p16 status, pathologic and clinical characteristics, biomolecular signature, and long-term outcomes in head and neck squamous cell carcinomas of unknown primary.

The purpose of this study was to report associations between p16 status, clinicopathologic characteristics, and outcomes for head and neck squamous cell carcinoma of unknown primary (CUP). Specimens of squamous cell CUP were reanalyzed. Human papillomavirus (HPV) status was determined by p16 stain. A tissue microarray (TMA) was constructed to evaluate biomarkers potentially prognostic in head and neck squamous cell carcinoma (HNSCC). A majority of the population (n = 26; 74%) was p16 positive (+). Prognostic factors benefiting survival were p16+ status (p < .0001), absence of macroscopic extracapsular extension (ECE; p = .004), younger age (p = .01), and higher grade (p = 0.007). The prognostic implication of worse overall survival (OS) with macroscopic ECE (p = .009) remained significant when limited to patients who were p16+ (p = .002). Exploratory TMA between unknown primary and controls suggested a biomolecular difference between squamous cell CUP and known-primary cancer. The majority of patients with squamous cell CUP were p16+, indicative of HPV association. P16 staining and ECE seem to be the most prognostic features in squamous cell CUP.