OBJECTIVE: Sinonasal squamous cell carcinoma (SNSCC) is rare in the general population. No clear and consistent etiologic correlation between human papillomavirus (HPV) and SNSCC has yet been delineated in the literature. p16 is a tumor suppressor protein used as a surrogate marker for HPV. This study aims to evaluate the relationship between p16 overexpression in SNSCC and its role in prognosis and survival. METHODS: A population-based retrospective analysis was performed using prospectively collected data from the Northern Alberta Head and Neck Tumour Board, the Alberta Cancer Registry, and the Alberta Cancer Research Biobank. p16 overexpression was analyzed from pathologic samples of patients meeting study criteria, and participants were dichotomized by status. Subsequently, nonparametric analysis of demographics, initial staging, and initial treatment were performed, and a Kapan-Meier curve was developed to assess differences in survival. RESULTS: Sixteen patients were included in the analysis. p16 overexpression was seen in 68.8% of patients. p16 positive and negative groups were comparable for age, gender, smoking status, stage, and treatment. A statistically significant 5-year survival advantage was observed in patients with p16 positive SNSCC ( CONCLUSIONS: This is the first Canadian study to demonstrate a high prevalence of p16 positivity in SNSCC and its presence denoting a statistically significant survival advantage. Results demonstrate a previously unconfirmed role of oncogenic HPV in SNSCC.