Human Papillomavirus and p16 in Oropharyngeal Cancer and Their Relationship to Tobacco Use

Objectives: Over the last decade, there has been a vast amount of research establishing the link between human papillomavirus (HPV) and oropharyngeal cancer. It has been hypothesized now that two distinct forms of oropharynx cancer exist: HPV associated disease and carcinogen induced. Correlation between oncologic outcomes and HPV status is ongoing. The objective of this study is to investigate the relationship between HPV markers and carcinogen status. Methods: Clinical data were collected both retrospectively and prospectively for 151 patients with squamous cell carcinoma of the oropharynx. Main clinical outcome measures included tobacco status (pack-years and CMS tobacco groupings) and alcohol use history. All tumors were evaluated for p16 by monoclonal antibody immunohistochemistry assay. HPV DNA was detected by in-situ hybridation probes for low and high risk subtypes. Statistical analysis was done by Pearson’s Chi-Squared analysis for tobacco use. Results: Patients with p16+ tumors or HPV+ tumors had significantly lower tobacco exposure (P < .001, P = .001 respectively) with p16 having higher significance. These relationships were enhanced in both circumstances when taking both HPV DNA and p16 positive status into account in combination. Conclusions: This study demonstrates that HPV+/p16+ tumors show the strongest correlation with low tobacco exposure. It has been hypothesized that p16+, HPV - tumors may represent a distinct subset of oropharynx cancers, with p16 having its own unique clinical relevancy. Further studies should be done to evaluate whether there is a difference in outcome measures for p16+, HPV - tumors relative to p16+, HPV+ tumors.