UPDATES FROM INHANCE
Erich M. Sturgis, MD, MPH, Associate Editor
International Head and Neck Cancer Epidemiology Consortium: Update no. 14 The International Head and Neck Cancer Epidemiology (INHANCE) consortium (http://inhance.iarc.fr) was established in 2004 to study the etiology of head and neck cancer by pooling individual subject data from its member epidemiologic studies, most of which are of case-control design. INHANCE is coordinated through the University of Utah School of Medicine and the Mt. Sinai School of Medicine, and also supported through the U.S. National Cancer Institute. Presently, INHANCE includes over 35 studies, which when taken collectively provide questionnaire data on over 25,000 cases and over 35,000 controls, and biological samples from a majority of the study populations. Cases are patients with cancers (>97% squamous cell carcinomas) of the oral cavity, oropharynx, hypopharynx, and larynx, while controls are for comparison persons without cancer. The consortium combined questionnaire data into a centralized database with standardization to allow for pooled analyses. The database includes sociodemographic, behavioral, life-style, and health fields in addition to biomarker data (chiefly human papillomavirus [HPV] and genetic) on a major subset. This section will provide periodic updates from INHANCE with an executive summary.
Cigar and pipe smoking and the risk of head and neck cancers Cigar and pipe smoke contain similar carcinogens as cigarette smoke and are established risk factors for head and neck cancer. However, previous epidemiological studies of cigar and pipe smoking as risk factors for head and neck cancer were often of limited sample size with imprecise estimates of head and neck cancer risk associated with cigar and/or pipe smoking and may not have
Executive summary.
adequately controlled for confounding (especially because of cigarette smoking). The INHANCE consortium has been able to estimate the independent effects of cigar and pipe smoking on head and neck cancer risk in a pooled analysis of 19 studies from Europe and the Americas including approximately 14,000 patients with head and neck cancer (4110 oral cavity, 3834 oropharynx, 1026 hypopharynx, 3461 larynx, and 1504 not specified) and almost 19,000 control subjects. Among those without a history of cigarette smoking and after multivariate adjustment, cigar and pipe ever smoking were each associated with a statistically significant 2.5-fold and 2-fold increased risk for head and neck cancer, respectively, and these risks increased with both the duration and frequency of smoking. Cigar and pipe smoking were consistently associated with an elevated risk of each subsite of head and neck cancer among those without a cigarette smoking history, although estimates were somewhat imprecise. Risk was particularly evident for laryngeal cancer (6-fold for ever cigar smoking and 3.5fold for ever pipe smoking) and hypopharyngeal cancer (4fold for ever pipe smoking). Finally, the risk estimates for head and neck cancer for those who were exclusive cigar, pipe, or both smokers were similar to that for exclusive cigarette smokers (3.5 to 4-fold) as compared to never smokers. This work was limited by less power for the sitespecific analyses, by a lack of HPV tumor data for a more precise classification of oropharyngeal cancers, the inclusion of nonsquamous histology, and heterogeneity in the types of cigar and pipe tobacco products across populations. Importantly, this study clearly suggests that cigar and pipe smoking are independent risk factors for head and neck cancer, and these risks are likely similar in magnitude to the risk for head and neck cancer associated with cigarette smoking.
Cigarette, cigar, and pipe smoking and the risk of head and neck cancers: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium Am J Epidemiol 2013;178:679–690. Wyss A, Hashibe M, Chuang SC, Amy Lee YC, Zhang ZF, Yu GP, Winn DM, Wei Q, Talamini R, SzeszeniaDabrowska N, Sturgis EM, Smith E, Shangina O, Schwartz SM, Schantz S, Rudnai P, Purdue MP, Eluf-Neto J, Muscat J, Morgenstern H, Michaluart P Jr, Menezes A, Matos E, Mates IN, Lissowska J, Levi F, Lazarus P, La Vecchia C, Koifman S, Herrero R, Hayes RB, Franceschi S, W€unsch-Filho V, Fernandez L, Fabianova E, Daudt AW, Dal Maso L, Curado MP, Chen C, Castellsague X, de Carvalho MB, Cadoni G, Boccia S, Brennan P, Boffetta P, Olshan AF. [By permission from Oxford University Press: Wyss A, et al. Cigarette, Cigar, and Pipe Smoking and the Risk of Head and Neck Cancers: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium. Am J Epidemiol 2013;178:679–690.] Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals (CIs) for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect
466
HEAD & NECK—DOI 10.1002/HED
APRIL 2014
UPDATES
FROM
INHANCE
estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% CI 5 1.93–3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI 5 1.55–2.81). These odds ratios increased with increasing frequency and duration of smoking (ptrend [le] .0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio 5 3.49; 95% CI 5 2.58– 4.73) or exclusive pipe smoking (odds ratio 5 3.71; 95% CI 5 2.59–5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers.
HEAD & NECK—DOI 10.1002/HED
APRIL 2014
467
Erich M. Sturgis, MD, MPH, Associate Editor
International Head and Neck Cancer Epidemiology Consortium: Update no. 14 The International Head and Neck Cancer Epidemiology (INHANCE) consortium (http://inhance.iarc.fr) was established in 2004 to study the etiology of head and neck cancer by pooling individual subject data from its member epidemiologic studies, most of which are of case-control design. INHANCE is coordinated through the University of Utah School of Medicine and the Mt. Sinai School of Medicine, and also supported through the U.S. National Cancer Institute. Presently, INHANCE includes over 35 studies, which when taken collectively provide questionnaire data on over 25,000 cases and over 35,000 controls, and biological samples from a majority of the study populations. Cases are patients with cancers (>97% squamous cell carcinomas) of the oral cavity, oropharynx, hypopharynx, and larynx, while controls are for comparison persons without cancer. The consortium combined questionnaire data into a centralized database with standardization to allow for pooled analyses. The database includes sociodemographic, behavioral, life-style, and health fields in addition to biomarker data (chiefly human papillomavirus [HPV] and genetic) on a major subset. This section will provide periodic updates from INHANCE with an executive summary.
Cigar and pipe smoking and the risk of head and neck cancers Cigar and pipe smoke contain similar carcinogens as cigarette smoke and are established risk factors for head and neck cancer. However, previous epidemiological studies of cigar and pipe smoking as risk factors for head and neck cancer were often of limited sample size with imprecise estimates of head and neck cancer risk associated with cigar and/or pipe smoking and may not have
Executive summary.
adequately controlled for confounding (especially because of cigarette smoking). The INHANCE consortium has been able to estimate the independent effects of cigar and pipe smoking on head and neck cancer risk in a pooled analysis of 19 studies from Europe and the Americas including approximately 14,000 patients with head and neck cancer (4110 oral cavity, 3834 oropharynx, 1026 hypopharynx, 3461 larynx, and 1504 not specified) and almost 19,000 control subjects. Among those without a history of cigarette smoking and after multivariate adjustment, cigar and pipe ever smoking were each associated with a statistically significant 2.5-fold and 2-fold increased risk for head and neck cancer, respectively, and these risks increased with both the duration and frequency of smoking. Cigar and pipe smoking were consistently associated with an elevated risk of each subsite of head and neck cancer among those without a cigarette smoking history, although estimates were somewhat imprecise. Risk was particularly evident for laryngeal cancer (6-fold for ever cigar smoking and 3.5fold for ever pipe smoking) and hypopharyngeal cancer (4fold for ever pipe smoking). Finally, the risk estimates for head and neck cancer for those who were exclusive cigar, pipe, or both smokers were similar to that for exclusive cigarette smokers (3.5 to 4-fold) as compared to never smokers. This work was limited by less power for the sitespecific analyses, by a lack of HPV tumor data for a more precise classification of oropharyngeal cancers, the inclusion of nonsquamous histology, and heterogeneity in the types of cigar and pipe tobacco products across populations. Importantly, this study clearly suggests that cigar and pipe smoking are independent risk factors for head and neck cancer, and these risks are likely similar in magnitude to the risk for head and neck cancer associated with cigarette smoking.
Cigarette, cigar, and pipe smoking and the risk of head and neck cancers: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium Am J Epidemiol 2013;178:679–690. Wyss A, Hashibe M, Chuang SC, Amy Lee YC, Zhang ZF, Yu GP, Winn DM, Wei Q, Talamini R, SzeszeniaDabrowska N, Sturgis EM, Smith E, Shangina O, Schwartz SM, Schantz S, Rudnai P, Purdue MP, Eluf-Neto J, Muscat J, Morgenstern H, Michaluart P Jr, Menezes A, Matos E, Mates IN, Lissowska J, Levi F, Lazarus P, La Vecchia C, Koifman S, Herrero R, Hayes RB, Franceschi S, W€unsch-Filho V, Fernandez L, Fabianova E, Daudt AW, Dal Maso L, Curado MP, Chen C, Castellsague X, de Carvalho MB, Cadoni G, Boccia S, Brennan P, Boffetta P, Olshan AF. [By permission from Oxford University Press: Wyss A, et al. Cigarette, Cigar, and Pipe Smoking and the Risk of Head and Neck Cancers: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium. Am J Epidemiol 2013;178:679–690.] Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals (CIs) for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect
466
HEAD & NECK—DOI 10.1002/HED
APRIL 2014
UPDATES
FROM
INHANCE
estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% CI 5 1.93–3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI 5 1.55–2.81). These odds ratios increased with increasing frequency and duration of smoking (ptrend [le] .0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio 5 3.49; 95% CI 5 2.58– 4.73) or exclusive pipe smoking (odds ratio 5 3.71; 95% CI 5 2.59–5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers.
HEAD & NECK—DOI 10.1002/HED
APRIL 2014
467
