Human Papillomavirus in Metastatic Lymph Nodes from Unknown Primary Head and Neck Squamous Cell Carcinoma

Objective. Determine human papillomavirus (HPV) incidence in unknown primary squamous cell carcinomas (SCCa) of the head and neck and assess if HPV status influenced survival. Study Design. Historical cohort study. Setting. Tertiary care center. Subjects. Patients with unknown primary SCCa despite a complete workup who underwent neck dissection or excisional biopsy and postoperative comprehensive +/- chemoradiotherapy between 2002 and 2009. Methods. HPV fluorescence in situ hybridization (FISH) and p16(INK4a) immunohistochemistry (p16 IHC) were performed. Results were compared with survival, age, race, gender, tobacco use, alcohol use, and nodal stage. Results. Twenty-five patients met the inclusion criteria, of whom 88% were > 10 pack year tobacco users. Twenty-eight percent were HPV positive defined by both p161 and FISH1. Five-year overall survival was 66.7% in HPV-positive and 48.5% in HPV-negative patients (P = .35). Similarly, 5-year disease-free survival rates were 66.7% in HPV-positive and 48.5% in HPV-negative patients (P = .54). All 3 HPV-positive nonsmokers were survivors, but this was not significant because of the small sample size (P > .05). No other characteristics were associated with survival (P > . 05). Conclusion. Twenty-eight percent of metastatic lymph nodes from occult primary tumors were HPV positive. There was no survival difference associated with HPV status. Most of the HPV-positive patients in this study were tobacco users who had similar survival to HPV-negative patients, so caution should be used in interpreting HPV status in these patients.