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Serum samples from 194 cases and 217 controls participating in a case-control study of invasive cervical cancer in Brazil were examined for antibodies to human papillomavirus (HPV) 16 virus-like particles (VLPs) by ELISA. The prevalence of antibody in cases and controls was 47.4 versus 24.4% (P0.001). The prevalence was higher in women who had HPV-16 DNA in the genital tract (54.2%) than in those with other HPVs (36.8%) or no HPVs (44.8%), but the differences were not statistically significant. Among cases and controls, HPV-16 VLP antibodies were associated with a greater number of lifetime sexual partners (chi2 for trend, P0.001). Among controls, age was inversely associated with HPV-16 VLP seroreactivity (chi2 for trend, P = 0.019). The sera were previously tested for antibodies to HPV-16 E6 and E7 oncoproteins; there was no correlation between antibody titers to HPV-16 E6 or E7 and VLPs. The HPV-16 serological assays were compared as screening tests for invasive cervical cancer. The sensitivity and specificity estimates were 47.4 and 75.6% for HPV-16 VLP serology, 63.4 and 89.9% for either HPV-16 E6 or E7 serology, and 53.6 and 93.6% for high titers of either HPV-16 E6 or E7 or VLP antibodies. The utility of HPV-16 VLP ELISA as a screening test for invasive cervical cancer is limited by a high seroprevalence in women with probable prior exposure to HVP 16 but without disease.

Masked sera from 194 cases and 217 controls participating in a case-control study of cervical cancer in Brazil were examined for antibodies to human papillomavirus (HPV) 16 E6 and E7 by radioimmunoprecipitation assay. Radiolabeled full-length E6 and E7 proteins expressed by in vitro transcription and translation in rabbit reticulocyte lysate were used as antigens. The antibody prevalences in cases and controls were: 54.1% versus 6% for E6; 30.4% versus 4.6% for E7; 63.4% versus 10.1% for either E6 or E7; and 21.1% versus 0.5% for both E6 and E7. The corresponding odds ratios were 35 ([95% confidence interval (CI)], 15-83), 10 (95% CI, 4-25), 28 (95% CI, 13-61) and 87 (95% CI, 10-736). The most marked contrast between cases and controls was observed for sera with high antibody titers (cpm6000) with an odds ratio of 239 (95% CI, 29-1946) for E6 or E7. Seroreactivity in cases was partially type specific; women who had HPV-16 DNA in the genital tract had higher antibody prevalence rates than those who were negative for HPV DNA. Reactivity to the E6 protein was associated with the stage of disease; the antibody prevalence was 62.7% in cases with stages II-IV and 31.0% in cases with stage I (P0.005). HPV-16 serology and HPV polymerase chain reaction were compared as markers for invasive cervical cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Head and neck cancer (HNC) risk is elevated among lean people and reduced among overweight or obese people in some studies; however, it is unknown whether these associations differ for certain subgroups or are influenced by residual confounding from the effects of alcohol and tobacco use or by other sources of biases. Methods: We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. Results: Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) =18.5 kg/m2 (2.13, 1.75-2.58) and reduced for BMI >25.0-30.0 kg/m2 (0.52, 0.44-0.60) and BMI =30 kg/m2 (0.43, 0.33-0.57), compared with BMI >18.5-25.0 kg/m2. These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI =18.5 kg/m2 was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m2 was present only in smokers and drinkers. Conclusions: In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies. © The Author 2010; Published by Oxford University Press on behalf of the International Epidemiological Association. All rights reserved.

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers. Genotyping performed at the Center for Inherited Disease Research (CIDR) was funded through the U.S. National Institute of Dental and Craniofacial Research (NIDCR) grant 1X01HG007780-0. Genotyping for shared controls with the Lung OncoArray initiative was funded through the grant X01HG007492-0. Corina Lesseur undertook this work during the tenure of a Postdoctoral Fellowship awarded by the International Agency for Research on Cancer. The funders did not participate in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. We acknowledge all of the participants involved in this research and the funders and support. We thank Dr. Leticia Fernandez (Instituto Nacional de Oncologia y Radiobiologia, La Habana, Cuba) for her contribution to the IARC ORC multicenter study. We are also grateful to Sergio Koifman (Escola Nacional de Saúde Pública, Rio de Janeiro, Brazil) for his contribution to the IARC Latin America multicenter study (Sergio Koifman passed away in May 2014) and to Xavier Castellsagué from the ARCAGE Barcelona Center who recently passed away (June 2016). The University of Pittsburgh head and neck cancer case-control study is supported by National Institutes of Health grants P50 CA097190 and P30 CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01-CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant numbers 04/12054-9 and 10/51168-0). The authors thank all the members of the GENCAPO team. The HN5000 study was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034), the views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Toronto study was funded by the Canadian Cancer Society Research Institute (020214) and the National Cancer Institute (U19 CA148127) and the Cancer Care Ontario Research Chair. The alcohol-related cancers and genetic susceptibility study in Europe (ARCAGE) was funded by the European Commission’s 5th Framework Program (QLK1-2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte, and Padova University (CPDA057222).The Rome Study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) IG 2011 10491 and IG2013 14220 to SB, and Fondazione Veronesi to SB. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97-0222), with additional funding from Fondo para la Investigacion Cientifica y Tecnologica (Argentina) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (01/01768-2). The IARC Central Europe study was supported by European Commission’s INCO-COPERNICUS Program (IC15-CT98-0332), NIH/National Cancer Institute grant CA92039, and the World Cancer Research Foundation grant WCRF 99A28.The IARC Oral Cancer Multicenter study was funded by: grant S06 96 202489 05F02 from Europe against Cancer; Grants FIS 97/0024, FIS 97/0662, and BAE 01/5013 from Fondo de Investigaciones Sanitarias, Spain; UICC Yamagiwa-Yoshida Memorial International Cancer Study; National Cancer Institute of Canada; Italian Association for Research on Cancer; and the Pan American Health Organization. The coordination of EPIC study is financially supported

Background: Cancers of the upper aerodigestive tract (UADT; including oral cavity, pharynx, larynx and oesophagus) have high incidence rates all over the world, and they are especially frequent in some parts of Latin America. However, the data on the role of the major risk factors in these areas are still limited. Methods: We have evaluated the role of alcohol and tobacco consumption, based on 2,252 upper aerodigestive squamous-cell carcinoma cases and 1,707 controls from seven centres in Brazil, Argentina, and Cuba. Results: We show that alcohol drinkers have a risk of UADT cancers that is up to five times higher than that of never-drinkers. A very strong effect of aperitifs and spirits as compared to other alcohol types was observed, with the ORs reaching 12.76 (CI 5.37-30.32) for oesophagus. Tobacco smokers were up to six times more likely to develop aerodigestive cancers than never-smokers, with the ORs reaching 11.14 (7.72-16.08) among current smokers for hypopharynx and larynx cancer. There was a trend for a decrease in risk after quitting alcohol drinking or tobacco smoking for all sites. The interactive effect of alcohol and tobacco was more than multiplicative. In this study, 65% of all UADT cases were attributable to a combined effect of alcohol and tobacco use. Conclusions: In this largest study on UADT cancer in Latin America, we have shown for the first time that a prevailing majority of UADT cancer cases is due to a combined effect of alcohol and tobacco use and could be prevented by quitting the use of either of these two agents. © 2011 Springer Science+Business Media B.V.

Cancers of the upper aerodigestive tract (UADT: oral cavity, oropharynx, hypopharynx, larynx, esophagus) have high incidence rates all over the world and they are especially frequent in some parts of Latin America. In this study, we have evaluated the role of the consumption of maté, a hot herb-based beverage, based on 1168 UADT squamous-cell carcinoma cases and 1,026 frequency-matched controls enrolled from four centers in Brazil and Argentina. The effect of maté drinking on the risk of head-and-neck cancers was borderline significant. A significant effect was observed only for cancer of the esophagus (OR 3.81 (95% CI 1.75-8.30)). While duration of maté drinking was associated with the risk of all UADT cancers, the association with cumulative maté consumption was restricted to esophageal cancer (p-value of linear trend 0.006). The analyses of temperature at which maté was drunk were not conclusive. The increased risk associated with maté drinking was more evident in never-smokers and never-alcohol drinkers than in other individuals. Our study strengthens the evidence of an association between maté drinking and esophageal cancer; the hypothesis of an association with other UADT cancers remains to be clarified. © 2010 Springer Science+Business Media B.V.

Cancers of the upper aerodigestive tract [(UADT): oral cavity, pharynx, larynx and oesophagus] have high incidence rates in some parts of South America. Alterations in the TP53 gene are common in these cancers. In our study, we have estimated the prevalence and patterns of TP53 mutations (exons 4-10) in 236 UADT tumours from South America in relation to lifestyle risk factors, such as tobacco smoking and alcohol drinking. Moreover, we have conducted a pilot study of EGFR mutations (exons 18-21) in 45 tumours from the same population. TP53 mutation prevalence was high: 59% of tumours were found to carry mutant TP53. We found an association between TP53 mutations and tobacco smoking and alcohol drinking. The mutation rate increased from 38% in never-smokers to 66% in current smokers (P-value for trend 5 0.09). G:C>T:A transversions were found only in smokers (15%). Alcohol drinkers carried more G:C>A:T transitions (P 5 0.08). Non-exposed individuals were more probable to carry G:C>A:T transitions at CpG sites (P 5 0.01 for neversmokers and P < 0.001 for never-drinkers). EGFR mutations were found in 4% of cases. Inactivation of TP53 by mutations is a crucial molecular event in the UADT carcinogenesis and it is closely related to exposure to lifestyle risk factors. EGFR mutations do not appear to be a common event in UADT carcinogenesis in this population. © The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.

Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (ψ) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (ψ = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases 60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases. (Cancer Epidemiol Biomarkers Prev 2009;18(2):541–50)

Although active tobacco smoking has been identified as a major risk factor for head and neck cancer, involuntary smoking has not been adequately evaluated because of the relatively low statistical power in previous studies. We took advantage of data pooled in the International Head and Neck Cancer Epidemiology Consortium to evaluate the role of involuntary smoking in head and neck carcinogenesis. Involuntary smoking exposure data were pooled across six case-control studies in Central Europe, Latin America, and the United States. Adjusted odds ratios (OR) and 95% confidence interval (95% CI) were estimated for 542 cases and 2,197 controls who reported never using tobacco, and the heterogeneity among the study-specific ORs was assessed. In addition, stratified analyses were done by subsite. No effect of ever involuntary smoking exposure either at home or at work was observed for head and neck cancer overall. However, long duration of involuntary smoking exposure at home and at work was associated with an increased risk (OR for >15 years at home, 1.60; 95% CI, 1.12-2.28; Ptrend < 0.01; OR for >15 years at work, 1.55; 95% CI, 1.04-2.30; Ptrend = 0.13). The effect of duration of involuntary smoking exposure at home was stronger for pharyngeal and laryngeal cancers than for other subsites. An association between involuntary smoking exposure and the risk of head and neck cancer, particularly pharyngeal and laryngeal cancers, was observed for long duration of exposure. These results are consistent with those for active smoking and suggest that elimination of involuntary smoking exposure might reduce head and neck cancer risk among never smokers. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1974–81)

Poor oral health has been reported as a risk factor in the etiology of head and neck cancer. Data on oral health were ascertained as part of two multicenter case-control studies comprising 924 cases and 928 controls in central Europe and 2,286 cases and 1,824 controls in Latin America. Incident cases of squamous cell carcinoma of the head and neck (oral cavity, pharynx, larynx) and esophagus, as well as age (in quinquennia)- and sex frequency-matched controls, were enrolled from 1998 to 2003. Poor condition of the mouth (central Europe: odds ratio (OR) = 2.89, 95% confidence interval (CI): 1.74, 4.81; Latin America: OR = 1.89, 95% CI: 1.47, 2.42), lack of toothbrush use (Latin America: OR = 2.36, 95% CI: 1.28, 4.36), and daily mouthwash use (Latin America: OR = 3.40, 95% CI: 1.96, 5.89) emerged as risk factors for head and neck cancer, independent of tobacco use and alcohol consumption. Missing between six and 15 teeth was an independent risk factor for esophageal cancer (central Europe: OR = 2.84, 95% CI: 1.26, 6.41; Latin America: OR = 2.18, 95% CI: 1.04, 4.59). These results indicate that periodontal disease (as indicated by poor condition of the mouth and missing teeth) and daily mouthwash use may be independent causes of cancers of the head, neck, and esophagus. © The Author 2007. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved.

Toporcov, Tatiana Natasha Znaor, Ariana Zhang, Zuo-Feng Yu, Guo-Pei Winn, Deborah M Wei, Qingyi Vilensky, Marta Vaughan, Thomas Thomson, Peter Talamini, Renato Szeszenia-Dabrowska, Neonila Sturgis, Erich M Smith, Elaine Shangina, Oxana Schwartz, Stephen M Schantz, Stimson Rudnai, Peter Richiardi, Lorenzo Ramroth, Heribert Purdue, Mark P Olshan, Andrew F Eluf-Neto, Jose Muscat, Joshua Moyses, Raquel Ajub Morgenstern, Hal Menezes, Ana McClean, Michael Matsuo, Keitaro Mates, Dana Macfarlane, Tatiana V Lissowska, Jolanta Levi, Fabio Lazarus, Philip La Vecchia, Carlo Lagiou, Pagona Koifman, Sergio Kjaerheim, Kristina Kelsey, Karl Holcatova, Ivana Herrero, Rolando Healy, Claire Hayes, Richard B Franceschi, Silvia Fernandez, Leticia Fabianova, Eleonora Daudt, Alexander W Curioni, Otavio Alberto Maso, Luigino Dal Curado, Maria Paula Conway, David I Chen, Chu Castellsague, Xavier Canova, Cristina Cadoni, Gabriella Brennan, Paul Boccia, Stefania Antunes, Jose Leopoldo Ferreira Ahrens, Wolfgang Agudo, Antonio Boffetta, Paolo Hashibe, Mia Lee, Yuan-Chin Amy Filho, Victor Wunsch eng FIRCA TW01500/TW/FIC NIH HHS/ K07CA104231/CA/NCI NIH HHS/ P01CA068384/CA/NCI NIH HHS/ P30ES010126/ES/NIEHS NIH HHS/ P50CA90388/CA/NCI NIH HHS/ R01CA048996/CA/NCI NIH HHS/ R01CA100264/CA/NCI NIH HHS/ R01CA30022/CA/NCI NIH HHS/ R01CA51845/CA/NCI NIH HHS/ R01CA61188/CA/NCI NIH HHS/ R01DA11386/DA/NIDA NIH HHS/ R01DE012609/DE/NIDCR NIH HHS/ R01DE11979/DE/NIDCR NIH HHS/ R01DE13110/DE/NIDCR NIH HHS/ R01DE13158/DE/NIDCR NIH HHS/ R01ES11740/ES/NIEHS NIH HHS/ R03CA113157/CA/NCI NIH HHS/ R03CA77954/CA/NCI NIH HHS/ R03DE016611/DE/NIDCR NIH HHS/ R21ES011667/ES/NIEHS NIH HHS/ T32CA09142/CA/NCI NIH HHS/ U01CA96134/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England 2015/01/24 06:00 Int J Epidemiol. 2015 Feb;44(1):169-85. doi: 10.1093/ije/dyu255. Epub 2015 Jan 22.; International audience; BACKGROUND: Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients. METHODS: We pooled data from 25 case-control studies and conducted separate analyses for adults 45 years old ('older adults', 17700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, = 19.9% (95% CI=9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking=5.3% (-11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR=2.27 (95% CI=1.26, 4.10)], but not in the older adults [OR=1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (-2.41%, 5.80%) in older adults. CONCLUSIONS: Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young adults may be due to the reduced length of exposure due to the lower age. Other characteristics, such as those that are inherited, may play a more important role in HNC in young adults compared with older adults.

Delahaye-Sourdeix, Manon Anantharaman, Devasena Timofeeva, Maria N Gaborieau, Valerie Chabrier, Amelie Vallee, Maxime P Lagiou, Pagona Holcatova, Ivana Richiardi, Lorenzo Kjaerheim, Kristina Agudo, Antonio Castellsague, Xavier Macfarlane, Tatiana V Barzan, Luigi Canova, Cristina Thakker, Nalin S Conway, David I Znaor, Ariana Healy, Claire M Ahrens, Wolfgang Zaridze, David Szeszenia-Dabrowska, Neonilia Lissowska, Jolanta Fabianova, Eleonora Mates, Ioan Nicolae Bencko, Vladimir Foretova, Lenka Janout, Vladimir Curado, Maria Paula Koifman, Sergio Menezes, Ana Wunsch-Filho, Victor Eluf-Neto, Jose Boffetta, Paolo Fernandez Garrote, Leticia Polesel, Jerry Lener, Marcin Jaworowska, Ewa Lubinski, Jan Boccia, Stefania Rajkumar, Thangarajan Samant, Tanuja A Mahimkar, Manoj B Matsuo, Keitaro Franceschi, Silvia Byrnes, Graham Brennan, Paul McKay, James D eng 1R03DE020116/DE/NIDCR NIH HHS/ R01CA092039 05/05S1/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural 2015/04/04 06:00 J Natl Cancer Inst. 2015 Apr 2;107(5). pii: djv037. doi: 10.1093/jnci/djv037. Print 2015 May.; International audience; Deleterious BRCA2 genetic variants markedly increase risk of developing breast cancer. A rare truncating BRCA2 genetic variant, rs11571833 (K3326X), has been associated with a 2.5-fold risk of lung squamous cell carcinoma but only a modest 26% increase in breast cancer risk. We analyzed the association between BRCA2 SNP rs11571833 and upper aerodigestive tract (UADT) cancer risk with multivariable unconditional logistic regression adjusted by sex and combinations of study and country for 5942 UADT squamous cell carcinoma case patients and 8086 control patients from nine different studies. All statistical tests were two-sided. rs11571833 was associated with UADT cancers (odds ratio = 2.53, 95% confidence interval = 1.89 to 3.38, P = 3x10(-10)) and was present in European, Latin American, and Indian populations but extremely rare in Japanese populations. The association appeared more apparent in smokers (current or former) compared with never smokers (P het = .026). A robust association between a truncating BRCA2 variant and UADT cancer risk suggests that treatment strategies orientated towards BRCA2 mutations may warrant further investigation in UADT tumors.

Background: The role of human papillomavirus (HPV) on head and neck squamous cell carcinoma (HNSCC) survival in regions with low HPV prevalence is not yet clear. We evaluated the HPV16 infection on survival of HNSCC Brazilian patient series. Methods: This cohort comprised 1,093 HNSCC cases recruited from 1998 to 2008 in four Brazilian cities and followed up until June 2009. HPV16 antibodies were analyzed by multiplex Luminex assay. In a subset of 398 fresh frozen or paraffin blocks of HNSCC specimens, we analyzed for HPV16 DNA by L1 generic primer polymerase chain reaction. HNSCC survival according to HPV16 antibodies was evaluated through Kaplan-Meier method and Cox regression. Results: Prevalence of HPV16 E6 and E6/E7 antibodies was higher in oropharyngeal cancer than in other head and neck tumor sites. HPV16 DNA positive in tumor tissue was also higher in the oropharynx. Seropositivity for HPV16 E6 antibodies was correlated with improved HNSCC survival and oropharyngeal cancer. The presence of HPV16 E6/E7 antibodies was correlated with improved HNSCC survival and oropharyngeal cancer survival. The death risk of oropharyngeal squamous cell carcinoma patients HPV16 E6/E7 antibodies positive was 78 % lower than to those who test negative. Conclusion: Oropharyngeal squamous cell carcinoma is less aggressive in the HPV16 E6/E7 positive serology patients. HPV16 E6/E7 antibody is a clinically sensible surrogate prognostic marker of oropharyngeal squamous cell carcinoma. © 2014 Springer International Publishing.

Wyss, Annah Hashibe, Mia Chuang, Shu-Chun Lee, Yuan-Chin Amy Zhang, Zuo-Feng Yu, Guo-Pei Winn, Deborah M Wei, Qingyi Talamini, Renato Szeszenia-Dabrowska, Neonila Sturgis, Erich M Smith, Elaine Shangina, Oxana Schwartz, Stephen M Schantz, Stimson Rudnai, Peter Purdue, Mark P Eluf-Neto, Jose Muscat, Joshua Morgenstern, Hal Michaluart, Pedro Jr Menezes, Ana Matos, Elena Mates, Ioan Nicolae Lissowska, Jolanta Levi, Fabio Lazarus, Philip La Vecchia, Carlo Koifman, Sergio Herrero, Rolando Hayes, Richard B Franceschi, Silvia Wunsch-Filho, Victor Fernandez, Leticia Fabianova, Eleonora Daudt, Alexander W Dal Maso, Luigino Curado, Maria Paula Chen, Chu Castellsague, Xavier de Carvalho, Marcos Brasilino Cadoni, Gabriella Boccia, Stefania Brennan, Paul Boffetta, Paolo Olshan, Andrew F eng R03 CA113157/CA/NCI NIH HHS/ R24 HD041025/HD/NICHD NIH HHS/ T32-CA09330/CA/NCI NIH HHS/ T32ES007018/ES/NIEHS NIH HHS/ Meta-Analysis Research Support, N.I.H., Extramural 2013/07/03 06:00 Am J Epidemiol. 2013 Sep 1;178(5):679-90. doi: 10.1093/aje/kwt029. Epub 2013 Jun 30.; International audience; 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 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 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% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend

Li, Qian Chuang, Shu-Chun Eluf-Neto, Jose Menezes, Ana Matos, Elena Koifman, Sergio Wunsch-Filho, Victor Fernandez, Leticia Daudt, Alexander W Curado, Maria Paula Winn, Deborah M Franceschi, Silvia Herrero, Rolando Castellsague, Xavier Morgenstern, Hal Zhang, Zuo-Feng Lazarus, Philip Muscat, Joshua McClean, Michael Kelsey, Karl T Hayes, Richard B Purdue, Mark P Schwartz, Stephen M Chen, Chu Benhamou, Simone Olshan, Andrew F Yu, Guopei Schantz, Stimson Ferro, Gilles Brennan, Paul Boffetta, Paolo Hashibe, Mia eng K07CA104231/CA/NCI NIH HHS/ P01CA068384/CA/NCI NIH HHS/ P30ES010126/ES/NIEHS NIH HHS/ P50CA90388/CA/NCI NIH HHS/ R01CA048896/CA/NCI NIH HHS/ R01CA078609/CA/NCI NIH HHS/ R01CA100679/CA/NCI NIH HHS/ R01CA51845/CA/NCI NIH HHS/ R01CA61188/CA/NCI NIH HHS/ R01DA11386/DA/NIDA NIH HHS/ R01DE012609/DE/NIDCR NIH HHS/ R01DE13158/DE/NIDCR NIH HHS/ R03 CA113157-01/CA/NCI NIH HHS/ R03 CA113157-02/CA/NCI NIH HHS/ R03 DE016611/DE/NIDCR NIH HHS/ R03 DE016611-01/DE/NIDCR NIH HHS/ R03 DE016611-02/DE/NIDCR NIH HHS/ R03CA113157/CA/NCI NIH HHS/ R03CA77954/CA/NCI NIH HHS/ R21ES011667/ES/NIEHS NIH HHS/ R24 HD050924/HD/NICHD NIH HHS/ T32CA09142/CA/NCI NIH HHS/ U01CA96134/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2011/12/17 06:00 Int J Cancer. 2012 Oct 1;131(7):1686-99. doi: 10.1002/ijc.27405. Epub 2012 Jan 27.; International audience; To investigate the potential role of vitamin or mineral supplementation on the risk of head and neck cancer (HNC), we analyzed individual-level pooled data from 12 case-control studies (7,002 HNC cases and 8,383 controls) participating in the International Head and Neck Cancer Epidemiology consortium. There were a total of 2,028 oral cavity cancer, 2,465 pharyngeal cancer, 874 unspecified oral/pharynx cancer, 1,329 laryngeal cancer and 306 overlapping HNC cases. Odds ratios (OR) and 95% confidence intervals (CIs) for self reported ever use of any vitamins, multivitamins, vitamin A, vitamin C, vitamin E, and calcium, beta-carotene, iron, selenium and zinc supplements were assessed. We further examined frequency, duration and cumulative exposure of each vitamin or mineral when possible and stratified by smoking and drinking status. All ORs were adjusted for age, sex, race/ethnicity, study center, education level, pack-years of smoking, frequency of alcohol drinking and fruit/vegetable intake. A decreased risk of HNC was observed with ever use of vitamin C (OR = 0.76, 95% CI = 0.59-0.96) and with ever use of calcium supplement (OR = 0.64, 95% CI = 0.42-0.97). The inverse association with HNC risk was also observed for 10 or more years of vitamin C use (OR = 0.72, 95% CI = 0.54-0.97) and more than 365 tablets of cumulative calcium intake (OR = 0.36, 95% CI = 0.16-0.83), but linear trends were not observed for the frequency or duration of any supplement intake. We did not observe any strong associations between vitamin or mineral supplement intake and the risk of HNC.

Chuang, Shu-Chun Jenab, Mazda Heck, Julia E Bosetti, Cristina Talamini, Renato Matsuo, Keitaro Castellsague, Xavier Franceschi, Silvia Herrero, Rolando Winn, Deborah M La Vecchia, Carlo Morgenstern, Hal Zhang, Zuo-Feng Levi, Fabio Dal Maso, Luigino Kelsey, Karl McClean, Michael D Vaughan, Thomas Lazarus, Philip Muscat, Joshua Ramroth, Heribert Chen, Chu Schwartz, Stephen M Eluf-Neto, Jose Hayes, Richard B Purdue, Mark Boccia, Stefania Cadoni, Gabriella Zaridze, David Koifman, Sergio Curado, Maria Paula Ahrens, Wolfgang Benhamou, Simone Matos, Elena Lagiou, Pagona Szeszenia-Dabrowska, Neonilla Olshan, Andrew F Fernandez, Leticia Menezes, Ana Agudo, Antonio Daudt, Alexander W Merletti, Franco Macfarlane, Gary J Kjaerheim, Kristina Mates, Dana Holcatova, Ivana Schantz, Stimson Yu, Guo-Pei Simonato, Lorenzo Brenner, Hermann Mueller, Heiko Conway, David I Thomson, Peter Fabianova, Eleonora Znaor, Ariana Rudnai, Peter Healy, Claire M Ferro, Gilles Brennan, Paul Boffetta, Paolo Hashibe, Mia eng K07CA104231/CA/NCI NIH HHS/ P01CA068384/CA/NCI NIH HHS/ P30 CA015704/CA/NCI NIH HHS/ P30ES010126/ES/NIEHS NIH HHS/ P50CA90388/CA/NCI NIH HHS/ R01 CA100679/CA/NCI NIH HHS/ R01 CA100679-09/CA/NCI NIH HHS/ R01 ES014843/ES/NIEHS NIH HHS/ R01CA048996/CA/NCI NIH HHS/ R01CA078609/CA/NCI NIH HHS/ R01CA100679/CA/NCI NIH HHS/ R01CA30022/CA/NCI NIH HHS/ R01CA51845/CA/NCI NIH HHS/ R01CA61188/CA/NCI NIH HHS/ R01DA11386/DA/NIDA NIH HHS/ R01DE012609/DE/NIDCR NIH HHS/ R01DE13158/DE/NIDCR NIH HHS/ R03CA113157/CA/NCI NIH HHS/ R03CA77954/CA/NCI NIH HHS/ R03DE016611/DE/NIDCR NIH HHS/ R21ES011667/ES/NIEHS NIH HHS/ R24 HD050924/HD/NICHD NIH HHS/ T32CA09142/CA/NCI NIH HHS/ U01CA96134/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Netherlands 2011/11/01 06:00 Cancer Causes Control. 2012 Jan;23(1):69-88. doi: 10.1007/s10552-011-9857-x. Epub 2011 Oct 29.; International audience; We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p (trend) < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p (trend) = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p (trend) = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p (trend) < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97).

The association of education, tobacco smoking, alcohol consumption, and interleukin-2 (IL-2 +114 and -384) and -6 (IL-6 -174) DNA polymorphisms with head and neck squamous cell carcinoma (HNSCC) was investigated in a cohort study of 445 subjects. IL-2 and IL-6 genotypes were determined by real-time PCR. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) of disease-specific survival according to anatomical sites of the head and neck. Mean age was 56 years and most patients were males (87.6%). Subjects with 5 or more years of schooling had better survival in larynx cancer. Smoking had no effect on HNSCC survival, but alcohol consumption had a statistically significant effect on larynx cancer. IL-2 gene +114 G/T (HR = 0.52; 95%CI = 0.15-1.81) and T/T (HR = 0.22; 95%CI = 0.02-3.19) genotypes were associated with better survival in hypopharynx cancer. IL-2 +114 G/T was a predictor of poor survival in oral cavity/oropharynx cancer and larynx cancer (HR = 1.32; 95%CI = 0.61-2.85). IL-2 -384 G/T was associated with better survival in oral cavity/oropharynx cancer (HR = 0.80; 95%CI = 0.45-1.42) and hypopharynx cancer (HR = 0.68; 95%CI = 0.21-2.20), but an inverse relationship was observed for larynx cancer. IL-6 -174 G/C was associated with better survival in hypopharynx cancer (HR = 0.68; 95%CI = 0.26-1.78) and larynx cancer (HR = 0.93; 95%CI = 0.42-2.07), and C/C reduced mortality in larynx cancer. In general, our results are similar to previous reports on the value of education, smoking, alcohol consumption, and IL-2 and IL-6 genetic polymorphisms for the prognosis of HNSCC, but the risks due to these variables are small and estimates imprecise.

Background: Recent studies support an important role for human papillomavirus (HPV) in a subgroup of head and neck squamous cell carcinomas (HNSCC). We have evaluated the HPV deoxyribonucleic acid (DNA) prevalence as well as the association between serological response to HPV infection and HNSCC in two distinct populations from Central Europe (CE) and Latin America (LA). Methods: Cases (n=2214) and controls (n=3319) were recruited from 1998 to 2003, using a similar protocol including questionnaire and blood sample collection. Tumour DNA from 196 fresh tissue biopsies was analysed for multiple HPV types followed by an HPV type-specific polymerase chain reaction (PCR) protocol towards the E7 gene from HPV 16. Using multiplex serology, serum samples were analysed for antibodies to 17 HPV types. Statistical analysis included the estimation of adjusted odds ratios (ORs) and the respective 95% confidence intervals (CIs). Results: HPV16 E7 DNA prevalence among cases was 3.1% (6/196), including 4.4% in the oropharynx (3/68), 3.8% in the hypopharynx/larynx (3/78) and 0% among 50 cases of oral cavity carcinomas. Positivity for both HPV16 E6 and E7 antibodies was associated with a very high risk of oropharyngeal cancer (OR=179, 95% CI 35.8-899) and hypopharyngeal/laryngeal cancer (OR=14.9, 95% CI 2.92-76.1).Conclusions: A very low prevalence of HPV DNA and serum antibodies was observed among cases in both CE and LA. The proportion of head and neck cancer caused by HPV may vary substantially between different geographical regions and studies that are designed to evaluate the impact of HPV vaccination on HNSCC need to consider this heterogeneity. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2010; all rights reserved.

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35). Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case–control studies. Results: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08–1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95–1.09, P = 0.66; P-heterogeneity (Phet) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12–1.34, P = 7 × 10−6) but not males (OR = 1.02, 95% CI = 0.97–1.08, P = 0.35; Phet = 6 × 10−4). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (Phet = 0.86). Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. Impact: Further research is warranted to elucidate the mechanisms underlying these observations. Cancer Epidemiol Biomarkers Prev; 20(4); 658–64. ©2011 AACR.

Background A higher burden of head and neck cancer has been reported to affect deprived populations. This study assessed the association between socioeconomic status and head and neck cancer, aiming to explore how this association is related to differences of tobacco and alcohol consumption across socioeconomic strata. Methods We conducted a case-control study in Sao Paulo, Brazil (1998–2006), including 1017 incident cases of oral, pharyngeal and laryngeal cancer, and 951 sex- and age-matched controls. Education and occupation were distal determinants in the hierarchical approach; cumulative exposure to tobacco and alcohol were proximal risk factors. Outcomes of the hierarchical model were compared with fully adjusted ORs. Results Individuals with lower education (OR 2.27; 95% CI 1.61 to 3.19) and those performing manual labour (OR 1.55; 95% CI 1.26 to 1.92) had a higher risk of disease. However, 54% of the association with lower education and 45% of the association with manual labour were explained by proximal lifestyle exposures, and socioeconomic status remained significantly associated with disease when adjusted for smoking and alcohol consumption. Conclusions Socioeconomic differences in head and neck cancer are partially attributable to the distribution of tobacco smoking and alcohol consumption across socioeconomic strata. Additional mediating factors may explain the remaining variation of socioeconomic status on head and neck cancer.

Background: Genetic variants in 15q25 have been identified as potential risk markers for lung cancer (LC), but controversy exists as to whether this is a direct association, or whether the 15q variant is simply a proxy for increased exposure to tobacco carcinogens. Methods: We performed a detailed analysis of one 15q single nucleotide polymorphism (SNP) (rs16969968) with smoking behaviour and cancer risk in a total of 17 300 subjects from five LC studies and four upper aerodigestive tract (UADT) cancer studies. Results: Subjects with one minor allele smoked on average 0.3 cigarettes per day (CPD) more, whereas subjects with the homozygous minor AA genotype smoked on average 1.2 CPD more than subjects with a GG genotype (P20 CPD) [odds ratio (OR)=1.13, 95% confidence interval (CI) 0.96-1.34, P=0.13 for heterozygotes and 1.81, 95% CI 1.39-2.35 for homozygotes, P

Background: Quitting tobacco or alcohol use has been reported to reduce the head and neck cancer risk in previous studies. However, it is unclear how many years must pass following cessation of these habits before the risk is reduced, and whether the risk ultimately declines to the level of never smokers or never drinkers. Methods: We pooled individual-level data from case-control studies in the International Head and Neck Cancer Epidemiology Consortium. Data were available from 13 studies on drinking cessation (9167 cases and 12 593 controls), and from 17 studies on smoking cessation (12 040 cases and 16 884 controls). We estimated the effect of quitting smoking and drinking on the risk of head and neck cancer and its subsites, by calculating odds ratios (ORs) using logistic regression models. Results: Quitting tobacco smoking for 1-4 years resulted in a head and neck cancer risk reduction [OR 0.70, confidence interval (CI) 0.61-0.81 compared with current smoking], with the risk reduction due to smoking cessation after =20 years (OR 0.23, CI 0.18-0.31), reaching the level of never smokers. For alcohol use, a beneficial effect on the risk of head and neck cancer was only observed after =20 years of quitting (OR 0.60, CI 0.40-0.89 compared with current drinking), reaching the level of never drinkers. Conclusions: Our results support that cessation of tobacco smoking and cessation of alcohol drinking protect against the development of head and neck cancer. © The Author 2009; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Alcohol and tobacco consumption are well-recognized risk factors for head and neck cancer (HNC). Evidence suggests that genetic predisposition may also play a role. Only a few epidemiologic studies, however, have considered the relation between HNC risk and family history of HNC and other cancers. We pooled individual-level data across 12 case-control studies including 8,967 HNC cases and 13,627 controls. We obtained pooled odds ratios (OR) using fixed and random effect models and adjusting for potential confounding factors. All statistical tests were two-sided. A family history of HNC in first-degree relatives increased the risk of HNC OR = 1.7, 95% confidence interval, CI, 1.2-2.3). The risk was higher when the affected relative was a sibling (OR = 2.2, 95% CI 1.6-3.1) rather than a parent (OR = 1.5, 95% CI 1.1-1.8) and for more distal HNC anatomic sites (hypopharynx and larynx). The risk was also higher, or limited to, in subjects exposed to tobacco. The OR rose to 7.2 (95% CI 5.5-9.5) among subjects with family history, who were alcohol and tobacco users. A weak but significant association (OR = 1.1, 95% CI 1.0-1.2) emerged for family history of other tobacco-related neoplasms, particularly with laryngeal cancer (OR = 1.3, 95% CI 1.1-1.5). No association was observed for family history of nontobacco-related neoplasms and the risk of HNC (OR = 1.0, 95% CI 0.9-1.1). Familial factors play a role in the etiology of HNC. In both subjects with and without family history of HNC, avoidance of tobacco and alcohol exposure may be the best way to avoid HNC. © 2008 Wiley-Liss, Inc.

Alcohol is an important risk factor for upper aerodigestive cancers and is principally metabolized by alcohol dehydrogenase (ADH) enzymes. We have investigated six ADH genetic variants in over 3,800 aerodigestive cancer cases and 5,200 controls from three individual studies. Gene variants rs1229984 (ADH1B) and rs1573496 (ADH7) were significantly protective against aerodigestive cancer in each individual study and overall (P = 10-10 and 10 -9, respectively). These effects became more apparent with increasing alcohol consumption (P for trend = 0.0002 and 0.065, respectively). Both gene effects were independent of each other, implying that multiple ADH genes may be involved in upper aerodigestive cancer etiology. © 2008 Nature Publishing Group.

Background: At least 75% of head and neck cancers are attributable to a combination of cigarette smoking and alcohol drinking. A precise understanding of the independent association of each of these factors in the absence of the other with the risk of head and neck cancer is needed to elucidate mechanisms of head and neck carcinogenesis and to assess the efficacy of interventions aimed at controlling either risk factor. Methods: We examined the extent to which head and neck cancer is associated with cigarette smoking among never drinkers and with alcohol drinking among never users of tobacco. We pooled individual-level data from 15 case - control studies that included 10 244 head and neck cancer case subjects and 15 227 control subjects, of whom 1072 case subjects and 5775 control subjects were never users of tobacco and 1598 case subjects and 4051 control subjects were never drinkers of alcohol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. All statistical tests were two-sided. Results: Among never drinkers, cigarette smoking was associated with an increased risk of head and neck cancer (OR for ever versus never smoking = 2.13, 95% CI = 1.52 to 2.98), and there were clear dose - response relationships for the frequency, duration, and number of pack-years of cigarette smoking. Approximately 24% (95% CI = 16% to 31%) of head and neck cancer cases among nondrinkers in this study would have been prevented if these individuals had not smoked cigarettes. Among never users of tobacco, alcohol consumption was associated with an increased risk of head and neck cancer only when alcohol was consumed at high frequency (OR for three or more drinks per day versus never drinking = 2.04, 95% CI = 1.29 to 3.21). The association with high-frequency alcohol intake was limited to cancers of the oropharynx/hypopharynx and larynx. Conclusions: Our results represent the most precise estimates available of the independent association of each of the two main risk factors of head and neck cancer, and they exemplify the strengths of large-scale consortia in cancer epidemiology. © The Author 2007. Published by Oxford University Press.