https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(14)70168-7.pdf

Respiratory risks from household air pollution in low and middle income countries

BACKGROUND
This case-referent study was conducted to elucidate the role of selected exogenous agents in the etiology of head and neck cancer. The factors studied were tobacco smoking, alcohol intake, the use of moist oral snuff, dietary factors, occupational exposures, and oral hygiene. In this first report, the authors discuss the impact of tobacco smoking, the use of oral snuff, and alcohol consumption.

METHODS
The study base was approximately 2 million person-years at risk and consisted of Swedish males age 40-79 years living in 2 geographic regions during the years 1988-1990. A total of 605 cases were identified in the base, and 756 controls were selected by stratified random sampling from population registries covering the base.

RESULTS
Among those who were tobacco smokers at the time of the study, the relative risk of head and neck cancer was 6.5% (95% confidence interval, 4.4-9.5%). After cessation of smoking, the risk gradually declined, and no excess risk was found after 20 years. The relative risk associated with alcohol consumption of 50 grams or more per day versus less than 10 grams per day was 5.5% (95% confidence interval, 3.1-9.6%). An almost multiplicative effect was found for tobacco smoking and alcohol consumption.

CONCLUSIONS
Tobacco smoking and alcohol intake had a strong interactive effect on the risk of squamous cell carcinoma of the head and neck. Moderate alcohol intake (10-19 grams per day) had little or no effect among nonsmokers. No increased risk was found for the use of Swedish oral snuff. Cancer 1998;82:1367-75. © 1998 American Cancer Society.

Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck: a population-based case-referent study in Sweden.

pReVIously ClAssIfIed by IARC As “CARCInogenIC to humAns (gRoup 1)” And wAs deVeloped by sIx sepARAte woRkIng gRoups: phARmACeutICAls; bIologICAl Agents; ARsenIC, metAls, fIbRes, And dusts; RAdIAtIon; peRsonAl hAbIts And IndooR CombustIons; ChemICAl Agents And RelAted oCCupAtIons. thIs Volume 100f CoVeRs ChemICAl Agents And RelAted oCCupAtIons, speCIfICAlly 4-AmInobIphenyl, benzIdIne, dyes metAbolIzed to benzIdIne, 4,4’-methylenebIs(2-ChloRoAnIlIne), 2-nAphthylAmIne, oRtho-toluIdIne, AuRAmIne And AuRAmIne pRoduCtIon, mAgentA And mAgentA pRoduCtIon, benzo[A]pyRene, CoAl gAsIfICAtIon, oCCupAtIonAl exposuRes duRIng CoAl-tAR dIstIllAtIon, CoAl-tAR pItCh, Coke pRoduCtIon, untReAted oR mIldly tReAted mIneRAl oIls, shAle oIls, soot, As found In oCCupAtIonAl exposuRe of ChImney-sweeps, oCCupAtIonAl exposuRes duRIng AlumInIum pRoduCtIon, AflAtoxIns, benzene, bIs(ChloRomethyl)etheR And ChloRomethyl methyl etheR, 1,3-butAdIene, 2,3,7,8-tetRAChloRodIbenzo-pARA-dIoxIn, 2,3,4,7,8-pentAChloRodIbenzofuRAn, And 3,3’,4,4’,5-pentAChloRobIphenyl, ethylene oxIde, foRmAldehyde, sulfuR mustARd, VInyl ChloRIde, IsopRopyl AlCohol mAnufACtuRe by the stRong-ACId pRoCess, mIsts fRom stRong InoRgAnIC ACIds, oCCupAtIonAl exposuRes duRIng IRon And steel foundIng, oCCupAtIonAl exposuRe As A pAInteR, oCCupAtIonAl exposuRes In the RubbeR mAnufACtuRIng IndustRy. beCAuse the sCope of Volume 100 Is so bRoAd, Its monogRAphs ARe foCused on key InfoRmAtIon. eACh monogRAph pResents A desCRIptIon of A CARCInogenIC Agent And how people ARe exposed, CRItICAl oVeRVIews of the epIdemIologICAl studIes And AnImAl CAnCeR bIoAssAys, And A ConCIse ReVIew of the Agent’s toxICokInetICs, plAusIble meChAnIsms of CARCInogenesIs, And potentIAlly susCeptIble populAtIons, And lIfe-stAges. detAIls of the desIgn And Results of IndIVIduAl epIdemIologICAl studIes And AnImAl CAnCeR bIoAssAys ARe summARIzed In tAbles. shoRt tAbles thAt hIghlIght key Results ARe pRInted In Volume 100, And moRe extensIVe tAbles thAt InClude All studIes AppeAR on the monogRAphs pRogRAmme websIte (http://monogRAphs.IARC.fR). It Is hoped thAt thIs Volume, by CompIlIng the knowledge ACCumulAted thRough seVeRAl deCAdes of CAnCeR ReseARCh, wIll stImulAte CAnCeR pReVentIon ACtIVItIes woRldwIde, And wIll be A VAlued ResouRCe foR futuRe ReseARCh to IdentIfy otheR Agents suspeCted of CAusIng CAnCeR In humAns. D es ig n by A ude la d es m ot s

iArc monogrAphs on the evAluAtion oF cArcinogenic risks to humAns

Head and neck cancers are a heterogeneous collection of malignancies of the upper aerodigestive tract, salivary glands and thyroid. In this Review, we primarily focus on the changing therapeutic landscape of head and neck squamous cell carcinomas (HNSCCs) that can arise in the oral cavity, oropharynx, hypopharynx and larynx. We highlight developments in surgical and non-surgical therapies (mainly involving the combination of radiotherapy and chemotherapy), outlining how these treatments are being used in the current era of widespread testing for the presence of human papillomavirus infection in patients with HNSCC. Finally, we describe the clinical trials that led to the approval of the first immunotherapeutic agents for HNSCC, and discuss the development of strategies to decrease the toxicity of different treatment modalities.

The changing therapeutic landscape of head and neck cancer.

Purpose Although p16 protein expression, a surrogate marker of oncogenic human papillomavirus (HPV) infection, is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC), its prevalence and significance have not been well established in cancer of the oral cavity, hypopharynx, or larynx, collectively referred as non-OPSCC, where HPV infection is less common than in the oropharynx. Patients and Methods p16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129, 0234, and 0522 studies were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). Hazard ratios from Cox models were expressed as positive or negative, stratified by trial, and adjusted for clinical characteristics. Results p16 expression was positive in 14.1% (12 of 85), 24.2% (23 of 95), and 19.0% (27 of 142) and HPV ISH was positive in 6.5% (six of 93), 14.6% (15 of 103), and 6.9% (seven of 101) of non-OPSCCs from RTOG 0129, 0234, and 0522 studies, respectively. Hazard ratios for p16 express...

p16 Protein Expression and Human Papillomavirus Status As Prognostic Biomarkers of Nonoropharyngeal Head and Neck Squamous Cell Carcinoma

We carried out two case-control studies on the relative risk of head and neck cancer in association with tobacco and alcohol consumption. The first study carried out at the ENT Department of the University hospitals of Heidelberg and Giessen (FRG) comprised 200 male patients with squamous cell cancer of the head and neck and 800 control subjects matched for sex, age, and residential area (1:4 matching design). Of the tumour patients, 4.5% had never smoked, in contrast to 29.5% of the control group. The average tobacco and alcohol consumption of the patients was approximately twice as high as in the control subjects. The highest alcohol and tobacco consumption was observed in patients suffering from oropharyngeal cancer. Tobacco and alcohol increased the risk of head and neck cancer in a dose-dependent fashion and acted as independent risk factors. In heavy smokers (> 60 pack-years) a relative risk of 23.4 (alcohol adjusted) was calculated. Combined alcohol and tobacco consumption showed a synergistic effect. The risk ratio increased more in a multiplicative than in an additive manner. Oral and laryngeal cancer were associated with the highest tobacco-associated risk values. The highest ethanol-associated risk values were associated with oropharyngeal and laryngeal cancer. The second study was carried out at the ENT Department of the University of Heidelberg on 164 males with squamous cell carcinoma of the larynx and 656 control subjects matched for sex, age and residential area (1:4 matching design). Of the cases, 4.2% had never smoked, compared with 28.5% of the control subjects. The risk of laryngeal cancer by tobacco consumption was dose dependent, reaching a maximum value of 9.1 (adjusted for alcohol) for a consumption of more than 50 tobacco-years (TY). The relative risk of laryngeal cancer associated with alcohol intake was also dose dependent, reaching a value of 9.0 (adjusted for tobacco) for a mean daily consumption of more than 75 g alcohol. An analysis of subsite specific risks showed that heavy smokers (> 50 TY) carried a nearly ten times higher risk of supraglottic cancer than of glottic cancer. The risk of supraglottic cancer from alcohol consumption was also higher than that of glottic cancer.

Tobacco and alcohol and the risk of head and neck cancer

A case-control study of squamous cell carcinoma of the upper aerodigestive tract conducted in Heidelberg and Giessen (FRG) provided information on occupational factors in 200 patients and 800 controls (adjusted to sex, age and area of living; 4:1 matched design). The number of subjects exposed to wood dusts, organic chemicals, coal products or to cement was significantly elevated in the tumour group. An increased risk for head and neck cancer was observed after exposition to wood dust (RR = 2,2), organic compounds (RR = 2,4), coal products (RR = 2,7) and especially to cement (RR = 4,4). The cancer risk due to cement exposition showed a positive correlation to the duration of exposition and remained significantly elevated after adjustment for alcohol and tobacco consumption.

[Occupational exposure to hazardous substances and risk of cancer in the area of the mouth cavity, oropharynx, hypopharynx and larynx. A case-control study]

We conducted a case-control study of squamous cell carcinoma of the larynx referred to occupational factors in 164 patients compared with 656 controls adjusted for sex, age and area of residence, using a 1-to-4 matched design. Most of the cancer patients (92%) were blue collar workers. Only 8% of the cancer patients had attended technical college, college or university, compared with 31.3% of the control subjects. After adjustment for alcohol and tobacco consumption we found an increased relative risk of laryngeal cancer in subjects chronically exposed to cement dust, pine wood dust and coal-tar products. The risk associated with cement dust and coal-tar products was predominantly related to supraglottic cancer (RR = 1.88, CI = 0.8-4.3, RR = 6.11, CI = 1.7-21.6), respectively, after adjustment for tobacco and alcohol use. The risk associated with pine wood dust was related predominantly to glottic cancer (RR = 3.18, CI = 1.1-9.0) after adjustment for tobacco and alcohol use.

[Laryngeal cancer and occupation--results of the Heidelberg laryngeal cancer study].

A case-control study of squamous cell carcinoma of the upper aerodigestive tract conducted in the ENT Departments of the University hospitals of Heidelberg and Giessen (FRG) provided information on the role of chronic tobacco and alcohol consumption as risk factors in 200 patients and 800 control subjects (4:1 matched design).--Only 4.5% of the tumour patients were non-smokers in contrast to 29.5% in the control group. The average tobacco and alcohol consumption in the patients was more than twice that high than in the control subjects. The highest alcohol and tobacco consumption was observed in patients suffering from oropharyngeal cancer.--It could be demonstrated that tobacco as well as alcohol increased the risk for head and neck cancer, in a dose-dependent fashion, as separate risk factors. In heavy smokers (greater than 60 pack years) a relative risk of 23.4 (alcohol-adjusted) was calculated. For heavy drinkers (greater than 100 g ethanol/day) a relative risk of 21.4 (tobacco-adjusted) was documented. Combined alcohol and tobacco consumption showed a synergistic effect and increased the cancer risk more in an multiplicative than in an additive manner: A daily ethanol consumption of more than 75 g/day combined with more than 50 pack years caused a risk value of 146.2.

Tabak- und alkoholassoziiertes Krebsrisiko im Bereich des oberen Atmungs- und Verdauungstraktes

From 1989 to 1991 a case-control study was conducted at the ENT Department of the University of Heidelberg. One hundred and one patients with parotid tumors (84 benign and 17 malignant) were compared with 404 control patients in a matched-pair study design. Using a questionnaire containing 21 sides, all interviews were conducted by the same interviewer. The questionnaire contained such aspects as "professional surroundings and exposure to environmental dusts", "consumption of tobacco and alcohol", "living area", "nutrition", "hobbies" and "social life". Questions about personal and familial diseases, consumption of medicine and exposure to irradiation were also asked. Differences in exposure to occupational dusts were seen. The highest relative risk (RR) for developing a parotid tumor was seen with weekly exposure to nickel during a period of more than 10 years (RR = 6.0; confidence interval, 1.4-25.5). Similar risk was found with exposure to chromium, asbestos and cement dusts (RR chromium = 3.4; confidence interval, 0.9-14.5; RR asbestos + cement = cement 3.0, confidence interval 1.0-8.9). Higher relative risks were also detected in patients exposed to diagnostic dental x-rays.

U. Gewelke

Papers

Tobacco and alcohol and the risk of head and neck cancer

[Occupational exposure to hazardous substances and risk of cancer in the area of the mouth cavity, oropharynx, hypopharynx and larynx. A case-control study]

[Laryngeal cancer and occupation--results of the Heidelberg laryngeal cancer study].

Tabak- und alkoholassoziiertes Krebsrisiko im Bereich des oberen Atmungs- und Verdauungstraktes

The epidemiology of parotid tumors. A case control study