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

Gioia Di Credico, Valeria Edefonti (Lead / Corresponding author), Jerry Polesel, Francesco Pauli, Nicola Torelli, Diego Serraino, Eva Negri, Daniele Luce, Isabelle Stucker, Keitaro Matsuo, Paul J. Brennan, Marta Vilensky, Leticia Fernandez, Maria Paula Curado, Ana Menezes, Alexander W. Daudt, Rosalina Koifman, Victor Wunsch-Filho, Ivana Holcatova, Wolfgang AhrensPagona Lagiou, 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, Stefania Boccia, Gabriella Cadoni, Richard B. Hayes, Mark Purdue, Maura Gillison, Stimson Schantz, Guo Pei Yu, Hermann Brenner, Gypsyamber D'Souza, Neil D. Gross, Shu Chun Chuang, Paolo Boffetta, Mia Hashibe, Yuan Chin Amy Lee, Luigino Dal Maso

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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.

Original languageEnglish
Pages (from-to)47-57
Number of pages11
JournalOral Oncology
Early online date17 May 2019
Publication statusPublished - 1 Jul 2019


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

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research


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