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

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 p16INK4a 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/p16INK4a 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.

Prevalence of HPV in Mexican Patients with Head and Neck Squamous Carcinoma and Identification of Potential Prognostic Biomarkers

“…This association was particularly evident in OPSCC (96.7% of HPV+ cases were also p16+). In agreement with previous reports, 39.2% of OPSCC were HPV+/16+ [ 9 , 29 ]. Other studies reported 22.4 [ 30 ] and 30% based on the presence of viral RNA [ 26 ].…”

“…The group led by Bryant has reported that p16 expression has the same prognostic impact in non-OPSCC as in OPSCC [ 39 ]. In contrast, Tabliabued et al found that HPV is related to better prognosis only in OPSCC [ 29 ], while Larque reported p16 overexpression due to mutations in CDKN2A in HPV− LASCC cases associated to worse prognosis [ 40 ]. Because of such diverse findings, it is necessary to take a closer look at the relation between HPV and the anatomical site and its clinical impact in relation to other risk factors, such as alcoholism and smoking, as well as to identify clinically relevant biomarkers in HNSCC, especially concerning the presence or absence of HPV.…”

Human Papillomavirus and Survival of Sinonasal Squamous Cell Carcinoma Patients: A Systematic Review and Meta-Analysis

“…These findings are notable in that the observed association is in line with that reported for OPSCC [29]. While HPV is widely accepted as a prognostic factor for OPSCC, the association with survival at other non-oropharyngeal head and neck subsites (e.g., oral cavity, larynx, hypopharynx and nasopharynx) has been much less clear with mixed results [5,[29][30][31][32][33][34][35][36].…”

A systematic review and meta‐analysis of the prognostic role of age in oral tongue cancer

“…Nowadays, the role of human papillomavirus (HPV) for oral tongue cancer appears undefined, but yet different from the oropharynx 30,31 . Dietary nutrients, specifically fruits and vegetables, have been consistently associated with lower oral cancer risk 32 …”