A risk prediction model for head and neck cancers incorporating lifestyle factors, HPV serology and genetic markers.

Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold-out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also included HPV serology showed substantially improved predictive accuracy for oropharyngeal cancer (AUC = 0.94, 95% CI = 0.92-0.95 in men and AUC = 0.92, 95% CI = 0.88-0.95 in women). The 5-year absolute risk estimates showed distinct trajectories by risk factor profiles. Based on the UK Biobank cohort, the risks of developing oropharyngeal cancer among 60 years old and HPV16 seropositive in the next 5 years ranged from 5.8% to 14.9% with an average of 8.1% for men, 1.3% to 4.4% with an average of 2.2% for women. Absolute risk was generally higher among individuals with heavy smoking, heavy drinking, HPV seropositivity and those with higher polygenic risk score. These risk models may be helpful for identifying people at high risk of developing head and neck cancer.

Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.

Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.

Mouth Cancer Awareness in General Population: Results from Grampian Region of Scotland, United Kingdom.

OBJECTIVES: The purpose of this project was to determine the level of mouth cancer awareness and to investigate the associated factors in a United Kingdom (UK) general population sample. MATERIAL AND METHODS: Adult Dental Health Survey (2010) was conducted in a sample of 3,353 adult residents in the Grampian region of the UK (adjusted participation rate 58%). Participants completed a questionnaire consisting of questions on oral health, health behaviour, quality of life and cancer awareness. RESULTS: Overall, 81% of participants were aware of mouth cancer. This was associated with younger age, higher levels of education and better general health. Current smokers and alcohol drinkers were more aware of mouth cancer. When asked about risk factors for mouth cancer, the following were identified by the respondents: smoking (84%), poor oral hygiene (60%), drinking alcohol heavily (59%), poor diet (37%), stress (15%), being overweight (6%), drinking hot liquids (5%), eating spicy food (3%), using mouthwash (2%) and kissing someone (1%). Smokers were more likely to identify smoking as a risk factor for mouth cancer. Similarly, those who consumed alcohol almost daily were more likely to identify heavy alcohol drinking as a risk factor. CONCLUSIONS: Awareness of mouth cancer is high in respondents from the general population, and participants were able to identify the most important risk factors. Knowledge of tobacco and alcohol as risk factors was highest amongst those exposed to them. The study proposed that the prevention strategies should focus not only on increasing knowledge, but also on changing health behaviour.

Joint effects of intensity and duration of cigarette smoking on the risk of head and neck cancer: A bivariate spline model approach.

OBJECTIVES: This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures. MATERIALS AND METHODS: We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework. RESULTS: For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30  years. In former smokers who quit ≥10  years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers. CONCLUSION: Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.

Genetic Contributions to The Association Between Adult Height and Head and Neck Cancer: A Mendelian Randomization Analysis.

With the aim to dissect the effect of adult height on head and neck cancer (HNC), we use the Mendelian randomization (MR) approach to test the association between genetic instruments for height and the risk of HNC. 599 single nucleotide polymorphisms (SNPs) were identified as genetic instruments for height, accounting for 16% of the phenotypic variation. Genetic data concerning HNC cases and controls were obtained from a genome-wide association study. Summary statistics for genetic association were used in complementary MR approaches: the weighted genetic risk score (GRS) and the inverse-variance weighted (IVW). MR-Egger regression was used for sensitivity analysis and pleiotropy evaluation. From the GRS analysis, one standard deviation (SD) higher height (6.9 cm; due to genetic predisposition across 599 SNPs) raised the risk for HNC (Odds ratio (OR), 1.14; 95% Confidence Interval (95%CI), 0.99-1.32). The association analyses with potential confounders revealed that the GRS was associated with tobacco smoking (OR = 0.80, 95% CI (0.69-0.93)). MR-Egger regression did not provide evidence of overall directional pleiotropy. Our study indicates that height is potentially associated with HNC risk. However, the reported risk could be underestimated since, at the genetic level, height emerged to be inversely associated with smoking.

The influence of smoking, age and stage at diagnosis on the survival after larynx, hypopharynx and oral cavity cancers in Europe: The ARCAGE study.

Head and neck cancer (HNC) is a preventable malignancy that continues to cause substantial morbidity and mortality worldwide. Using data from the ARCAGE and Rome studies, we investigated the main predictors of survival after larynx, hypopharynx and oral cavity (OC) cancers. We used the Kaplan-Meier method to estimate overall survival, and Cox proportional models to examine the relationship between survival and sociodemographic and clinical characteristics. 604 larynx, 146 hypopharynx and 460 OC cancer cases were included in this study. Over a median follow-up time of 4.6 years, nearly 50% (n = 586) of patients died. Five-year survival was 65% for larynx, 55% for OC and 35% for hypopharynx cancers. In a multivariable analysis, we observed an increased mortality risk among older (≥71 years) versus younger (≤50 years) patients with larynx/hypopharynx combined (LH) and OC cancers [HR = 1.61, 95% CI 1.09-2.38 (LH) and HR = 2.12, 95% CI 1.35-3.33 (OC)], current versus never smokers [HR = 2.67, 95% CI 1.40-5.08 (LH) and HR = 2.16, 95% CI 1.32-3.54 (OC)] and advanced versus early stage disease at diagnosis [IV versus I, HR = 2.60, 95% CI 1.78-3.79 (LH) and HR = 3.17, 95% CI 2.05-4.89 (OC)]. Survival was not associated with sex, alcohol consumption, education, oral health, p16 expression, presence of HPV infection or body mass index 2 years before cancer diagnosis. Despite advances in diagnosis and therapeutic modalities, survival after HNC remains low in Europe. In addition to the recognized prognostic effect of stage at diagnosis, smoking history and older age at diagnosis are important prognostic indicators for HNC.

Oral Health and Risk of Arthritis in the Scottish Population: Results from the Scottish Health Survey.

OBJECTIVES: To investigate the link between self-reported oral health and arthritis in the Scottish population using data from the Scottish Health Survey. MATERIAL AND METHODS: Data were available from 2008 to 2013 on self-reported arthritis, oral health conditions and oral hygiene habits from the Scottish Health Survey. Arthritis was defined in this survey by self-reported long standing illness, those who reported having arthritis, rheumatism and/or fibrositis. Oral conditions were defined by self-reported bleeding gums, toothache, biting difficulties and/or edentulousness. Oral hygiene habits were defined by self-reported brushing teeth and/or using dental floss on daily basis. Logistic regression was used for statistical analysis adjusted for age, gender, qualification, smoking and body mass index. RESULTS: Prevalence of self-reported arthritis was 9.3% (95% confidence interval [CI] = 9.03 to 9.57). Those who reported having bleeding gums (adjusted odds ratio [OR] = 1.63; 95% CI = 1.35 to 1.96), toothache (OR = 1.32; 95% CI = 1.16 to 1.5), biting difficulties (OR = 1.95; 95% CI = 1.62 to 2.34), and being edentulous (OR = 1.22; 95% CI = 1.08 to 1.37) had an increased risk of arthritis. Brushing teeth (OR = 1.25; 95% CI = 0.74 to 2.12), and using dental floss (OR = 1.11; 95% CI = 0.89 to 1.39) were not associated with arthritis. CONCLUSIONS: Self-reported oral conditions were associated with increased risk of self-reported arthritis. Oral hygiene habits were not associated with self-reported arthritis. Further investigation is required to assess the causal association between oral hygiene, oral disease and arthritis.

Designing for Safety: Implications of a Fifteen Year Review of Swallowed and Aspirated Dentures.

OBJECTIVES: Dentures are worn by around 20% of the population, yet if they become displaced they may enter the gastrointestinal or respiratory system, sometimes with grave consequences. The aim of this study was to review recent published literature in order to identify the epidemiology of patients and characteristics of swallowed and aspirated dental prostheses, and propose strategies to minimise these risks. MATERIAL AND METHODS: A fifteen year retrospective of published case series and case reports was carried out. Photographs, radiographs and descriptions of the dental prostheses were gathered, as well as the patient's presenting complaint, the anatomical site where the denture was caught and the procedure required to remove the denture. RESULTS: Ninety one separate events of swallowed or aspirated dentures were identified from 83 case reports and series from 28 countries. Average age was 55 years, and these were 74% male. Photographs were retrieved for 49 of these dentures. Clasps were present in 25 of the dentures. There was no significant difference between clasped and unclasped dentures for perforation rates, need for open surgery and spontaneously passed dentures. CONCLUSIONS: We discuss the implications of this study regarding denture designs, specifically the importance of using a radiopaque acrylic, using clasps when required even if there is a risk of aspiration, advising patients to return if a denture is loose or damaged, and finally that all patients who wear a denture are at risk of aspiration and swallowing events, and associated morbidity and mortality.

Is alcohol consumption related to likelihood of reporting chronic widespread pain in people with stable consumption? Results from UK biobank.

Studies have suggested that alcohol consumption is strongly related to reduced reporting of chronic widespread pain (CWP) and level of disability in people with CWP or fibromyalgia. Direction of causality has not been established, that is whether the association is due to people's health influencing their alcohol consumption or vice versa. UK Biobank recruited over 500,000 people aged 40 to 69 years, registered at medical practices nationwide. Participants provided detailed information on health and lifestyle factors including pain and alcohol consumption. Total units consumed per week were calculated for current drinkers. Information was also collected on changes in alcohol consumption and reasons for such changes. Analysis was performed with logistic regression expressed as odds ratios (ORs) with 95% confidence intervals, then adjusted for a large number of potential confounding factors (adjORs). In males who reported drinking the same as 10 years previously, there was a U-shaped relationship between amount drunk and odds of reporting CWP (nondrinkers CWP prevalence 2.4%, 19.1-32.1 units/wk 0.4%, >53.6 units/wk 1.0%; adjORs 2.53 95% confidence intervals [1.78-3.60] vs 1 vs 1.52 [1.05-2.20]). In females, there was a decrease in the proportion reporting CWP up to the modal category of alcohol consumption with no further change in those drinking more (nondrinkers CWP prevalence 3.4%, 6.4-11.2 units/wk 0.7%, >32.1 units/wk 0.7%; adjORs 2.11 [1.67-2.66] vs 1 vs 0.86 [0.54-1.39]). This large study has shown a clear relationship between alcohol consumption and reporting of pain even in people who had not reported changing consumption because of health concerns, after adjustment for potential confounding factors.

Combined effects of smoking and HPV16 in oropharyngeal cancer.

BACKGROUND: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood. METHODS: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multi-centre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression. RESULTS: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer. CONCLUSIONS: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.

Aspirin and other non-steroidal anti-inflammatory drug prescriptions and survival after the diagnosis of head and neck and oesophageal cancer.

BACKGROUND: Aspirin and other NSAIDs are widely used as analgesics and the former is a preventative agent for vascular events. It is unclear whether their long-term use affects cancer risk. Data on the chemopreventative role of these drugs on the mortality in patients with upper aerodigestive tract cancer (UADT) are insufficient. The aim of this study was to investigate the effect of aspirin and other NSAIDs on survival in UADT cancer patients. METHODS: An observational cohort study of patients with UADT cancer was undertaken using Primary Care Clinical Informatics Unit (PCCIU) database of electronic medical records in Scotland. Information was available on all prescriptions of aspirin and other NSAIDs before and after diagnosis. The main outcome measure was all-cause mortality. Cox regression was used for statistical data analysis. RESULTS: There were 2392 patients diagnosed with UADT cancer between 1996 and 2010. Mean age of patients was 66 years (SD 12) and most were male (63%). Median survival in head and neck (HNC) patients was 94 months, while median survival in oesophageal cancer patients was 10 months. For HNC improved survival was observed with aspirin prescription (ever vs never hazard ratio (HR) 0.56 95% Confidence Interval (CI) 0.44, 0.71), there was no association with Cyclooxygenase 2 Inhibitors (COX-2) prescriptions. Improved survival was observed with other NSAIDs prescription (ever vs never HR 0.74 95% CI 0.60, 0.90). For oesophageal cancer patients, improved survival was observed with aspirin prescriptions (ever vs never HR 0.54 95% CI 0.45, 0.64), COX-2 prescriptions (HR 0.78 95% CI 0.62, 0.98) and other NSAIDs (HR 0.67 95% CI 0.56, 0.80). CONCLUSIONS: Aspirin and other NSAIDs prescriptions after diagnosis are associated with a reduced all-cause mortality in UADT cancer patients.

A rare truncating BRCA2 variant and genetic susceptibility to upper aerodigestive tract cancer.

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.

The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract.

Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10(-4)). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3)) and LUSC (p = 9x10(-4)) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48) and p = 3x10(-29) in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.

Risk factors for head and neck cancer in young adults: a pooled analysis in the INHANCE consortium.

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 ('young adults', 2010 cases and 4042 controls) and >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.

Human Papillomavirus 16 E6 Antibodies in Individuals without Diagnosed Cancer: A Pooled Analysis.

BACKGROUND: The increasing incidence of oropharyngeal cancer in many developed countries has been attributed to human papillomavirus type 16 (HPV16) infections. Recently, HPV16 E6 serology has been identified as a promising early marker for oropharyngeal cancer. Therefore, characterization of HPV16 E6 seropositivity among individuals without cancer is warranted. METHODS: A total of 4,666 controls were pooled from several studies of cancer and HPV seropositivity, all tested within the same laboratory. HPV16 E6 seropositive controls were classified as having (i) moderate [mean fluorescent intensity (MFI) ≥ 484 and <1,000] or (ii) high seroreactivity (MFI ≥ 1,000). Associations of moderate and high HPV16 E6 seroreactivity with (i) demographic risk factors; and seropositivity for (ii) other HPV16 proteins (E1, E2, E4, E7, and L1), and (iii) E6 proteins from non-HPV16 types (HPV6, 11, 18, 31, 33, 45, and 52) were evaluated. RESULTS: Thirty-two (0.7%) HPV16 E6 seropositive controls were identified; 17 (0.4%) with moderate and 15 (0.3%) with high seroreactivity. High HPV16 E6 seroreactivity was associated with former smoking [odds ratio (OR), 5.5; 95% confidence interval (CI), 1.2-51.8], and seropositivity against HPV16 L1 (OR, 4.8; 95% CI, 1.3-15.4); E2 (OR, 7.7; 95% CI, 1.4-29.1); multiple HPV16 proteins (OR, 25.3; 95% CI, 2.6-119.6 for three HPV16 proteins beside E6) and HPV33 E6 (OR, 17.7; 95% CI, 1.9-81.8). No associations were observed with moderate HPV16 E6 seroreactivity. CONCLUSIONS: High HPV16 E6 seroreactivity is rare among individuals without diagnosed cancer and was not explained by demographic factors. IMPACT: Some HPV16 E6 seropositive individuals without diagnosed HPV-driven cancer, especially those with seropositivity against other HPV16 proteins, may harbor a biologically relevant HPV16 infection.

Estimating and explaining the effect of education and income on head and neck cancer risk: INHANCE consortium pooled analysis of 31 case-control studies from 27 countries.

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels.

Self-Reported Facial Pain in UK Biobank Study: Prevalence and Associated Factors.

OBJECTIVES: To determine the prevalence of facial pain and to examine the hypothesis that symptoms are associated with socio-demographic, dental, adverse psychological factors and pain elsewhere in the body. MATERIAL AND METHODS: Cross-sectional population data were obtained from UK Biobank (www.ukbiobank.ac.uk/) study which was conducted in 2006 - 2010 and recruited over 500,000 people. RESULTS: The overall prevalence of facial pain (FP) was 1.9% (women 2.4%, men 1.2%) of which 48% was chronic. The highest prevalence was found in the 51 - 55 age group (2.2%) and the lowest in the 66 - 73 age group (1.4%). There was a difference in prevalence by ethnicity (0.8% and 2.7% in persons reporting themselves as Chinese and Mixed respectively). Prevalence of FP significantly associated with all measures of social class with the most deprived and on lowest income showing the highest prevalence (2.5% and 2.4% respectively). FP was more common in individuals who rated themselves as extremely unhappy, had history of depression and reported sleep problems. Smoking associated with increase in reporting FP while alcohol consumption had inverse association. FP associated with history of painful gums, toothache and all types of regional pain. CONCLUSIONS: This is the largest ever study to provide estimates of facial pain prevalence. It demonstrates unique features (lower prevalence than previously reported) and common features (more common in women) and confirms multifactorial aetiology of facial pain. Significant association with psychological distress and a strong relationship to pain elsewhere in the body suggests that aetiology is not specific to this regional pain.

Oral health, dental care and mouthwash associated with upper aerodigestive tract cancer risk in Europe: the ARCAGE study.

OBJECTIVE: We aimed to assess the association of oral health (OH), dental care (DC) and mouthwash with upper-aerodigestive tract (UADT) cancer risk, and to examine the extent that enzymes involved in the metabolism of alcohol modify the effect of mouthwash. MATERIALS AND METHODS: The study included 1963 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1993 controls. Subjects were interviewed about their oral health and dental care behaviors (which were converted to scores of OH and DC respectively), as well as smoking, alcohol drinking, diet, occupations, medical conditions and socio-economic status. Blood samples were taken for genetic analyses. Mouthwash use was analyzed in relation to the presence of polymorphisms of alcohol-metabolizing genes known to be associated with UADT. Adjusted odds ratios (ORs) and 95%-confidence intervals [CI] were estimated with multiple logistic regression models adjusting for multiple confounders. RESULTS: Fully adjusted ORs of low versus high scores of DC and OH were 2.36[CI=1.51-3.67] and 2.22[CI=1.45-3.41], respectively, for all UADT sites combined. The OR for frequent use of mouthwash use (3 or more times/day) was 3.23[CI=1.68-6.19]. The OR for the rare variant ADH7 (coding for fast ethanol metabolism) was lower in mouthwash-users (OR=0.53[CI=0.35-0.81]) as compared to never-users (OR=0.97[CI=0.73-1.29]) indicating effect modification (pheterogeneity=0.065) while no relevant differences were observed between users and non-users for the variant alleles of ADH1B, ADH1C or ALDH2. CONCLUSIONS: Poor OH and DC seem to be independent risk factors for UADT because corresponding risk estimates remain substantially elevated after detailed adjustment for multiple confounders. Whether mouthwash use may entail some risk through the alcohol content in most formulations on the market remains to be fully clarified.

Smoking addiction and the risk of upper-aerodigestive-tract cancer in a multicenter case-control study.

Although previous studies on tobacco and alcohol and the risk of upper-aerodigestive-tract (UADT) cancers have clearly shown dose-response relations with the frequency and duration of tobacco and alcohol, studies on addiction to tobacco smoking itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is an independent risk factor or a refinement to smoking variables (intensity and duration) for UADT squamous cell carcinoma (SCC) risk in the multicenter case-control study (ARCAGE) in Western Europe. The analyses included 1,586 ever smoking UADT SCC cases and 1,260 ever smoking controls. Addiction was measured by a modified Fagerström score (first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden and cigarettes per day). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for UADT cancers with addiction variables were estimated with unconditional logistic regression. Among current smokers, the participants who smoked their first cigarette within 5 min of waking up were two times more likely to develop UADT SCC than those who smoked 60 min after waking up. Greater tobacco smoking addiction was associated with an increased risk of UADT SCC among current smokers (OR = 3.83, 95% CI: 2.56-5.73 for score of 3-7 vs. 0) but not among former smokers. These results may be consistent with a residual effect of smoking that was not captured by the questionnaire responses (smoking intensity and smoking duration) alone, suggesting addiction a refinement to smoking variables.

Human papillomavirus infections and upper aero-digestive tract cancers: the ARCAGE study.

BACKGROUND: Human papillomavirus (HPV) is causally implicated in a subset of cancers of the upper aero-digestive tract (UADT). METHODS: Associations between type-specific HPV antibodies were examined among 1496 UADT cancer case subjects and 1425 control subjects by estimating odds ratios (ORs) in logistic regression analyses adjusted for potential confounders. The agreement between serology and tumor markers of HPV infection, including presence of HPV DNA and p16 expression, were examined in a subset of tumors. RESULTS: HPV16 L1 seropositivity was associated with increased risk of oral cavity and oropharyngeal cancer (OR = 1.94, 95% confidence interval [CI] = 1.03 to 3.65; OR = 8.60, 95% CI = 5.21 to 14.20, respectively). HPV16 E6 antibodies were present in 30.2% of oropharyngeal case subjects and only 0.8% of control subjects (OR = 132.0, 95% CI = 65.29 to 266.86). Combined seropositivity to HPV16 E6 and E7 was rare (n = 1 of 1425 control subjects). An agreement of 67% was observed between HPV16 E6 serology and the corresponding presence of an HPV-related cancer: four of six HPV DNA-positive/p16-overexpressing tumors were HPV16 E6 antibody positive. An HPV16 independent association was observed for HPV18 and oropharyngeal cancer (OR = 8.14, 95% CI = 2.21 to 29.99 for HPV18 E6 seropositivity) and HPV6 and laryngeal cancer (OR = 3.25, 95% CI = 1.46 to 7.24 for HPV6 E7 seropositivity). CONCLUSIONS: These results confirm an important role for HPV16 infection in oropharyngeal cancer. HPV16 E6 antibodies are strongly associated with HPV16-related oropharyngeal cancers. Continuing efforts are needed to consider both HPV serology and p16 staining as biomarkers relevant to the etiology and natural history of HPV16-related oropharyngeal tumors. These results also support a marginal role for HPV18 in oropharyngeal cancer and HPV6 in laryngeal cancer.