The Prevalence of HPV-Associated Head and Neck Cancers and Positive Predictive Value of p16: A Retrospective and Prospective Analysis of 375 Patients

Abstract Squamous cell carcinoma (SCC) of the head and neck is the sixth most common cancer. Common sites for head and neck cancers (HNCs) include oral cavity, oropharynx, tongue, tonsils, and larynx. Multiple etiologies have been described for these cancers, including infection with human papillomavirus. Recent studies point toward a rise in human papillomavirus–associated head and neck cancers and a comparative decrease in smoking-related HNCs. Objectives Our aim was to document prevalence of HPV-associated head and neck cancer and calculate the positive predictive value of p16 as a surrogate marker in surgical pathology specimens. Methods Head and neck cancer cases from the pathology department at Icahn School of Medicine at Mount Sinai Hospital were retrospectively reviewed from 2013 to 2000 and prospectively reviewed from 2013 to 2016. Results In total, 375 cases with a diagnosis of head and neck cancers, including squamous cell carcinoma (SCC), nonkeratinizing SCC, keratinizing SCC, basaloid SCC, and hypopharyngeal SCC, were identified. On PCR testing, 154 (41%) cases were positive for high-risk HPV 16 and 186 cases (49%) for HPV wide spectrum. Subsequently immunohistochemistry for p16 was compared with PCR results as reference, revealing 146 of 154 cases being diffusely positive for HPV 16 (sensitivity 94.8%) and 164 of 186 for HPV wide spectrum (sensitivity 88%). Our data suggest p16 to have a positive predictive value of 87% for wide-spectrum HPV and 78% for HPV 16. Similarly, negative predictive value for wide-spectrum HPV infection is 97% and 98.8% for HPV 16. Conclusion Although widely used as a surrogate marker for HPV infection, our analysis shows that p16 has a positive predictive value below 90%. Other methods including PCR testing should be employed for virus detection, especially given the prognostic significance, change in management, and the new AJCC staging system that downgrades the HPV-associated head and neck cancers.