Combined effects of smoking and HPV16 in oropharyngeal cancer.

Devasena Anantharaman, David C Muller, Pagona Lagiou, Wolfgang Ahrens, Ivana Holcátová, Franco Merletti, Kristina Kjærheim, Jerry Polesel, Lorenzo Simonato, Cristina Canova, Xavier Castellsague, Tatiana V Macfarlane, Ariana Znaor, Peter Thomson, Max Robinson, David I Conway, Claire M Healy, Anne Tjønneland, Ulla Westin, Johanna Ekström, Jenny Chang-Claude, Rudolf Kaaks, Kim Overvad, Dagmar Drogan, Göran Hallmans, Göran Laurell, H B Bueno-de-Mesquita, Petra H Peeters, Antonio Agudo, Nerea Larrañaga, Ruth C Travis, Domenico Palli, Aurelio Barricarte, Antonia Trichopoulou, Saitakis George, Dimitrios Trichopoulos, J Ramón Quirós, Sara Grioni, Carlotta Sacerdote, Carmen Navarro, María-José Sánchez, Rosario Tumino, Gianluca Severi, Marie-Christine Boutron-Ruault, Francoise Clavel-Chapelon, Salvatore Panico, Elisabete Weiderpass, Eiliv Lund, Inger T Gram, Elio Riboli, Michael Pawlita, Tim Waterboer, Aimée R Kreimer, Mattias Johansson, Paul Brennan

Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood. Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multi-centre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression. Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer. Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.