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

• Main Authors: Marta Tagliabue, Marisa Mena, Fausto Maffini, Tarik Gheit, Beatriz Quirós Blasco, Dana Holzinger, Sara Tous, Daniele Scelsi, Debora Riva, Enrica Grosso, Francesco Chu, Eric Lucas, Ruediger Ridder, Susanne Rrehm, Johannes Paul Bogers, Daniela Lepanto, Belén Lloveras Rubio, Rekha Vijay Kumar, Nitin Gangane, Omar Clavero, Michael Pawlita, Devasena Anantharaman, Madhavan Radhakrishna Pillai, Paul Brennan, Rengaswamy Sankaranarayanan, Marc Arbyn, Francesca Lombardi, Miren Taberna, Sara Gandini, Fausto Chiesa, Mohssen Ansarin, Laia Alemany, Massimo Tommasino, Susanna Chiocca, The HPV-AHEAD Study Group
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: Cancers
• Subjects: head and neck cancer; human papillomavirus; oropharyngeal cancer; virus-related cancers; human papillomavirus diagnosis
• Online Access: https://www.mdpi.com/2072-6694/12/12/3567

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.