Background HPV-mediated oropharyngeal cancers have shown improved oncologic outcomes compared to traditional head and neck squamous cell carcinoma (HNSCC). P16, a surrogate marker for HPV, is also overexpressed in non-oropharyngeal squamous cell carcinoma (non-OPSCC), but its clinical impact remains unclear. This study evaluates the effect of p16 status in non-OPSCC. Methods A retrospective chart review of non-OPSCC patients from January 2017 to November 2023 was conducted.