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 MacFarlane, Ariana Znaor, Peter Thomson, Max Robinson, David I Conway, Claire M Healy, Anne Tjønneland, Ulla Westin, Johanna EkströmJenny 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

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)


BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)752-761
Number of pages10
JournalInternational Journal of Epidemiology
Issue number3
Early online date19 May 2016
Publication statusPublished - Jun 2016

Bibliographical note

The ARCAGE study was supported by a grant from the European
Commission’s 5th Framework Program (contract QLK1-2001-
00182). The EPIC study has been supported by the Europe Against
Cancer Program of the European Commission (SANCO); Deutsche
Krebshilfe, Deutsches Krebsforschungszentrum, German Federal
Ministry of Education and Research; Danish Cancer Society; Health
Research Fund (FIS) of the Spanish Ministry of Health, Spanish
Regional Governments of Andalucia, Asturias, Basque Country,
Murcia and Navarra; Catalan Institute of Oncology, Spain; the
ISCIII of the Spanish Ministry of Health (RETICC DR06/0020);
Cancer Research UK; Medical Research Council, UK; Greek
Ministry of Health; Stavros Niarchos Foundation; Hellenic Health
Foundation; Italian Association for Research on Cancer (AIRC);
Italian National Research Council, Fondazione-IstitutoBanco
Napoli, Italy; Associazione Italiana per la Ricerca sul Cancro-AIRC
Milan; Compagnia di San Paolo; Dutch Ministry of Public Health Welfare and Sports; World Cancer Research Fund; Swedish Cancer
Society; Swedish Scientific Council; Regional Government of
Vasterbotten, Sweden; NordForsk (Centre of excellence programme HELGA), Norway; French League against Cancer (LNCC), France; National Institute for Health and Medical Research (INSERM), France; Mutuelle Generale de l’Education Nationale (MGEN), France; 3M Co, France; Gustave Roussy Institute (IGR), France; and General Councils of France. The serology testing of EPIC prospective study was supported by the National Cancer Institute Intramural Research Program. The work done in this study was supported in part by a grant from the European Commission’s 7th Framework Program (contract FP7-HEALTH-2011–282562) and partly by the Health General Directorate of the French Social Affairs and Health Ministry.


  • human papillomavirus
  • tobacco smoking
  • interaction
  • head and neck cancer risk
  • oropharynx cancer


Dive into the research topics of 'Combined effects of smoking and HPV16 in oropharyngeal cancer'. Together they form a unique fingerprint.

Cite this