Protective effects of metformin, statins and anti-inflammatory drugs on head and neck cancer: A systematic review.

The main objective of this study was to evaluate the effect of metformin, statins and anti-inflammatory drugs (NSAIDs) on head and neck cancer (HNC). Specifically, the potential beneficial effects on risk, survival and recurrence based on epidemiological studies. PRISMA guidelines were followed. After searching MEDLINE (PubMed), IBECS, LILACS and the Cochrane Central Register for Controlled Trials, 13 studies met the inclusion criteria and so underwent qualitative synthesis (six studies for metformin and seven for NSAIDs). No studies were found for statins. Studies varied in their methodological quality. Meta-analyses showed that metformin exerts significant beneficial effects on HNC risk (RR = 0.71 95% CI 0.61-0.84) and overall survival (RR = 1.71 95% CI 1.20-2.42). Qualitative synthesis also suggests an apparently dose-response relationship and increased benefit when administered alone. The pooled-analyses yielded an almost significant effect of NSAIDs on HNC risk (RR = 0.86 95% CI 0.74-1.01). No associations were found between aspirin use and the risk of HNC (RR = 0.98 95% CI 0.77-1.24) and overall survival (RR = 1.10 95% CI 0.89-1.36). Metformin appears to have beneficial effects on HNC risk and overall survival, with an apparently dose-response relationship and increased benefit when administered alone. NSAIDs also seem to have a modest beneficial effect on HNC risk. No definitive conclusions can be reached for aspirin as the evidence available was proved inconsistent. Further research by means of well designed and conducted studies are needed to determine firm clinical implications. Standardized assessment methods for HNC outcomes should be established and account for known confounding factors such as smoking and alcohol consumption.

HPV Vaccination and the Role of the Pediatric Dentist: Survey of Graduate Program Directors.

PURPOSE: This study's purpose was to evaluate what is currently being taught in graduate pediatric dental programs regarding the human papillomavirus (HPV), the HPV vaccine, and risk factors associated with oropharyngeal cancer (OPC). METHODS: A 42-question survey was administered via paper-and-pen survey instrument to attendees at the 2016 American Academy of Pediatric Dentistry (AAPD) annual meeting for graduate and associate program directors. The survey included questions evaluating attitudes/beliefs toward the HPV vaccine and current training in graduate pediatric dentistry programs and aimed to define whether the directors believe that the discussion of HPV vaccination and associated risk factors was within the scope of practice for pediatric dentists. RESULTS: Sixty-four of 71 attendees completed the survey; 77 percent of respondents believe they should be discussing the HPV vaccine with patients/parents. Increased age of respondent was correlated with the idea of discussion of sexual health and its link to OPC being within the scope of practice of pediatric dentistry (r equals 0.35, P=.005). CONCLUSIONS: A majority (77 percent) of graduate and associate program directors believe they should be discussing the human papillomavirus vaccine with patients and parents; however, only 25 percent of respondents currently include information about HPV and the vaccine in their curricula.

Coffee is protective against oral and pharyngeal cancer: A systematic review and meta-analysis.

OBJECTIVES: Coffee is one of the most popular and consumable drinks worldwide. However, there are conflicting results on the influence of this drink in oral and pharyngeal cancer risk. To clarify this, we aimed to systemically review and carry out a meta-analysis of the relevant literature on the association between coffee and oral and pharyngeal cancer. STUDY DESIGN: We carried out an electronic search of publications up to August 2016 from PubMed, National Library of Medicines Medline, Embase, Science Direct and the Cochrane Central Register. The Newcastle-Ottawa scale was used to address the quality of the studies a meta-analysis was carried out using random-effects models. RESULTS: From the 22,515 entries identified in the search, 13 case-control and 4 cohort studies were selected. With regards to quality on the Newcastle-Ottawa scale, an overall value of 6.06 was obtained. The analysis for oral and pharyngeal cancer grouped together indicated a pooled OR of .69 (95% CI of .57-.84; p<.001) for high versus low coffee consumption with a moderate heterogeneity (I2: 50.3%; p=.009). Regarding studies on oral cavity cancers we observed a pooled OR of 0.82; 95% CI =.58-1.16; p=.257) and for pharyngeal cancers a pooled OR of .72 (95% CI of 0.54-.95; p=.019). There was no significant publication bias. CONCLUSION: The results show an inverse association between high coffee consumption and the risk of oral and pharyngeal cancers, which indicates that coffee may have a protective role against these cancers. Further larger prospective observational cohort studies are needed to address any effect of other possible co-factors.

A Second Shot at HPV.

HPV vaccination rates remain stubbornly low, and some studies show physician hesitancy about promoting the vaccine is the single biggest problem. TMA's HPV Work Group plans to coordinate with like-minded state and national organizations and agencies to come up with an action plan to improve HPV vaccination rates.

Association between Mediterranean diet and head and neck cancer: results of a large case-control study in Italy.

The Mediterranean diet (MD) is a known protective factor for head and neck cancer (HNC); however, there is still a lack of studies investigating this association by HNC subsite. The aim of the present study was therefore to evaluate the association between adherence to MD and HNC overall and by cancer subsite, as well as the effect of the individual food components on HNC risk. A case-control study was carried out at the Gemelli Hospital of Rome (Italy). A total of 500 HNC cases and 433 controls were interviewed. Dietary intake was assessed through a validated food frequency questionnaire that collected information on over 25 food items. Odds ratios (ORs) and 95% confidence intervals (CI) of HNC were calculated using a multiple logistic regression model. We found a reduced risk of both oral cavity and pharynx cancer (OR=0.61; CI: 0.54-0.70) and larynx cancer (OR=0.64; CI: 0.56-0.73) with increasing adherence to MD. We also found a high consumption of fruit, vegetables, and legumes to be significantly associated with a lower risk of larynx as well as oral cavity and pharynx cancers. Our study showed that adherence to MD acts protectively against HNC overall and by cancer subsite.

Effects of Black Raspberry Extract and Protocatechuic Acid on Carcinogen-DNA Adducts and Mutagenesis, and Oxidative Stress in Rat and Human Oral Cells.

Effects of black raspberry (BRB) extract and protocatechuic acid (PCA) on DNA adduct formation and mutagenesis induced by metabolites of dibenzo[a,l]pyrene (DBP) were investigated in rat oral fibroblasts. The DBP metabolites, (±)-anti-11,12-dihydroxy-11,12,-dihydrodibenzo[a,l]pyrene (DBP-diol) and 11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DBPDE) induced dose-dependent DNA adducts and mutations. DBPDE was considerably more potent, whereas the parent compound had no significant effect. Treatment with BRB extract (BRBE) and PCA resulted in reduced DBP-derived DNA adduct levels and reduced mutagenesis induced by DBP-diol, but only BRBE was similarly effective against (DBPDE). BRBE did not directly inactivate DBPDE, but rather induced a cellular response-enhanced DNA repair. When BRBE was added to cells 1 day after the DBP-diol, the BRBE greatly enhanced removal of DBP-derived DNA adducts. As oxidative stress can contribute to several stages of carcinogenesis, BRBE and PCA were investigated for their abilities to reduce oxidative stress in a human leukoplakia cell line by monitoring the redox indicator, 2',7'-dichlorodihydrofluorescein diacetate (H2DCF) in cellular and acellular systems. BRBE effectively inhibited the oxidation, but PCA was only minimally effective against H2DCF. These results taken together provide evidence that BRBE and PCA can inhibit initiation of carcinogenesis by polycyclic aromatic hydrocarbons; and in addition, BRBE reduces oxidative stress. Cancer Prev Res; 9(8); 704-12. ©2016 AACR.

Determinants of First-Time Cancer Examinations in a Rural Community: A Mechanism for Behavior Change.

OBJECTIVES: After conducting a media campaign focusing on the importance of oral and pharyngeal cancer (OPC) examinations, we assessed mechanisms of behavior change among individuals receiving an OPC examination for the first time. METHODS: We used data from 2 waves of telephone surveys of individuals residing in 36 rural census tracts in northern Florida (n = 806). The second survey occurred after our media intervention. We developed media messages and modes of message delivery with community members via focus groups and intercept interviews. We performed a mediation analysis to examine behavior change mechanisms. RESULTS: Greater exposure to media messages corresponded with heightened concern about OPC. Heightened concern, in turn, predicted receipt of a first-time OPC examination, but only among men. CONCLUSIONS: We extended earlier studies by measuring an outcome behavior (receipt of an OPC examination) and demonstrating that the putative mechanism of action (concern about the disease) explained the link between a media intervention and engaging in the target behavior. Improving the quality of media campaigns by engaging community stakeholders in selecting messages and delivery methods is an effective strategy in building public health interventions aimed at changing behaviors.

Baseline data of oral and pharyngeal cancer before introducing an oral cancer prevention campaign in Germany.

OBJECTIVES: Oral and pharyngeal cancer is still a serious health problem with an annual incidence of about 13,000 in Germany. This study aimed at describing trends of incidence and mortality in Germany by age, sex, and sub-site as a baseline for an oral cancer prevention campaign. METHODS: Using data from the National Association of Population-based Cancer Registries, incidence rates for oral and pharyngeal cancer (ICD-10, C00-C14) from 2003 to 2011 and mortality rates from 1990 to 2012 were analysed by age, sex, and sub-site (C00-C06, C07-C08, C09-C14). Trends were described by annual percentage changes. RESULTS: Men are 2.5-times more likely than women to be diagnosed and 3-times more likely to die from this tumour. Incidence and mortality in women increased slightly during the last decade, while incidence and mortality in men remained stable at a high level. While a decline was observed for younger age groups, an increase was seen in the elderly. For some sub-sites a deviation from this overall pattern was observed. CONCLUSIONS: The decrease in this tumour in younger age groups is pleasing and may be attributed to public efforts in non-smoker protection in recent years. Further efforts are needed to counteract the increasing burden of disease in older age groups and in men.

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

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

Cytochrome p450 metabolism of betel quid-derived compounds: implications for the development of prevention strategies for oral and pharyngeal cancers.

Betel quid (BQ) products, with or without tobacco, have been classified by the International Agency for Research on Cancer (IARC) as group I human carcinogens that are associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. There are estimated 600 million BQ users worldwide. In Taiwan alone there are 2 million habitual users (approximately 10% of the population). Oral and pharyngeal cancers result from interactions between genes and environmental factors (BQ exposure). Cytochrome p450 (CYP) families are implicated in the metabolic activation of BQ- and areca nut-specific nitrosamines. In this review, we summarize the current knowledge base regarding CYP genetic variants and related oral disorders. In clinical applications, we focus on cancers of the oral cavity and pharynx and OPMDs associated with CYP gene polymorphisms, including CYP1A1, CYP2A6, CYP2E1, and CYP26B1. Our discussion of CYP polymorphisms provides insight into the importance of screening tests in OPMDs patients for the prevention of oral and pharyngeal cancers. Future studies will establish a strong foundation for the development of chemoprevention strategies, polymorphism-based clinical diagnostic tools (e.g., specific single-nucleotide polymorphism (SNP) "barcodes"), and effective treatments for BQ-related oral disorders.

Influence of continuing education on dental hygienists' knowledge and behavior related to oral cancer screening and tobacco cessation.

PURPOSE: There are more than 35,000 new cases of oral and pharyngeal cancers (OPC) diagnosed each year. Most OPCs are diagnosed in advanced stages, requiring aggressive treatment and resulting in higher morbidity and mortality than when diagnosed early. The overall 5 year survival rate of OPC is about 60%. Early detection of OPC lesions are the key to survival. A major risk factor for OPC is chronic tobacco use. The purpose of this paper is to report changes in dental hygienists' knowledge, attitudes and behaviors 6 months after attending a standardized lecture format continuing education (CE) course on early OPC detection and tobacco cessation counseling compared to baseline values. METHODS: A total of 64 CE courses were given for dental professionals throughout the 10 U.S. public health districts to determine if OPC screenings and tobacco cessation counseling behaviors could be modified at 6 months post-training. Questionnaires were obtained at baseline and 6 months later using a pre-/post-test design. RESULTS: A total of 1,463 dental hygienists participated at baseline and 543 at a 6 month follow-up. Data showed a significant difference in knowledge and behavior compared to baseline values. CONCLUSION: CE appeared to have a significant influence on participants' OPC and tobacco cessation knowledge and behavior, and could potentially make a difference on prevention, early detection and ultimately on OPC control.

Transoral resection of pharyngeal cancer: summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting, November 6-7, 2011, Arlington, Virginia.

Recent advances now permit resection of many pharyngeal tumors through the open mouth, an approach that can greatly reduce the morbidity of surgical exposure. These transoral techniques are being rapidly adopted by the surgical community and hold considerable promise. On November 6-7, 2011, the National Cancer Institute sponsored a Clinical Trials Planning Meeting to address how to further investigate the use of transoral surgery, both in the good prognosis human papillomavirus (HPV)-initiated oropharyngeal cancers, and in those with HPV-unrelated disease. The proceedings of this meeting are summarized.

US mortality rates for oral cavity and pharyngeal cancer by educational attainment.

OBJECTIVE: To describe trends in mortality rates for patients with oral cavity and pharynx cancer by educational attainment, race/ethnicity, sex, and association with human papillomavirus infection. DESIGN: Study of age-standardized mortality rates for patients with oral cavity and pharynx cancer by level of education using National Center for Health Statistics data. SETTING: Twenty-six states. PATIENTS: White and black men and women aged 25 to 64 years. MAIN OUTCOME MEASURE: Age-standardized mortality rates for 2005 to 2007 and trends for 1993 to 2007. RESULTS: From 1993 to 2007, overall mortality rates for patients with oral cavity and pharynx cancer decreased among black and white men and women; however, rates among white men have stabilized since 1999. The largest decreases in mortality rates were among black men and women with 12 years of education (-4.95% and -3.72%, respectively). Mortality rates for patients with oral cavity and pharynx cancers decreased significantly among men and women with more than 12 years of education, regardless of race/ethnicity (except for black women), whereas rates increased among white men with less than 12 years of education. Mortality trends vary substantially for human papillomavirus-related and human papillomavirus-unrelated sites. CONCLUSIONS: We observed decreasing mortality rates for patients with oral cavity and pharyngeal cancer among whites and blacks; however, decreases were greatest among those with at least 12 years of education. This difference in mortality trends may reflect the changing prevalence of smoking and sexual behaviors among populations of different educational attainment.

Derivation and validation of a risk-factor model for detection of oral potentially malignant disorders in populations with high prevalence.

BACKGROUND: Oral and pharyngeal cancers constitute the sixth most common type of cancer globally, with high morbidity and mortality. In many countries, most cases of oral cancer arise from long-standing, pre-existing lesions, yet advanced malignancies prevail. A new approach to early detection is needed. We aimed to validate a model for screening so that only high-risk individuals receive the clinical examination. METHODS: A community-based case-control study (n=1029) in rural Sri Lanka assessed risk factors and markers for oral potentially malignant disorders (OPMD) by administering a questionnaire followed by an oral examination. We then developed a model based on age, socioeconomic status and habits of betel-quid chewing, alcohol drinking and tobacco smoking, with weightings based on odds ratios from the multiple logistic regression. A total, single score was calculated per individual. Standard receiver-operator characteristic curves were plotted for the total score and presence of OPMD. The model was validated on a new sample of 410 subjects in a different community. RESULTS: A score of 12.0 produced optimal sensitivity (95.5%), specificity (75.9%), false-positive rate (24.0%), false-negative rate (4.5%), positive predictive value (35.9%) and negative predictive value (99.2%). CONCLUSION: This model is suitable for detection of OPMD and oral cancer in high-risk communities, for example, in Asia, the Pacific and the global diaspora therefrom. A combined risk-factor score of 12.0 was optimal for participation in oral cancer/OPMD screening in Sri Lanka. The model, or local adaptations, should have wide applicability.

Oral and pharyngeal cancer control and early detection.

Sixty-four standardized continuing education courses were given for dentists throughout the ten public health districts of the USA to determine if certain behaviors regarding oral and pharyngeal cancer (OPC) control could be modified. Questionnaires were obtained at baseline and at 6 months along with matched control groups. One thousand eight hundred two general dentists participated at baseline and 988 at a 6-month questionnaire follow-up. Analysis of the data indicated that continuing education courses had a positive influence on participants' oral cancer attitudes, knowledge, and behavior that potentially could make a difference on prevention, early detection, and ultimately OPC control.

Oral and pharyngeal cancer control through continuing education.

A standardized continuing education course was developed to determine if behavior in dental practices could be modified to improve office participation in oral and pharyngeal cancer control through early detection and tobacco-use cessation.

Dietary patterns and risk of oral and pharyngeal cancer: a case-control study in Rio de Janeiro, Brazil.

The study investigated the association between dietary patterns and oral cancer as part of a Latin American multicenter hospital-based case-control study, and included 210 incident cases of oral cancer and 251 controls. Dietary data were collected using a Food Frequency Questionnaire (FFQ). Factor analysis was used to define dietary patterns, which were categorized into terciles. Odds ratios (OR) with 95% confidence intervals (95%CI) were calculated using unconditional multiple logistic regression. The patterns 'prudent', characterized mainly by vegetables and fruits, and 'traditional', by rice, and pulses showed an inverse association with oral cancer for the higher tercile, respectively, OR = 0.44; 95%CI: 0.25-0.75, p value for trend (p tend) = 0.03; OR = 0.53; 95%CI: 0.30-0.93, p tend = 0.06. The 'snacks pattern' was not associated with oral cancer. Besides the protective effect of a diet rich in vegetables and fruit, our data suggest that the traditional Brazilian diet, consisting mostly of rice and beans, may improve protection against oral cancer.

Dietary patterns and risk of oral and pharyngeal cancer: a case-control study in Rio de Janeiro, Brazil / Padrões dietéticos e câncer oral e de faringe: um estudo caso-controle no Rio de Janeiro, Brasil

The study investigated the association between dietary patterns and oral cancer as part of a Latin American multicenter hospital-based case-control study, and included 210 incident cases of oral cancer and 251 controls. Dietary data were collected using a Food Frequency Questionnaire (FFQ). Factor analysis was used to define dietary patterns, which were categorized into terciles. Odds ratios (OR) with 95 percent confidence intervals (95 percentCI) were calculated using unconditional multiple logistic regression. The patterns "prudent", characterized mainly by vegetables and fruits, and "traditional", by rice, and pulses showed an inverse association with oral cancer for the higher tercile, respectively, OR = 0.44; 95 percentCI: 0.25-0.75, p value for trend (p tend) = 0.03; OR = 0.53; 95 percentCI: 0.30-0.93, p tend = 0.06. The "snacks pattern" was not associated with oral cancer. Besides the protective effect of a diet rich in vegetables and fruit, our data suggest that the traditional Brazilian diet, consisting mostly of rice and beans, may improve protection against oral cancer.

Investigou-se a associação entre padrões de dieta e câncer oral, como parte de um estudo multicêntrico latino-americano caso-controle de base hospitalar e incluiu 210 casos incidentes e 251 controles. Dados de consumo alimentar foram coletados por Questionário de Freqüência de Consumo Alimentar (QFCA). Análise fatorial identificou padrões alimentares, que foram categorizados em tercis. Calculou-se odds ratio (OR) com intervalo de 95 por cento de confiança (IC95 por cento) por regressão logística múltipla não condicional. Os padrões "prudente", caracterizado em maioria por frutas e vegetais, e o padrão tradicional, por arroz e feijão, apresentaram associação inversa com o câncer oral para o mais elevado tercil, respectivamente: OR = 0,44; IC95 por cento: 0,25-0,75, valor de p de tendência (p tend) = 0,03; OR = 0,53; IC95 por cento: 0,30-0,93, p tend = 0,06. O padrão "lanches" não foi associado ao câncer oral. Além da proteção ao câncer oral conferida por dieta rica em vegetais e frutas, nossos dados sugerem que a dieta "tradicional" brasileira contendo em sua maioria arroz e feijão pode oferecer proteção ao câncer oral.