Low Prevalence of HPV Related Oropharyngeal Carcinogenesis in Northern Sardinia

Simple Summary Oropharyngeal squamous cell carcinomas (OPSCCs) are the only head and neck malignancy with a clear increase in prevalence in Western countries, due to the HPV epidemics with an increasing proportion of HPV-related OPSCCs. Such figures, however, are extremely variable around the globe. The present report is the first to assess the prevalence of HPV-related OPSCC in Sardinia, a relatively isolated population in the West. The rate of HPV-driven OPSCC in such a population is close to that of less developed areas, with clear implications on epidemiology, prognosis, and reliability of methods for assessing HPV-related carcinogenesis. In fact, in the present setting, the specificity of p16 IHC alone in diagnosing HPV-related carcinogenesis is only 75% with a 25% false positive rate. HPV infection is a clear etiopathogenetic factor in oropharyngeal carcinogenesis and is associated with a markedly better prognosis than in smoking- and alcohol-associated cases, as specified by AJCC classification. The aim of the present work is to evaluate the prevalence of HPV-induced OPSCC in an insular area in the Mediterranean and to assess the reliability of p16 IHC (immunohistochemistry) alone, as accepted by AJCC, in the diagnosis of HPV-driven carcinogenesis in such a setting. All patients with OPSCC consecutively managed by the referral center in North Sardinia of head and neck tumor board of AOU Sassari, were recruited. Diagnosis of HPV-related OPCSS was carried out combining p16 IHC and DNA testing on FFPE samples and compared with the results of p16 IHC alone. Roughly 14% (9/62) of cases were positive for HPV-DNA and p16 IHC. Three more cases showed overexpression of p16, which has a 100% sensitivity, but only 75% specificity as standalone method for diagnosing HPV-driven carcinogenesis. The Cohen's kappa coefficient of p16 IHC alone is 0.83 (excellent). However, if HPV-driven carcinogenesis diagnosed by p16 IHC alone was considered the criterion for treatment deintensification, 25% of p16 positive cases would have been wrongly submitted to deintensified treatment for tumors as aggressive as a p16 negative OPSCC. The currently accepted standard by AJCC (p16 IHC alone) harbors a high rate of false positive results, which appears risky for recommending treatment deintensification, and for this aim, in areas with a low prevalence of HPV-related OPSCC, it should be confirmed with HPV nucleic acid detection.