Impact of p16 expression, nodal status, and smoking on oncologic outcomes of patients with head and neck unknown primary squamous cell carcinoma

BACKGROUND: The prognostic significance of human papillomavirus (HPV) in the context of head and neck squamous cell carcinoma (HNSCC) of cancer of unknown primary (CUP) origin is unclear. METHODS: Patients treated for CUP at the Princess Margaret Cancer Centre between 2001 and 2013 were stratified by p16 status and retrospectively reviewed. RESULTS: Of the 73 patients included, those with p16-positive tumors (63%) had less advanced nodal status (N1-N2b; 52% vs 89%; p = .035) and less aggressive treatment. Patients with p16-positive tumors had improved 3-year disease-free survival (DFS; 79% vs 56%; p = .012) independent of nodal status and treatment in multivariable analysis (hazard ratio [HR] = 0.27; 95% confidence interval [CI] = 0.08-0.95). CONCLUSION: Among patients with CUP, p16-positive status is an independent predictor of DFS but not overall survival (OS).