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.

Impact of EMA regulatory label changes on hydroxyzine initiation, discontinuation and switching to other medicines in Denmark, Scotland, England and the Netherlands: An interrupted time series regression analysis.

BACKGROUND: Hydroxyzine is indicated for the management of anxiety, skin and sleep disorders. In 2015, the European Medicines Agency (EMA) concluded that hydroxyzine was pro-arrhythmogenic and changes to the product information were implemented in Europe. This study aimed to evaluate their impact in Denmark, Scotland, England and the Netherlands. METHOD: Quarterly time series analyses measuring hydroxyzine initiation, discontinuation, and switching to other antihistamines, benzodiazepines and antidepressants in Denmark, England, Scotland and the Netherlands from 2009 to 2018. Data were analysed using interrupted time series regression. RESULTS: Hydroxyzine initiation in quarter one 2010 in Denmark, Scotland, England and the Netherlands per 100 000 was: 23.5, 91.5, 35.9 and 34.4 respectively. Regulatory action was associated with a significant: immediate fall in hydroxyzine initiation per 100 000 in England (-12.05, 95%CI -18.47 to -5.63) and Scotland (-19.01, 95%CI -26.99 to -11.02); change to a negative trend in hydroxyzine initiation per 100 000/quarter in England (-1.72, 95%CI -2.69 to -0.75) and Scotland (-2.38, 95%CI -3.32 to -1.44). Regulatory action was associated with a significant: immediate rise in hydroxyzine discontinuation per 100 000 in England (3850, 95%CI 440-7240). No consistent changes were observed in the Netherlands or Denmark. Regulatory action was associated with no switching to other antihistamines, benzodiazepines or antidepressants following hydroxyzine discontinuation in any country. CONCLUSION: The 2015 EMA regulatory action was associated with heterogeneous impact with reductions in hydroxyzine initiation varying by country. There was limited impact on discontinuation with no strong evidence suggesting unintended consequences of major switching to other antihistamines, benzodiazepines or antidepressants.

The effect of indapamide vs. bendroflumethiazide for primary hypertension: a systematic review.

The aims of the current review were to compare the efficacy of monotherapy with bendroflumethiazide vs. indapamide on mortality, cardiovascular outcomes, blood pressure, need for intensification of treatment and treatment withdrawal. Two authors independently screened the results of a literature search, assessed the risk of bias and extracted relevant data. Randomized clinical trials of hypertensive patients of at least a 1-year duration were included. When there was disagreement, a third reviewer was consulted. Risk ratio (RR) and mean differences were used as measures of effect. Two trials comparing bendroflumethiazide against placebo, one comparing indapamide with placebo and three of short duration directly comparing indapamide and Bendroflumethiazide, were included. No statistically significant difference was found between indapamide and bendroflumethiazide for all deaths [RR 0.82; 95% confidence interval (CI) 0.57, 1.18], cardiovascular deaths (RR 0.82; 95% CI 0.55, 1.20), noncardiovascular deaths (0.81; 95% CI 0.54, 1.22), coronary events (RR 0.73; 95% CI 0.30, 1.79) or all cardiovascular events (RR 0.89; 95% CI 0.67, 1.18). Indapamide performed worse for stroke (RR 2.21; 95% CI 1.19, 4.11), even though a reduction in RR compared with placebo was observed in both groups. There was no statistically or clinically significant difference between indapamide and bendroflumethiazide in blood pressure reduction (mean absolute difference <1 mmHg). The present review highlights a lack of studies to answer the review question but also a lack of evidence of superiority of one drug over the other. Therefore, there is a clear need for new studies directly comparing the effect of these drugs on the outcomes of interest.

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.

Adhesives for fixed orthodontic brackets.

BACKGROUND: Bonding of orthodontic brackets to teeth is important to enable effective and efficient treatment with fixed appliances. The problem is bracket failure during treatment which increases operator chairside time and lengthens treatment time. A prolonged treatment is likely to increase the oral health risks of orthodontic treatment with fixed appliances one of which is irreversible enamel decalcification. This is an update of the Cochrane Review first published in 2003. A new full search was conducted on 26 September 2017 but no new studies were identified. We have only updated the search methods section in this new version. The conclusions of this Cochrane Review remain the same. OBJECTIVES: To evaluate the effects of different orthodontic adhesives for bonding. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 26 September 2017), the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8) in the Cochrane Library (searched 26 September 2017), MEDLINE Ovid (1946 to 26 September 2017), and Embase Ovid (1980 to 26 September 2017). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: Trials were selected if they met the following criteria: randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing two different adhesive groups. Participants were patients with fixed orthodontic appliances. The interventions were adhesives that bonded stainless steel brackets to all teeth except the molars. The primary outcome was debond or bracket failure. DATA COLLECTION AND ANALYSIS: Data were recorded on decalcification as a secondary outcome, if present. Information regarding methods, participants, interventions, outcome measures and results were extracted in duplicate by pairs of review authors. Since the data were not presented in a form that was amenable to meta-analysis, the results of the review are presented in narrative form only. MAIN RESULTS: Three trials satisfied the inclusion criteria. A chemical cured composite was compared with a light cured composite (one trial), a conventional glass ionomer cement (one trial) and a polyacid-modified resin composite (compomer) (one trial). The quality of the trial reports was generally poor. AUTHORS' CONCLUSIONS: There is no clear evidence on which to make a clinical decision of the type of orthodontic adhesive to use.

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.

A possible link between ankylosing spondylitis and periodontitis: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to examine the link between AS and periodontitis. METHODS: Medline, Embase, AMED, CINAHL, Web of Science and Google Scholar were searched to identify eligible studies that were selected and reviewed independently by at least two authors. RESULTS: Six case-control studies were included in the review. Study size ranged from 90 to 40 926 participants. The prevalence of periodontitis ranged from 38% to 88% in AS patients and from 26% to 71% in controls. As there was low-level heterogeneity (I(2) = 13%), using fixed effects analysis the overall pooled estimate of the odds ratios for periodontitis was 1.85 (95% CI 1.72, 1.98). There was no evidence of publication bias. CONCLUSION: The results led to the need for a further large study with sufficient statistical power to detect the desired effect size, taking into account potential confounding factors and using validated measures of AS and periodontitis.

Validating the Clinical Use of the Modified Huddart and Bodenham Scoring System for Outcome in Cleft Lip and/or Palate.

OBJECTIVE: The aim of this study was to validate the clinical use of the modified Huddart and Bodenham scoring system for the measurement of maxillary arch constriction in children born with cleft lip and/or palate. DESIGN: The study design consisted of a reliability assessment between clinical and study model scoring. SETTING: The study was carried out in cleft clinics at three hospital-based orthodontic units. PARTICIPANTS: A total of 53 subjects were recruited when attending routine clinic appointments and gave informed consent to participate. INTERVENTION: The modified Huddart and Bodenham scoring system was applied to study models for 53 subjects by all examiners; whereas, one examiner scored 53 subjects clinically, the other two examiners scored 25 and 28 subjects, respectively, on two occasions at least 1 month apart. MAIN OUTCOME MEASURE: Reliability of modified Huddart and Bodenham scoring clinically and on study models was compared. RESULTS: When scoring clinically with the modified Huddart and Bodenham index on two occasions, the intraexaminer and interexaminer intraclass correlation coefficients (ICC) indicated a high level of repeatability and reliability (ICC range, 0.941 to 0.989). The Bland-Altman plots did not show any areas of systematic bias. The ICC between clinical and model scores for each examiner ranged between 0.923 and 0.959. The Bland-Altman plots did not show any areas of systematic bias. The ICC between clinical and model scores for each examiner ranged between 0.923 and 0.959. Canines had lower reliability than molars and incisors. CONCLUSIONS: There was excellent intraexaminer and interexaminer agreement both on study models and in the intraoral scoring using the modified Huddart and Bodenham index. In addition, there was a high degree of correlation between study model and clinical scores using this index.

A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻8); rs1229984-ADH1B, p = 7 × 10⁻9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Prevalence of hypodontia and associated factors: a systematic review and meta-analysis.

OBJECTIVES: To determine the prevalence and factors associated with hypotonia. DESIGN: Systematic review and meta-analysis. DATA SOURCE: A search strategy was developed along with inclusion criteria and run in MEDLINE and EMBASE (published from 2002 to August 2012) databases to reveal all studies on the prevalence of hypodontia or associated factors. A hand search of reference lists and a Google search aimed to improve the sensitivity of the literature search. SELECTION CRITERIA: All studies on the prevalence of hypodontia or associated factors published from 2002 onwards were included. Abstracts of non-English papers were also analyzed. DATA SELECTION AND EXTRACTION: All potential articles were checked against the inclusion criteria independently, and in duplicate by two investigators. A checklist was used to assess the quality of selected studies. MAIN OUTCOME: Prevalence of hypodontia, excluding third molars. RESULTS: The overall prevalence of hypodontia was found to be 6.4% (95% CI: 5.7, 7.2). There was a statistically significant difference in the prevalence of hypodontia by continent (Q = 34.18, P<0.001). Prevalence of hypodontia was the highest in Africa: 13.4% (95% CI: 9.7, 18.0), followed by Europe (7% CI: 6.0-8.0%), Asia (6.3% CI: 4.4, 9.1) and Australia (6.3% CI: 5.3, 7.4) with a lower prevalence in North America (5.0% CI: 4.1-5.9) and Latin America and Caribbean (4.4% CI: 3.2-6.1). Females were found to have a higher prevalence than males (combined OR 1.22; 95% CI: 1.14, 1.30). The most commonly affected teeth were mandibular second premolars followed by maxillary lateral incisors and maxillary second premolars. The prevalence of mild, moderate and severe hypodontia was found to be 81.6, 14.3 and 3.1% respectively. CONCLUSIONS: There was a high variation in the prevalence of hypodontia between the studies. African populations were found to have a higher risk for tooth agenesis and there was an increased risk for females to have hypodontia than males.

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.

Patient perceptions regarding benefits of single visit scale and polish: a randomised controlled trial.

BACKGROUND: Single visit scale and polish is frequently carried out in dental practices however there is little evidence to support (or refute) its clinical effectiveness. The purpose of this research was to compare patient-reported outcomes between groups receiving a scale and polish at 6-, 12-, and 24-month intervals. Outcomes recorded included participants' subjective assessment of their oral cleanliness; the perceived importance of scale and polish for oral health and aesthetics; and frequency at which this treatment is required. METHODS: A practice-based randomised control trial was undertaken, with a 24-month follow-up period. Participants were healthy adults with no significant periodontal disease (BPE codes <3) randomly allocated to three groups to receive scale and polish at 6-, 12-, or 24-month intervals. Patient-reported outcomes were recorded at baseline and follow-up. Oral cleanliness was reported using a 5-point scale and recorded by examiners blinded to trial group allocation. A self-completed questionnaire enabled participants to report perceived importance of scale and polish (5-point scale), and required frequency of treatment (6-point scale). The main hypothesis was that participants receiving 6-monthly scale and polish would report higher levels of oral cleanliness compared to participants receiving scale and polish at 12- and 24-month intervals. RESULTS: 369 participants were randomised: 125 to the 6-month group; 122 to the 12-month group; and 122 to the 24-month group. Complete data set analysis was carried out to include 107 (6-month group), 100 (12-month group) and 100 (24-month group) participants. Multiple imputation analyses were conducted where follow-up data was missing. The difference in the proportions of participants reporting a 'high' level of oral cleanliness at follow-up was significant (Chi-squared P = 0.003): 52.3% (6-month group), 47.0% (12-month group) and 30.0% (24-month group). Scale and polish was thought to be important by the majority in each group for keeping mouths clean and gums healthy, whitening teeth, and preventing bad breath and tooth decay; there were no statistically significant differences between groups at follow-up. Most participants at follow-up thought that the frequency of scale and polish should be "every 6 months" or more frequently: 77.9% (6-month group), 64.6% (12-month group), 71.7% (24-month group); differences between groups were not statistically significant (Chi squared P = 0.126). The results suggest that participants in the 24-month trial group were more likely to choose a scale and polish interval of "once a year" or less frequently (OR 2.89; 95% CI 1.36, 6.13). CONCLUSIONS: The majority of healthy adults regarded 6-monthly single-visit scale and polish as being beneficial for their oral health. Receiving the treatment at different frequencies did not alter this belief; and those with the longest interval between scale and polish provision perceived that their mouth was less clean. In the absence of a strong evidence base to support (or refute) the effectiveness of single-visit scale and polish, the beliefs and preferences of patients regarding scale and polish may be influential drivers for maintaining provision of this treatment.

Occupation and risk of upper aerodigestive tract cancer: the ARCAGE study.

We investigated the association between occupational history and upper aerodigestive tract (UADT) cancer risk in the ARCAGE European case-control study. The study included 1,851 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1,949 controls. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ever employment in 283 occupations and 172 industries, adjusting for smoking and alcohol. Men (1,457 cases) and women (394 cases) were analyzed separately and we incorporated a semi-Bayes adjustment approach for multiple comparisons. Among men, we found increased risks for occupational categories previously reported to be associated with at least one type of UADT cancer, including painters (OR = 1.74, 95% CI: 1.01-3.00), bricklayers (1.58, 1.05-2.37), workers employed in the erection of roofs and frames (2.62, 1.08-6.36), reinforced concreters (3.46, 1.11-10.8), dockers (2.91, 1.05-8.05) and workers employed in the construction of roads (3.03, 1.23-7.46), general construction of buildings (1.44, 1.12-1.85) and cargo handling (2.60, 1.17-5.75). With the exception of the first three categories, risks both increased when restricting to long duration of employment and remained elevated after semi-Bayes adjustment. Increased risks were also found for loggers (3.56, 1.20-10.5) and cattle and dairy farming (3.60, 1.15-11.2). Among women, there was no clear evidence of increased risks of UADT cancer in association with occupations or industrial activities. This study provides evidence of an association between some occupational categories and UADT cancer risk among men. The most consistent findings, also supported by previous studies, were obtained for specific workers employed in the construction industry.

Risk of upper aerodigestive tract cancer and type of alcoholic beverage: a European multicenter case-control study.

The general relationship between cancers of the upper aerodigestive tract (UADT) and alcohol drinking is established. Nevertheless, it is uncertain whether different types of alcoholic beverages (wine, beer and liquor) carry different UADT cancer risks. Our study included 2,001 UADT cancer cases and 2,125 controls from 14 centres in 10 European countries. All cases were histologically or cytologically confirmed squamous cell carcinomas. Controls were frequency matched by sex, age and centre. Logistic regression models were used to estimate odds ratios (OR) and 95 % confidence intervals (95 %CI) adjusted for age, sex, centre, education level, vegetable and fruit intake, tobacco smoking and alcohol drinking, where appropriate. Risk of beverage-specific alcohol consumption were calculated among 'pure drinker' who consumed one beverage type exclusively, among 'predominant drinkers' who consumed one beverage type to more than 66 % and among 'mixed drinkers' who consumed more than one beverage type to similar proportions. Compared to never drinkers and adjusted for cumulative alcohol consumption, the OR and 95 %CI for wine, beer and liquor drinking, respectively, were 1.24 (0.86, 1.78), 1.54 (1.05, 2.27) and 0.94 (0.53, 1.64) among 'pure drinkers' (p value for heterogeneity across beverage types = 0.306), 1.05 (0.76,1.47), 1.25 (0.87,1.79) and 1.43 (0.95, 2.16) among 'predominant drinkers' (p value = 0.456), and 1.09 (0.79, 1.50), 1.20 (0.88, 1.63) and 1.12 (0.82, 1.53) among 'mixed drinkers' (p value = 0.889). Risk of UADT cancer increased with increasing consumption of all three alcohol beverage types. Our findings underscore the strong and comparable carcinogenic effect of ethanol in wine, beer and liquor on organs of the UADT.

The association between change in body mass index and upper aerodigestive tract cancers in the ARCAGE project: multicenter case-control study.

Previous studies reported an inverse relationship between body mass index (BMI) and upper aerodigestive tract (UADT) cancers. Examining change in BMI over time may clarify these previous observations. We used data from 2,048 cases and 2,173 hospital- and population-based controls from ten European countries (alcohol-related cancers and genetic susceptibility in Europe study) to investigate the relationship with BMI and adult change in BMI on UADT cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between BMI at three time intervals and BMI change on UADT cancer development, adjusting for center, age, sex, education, fruit and vegetable intake, smoking and alcohol consumption. We found an inverse relationship between UADT cancers and BMI at time of interview and 2 years before interview. No association was found with BMI at 30 years of age. Regarding BMI change between age 30 and 2 years before interview, BMI decrease (BMI change <-5%) vs. BMI stability (-5% ≤ BMI change <5%) showed no overall association with UADT cancers (OR = 1.15; 95% CI = 0.89, 1.49). An increase in BMI (BMI change ≥+5%) was inversely associated with UADT cancers (OR = 0.74; 95% CI = 0.62, 0.89). BMI gain remained inversely associated across all subsites except for esophageal cancer. When stratified by smoking or by drinking, association with BMI gain was detected only in drinkers and smokers. In conclusion, BMI gain is inversely associated with UADT cancers. These findings may be influenced by smoking and/or drinking behaviors and/or the development of preclinical UADT cancers and should be corroborated in studies of a prospective nature.

Clinical outcomes of single-visit oral prophylaxis: a practice-based randomised controlled trial.

BACKGROUND: Practice-based general dental practitioners routinely provide "scale and polish" or "oral prophylaxis" to patients attending their practices. Despite its routine provision, there is no evidence to support the clinical effectiveness of single-visit scale and polish, nor the frequency at which it should be provided. A recent systematic review recommended that future trials investigating scale and polish should involve dental practice patients. METHODS: A practice-based parallel randomised controlled trial with 24-month follow-up was conducted. Healthy adults (Basic Periodontal Examination [BPE] codes <3) were randomly assigned to 3 groups (6-month, 12-month, or 24-month interval between scale and polish). The primary outcome was gingival bleeding with the hypothesis that 6-monthly scale and polish would result in lower prevalence than 12-month or 24-month frequency. Follow-up measurements were recorded by examiners blinded to the allocation. 125, 122 and 122 participants were randomised to the 6-month, 12-month and 24-month groups respectively. Complete data set analyses were conducted for 307 participants: 107, 100, and 100 in the 6-month, 12-month and 24-month groups respectively. Chi-square test and ANOVA were used to compare treatment groups at follow-up. Logistic regression and ANCOVA were used to estimate the relationship between outcome and treatment group, adjusted for baseline values. Multiple imputation analyses were also carried out for participants with incomplete data sets. RESULTS: Prevalence of gingival bleeding at follow-up was 78.5% (6-month), 78% (12-month) and 82% (24-month) (p = 0.746). There were no statistically significant differences between groups with respect to follow-up prevalence of plaque and calculus. Statistically significant differences detected in the amount (millimetres) of calculus were too small to be clinically significant. Seventeen (4.6%) participants were withdrawn from the trial to receive additional treatment. CONCLUSIONS: This trial could not identify any differences in outcomes for single-visit scale and polish provided at 6, 12 and 24 month frequencies for healthy patients (with no significant periodontal disease). However, this is the first trial of scale and polish which has been conducted in a general practice setting and the results are not conclusive. Larger trials with more comprehensive measurement and long-term follow up need to be undertaken to provide a firm evidence base for this intervention. This trial informs the design of future practice-based trials on this subject.

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.

The aetiology of upper aerodigestive tract cancers among young adults in Europe: the ARCAGE study.

BACKGROUND: The incidence of cancers of the upper aerodigestive tract (UADT) is increasing throughout the world. To date the increases have been proportionally greatest among young people. Several reports have suggested that they often do not have a history of tobacco smoking or heavy alcohol consumption. OBJECTIVE: To determine the contribution of lifestyle factors to the etiology of UADT cancers occurring in those aged less than 50 years. METHODS: A case-control study was conducted in 10 European countries. Cases were cancers of the oral cavity and pharynx, larynx and esophagus, and hospital or population controls were age and sex matched. RESULTS: There were 356 cases younger than 50 years and 419 controls. Risk was strongly related to current smoking [odds ratio (OR) 5.5 95%; confidence interval (CI) (3.3, 9.2)], and risk increased with number of pack-years smoked. Risk was also related to alcohol consumption for both current (OR 1.8; 0.97, 3.3) and past (OR 3.4; 1.6, 7.4) drinkers, and risk increased with number of drink-years. Persons frequently consuming fruits and vegetables were at significantly reduced risk. CONCLUSIONS: Risk factors already identified as being important for UADT cancers in adults are also important influences on risk in younger adults. The implication of these results is that the public health message in preventing UADT cancers remains the same to young and old alike.

Whether the weather influences pain? Results from the EpiFunD study in North West England.

OBJECTIVE: To determine whether the report of pain is influenced by meteorological conditions. METHODS: A population-based study (Epidemiology of Functional Disorders) was conducted in North West England. Subjects were mailed a questionnaire that enquired about pain on the day of completion ('any pain') and chronic widespread pain (CWP) as defined by the ACR, as well as about the potential mediating factors, sleep quality, exercise and mood, between the weather and pain. Hourly information on sunshine, precipitation, air temperature and pressure was available from a local weather station. Analysis of relationships was done by Cox regression and described as prevalence ratios (PRs) with 95% CIs. RESULTS: Between January 2005 and December 2006, questionnaires from 2491 subjects were returned: 42% of the subjects reported 'any pain' on the day of completion, whereas 15% of the subjects had CWP. For both 'any pain' and CWP, the PR was the highest in winter (46.1 and 22.2%, respectively) followed by autumn (45.4 and 17.9%, respectively) and spring (41.9 and 14.7%, respectively) and lowest in summer (35.6 and 9.5%, respectively). Persons were less likely to report pain on days with >5.8 h of sunshine (any pain: PR = 0.87, 95% CI 0.82, 0.93; CWP: PR = 0.56; 95% CI 0.38, 0.84) and with average temperature of >17.5 degrees C (any pain: PR = 0.74, 95% CI 0.66, 0.83; CWP: PR = 0.40; 95% CI 0.34, 0.48). These relationships were partly explained by persons reporting taking more exercise and having better sleep quality and a more positive mood on days with sunshine and higher temperatures. CONCLUSIONS;. Although a strong relationship between lack of sunshine, lower temperatures and pain reporting has been demonstrated, pain is not an inevitable consequence of such climatic conditions.

A methodology to establish a database to study gene environment interactions for childhood asthma.

BACKGROUND: Gene-environment interactions are likely to explain some of the heterogeneity in childhood asthma. Here, we describe the methodology and experiences in establishing a database for childhood asthma designed to study gene-environment interactions (PAGES--Paediatric Asthma Gene Environment Study). METHODS: Children with asthma and under the care of a respiratory paediatrician are being recruited from 15 hospitals between 2008 and 2011. An asthma questionnaire is completed and returned by post. At a routine clinic visit saliva is collected for DNA extraction. Detailed phenotyping in a proportion of children includes spirometry, bronchodilator response (BDR), skin prick reactivity, exhaled nitric oxide and salivary cotinine. Dietary and quality of life questionnaires are completed. Data are entered onto a purpose-built database. RESULTS: To date 1045 children have been invited to participate and data collected in 501 (48%). The mean age (SD) of participants is 8.6 (3.9) years, 57% male. DNA has been collected in 436 children. Spirometry has been obtained in 172 children, mean % predicted (SD) FEV1 97% (15) and median (IQR) BDR is 5% (2, 9). There were differences in age, socioeconomic status, severity and %FEV1 between the different centres (p≤0.024). Reasons for non-participation included parents not having time to take part, children not attending clinics and, in a small proportion, refusal to take part. CONCLUSIONS: It is feasible to establish a national database to study gene-environment interactions within an asthmatic paediatric population; there are barriers to participation and some different characteristics in individuals recruited from different centres. Recruitment to our study continues and is anticipated to extend current understanding of asthma heterogeneity.