Role of human papillomavirus in non-oropharyngeal head and neck cancers

Accurate estimates of the fraction of head and neck cancer (HNC) attributable to human papillomavirus (HPV) infection are essential to predict the effectiveness of interventions based on vaccination against HPV or HPV-testing. In addition, if supported by currently on-going clinical trials, attribution of a HNC to HPV may allow better and less toxic treatments. Here we focused on studies in which the prevalence of molecular and serological HPV markers was similarly assessed in oropharyngeal and non-oropharyngeal HNC. Large data on HPV DNA detection by PCR and p16 expression in HNC biopsies suggests that the probability of a cancer of the oral cavity, larynx, and hypopharynx being attributable to HPV is at least 5-fold lower than that for oropharyngeal cancer. Seropositivity for HPV16 E6 or E7 shows larger differences across sites, but findings vary between studies. Because HPV DNA and p16 detection lack specificity, and E6 and E7 antibody detection lacks sensitivity, these tests are not totally satisfactory. Limited data on in situ hybridization or HPV E6/E7 mRNA, mainly from the United States, suggests that HPV-attributable HNC is rare in the oral cavity (∼3%), larynx (∼7%), and hypopharynx (∼0%). Data on HPV in other rarer HNCs are extremely limited and essentially negative. Available data do not allow the establishment of the way HPV infection and tobacco may interact in non-oropharyngeal HNC. The exclusion of oropharynx as a site of tumor origin and the identification of robust fingerprints of HPV-driven carcinogenesis are the priorities to improve the estimate of HPV-attributable non-oropharyngeal HNC.