HRN16 subtypes. There was a trend for better EFS for HPV35. Conclusions: HRN16 genotype may not meaningfully impact patient outcomes in HNSCC. Larger multivariate analyses may identify specific site and genotype differences in survival comparedwith HPV16-assoicated disease and indicate if patients with selected HRN16 subtypes are candidates for treatment de-escalation.