Evaluation of Human Papillomavirus Antibodies and Risk of Subsequent Head and Neck Cancer

Aimée R. Kreimer, Mattias Johansson, Tim Waterboer, Rudolf Kaaks, Jenny Chang-Claude, Dagmar Drogen, Anne Tjønneland, Kim Overvad, J. Ramón Quirós, Carlos A. González, Maria José Sánchez, Nerea Larrañaga, Carmen Navarro, Aurelio Barricarte, Ruth C. Travis, Kay-Tee Khaw, Nick Wareham, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Petra H.M. Peeters, Salvatore Panico, Giovanna Masala, Sara Grioni, Rosario Tumino, Paolo Vineis, H. Bas Bueno-de-Mesquita, Göran Laurell, Göran Hallmans, Jonas Manjer, Johanna Ekström, Guri Skeie, Eiliv Lund, Elisabete Weiderpass, Pietro Ferrari, Graham Byrnes, Isabelle Romieu, Elio Riboli, Allan Hildesheim, Heiner Boeing, Michael Pawlita, Paul Brennan

Human papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera. We identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers as well as 1,599 comparable controls from within the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples from patients (collected, on average, 6 years before diagnosis) and control participants were analyzed for antibodies against multiple proteins of HPV16 as well as HPV6, HPV11, HPV18, HPV31, HPV33, HPV45, and HPV52. Odds ratios (ORs) of cancer and 95% CIs were calculated, adjusting for potential confounders. All-cause mortality was evaluated among patients using Cox proportional hazards regression. HPV16 E6 seropositivity was present in prediagnostic samples for 34.8% of patients with oropharyngeal cancer and 0.6% of controls (OR, 274; 95% CI, 110 to 681) but was not associated with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis. The all-cause mortality ratio among patients with oropharyngeal cancer was 0.30 (95% CI, 0.13 to 0.67), for patients who were HPV16 E6 seropositive compared with seronegative. HPV16 E6 seropositivity was present more than 10 years before diagnosis of oropharyngeal cancers.