Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jul:94:47-57.
doi: 10.1016/j.oraloncology.2019.05.006. Epub 2019 May 17.

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  1 , Valeria Edefonti  2 , Jerry Polesel  3 , Francesco Pauli  4 , Nicola Torelli  4 , Diego Serraino  3 , Eva Negri  5 , Daniele Luce  6 , Isabelle Stucker  7 , Keitaro Matsuo  8 , Paul Brennan  9 , Marta Vilensky  10 , Leticia Fernandez  11 , Maria Paula Curado  12 , Ana Menezes  13 , Alexander W Daudt  14 , Rosalina Koifman  15 , Victor Wunsch-Filho  16 , Ivana Holcatova  17 , Wolfgang Ahrens  18 , Pagona Lagiou  19 , Lorenzo Simonato  20 , Lorenzo Richiardi  21 , Claire Healy  22 , Kristina Kjaerheim  23 , David I Conway  24 , Tatiana V Macfarlane  25 , Peter Thomson  26 , Antonio Agudo  27 , Ariana Znaor  9 , Leonardo F Boaventura Rios  28 , Tatiana N Toporcov  16 , Silvia Franceschi  3 , Rolando Herrero  9 , Joshua Muscat  29 , Andrew F Olshan  30 , Jose P Zevallos  31 , Carlo La Vecchia  32 , Deborah M Winn  33 , Erich M Sturgis  34 , Guojun Li  34 , Eleonora Fabianova  35 , Jolanda Lissowska  36 , Dana Mates  37 , Peter Rudnai  38 , Oxana Shangina  39 , Beata Swiatkowska  40 , Kirsten Moysich  41 , Zuo-Feng Zhang  42 , Hal Morgenstern  43 , Fabio Levi  44 , Elaine Smith  45 , Philip Lazarus  46 , Cristina Bosetti  47 , Werner Garavello  48 , Karl Kelsey  49 , Michael McClean  50 , Heribert Ramroth  51 , Chu Chen  52 , Stephen M Schwartz  52 , Thomas L Vaughan  52 , Tongzhang Zheng  53 , Gwenn Menvielle  54 , Stefania Boccia  55 , Gabriella Cadoni  56 , Richard B Hayes  57 , Mark Purdue  33 , Maura Gillison  58 , Stimson Schantz  59 , Guo-Pei Yu  60 , Hermann Brenner  61 , Gypsyamber D'Souza  62 , Neil D Gross  63 , Shu-Chun Chuang  64 , Paolo Boffetta  65 , Mia Hashibe  66 , Yuan-Chin Amy Lee  67 , Luigino Dal Maso  3
Affiliations

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 et al. Oral Oncol. 2019 Jul.

Abstract

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.

Keywords: Bivariate spline models; Cigarette smoking duration; Cigarette smoking intensity; Head and neck cancer; INHANCE; Laryngeal cancer; Oral cavity and pharyngeal cancers.

PubMed Disclaimer

Figures

Figure 1 –
Figure 1 –
Flow chart of subjects’ selection
Figure 1 –
Figure 1 –
Flow chart of subjects’ selection
Figure 2 –
Figure 2 –. Odds ratiosa,b of oral and pharyngeal cancer and laryngeal cancer in current smokers, for the joint effect of intensity (cigarettes/day) and duration (years) of cigarette smoking estimated through bivariate spline models. INHANCE consortium
a Fitted models included adjustment for age, sex, race, study, education, drinking status, drinking intensity, and drinking duration. The reference category was defined as “Never smokers”. b On the grid, black thicker lines represent knot locations: 16 cigarettes/day and 33 years of duration for oral and pharyngeal cancer and 25 cigarettes/day and 30 years of duration for laryngeal cancer, respectively. Dark grey lines in contour plots indicate iso-risk curves at defined levels of risk.
Figure 3 –
Figure 3 –. Odds ratiosa,b of oral and pharyngeal cancer in current smokers by alcohol drinking intensity, for the joint effect of intensity (cigarettes/day) and duration (years) of cigarette smoking, estimated through bivariate spline models. INHANCE consortium
a Fitted models included adjustment for age, sex, race, study, education, and alcohol drinking status. The reference category was defined as “Never smokers”, in each strata of alcohol drinking intensity. b On the grid, black thicker lines represent knot locations: 32 years of duration for never drinkers, and 12 cigarettes/day and 25 years of duration for heavy drinkers, respectively. Dark grey lines in contour plots indicate iso-risk curves at defined levels of risk.
Figure 4 –
Figure 4 –. Odds ratioa,b of oral and pharyngeal cancer and laryngeal cancer in former smokers who quit ≥10 years ago, for the joint effect of intensity (cigarettes/day) and duration (years) of cigarette smoking estimated through bivariate spline models. INHANCE consortium
a Fitted models included adjustment for age, sex, race, study, education, drinking status, drinking intensity, and drinking duration. The reference category was defined as “Never smokers”. b On the grid, the black thicker line represents the knot location: 27 cigarettes/day for laryngeal cancer. Dark grey lines in contour plots indicate iso-risk curves at defined levels of risk.
See this image and copyright information in PMC

Comment in

References

    1. World Health Organization. WHO global report: mortality attributable to tobacco. Geneva: WHO; 2012.
    1. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer; Available from: https://gco.iarc.fr/today, accessed [21 March 2019].
    1. IARC. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 38 Tobacco Smoking. Lyon: IARC Press; 1986.
    1. IARC. IARC Monographs on the evaluation of carcinogenic risks to Humans, Volume 83: Tobacco smoke and involuntary smoking. Lyon: IARC Press; 2004. - PMC - PubMed
    1. Lubin JH, Purdue M, Kelsey K, et al. Total exposure and exposure rate effects for alcohol and smoking and risk of head and risk of neck cancer: a pooled analysis of case-control studies. Am J Epidemiol 2009;170:937–47. - PMC - PubMed

Publication types