Folate intake and the risk of oral cavity and pharyngeal cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology Consortium.

There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual-level data from ten case-control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43-0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43-0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45-0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43-4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4-20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34-3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41-20.8%). Our project of a large pool of case-control studies supports a protective effect of total folate intake on OPC risk.

Tea intake and risk of oral, pharyngeal, and laryngeal carcinoma: a meta-analysis.

BACKGROUND: The association between tea intake and risk of oral, pharyngeal, and laryngeal carcinoma is still unclear. The aim of this meta-analysis was to quantify the effect of tea consumption on the incidence of oral, pharyngeal, and laryngeal cancer to provide a better understanding on this issue. MATERIAL/METHODS: A literature search was conducted before January 2014 in MEDLINE and EMBASE databases. The relative risk (RR) estimates that extracted or calculated from all included studies were combined together. Given the existing heterogeneity in the study design and data source, a random-effects model was obtained. RESULTS: A total of 20 articles were included in the quantitative synthesis. Fourteen RR estimates (11 from case-control studies and 3 from cohort studies) were pooled together and the result demonstrated that tea consumption reduced the incidence of oral cancer (RR=0.85; 95% CI 0.76-0.96). The summary RR of 4 observational studies (3 case-control studies and 1 cohort study) for pharyngeal cancer was 0.87 (95% CI 0.74-1.04). The association between tea consumption and oral and pharyngeal carcinoma was reported. The summary RR for laryngeal carcinoma was 1.05 (95% CI 0.70-1.57). The Begg's funnel plot and the Egger's test showed no evidence of publication bias. CONCLUSIONS: Tea consumption was associated with decreased risk of oral cancer, while no association was detected with oral/pharyngeal, pharyngeal, or laryngeal cancer.

Coffee, tea, and fatal oral/pharyngeal cancer in a large prospective US cohort.

Epidemiologic studies suggest that coffee intake is associated with reduced risk of oral/pharyngeal cancer. The authors examined associations of caffeinated coffee, decaffeinated coffee, and tea intake with fatal oral/pharyngeal cancer in the Cancer Prevention Study II, a prospective US cohort study begun in 1982 by the American Cancer Society. Among 968,432 men and women who were cancer free at enrollment, 868 deaths due to oral/pharyngeal cancer occurred during 26 years of follow-up. Cox proportional hazards regression was used to estimate multivariable-adjusted relative risk. Intake of >4 cups/day of caffeinated coffee was associated with a 49% lower risk of oral/pharyngeal cancer death relative to no/occasional coffee intake (relative risk = 0.51, 95% confidence interval: 0.40, 0.64) (1 cup/day = 237 ml). A dose-related decline in relative risk was observed with each single cup/day consumed (P(trend) < 0.001). The association was not modified by sex, smoking status, or alcohol use. An inverse association for >2 cups/day of decaffeinated coffee intake was suggested (relative risk = 0.61, 95% confidence interval: 0.37, 1.01). No association was found for tea drinking. In this large prospective study, caffeinated coffee intake was inversely associated with oral/pharyngeal cancer mortality. Research is needed to elucidate biologic mechanisms whereby coffee might help to protect against these often fatal cancers.

Coffee and cancers of the upper digestive and respiratory tracts: meta-analyses of observational studies.

BACKGROUND: Data of epidemiological studies on the relation between coffee drinking and upper aerodigestive tract cancer risk are scattered and inconclusive. We therefore conducted systematic meta-analyses of observational studies published before October 2009. MATERIALS AND METHODS: We combined relative risks (RR) with 95% confidence intervals (CI) for cancers of the oral cavity/pharynx (OP) and larynx, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), comparing the highest versus the lowest categories of coffee consumption, using random-effects models. RESULTS: For OP cancer, the pooled RR was 0.64 (95% CI 0.51-0.80) for highest versus lowest coffee drinking, based on a total of 2633 cases from one cohort and eight case-control studies, with no significant heterogeneity across studies. The RRs were 0.61 (95% CI 0.41-0.89) for European, 0.58 (95% CI 0.36-0.94) for American and 0.74 (95% CI 0.48-1.15) for Asian studies, where coffee consumption is lower. The corresponding RRs were 1.56 (95% CI 0.60-4.02) for laryngeal cancer (732 cases from three case-control studies), 0.87 (95% CI 0.65-1.17) for ESCC (2115 cases from one cohort and six case-control studies) and 1.18 (95% CI 0.81-1.71) for EAC (415 cases from three case-control studies). CONCLUSION: Coffee drinking is inversely related to OP cancer risk, while there is no relation with laryngeal cancer, ESCC and EAC.

Coffee and tea intake and risk of head and neck cancer: pooled analysis in the international head and neck cancer epidemiology consortium.

BACKGROUND: Only a few studies have explored the relation between coffee and tea intake and head and neck cancers, with inconsistent results. METHODS: We pooled individual-level data from nine case-control studies of head and neck cancers, including 5,139 cases and 9,028 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI), adjusting for potential confounders. RESULTS: Caffeinated coffee intake was inversely related with the risk of cancer of the oral cavity and pharynx: the ORs were 0.96 (95% CI, 0.94-0.98) for an increment of 1 cup per day and 0.61 (95% CI, 0.47-0.80) in drinkers of >4 cups per day versus nondrinkers. This latter estimate was consistent for different anatomic sites (OR, 0.46; 95% CI, 0.30-0.71 for oral cavity; OR, 0.58; 95% CI, 0.41-0.82 for oropharynx/hypopharynx; and OR, 0.61; 95% CI, 0.37-1.01 for oral cavity/pharynx not otherwise specified) and across strata of selected covariates. No association of caffeinated coffee drinking was found with laryngeal cancer (OR, 0.96; 95% CI, 0.64-1.45 in drinkers of >4 cups per day versus nondrinkers). Data on decaffeinated coffee were too sparse for detailed analysis, but indicated no increased risk. Tea intake was not associated with head and neck cancer risk (OR, 0.99; 95% CI, 0.89-1.11 for drinkers versus nondrinkers). CONCLUSIONS: This pooled analysis of case-control studies supports the hypothesis of an inverse association between caffeinated coffee drinking and risk of cancer of the oral cavity and pharynx. IMPACT: Given widespread use of coffee and the relatively high incidence and low survival of head and neck cancers, the observed inverse association may have appreciable public health relevance.

Nutrient-based dietary patterns and the risk of oral and pharyngeal cancer.

The relationship between diet and oral and pharyngeal cancer has been rarely addressed considering dietary patterns. We examined this issue using data from a case-control study carried out between 1992 and 2005. Cases were 804 incident oral cancers hospitalized in 3 Italian areas. Controls were 2080 subjects hospitalized for non-neoplastic diseases. Dietary habits were investigated through a validated 78-item food-frequency questionnaire. Overall and individual measures of sampling adequacy were calculated to assess if applying a factor analysis or not. A posteriori dietary patterns were identified through a principal component factor analysis performed on a selected set of 29 nutrients. The internal reproducibility, robustness and reliability of the identified patterns were evaluated. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models on quintiles of factor scores. The measures of sampling adequacy were generally satisfactory. We identified five major dietary patterns named Animal products, Starch-rich, Vitamins and fiber, Unsaturated fats and Retinol and niacin. The Animal products pattern was positively associated with oral cancer (OR=1.56, 95% CI: 1.13-2.15 for the highest vs. the lowest score quintile), whereas the Starch-rich pattern (OR=0.71, 95% CI: 0.50-0.99), the Vitamins and fiber pattern (OR=0.47, 95% CI: 0.34-0.65) and the Unsaturated fats pattern (OR=0.63, 95% CI: 0.45-0.86) were inversely associated with it. These findings confirm that diets rich in animal origin and animal fats are positively, and those rich in fruit and vegetables, and vegetable fats inversely related to oral and pharyngeal cancer risk.

Maté drinking and oral and oro-pharyngeal cancer: a systematic review and meta-analysis.

In Latin America, maté is consumed as a beverage regularly. Among the cancers that are associated with maté drinking is oral and oro-pharyngeal cancer, incidence of which is high in the region. In order to further understand this association between maté drinking and the risk of oral and oro-pharyngeal cancer, we performed a systematic review and meta-analysis of related studies. All relevant studies published in English as original articles up to June 2009 were identified through a literature search using PubMed and Medline and by reviewing the references from the retrieved articles. Four case-control studies done in Latin America were identified. There were 879 maté users and 1128 non- or low-maté users in those studies with a total of 566 oral and oro-pharyngeal cancers. The adjusted association between maté drinking and oral and oro-pharyngeal cancer was significant within 3 of those studies. Meta-analysis yielded a significant summary odds ratio (OR) of 2.11 (95% confidence interval=1.39-3.19). Population Attributable Risk for maté drinking was 16%. While the epidemiological data indicate that maté users have an increased risk of oral and oro-pharyngeal cancer, little is known about whether this increased risk is due to the high temperature of the beverage when it is consumed or due to certain carcinogenic constituents that are present in maté. More human and animal studies are needed before a conclusion can be made on the oral and oro-pharyngeal carcinogenic risk of maté to humans.

Coffee consumption and the risk of oral, pharyngeal, and esophageal cancers in Japan: the Miyagi Cohort Study.

An inverse association between coffee consumption and the risk of oral, pharyngeal, and esophageal cancers has been suggested in case-control studies, but few results from prospective studies are available. Data from the Miyagi Cohort Study in Japan were used to clarify the association between coffee consumption and the risk of these cancers. Information about coffee consumption was obtained from self-administered food frequency questionnaires in 1990. Among 38,679 subjects aged 40-64 years with no previous history of cancer, 157 cases of oral, pharyngeal, and esophageal cancers were identified during 13.6 years of follow-up. Hazard ratios were estimated by the Cox proportional hazards regression model. The risk of oral, pharyngeal, and esophageal cancers was inversely associated with coffee consumption. The multivariate-adjusted hazard ratio of these cancers for > or =1 cups of coffee per day compared with no consumption was 0.51 (95% confidence interval: 0.33, 0.77). This inverse association was consistent regardless of sex and cancer site and was observed both for subjects who did not drink or smoke and for those who currently drank or smoked at baseline. In conclusion, coffee consumption was associated with a lower risk of oral, pharyngeal, and esophageal cancers, even in the group at high risk of these cancers.

Effect of dietary antioxidants and risk of oral, pharyngeal and laryngeal squamous cell carcinoma according to smoking and drinking habits.

Several intervention trials and prospective studies have reported that beta-carotene supplementation is not associated with a decreased risk of several cancers among smokers and drinkers, and that it may even have adverse effects in these groups. The relationship between dietary antioxidant intake and the risk of head and neck squamous cell carcinoma (HNSCC) has been examined intensively, but little is known about the effects of antioxidants on HNSCC with respect to smoking and drinking habits. Here, we conducted a case-control study of 385 histologically confirmed cases of HNSCC (193 oral, 132 pharyngeal and 60 laryngeal), excluding nasal and paranasal cancer, and 1925 age-matched and sex-matched cancer-free outpatient controls using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center, Japan. The intake of nutrients and food groups was assessed with a food frequency questionnaire, and multivariate-adjusted odds ratios for cancer were estimated for smoking and drinking habits using logistic models. The results showed an overall inverse association between the intake of dietary antioxidants, including carotene, and vitamins C and E, and risk of HNSCC. The protective effect of these antioxidants was seen in both men and women. High consumption of antioxidants was associated with a decreased risk of HNSCC among smokers, drinkers and those with both smoking and drinking habits. These findings suggest that dietary antioxidant intake prevents HNSCC in smokers and drinkers.

Tobacco use and oral cancer: a global perspective.

For both genders, cancer of the mouth and pharynx ranks sixth overall in the world; it is also the third most common site among males in developing countries. In industrialized countries, men are affected two to three times as often as women, largely due to higher use of alcohol and tobacco. Ethnicity strongly influences prevalence due to social and cultural practices, as well as socioeconomic differences. In population terms, survival rates around the world show little improvement. In terms of etiology, the effects of tobacco use, heavy alcohol consumption, and poor diet together explain over 90 percent of cases of head and neck cancer. All forms of tobacco represent risk factors for oral cancer, but on present evidence, snuff habits as they exist in Scandinavia and probably in the United States carry lower risks of serious health hazards, including oral cancer. Alcohol synergizes with tobacco as a risk factor for all upper aerodigestive tract SCC: this is super-multiplicative for the mouth, additive for the larynx, and between additive and multiplicative for the esophagus. The increase in oral cancer in the Western world has been related to rising alcohol use.

[Surgical treatment of neck lymph nodes in squamous cell carcinoma of the pyriform sinus]. / Il trattamento chirurgico dei linfonodi del collo nel carcinoma squamocellulare del seno piriforme.

The present study reports the results of 66 patients surgically treated for squamous cell carcinoma of the pyriform sinus between 1984 and 1996. Twenty eight patients underwent mono!ateral neck dissection and bilateral neck dissection was performed in 38 cases, for a total of 104 radical neck dissections. Of these, 73 (71%) were modified type III dissections, 17 (16%) were classical, and 14 (13%) were modified type I and II dissections. The primary lesion was strictly lateralized in 47 cases (71%), while median structures were involved in 19 patients. The primary tumor was staged pT1 in 2 patients, pT2 in 29, pT3 in 19, and pT4 in 16. The overall incidence of lymph node metastases was 79% (9 pN1, 3 pN2a, 33 pN2b, 7 pN2c) which was not correlated with T stage (50% pT1, 72% pT2, 89% pT3, 81% pT4). Occult nodal metastases were present in 42% of cases (8/19) with an incidence that increased from 11% (1/9) for pT1-2 to 70% for pT3-4 (7/10). The bilateral metastases (11%) were uniformly distributed between strictly lateral neoplasms and those tumors involving the midline. The incidence of bilateral metastases reached 19% only in patients with T4 cancers. Occult controlateral metastases were found in 12% of patients not having clinical evidence of metastases on the contro-lateral side of neck dissection (4/33). Nodal metastases never involved the I and V levels. Our data did not permit an assessment of the incidence of retropharyngeal lymph node metastases. In view of these results and considering current knowledge of the anatomy of lymphatic drainage, a selective II-IV dissection extending to the level VI on the side of the tumor appears justified in cases clinically staged as NO. In our view, when the lesion involves the posterior wall of the pharynx, neck dissection should be extended to the lateral retropharyngeal lymph nodes. Selective dissection of the controlateral side of the neck should be performed in patients having either locally advanced primary lesions or with lesions approaching the midline. In the presence of metastases which are either clinically or intraoperatively evident, neck dissection should be extended to additional lymph node levels.

[Elements of epidemiology and initiation of carcinogenesis in carcinomas of the upper aerodigestive tract. Future therapeutic consequence?]. / Eléments d'épidémiologie et initiation de la cancérogénèse dans les carcinomes des VADS. Conséquence thérapeutique future?

The study of epidemiology and of the carcinogenesis in epidermoid carcinomas of the upper aerodigestive tract shows that their occurrence is not random. Tobacco abuse plays a major role, especially because of benzopyrene, mutagen of the P53 gene, however it is associated with many other potentiating factors: alcohol, metals, hydrocarbures, virus, food, climate, genetic fragility that create genetic lesions at the origin of carcinogenesis. The latter occurs as "field cancerization" with multiple alterations of the mucosa and general attack of the control systems of the differentiation, growth and cell apoptosis which usually protect the cell against the phenomena of carcinogenesis. The P53 protein gene, retinoid receptors as well as the system of detoxifying glutathion S transferase are modified at the very early stage of these diseases, these abnormalities can be logically related to epidemiological data. These data lead us therefore to imagine complementary specific reverting therapies of induced genetic abnormalities, through the reexpression of non mutated gene encoding P53 protein and the use of retinoid. These various modalities are reported hereafter.

Diagnostico e tratamento do cancer da faringe / Diagnosis and treatment of pharyngeal cancer

As afeccoes malignas das tres regioes da faringe - nasofaringe, orofaringe e hipofaringe - sao bastante distintas entre si no que diz respeito ao quadro clinico e ao tratamento. Enquanto na nasofaringe os tumores sao menos diferenciados e tratados principalmente pela radioterapia, os tumores da orofaringe e da hipofaringe sao mais diferenciados e, como regra, respondem melhor a terapeutica cirurgica associada a radioterapia pos-operatoria. Na terapeutica dos tumores da faringe, os linfonodos cervicais devem ser tratados pelo esvaziamento cervical e / ou pela radioterapia

Maté, coffee, and tea consumption and risk of cancers of the upper aerodigestive tract in southern Brazil.

Consumption of maté, a tea-like infusion of the herb Ilex paraguariensis, is common in South America. Drinkers have high risks of upper aerodigestive tract cancers, but it is conceivable that this high risk may be attributable to confounding by smoking alcohol, and other exposures. To test this hypothesis, we analyzed the data from a case-control study of upper aerodigestive tract cancers conducted in Southern Brazil. We matched noncancer controls (N = 756) to cases (N = 378) on the basis of age, sex, and period of admission. We estimated the effect of mateé consumption by conditional logistic regression with adjustment for smoking, alcohol, sociodemographics, and several dietary items, considered as confounders. The unadjusted relative risk (RR) for all upper aerodigestive tract cancers was 2.1 [95% confidence interval (CI) = 1.6-2.7]. Some excess risk persisted after adjustment for potential confounders (RR = 1.6; 95% CI = 1.2-2.2). Most of the excess risk for maté drinkers was for oral (RR = 1.9; 95% CI = 1.1-3.3) and laryngeal (RR = 2.2; 95% CI = 2.2; 95% CI = 1.1-4.5) cancers. There was no evidence of associations with coffee and tea drinking. We conclude that the association of maté consumption with upper aerodigestive tract cancer risk is unlikely to result from insufficient control of confounding by critical exposures. Owing to its high prevalence in Southern South America, maté drinking may be linked to as many as 20% of all cases occurring in this region.

Coffee and cancer: a prospective study of 43,000 Norwegian men and women.

Relationships between coffee drinking and cancer incidence were examined in a 10-year complete follow-up of 21,735 men and 21,238 women aged 35-54 years. The study population participated in a cardiovascular screening in three countries in Norway during 1977-82. Data on coffee and smoking habits were based on information from a self-administered questionnaire. There was no association between coffee consumption and overall risk of cancer. A positive association was found between coffee drinking and risk of lung cancer, also after adjustment for age, cigarette smoking, and county of residence. Residual confounding by cigarette smoking and other lifestyle factors cannot be ruled out. A negative association was found with cancer of buccal cavity and pharynx and with malignant melanoma in women. No significant associations were found between coffee drinking and incidence of cancer of the pancreas or the bladder.

Vitamin supplement use and reduced risk of oral and pharyngeal cancer.

Use of vitamin and mineral supplements was assessed in a population-based case-control study of oral and pharyngeal cancer, conducted during 1984-1985 in four areas of the United States. There was no association with intake of multivitamin products, but users of supplements of individual vitamins, including vitamins A, B, C, and E, were at lower risk after controlling for the effects of tobacco, alcohol, and other risk factors for these cancers. After further adjustment for use of other supplements, vitamin E was the only supplement that remained associated with a significantly reduced cancer risk. The adjusted odds ratio of oral and pharyngeal cancer for "ever regularly used" vitamin E was 0.5 (95% confidence interval 0.4-0.6). To the authors' knowledge, this is the first epidemiologic study to show a reduced oral cancer risk with vitamin E use. Although it is not clear that the lower risk among consumers of vitamin E supplements is due to the vitamin per se, the findings are consistent with experimental evidence and should prompt further research on the role of vitamin E and other micronutrients as inhibitors of oral and pharyngeal cancer.

Diet and pharyngeal cancer.

A population-based case-control study was conducted to examine the effect of ingestion of vitamin C, carotenoids and retinol on risk of pharyngeal cancer. Data were available from 166 cases of pharyngeal cancer or their next-of-kin, and from 547 controls similar in age and sex to the cases. Odds ratios (ORs) relating consumption of vitamin C, carotenoids and retinol from foods and vitamins C and A from supplements to risk of pharyngeal cancer were calculated using multiple logistic regression analysis. After adjustment for smoking and alcohol consumption, a significant increase in risk associated with low intake of vitamin C from foods was observed. Compared to the highest quartile, the OR for the lowest quartile of intake was 2.5 (95% confidence interval, 1.5-4.2). No overall effect of dietary carotenoid or retinol consumption was noted after adjustment for smoking and alcohol. Decreasing use of either vitamin C or vitamin A supplements was associated with increasing cancer risk among the case group as a whole. However, the effect of vitamin C supplement use was substantially lower when next-of-kin respondents were excluded from analysis. Also, the OR for use of vitamin A supplements is based on a very small number of cases reporting use, and must be viewed with caution. The results of our study suggest that intake of vitamin C may be protective against pharyngeal cancer, and are consistent with the results of previous studies which reported a decreased risk of pharyngeal cancer associated with intake of fruits and vegetables.

Cancer of the oral cavity, pharynx/larynx and lung in North Thailand: case-control study and analysis of cigar smoke.

The unusually high relative frequency of cancer in the laryngeal region in males (18% of all histologically diagnosed cancers) and a sex ratio of unity for lung cancer in Northern Thailand were further explored in a hospital-based case-control study in Chiang Mai. This compared patients having cancers of the oral cavity (including oropharynx), larynx, hypopharynx and lung, with controls in relation to smoking and chewing habits. Statistical analysis indicated that chewing betel is strongly associated with the occurrence of oral cancer in both sexes, and with cancer of the laryngeal region in males. No factors were strongly linked to lung cancer in men, but, in women, urban residence and miang chewing were associated with lung cancer. Analysis of smoke from the two main types of cigars smoked in the region showed that both had high tar content, but there were marked differences in pH. Smoking cigars with alkaline smoke and high tar had an increased risk for laryngeal cancer in males, whereas other cigars with acid smoke and high tar together with manufactured cigarettes had increased risks for lung cancer. These increased risks were not, however, statistically significant.

Habits and dietary pattern of cases of carcinoma of the oral cavity and oropharynx.

In 1192 biopsy proven cases of carcinoma of the oral cavity and oropharynx information was collected on the use of various chewing, smoking, and eating habits. The quantity used and the duration of use were also recorded. Information was also collected on the frequency of use of cereals, dairy products, meat, fish, fruits and vegetables. The information from carcinoma cases was compared with that from apparently healthy individuals.