Disease Site‐Specific Outcomes in p 16‐Positive Non‐Oropharyngeal Mucosal Head and Neck Cancer

OBJECTIVES: To report disease-free survival (DFS) in p16-positive non-oropharyngeal head-and-neck squamous-cell carcinoma (HNSCC). METHODS: Curatively-treated non-oropharyngeal HNSCC (2009-2021) were reviewed. DFS was compared among p16-positive, p16-negative, and p16-untested cases for the overall cohort and by disease site. Multivariable analysis estimated adjusted hazard ratio (aHR) for p16-positivity. RESULTS: Among 3061 non-oropharyngeal HNSCC, 91 p16+, 375 p16-, 2595 untested; median follow-up 4.7 years. P16-positive patients had superior 5-year DFS versus p16-/untested (74% vs. 48%/59%; aHR 0.40 [0.26-0.61], p < 0.001). This advantage was evident in the larynx (86% vs. 52%/63%; aHR 0.26 [0.09-0.71], p = 0.005), hypopharynx (70% vs. 25%/37%; aHR 0.55 [0.10-0.50], p < 0.001), and nasal cavity (82% vs. 38%/66%; aHR 0.31 [0.11-0.88], p = 0.028). No significant DFS differences were seen in paranasal sinus (40% vs. 64%/41%; p = 0.39) or oral cavity (50% vs. 57%/58%; p = 0.94). CONCLUSION: p16-positivity confers a DFS benefit in larynx/hypopharynx/nasal cavity, but not in paranasal sinus or oral SCC.