Squamous cell carcinoma of the head and neck outside the oropharynx is rarely human papillomavirus related

Objectives/Hypothesis The incidence of human papillomavirus (HPV)-driven disease beyond the oropharynx varies greatly in the reported literature. Study Design Case series. Methods Two hundred twenty-one samples were strictly classified to the subsites of oral cavity, larynx, or hypopharynx at the time of primary surgery. Formalin-fixed paraffin-embedded samples were subjected to a validated, tiered, diagnostic algorithm of p16 immunohistochemistry, high-risk HPV in situ hybridization, and quantitative polymerase chain reaction for HPV E6 DNA. An additional 60 oropharyngeal cases acted as an internal biological control. Results An incidence of 4% of HPV-driven cases was observed across the subsites outside the oropharynx compared to 70% of tumors confined within it. Conclusions This is the first reporting of a broad range of nonoropharyngeal HPV rates using this validated diagnostic algorithm. It remains unclear whether patients with HPV-driven disease originating outside the oropharynx enjoy the same survival advantage apparent in those patients with oropharyngeal squamous cell carcinomas. Level of Evidence 4 Laryngoscope, 124:2739–2744, 2014