Role of Human Papillomavirus Infection in Head and Neck Cancer in Italy: The HPV-AHEAD Study

SIMPLE SUMMARY: This is the largest and most comprehensive assessment of the role of human papillomavirus (HPV) in head and neck cancer (HNC) in Italy, which is a region currently considered bearing a low burden of HPV-driven HNC. p16(INK4a), HPV-DNA, and HPV RNA biomarkers were used to assess the HPV status in head and neck cancer in a retrospective cohort of approximately 700 patients. In our study, HPV prevalence in oropharyngeal cancers was much higher than in oral and laryngeal cancers, and HPV positivity conferred better prognosis only in oropharyngeal cancers. Importantly, we have observed an increase of the prevalence of HPV positivity in oropharyngeal cancers in the most recent calendar periods, suggesting that this disease is increasing in Italy, as has happened before in other developed regions. ABSTRACT: Literature on the role of human papillomavirus (HPV) in head and neck cancer (HNC) in Italy is limited, especially for non-oropharyngeal tumours. Within the context of the HPV-AHEAD study, we aimed to assess the prognostic value of different tests or test algorithms judging HPV carcinogenicity in HNC and factors related to HPV positivity at the European Institute of Oncology. We conducted a retrospective cohort study (2000–2010) on a total of 696 primary HNC patients. Formalin-fixed, paraffin-embedded cancer tissues were studied. All HPV-DNA-positive and a random sample of HPV-DNA-negative cases were subjected to HPV-E6*I mRNA detection and p16(INK4a) staining. Multivariate models were used to assess for factors associated with HPV positivity and proportional hazards for survival and recurrence. The percentage of HPV-driven cases (considering HPV-E6*I mRNA positivity) was 1.8, 2.2, and 40.4% for oral cavity (OC), laryngeal (LC), and oropharyngeal (OPC) cases, respectively. The estimates were similar for HPV-DNA/p16(INK4a) double positivity. Being a non-smoker or former smoker or diagnosed at more recent calendar periods were associated with HPV-E6*I mRNA positivity only in OPC. Being younger was associated with HPV-E6*I mRNA positivity in LC. HPV-driven OPC, but not HPV-driven OC and LC, showed better 5 year overall and disease-free survival. Our data show that HPV prevalence in OPC was much higher than in OC and LC and observed to increase in most recent years. Moreover, HPV positivity conferred better prognosis only in OPC. Novel insights on the role of HPV in HNC in Italy are provided, with possible implications in the clinical management of these patients.