Joint effects of intensity and duration of cigarette smoking on the risk of head and neck cancer: A bivariate spline model approach

Stefania Boccia, Gabriella Cadoni, Pagona Lagiou, Paolo Boffetta, Gioia Di Credico, Valeria Edefonti, Jerry Polesel, Francesco Pauli, Nicola Torelli, Diego Serraino, Eva Negri, Daniele Luce, Isabelle Stucker, Keitaro Matsuo, Paul Brennan, Marta Vilensky, Leticia Fernandez, Maria Paula Curado, Ana Menezes, Alexander W. DaudtRosalina Koifman, Victor Wunsch-Filho, Ivana Holcatova, Wolfgang Ahrens, Lorenzo Simonato, Lorenzo Richiardi, Claire Healy, Kristina Kjaerheim, David I. Conway, Tatiana V. Macfarlane, Peter Thomson, Antonio Agudo, Ariana Znaor, Leonardo F. Boaventura Rios, Tatiana N. Toporcov, Silvia Franceschi, Rolando Herrero, Joshua Muscat, Andrew F. Olshan, Jose P. Zevallos, Carlo La Vecchia, Deborah M. Winn, Erich M. Sturgis, Guojun Li, Eleonora Fabianova, Jolanda Lissowska, Dana Mates, Peter Rudnai, Oxana Shangina, Beata Swiatkowska, Kirsten Moysich, Zuo-Feng Zhang, Hal Morgenstern, Fabio Levi, Elaine Smith, Philip Lazarus, Cristina Bosetti, Werner Garavello, Karl Kelsey, Michael Mcclean, Heribert Ramroth, Chu Chen, Stephen M. Schwartz, Thomas L. Vaughan, Tongzhang Zheng, Gwenn Menvielle, Richard B. Hayes, Mark Purdue, Maura Gillison, Stimson Schantz, Guo-Pei Yu, Hermann Brenner, Gypsyamber D'Souza, Neil D. Gross, Shu-Chun Chuang, Mia Hashibe, Yuan-Chin Amy Lee, Luigino Dal Maso

Risultato della ricerca: Contributo in rivistaArticolo in rivista

11 Citazioni (Scopus)


Objectives: This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures. Materials and Methods: We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework. Results: For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30 years. In former smokers who quit ≥10 years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers. Conclusion: Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.
Lingua originaleEnglish
pagine (da-a)47-57
Numero di pagine11
RivistaOral Oncology
Stato di pubblicazionePubblicato - 2019


  • Bivariate spline models
  • Cigarette smoking duration
  • Cigarette smoking intensity
  • Head and neck cancer
  • Laryngeal cancer
  • Oral cavity and pharyngeal cancers


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