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 p16+ and FISH+. 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.