Head and neck cancer prevention: from primary prevention to impact of clinicians on reducing burden.

Survival from head and neck cancers (HNCs) of the lip, oral cavity, pharynx, and larynx has increased by 10% over the past few decades. Little over half of patients who develop HNCs will survive beyond 5 years. Survival is lower for individuals in many countries where traditional risk factors such as tobacco smoking, alcohol drinking, and betel quid chewing are highly prevalent but tertiary health care center access is limited or unavailable. Early diagnosis of HNC is the most important prognostic factor for each tumor site. Molecular-based research on HNC tumors holds promise for early stage detection, screening, vaccination, disease follow-up, and progression. Future investments for HNC control must consider both effectiveness and sustainability for both high- and low-resource countries alike, with priority toward risk factor prevention and earlier diagnosis.

Shared and Study-specific Dietary Patterns and Head and Neck Cancer Risk in an International Consortium.

BACKGROUND: A few papers have considered reproducibility of a posteriori dietary patterns across populations, as well as pattern associations with head and neck cancer risk when multiple populations are available. METHODS: We used individual-level pooled data from seven case-control studies (3844 cases; 6824 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We simultaneously derived shared and study-specific a posteriori patterns with a novel approach called multi-study factor analysis applied to 23 nutrients. We derived odds ratios (ORs) and 95% confidence intervals (CIs) for cancers of the oral cavity and pharynx combined, and larynx, from logistic regression models. RESULTS: We identified three shared patterns that were reproducible across studies (75% variance explained): the Antioxidant vitamins and fiber (OR = 0.57, 95% CI = 0.41, 0.78, highest versus lowest score quintile) and the Fats (OR = 0.80, 95% CI = 0.67, 0.95) patterns were inversely associated with oral and pharyngeal cancer risk. The Animal products and cereals (OR = 1.5, 95% CI = 1.1, 2.1) and the Fats (OR = 1.8, 95% CI = 1.4, 2.3) patterns were positively associated with laryngeal cancer risk, whereas a linear inverse trend in laryngeal cancer risk was evident for the Antioxidant vitamins and fiber pattern. We also identified four additional study-specific patterns, one for each of the four US studies examined. We named them all as Dairy products and breakfast cereals, and two were associated with oral and pharyngeal cancer risk. CONCLUSION: Multi-study factor analysis provides insight into pattern reproducibility and supports previous evidence on cross-country reproducibility of dietary patterns and on their association with head and neck cancer risk. See video abstract at, http://links.lww.com/EDE/B430.

Alcohol and cigarette consumption predict mortality in patients with head and neck cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.

BACKGROUND: This study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC. PATIENTS AND METHODS: We conducted a pooled analysis, including 4759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis. RESULTS: Five-year OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined: 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR = 2.54, 95% CI 1.01-6.38, for high school or lower versus college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR = 1.73, 95% CI 1.16-2.58) and HNC-specific survival (current drinkers HR = 2.11, 95% CI 1.22-3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity (>20 cigarettes/day HR = 1.41, 95% CI 1.03-1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity. CONCLUSIONS: OS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, whereas pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low educational level is an unfavourable prognostic factor for OS in laryngeal cancer patients.

The role of oral hygiene in head and neck cancer: results from International Head and Neck Cancer Epidemiology (INHANCE) consortium.

BACKGROUND: Poor oral hygiene has been proposed to contribute to head and neck cancer (HNC) risk, although causality and independency of some indicators are uncertain. This study investigates the relationship of five oral hygiene indicators with incident HNCs. METHODS: In a pooled analysis of 8925 HNC cases and 12 527 controls from 13 studies participating in the International Head and Neck Cancer Epidemiology Consortium, comparable data on good oral hygiene indicators were harmonized. These included: no denture wear, no gum disease (or bleeding), <5 missing teeth, tooth brushing at least daily, and visiting a dentist ≥once a year. Logistic regression was used to estimate the effects of each oral hygiene indicator and cumulative score on HNC risk, adjusting for tobacco smoking and alcohol consumption. RESULTS: Inverse associations with any HNC, in the hypothesized direction, were observed for <5 missing teeth [odds ratio (OR) = 0.78; 95% confidence interval (CI) 0.74, 0.82], annual dentist visit (OR = 0.82; 95% CI 0.78, 0.87), daily tooth brushing (OR = 0.83, 95% CI 0.79, 0.88), and no gum disease (OR = 0.94; 95% CI 0.89, 0.99), and no association was observed for wearing dentures. These associations were relatively consistent across specific cancer sites, especially for tooth brushing and dentist visits. The population attributable fraction for ≤ 2 out of 5 good oral hygiene indicators was 8.9% (95% CI 3.3%, 14%) for oral cavity cancer. CONCLUSION: Good oral hygiene, as characterized by few missing teeth, annual dentist visits, and daily tooth brushing, may modestly reduce the risk of HNC.

Multigene testing of moderate-risk genes: be mindful of the missense.

BACKGROUND: Moderate-risk genes have not been extensively studied, and missense substitutions in them are generally returned to patients as variants of uncertain significance lacking clearly defined risk estimates. The fraction of early-onset breast cancer cases carrying moderate-risk genotypes and quantitative methods for flagging variants for further analysis have not been established. METHODS: We evaluated rare missense substitutions identified from a mutation screen of ATM, CHEK2, MRE11A, RAD50, NBN, RAD51, RINT1, XRCC2 and BARD1 in 1297 cases of early-onset breast cancer and 1121 controls via scores from Align-Grantham Variation Grantham Deviation (GVGD), combined annotation dependent depletion (CADD), multivariate analysis of protein polymorphism (MAPP) and PolyPhen-2. We also evaluated subjects by polygenotype from 18 breast cancer risk SNPs. From these analyses, we estimated the fraction of cases and controls that reach a breast cancer OR≥2.5 threshold. RESULTS: Analysis of mutation screening data from the nine genes revealed that 7.5% of cases and 2.4% of controls were carriers of at least one rare variant with an average OR≥2.5. 2.1% of cases and 1.2% of controls had a polygenotype with an average OR≥2.5. CONCLUSIONS: Among early-onset breast cancer cases, 9.6% had a genotype associated with an increased risk sufficient to affect clinical management recommendations. Over two-thirds of variants conferring this level of risk were rare missense substitutions in moderate-risk genes. Placement in the estimated OR≥2.5 group by at least two of these missense analysis programs should be used to prioritise variants for further study. Panel testing often creates more heat than light; quantitative approaches to variant prioritisation and classification may facilitate more efficient clinical classification of variants.

Sexual behaviours and head and neck cancer: A systematic review and meta-analysis.

Human papillomaviruses (HPV) are associated with head and neck cancers (H&NC). Transmission of HPV to the upper aerodigestive tract occurs plausibly through sexual contact, although epidemiologic evidence on the role of sexual behaviours in H&NC aetiology is inconsistent. We conducted a meta-analysis of studies examining the association between four indicators of sexual behaviours (number of sexual partners and oral sex partners, oral sex practice, and age at first intercourse) and H&NC. Summary odds ratios (OR) and 95% confidence intervals (CI) were estimated using fixed and random effects models for each indicator, contrasting 'highest' to 'lowest', 'ever' to 'never', or 'youngest' to 'oldest' categories. Twenty case-control studies were included out of 3838 identified publications. Using random effects models, summary ORs suggested an increased risk of H&NC for number of sexual partners [OR=1.29, 95% CI: 1.02-1.63] (19 studies) and number of oral sex partners [OR=1.69, 95% CI: 1.00-2.84] (5 studies), whereas no effect was observed with oral sex practice [OR=1.09, 95% CI: 0.88-1.35] (17 studies) and age at first intercourse [OR=1.40, 95% CI: 0.71-2.79] (6 studies). For number of sexual partners and oral sex practice, which were assessed in more studies, we further excluded studies contributing to heterogeneity and those not adjusted for age, sex, smoking, and alcohol consumption. The summary ORs were 0.95 (95% CI: 0.75-1.20) for number of sexual partners and 1.03 (95% CI: 0.84-1.26) for oral sex practice. Our findings highlight that observed associations might be partly attributed to confounding effects of sociodemographic and behavioural factors.

Vitamin E intake from natural sources and head and neck cancer risk: a pooled analysis in the International Head and Neck Cancer Epidemiology consortium.

BACKGROUND: Evidence for the possible effect of vitamin E on head and neck cancers (HNCs) is limited. METHODS: We used individual-level pooled data from 10 case-control studies (5959 cases and 12 248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium to assess the association between vitamin E intake from natural sources and cancer of the oral cavity/pharynx and larynx. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models applied to quintile categories of non-alcohol energy-adjusted vitamin E intake. RESULTS: Intake of vitamin E was inversely related to oral/pharyngeal cancer (OR for the fifth vs the first quintile category=0.59, 95% CI: 0.49-0.71; P for trend <0.001) and to laryngeal cancer (OR=0.67, 95% CI: 0.54-0.83, P for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral/pharyngeal cancer. Inverse associations were generally observed for the anatomical subsites of oral and pharyngeal cancer and within covariate strata for both sites. CONCLUSION: Our findings suggest that greater vitamin E intake from foods may lower HNC risk, although we were not able to explain the heterogeneity observed across studies or rule out certain sources of bias.

The INHANCE consortium: toward a better understanding of the causes and mechanisms of head and neck cancer.

The International Head and Neck Cancer Epidemiology (INHANCE) consortium is a collaboration of research groups leading large epidemiology studies to improve the understanding of the causes and mechanisms of head and neck cancer. The consortium includes investigators of 35 studies who have pooled their data on 25 500 patients with head and neck cancer (i.e., cancers of the oral cavity, oropharynx, hypopharynx, and larynx) and 37 100 controls. The INHANCE analyses have confirmed that tobacco use and alcohol intake are key risk factors of these diseases and have provided precise estimates of risk and dose response, the benefit of quitting, and the hazard of smoking even a few cigarettes per day. Other risk factors include short height, lean body mass, low education and income, and a family history of head and neck cancer. Risk factors are generally similar for oral cavity, pharynx, and larynx, although the magnitude of risk may vary. Some major strengths of pooling data across studies include more precise estimates of risk and the ability to control for potentially confounding factors and to examine factors that may interact with each other. The INHANCE consortium provides evidence of the scientific productivity and discoveries that can be obtained from data pooling projects.

Maternal and neonatal outcomes for pregnancies before and after gastric bypass surgery.

BACKGROUND: Interaction between maternal obesity, intrauterine environment and adverse clinical outcomes of newborns has been described. METHODS: Using statewide birth certificate data, this retrospective, matched-control cohort study compared paired birth weights and complications of infants born to women before and after Roux-en-Y gastric bypass surgery (RYGB) and to matched obese non-operated women in several different groups. Women who had given birth to a child before and after RYGB (group 1; n=295 matches) and women with pregnancies after RYGB (group 2; n=764 matches) were matched to non-operated women based on age, body mass index (BMI) prior to both pregnancy and RYGB, mother's race, year of mother/s birth, date of infant births and birth order. In addition, birth weights of 13 143 live births before and/or after RYGB of their mothers (n=5819) were compared (group 3). RESULTS: Odds ratios (ORs) for having a large-for-gestational-age (LGA) neonate were significantly less after RYGB than for non-surgical mothers: ORs for groups 1 and 2 were 0.19 (0.08-0.38) and 0.33 (0.21-0.51), respectively. In contrast, ORs in all three groups for risk of having a small for gestational age (SGA) neonate were greater for RYGB mothers compared to non-surgical mothers (ORs were 2.16 (1.00-5.04); 2.16 (1.43-3.32); and 2.25 (1.89-2.69), respectively). Neonatal complications were not different for group 1 RYGB and non-surgical women for the first pregnancy following RYGB. Pregnancy-induced hypertension and gestational diabetes were significantly lower for the first pregnancy of mothers following RYGB compared to matched pregnancies of non-surgical mothers. CONCLUSION: Women who had undergone RYGB not only had lower risk for having an LGA neonate compared to BMI-matched mothers, but also had significantly higher risk for delivering an SGA neonate following RYGB. RYGB women were less likely than non-operated women to have pregnancy-related hypertension and diabetes.

Indoor air pollution from solid fuels and risk of upper aerodigestive tract cancers in central and eastern Europe.

BACKGROUND: Indoor air pollution from solid fuels is a potentially important risk factor for cancer, yet data on cancers from organs other than the lung are scarce. We investigated if indoor air pollution from coal and wood are risk factors for additional cancers, particularly that of the upper aerodigestive tract (oral cavity, larynx, pharynx and esophagus) in the high-risk areas of central and eastern Europe. METHODS: We used data from multi-center hospital-based case-control study of 1065 histologically confirmed upper aerodigestive tract cancer cases and 1346 controls. Standardized questionnaires were used to collect information on residential fuel use for cooking and heating. Using unconditional logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for upper aerodigestive tract cancer risk after adjusting for potential confounders. RESULTS: Lifelong wood use was associated with pharyngeal and esophageal (OR 4.05, 95% CI: 1.30-12.68 and OR 2.71, 95% CI: 1.21-6.10, respectively). We observed an exposure-response relationship between duration of wood use and risk of pharyngeal cancer among those who had never used coal (P(trend)=0.04), ruling out the possibility of residual confounding by coal. Similarly, we observed an increased risk of laryngeal cancers and head & neck cancers among those who always used coal, with a noted exposure-response relationship (P(trend)<0.01). CONCLUSIONS: Our results suggest a possible role of indoor air pollution from solid fuel use in head and neck carcinogenesis in the high risk area of central and eastern Europe.

Nutrient-based dietary patterns and the risk of head and neck cancer: a pooled analysis in the International Head and Neck Cancer Epidemiology consortium.

BACKGROUND: The association between dietary patterns and head and neck cancer has rarely been addressed. PATIENTS AND METHODS: We used individual-level pooled data from five case-control studies (2452 cases and 5013 controls) participating in the International Head and Neck Cancer Epidemiology consortium. A posteriori dietary patterns were identified through a principal component factor analysis carried out on 24 nutrients derived from study-specific food-frequency questionnaires. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using unconditional logistic regression models on quintiles of factor scores. RESULTS: We identified three major dietary patterns named 'animal products and cereals', 'antioxidant vitamins and fiber', and 'fats'. The 'antioxidant vitamins and fiber' pattern was inversely related to oral and pharyngeal cancer (OR=0.57, 95% CI 0.43-0.76 for the highest versus the lowest score quintile). The 'animal products and cereals' pattern was positively associated with laryngeal cancer (OR=1.54, 95% CI 1.12-2.11), whereas the 'fats' pattern was inversely associated with oral and pharyngeal cancer (OR=0.78, 95% CI 0.63-0.97) and positively associated with laryngeal cancer (OR=1.69, 95% CI 1.22-2.34). CONCLUSIONS: These findings suggest that diets rich in animal products, cereals, and fats are positively related to laryngeal cancer, and those rich in fruit and vegetables inversely related to oral and pharyngeal cancer.

Risks of second primary cancer among patients with major histological types of lung cancers in both men and women.

BACKGROUND: Patterns of second primary cancers (SPCs) following first primary lung cancers (FPLCs) may provide aetiological insights into FPLC. METHODS: Cases of FPLCs in 13 cancer registries in Europe, Australia, Canada, and Singapore were followed up from the date of FPLC diagnosis to the date of SPC diagnosis, date of death, or end of follow-up. Standardised incidence ratios (SIRs) were calculated to estimate the magnitude of SPC development following squamous cell carcinoma (SCC), small cell lung carcinoma (SCLC), and adenocarcinoma (ADC). RESULTS: Among SCC patients, male SIR=1.58 (95% confidence interval (CI)=1.50-1.66) and female SIR=2.31 (1.94-2.72) for smoking-related SPC. Among SCLC patients, the respective ratios were 1.39 (1.20-1.60) and 2.28 (1.73-2.95), and among ADC patients, they were 1.73 (1.57-1.90) and 2.24 (1.91-2.61). We also observed associations between first primary lung ADC and second primary breast cancer in women (SIR=1.25, 95% CI=1.05-1.48) and prostate cancer (1.56, 1.39-1.79) in men. CONCLUSION: The FPLC patients carried excess risks of smoking-related SPCs. An association between first primary lung ADC and second primary breast and ovarian cancer in women at younger age and prostate cancers in men may reflect an aetiological role of hormones in lung ADC.

Life course social mobility and risk of upper aerodigestive tract cancer in men.

The aim of this study was to explore associations between social mobility and tumours of the upper aero-digestive tract (UADT), focussing on life-course transitions in social prestige (SP) based on occupational history. 1,796 cases diagnosed between 1993 and 2005 in ten European countries were compared with 1585 controls. SP was classified by the Standard International Occupational Prestige Scale (SIOPS) based on job histories. SIOPS was categorised in high (H), medium (M) and low (L). Time weighted average achieved and transitions between SP with nine trajectories: H --> H, H --> M, H --> L, M --> H, M --> M, M --> L, L --> H, L --> M and L --> L were analysed. Odds ratios (ORs) and 95%-confidence intervals [95%-CIs] were estimated with logistic regression models including age, consumption of fruits/vegetables, study centre, smoking and alcohol consumption. The adjusted OR for the lowest versus the highest of three categories (time weighted average of SP) was 1.28 [1.04-1.56]. The distance of SP widened between cases and controls during working life. The downward trajectory H --> L gave an OR of 1.71 [0.75-3.87] as compared to H --> H. Subjects with M --> M and L --> L trajectories ORs were also elevated relative to subjects with H --> H trajectories. The association between SP and UADT is not fully explained by confounding factors. Downward social trajectory during the life course may be an independent risk factor for UADT cancers.

Home and workplace smoking bans in Italy, Ireland, Sweden, France and the Czech Republic.

The purpose of this study was to report predictors and prevalence of home and workplace smoking bans in five European countries. We conducted a population-based telephone survey of 4,977 females, ascertaining factors associated with smoking bans. Odds ratios and 95% confidence intervals were derived using unconditional logistic regression. A complete home smoking ban was reported by 59.5% of French, 63.5% of Irish, 61.3% of Italian, 74.4% of Czech and 87.0% of Swedish females. Home smoking bans were associated with younger age and being bothered by secondhand smoke, and among smokers, inversely associated with greater tobacco dependence. Among nonsmokers, bans were also related to believing smoking is harmful (OR 1.20, 95% CI 1.11-1.30) and having parents who smoke (OR 0.62, 95% CI 0.52-0.73). Workplace bans were reported by 92.6% of French, 96.5% of Irish, 77.9% of Italian, 79.1% of Czech and 88.1% of Swedish females. Workplace smoking bans were reported less often among those in technical positions (OR 0.64, 95% CI 0.50-0.82) and among skilled workers (OR 0.53, 95% CI 0.32-0.88) than among professional workers. Workplace smoking bans are in place for most workers in these countries. Having a home smoking ban was based on smoking behaviour, demographics, beliefs and personal preference.

Socioeconomic factors associated with risk of upper aerodigestive tract cancer in Europe.

INTRODUCTION: In the European Union, there are 180,000 new cases of upper aerodigestive tract (UADT) cancer cases per year--more than half of whom will die of the disease. Socioeconomic inequalities in UADT cancer incidence are recognised across Europe. We aimed to assess the components of socioeconomic risk both independently and through their influence on the known behavioural risk factors of smoking, alcohol consumption and diet. PATIENTS AND METHODS: A multicentre case-control study with 2198 cases of UADT cancer and 2141 controls from hospital and population sources was undertaken involving 14 centres from 10 countries. Personal interviews collected information on demographics, lifetime occupation history, smoking, alcohol consumption and diet. Socioeconomic status was measured by education, occupational social class and unemployment. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression. RESULTS: When controlling for age, sex and centre significantly increased risks for UADT cancer were observed for those with low versus high educational attainment OR=1.98 (95% CI 1.67, 2.36). Similarly, for occupational socioeconomic indicators--comparing the lowest versus highest International Socio-Economic Index (ISEI) quartile for the longest occupation gave OR=1.60 (1.28, 2.00); and for unemployment OR=1.64 (1.24, 2.17). Statistical significance remained for low education when adjusting for smoking, alcohol and diet behaviours OR=1.29 (1.06, 1.57) in the multivariate analysis. Inequalities were observed only among men but not among women and were greater among those in the British Isles and Eastern European countries than in Southern and Central/Northern European countries. Associations were broadly consistent for subsite and source of controls (hospital and community). CONCLUSION: Socioeconomic inequalities for UADT cancers are only observed among men and are not totally explained by smoking, alcohol drinking and diet.

Dietary risk factors for squamous cell carcinoma of the upper aerodigestive tract in central and eastern Europe.

OBJECTIVE: The incidence of squamous cell carcinoma of upper aerodigestive tract (UADT: oral cavity, pharynx, larynx, and esophagus) has been increasing in central and eastern European countries. We investigated the relationship between diet and UADT cancers in these high risk areas. METHODS: We used data from hospital-based case-control study of 948 UADT cancer cases and 1,228 controls conducted in Romania, Hungary, Poland, Russia, Slovakia, and Czech Republic. Standardized questionnaire were used to collect information on 23 different food items, along with alcohol and tobacco consumptions. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the UADT cancers after adjusting for center, age, sex, tobacco & alcohol intake, and other food groups. RESULTS: Consumption of dairy product was negatively associated with selected UADT cancers: larynx (OR: 0.38, CI: 0.23-0.62) and esophagus (OR: 0.55, CI: 0.33-0.93). While consumption of yellow/orange vegetables were inversely associated with oral/pharyngeal and laryngeal cancer (OR: 0.53, CI: 0.35-0.81 and OR: 0.62, CI: 0.38-1.00, respectively), preserved vegetable was positively associated with oral/pharyngeal and laryngeal cancer risk (p (trend) < 0.01 for both). CONCLUSION: Specific dietary components may play a role in the development of UADT cancers in the high-risk region of central and eastern Europe.

Socioeconomic status, lifestyle factors and oral premalignant lesions.

Several studies have suggested that low socioeconomic status (SES) is associated with a higher risk of oral cancer, but the association with oral premalignant lesions has not yet been explored. The aim of this study was to examine the association of education, occupation, income and SES index with oral premalignant lesions. A case-control study was conducted with data from the baseline screening of a randomized oral cancer screening trial in Kerala, India. There were a total of 927 oral leukoplakia, 170 oral submucous fibrosis, 100 erythroplakia and 115 multiple oral premalignant lesion cases and 47,773 controls. Subjects with high SES index had protective ORs for oral premalignant lesions, ranging from 0.6 to 0.7, after adjustment for age, sex, BMI, tobacco chewing, smoking, drinking and fruit/vegetable intake. Higher education levels were also associated with decreased risk of all four oral premalignant lesions. Protective ORs for income were observed for oral leukoplakia and possibly oral submucous fibrosis and erythroplakia. SES may be associated with oral premalignant lesions because of access to medical care, health related behaviors, living environment or psychosocial factors. Though the mechanism for the association is not clear, higher SES index, education and income were associated with decreased risk of oral premalignant lesions in our study.

Cystectomy for bladder cancer: a contemporary series.

PURPOSE: To validate the current TNM staging system, we analyzed our contemporary experience with 300 cystectomies. MATERIALS AND METHODS: The pathological material and medical records of 300 patients treated with cystectomy were reviewed, and the new TNM classification was adopted. RESULTS: The median followup of patients with no evidence of disease was 65 months, and overall survival rate was 45% with a median survival of 50 months. In a Cox regression analysis only patient age, pT stage and neoadjuvant chemotherapy were significant factors for survival. The disease specific survival was 67% with a median survival of 94 months. In a multiple proportional hazards analysis only pT stage and previous chemotherapy were significant factors of disease specific survival. A significant difference was seen in the overall and disease specific survival between patients with organ confined and nonorgan confined tumors. We did not observe a difference in the survival rate among patients with pT4a to pT3 tumors. Significant differences were not seen in survival rates between sexes or among patients of different age groups. Transitional cell carcinoma was the predominant histological type, and no significant difference was found in patient outcome among the different histological subtypes. CONCLUSIONS: Bladder cancer can be categorized into organ confined and nonorgan confined tumors. This dichotomous grouping is better suited for evaluating adjuvant clinical trials. The pT stage of the bladder and prostate should be prospectively analyzed together to better define the clinical implications of prostatic involvement. In our opinion the histological subtypes do not affect outcome.

Alcohol drinking, body mass index and the risk of oral leukoplakia in an Indian population.

Although tobacco habits have been associated with the risk of oral leukoplakia, alcohol drinking and body mass index (BMI) as risk factors have not been well established. The purpose of this study is to evaluate the independent effects of drinking, BMI, tobacco chewing and smoking on the risk of oral leukoplakia. A case-control study was conducted, with data from an ongoing randomized oral cancer screening trial in Kerala, India. Trained health workers conducted interviews and performed oral visual inspections to identify oral premalignant lesions such as leukoplakia. The logistic regression model in SAS was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). A total of 927 leukoplakia cases and 47,773 controls were included in the analysis. Ever alcohol drinking was a significant risk factor for oral leukoplakia among nonsmokers (OR=2.1, 95%CI=1.3, 3.4) and non-chewers (OR=1.8, 95%CI=1. 3, 2.5) after adjusting for age, sex, education, BMI and tobacco habits. The association with alcohol drinking was stronger among women (OR=3.9, 95%CI=1.5, 10.4) than men (OR=1.5, 95%CI=1.3, 1.9). An inverse dose-response relationship was observed between BMI and the risk of oral leukoplakia (p for trend=0.0075). Tobacco chewing was a stronger risk factor for women (OR=37.7, 95%CI=24.2, 58.7) than for men (OR=3.4, 95%CI=2.8, 4.1). Smoking was a slightly stronger risk factor for men (OR=3.3, 95%CI=2.5, 4.3) than for women (OR=2.0, 95%CI=1.5, 2.9). In conclusion, alcohol drinking was found to be an independent risk factor while BMI might be inversely associated with the risk of oral leukoplakia in an Indian population.

Chewing tobacco, alcohol, and the risk of erythroplakia.

Although chewing tobacco, smoking, and alcohol drinking have been suggested as risk factors for oral cancer, no study has examined the relationship between those factors and the risk of erythroplakia, an uncommon but severe oral premalignant lesion. In this study, we have analyzed the effects of chewing tobacco, smoking, alcohol drinking, body mass index, and vegetable, fruit, and vitamin/iron intake on the risk of erythroplakia and explored potential interactions between those factors in an Indian population. A case-control study including 100 erythroplakia cases and 47,773 controls was conducted, as part of an on-going randomized oral cancer screening trial in Kerala, India. The analysis was based on the data from the baseline screening for the intervention group, where the diagnostic information was available. The information on epidemiological risk factors was collected with interviews conducted by trained health workers. The erythroplakia cases were identified by health workers with oral visual inspections, and then confirmed by dentists and oncologists who made the final diagnosis. The odds ratios (OR) and their 95% confidence intervals (CIs) were calculated by the logistic regression model using SAS software. The adjusted OR for erythroplakia was 19.8 (95% CI, 9.8-40.0) for individuals who had ever chewed tobacco, after controlling for age, sex, education, body mass index, smoking, and drinking. The adjusted OR for ever-alcohol-drinkers was 3.0 (95% CI, 1.6-5.7) after controlling for age, sex, education, body mass index, chewing tobacco, and smoking. For ever-smokers, the adjusted OR was 1.6 (95% CI, 0.9-2.9). A more than additive interaction on the risk of erythroplakia was suggested between tobacco chewing and low vegetable intake, whereas a more than multiplicative interaction was indicated between alcohol drinking and low vegetable intake, and between drinking and low fruit intake. We concluded that tobacco chewing and alcohol drinking are strong risk factors for erythroplakia in the Indian population. Because the CIs of interaction terms were wide and overlapping with those of the main effects, only potential interactions are suggested.