Betel-nut chewing does not influence PD-L1 expression rates in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC): A prospective biomarker prevalence study.

This study explored the relationship between betel-nut chewing and programmed death-ligand 1 (PD-L1) expression in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients in Taiwan. A total 280 R/M HNSCC patients, predominantly male, were evaluated; 75.4 % of whom chewed betel-nut. The prevalence of PD-L1 expression (combined positive score ≥1) was 94.3 % with similar PD-L1 expression rates between betel-nut-exposed and non-exposed groups. PD-L1 prevalence did not differ in those who received prior first-or second-line systemic therapy. In summary, betel-nut exposure did not notably affect PD-L1 expression rates in R/M HNSCC patients in Taiwan.

Association of alcohol consumption, betel nut chewing, and cigarette smoking with mortality in patients with head and neck cancer among the Taiwanese population: A nationwide population-based cohort study.

OBJECTIVES: This study investigated the association of alcohol consumption, betel nut chewing, and cigarette smoking (ABC) with mortality in patients with head and neck cancer (HNC). This nationwide population-based cohort study determined whether ABC habits were associated with overall or cancer-specific mortality in patients with HNC in Taiwan. METHODS: Data from the Taiwan Cancer Registry and Taiwan's National Health Insurance Research Database were used to identify patients with HNC from 2011 to 2017. All the identified patients were monitored until the date of death or the end of 2017. Poisson regression models were employed to estimate the incidence rate ratios (IRRs) and 95% confidence intervals (CIs) associated with the effect of ABC habits on mortality. RESULTS: A total of 31,246 patients with HNC were analyzed in this study. The results revealed that betel nut chewing alone exhibited the strongest effect, significantly increasing the risk of overall mortality (adjusted IRR = 1.44, 95% CI = 1.27-1.63). Additionally, betel nut chewing alone was significantly associated with cancer-specific mortality (adjusted IRR = 1.51, 95% CI = 1.30-1.44). Stratified analyses by sex and tumor location indicated that the effect of betel nut chewing alone on overall or cancer-specific mortality remained significant across both sexes, and among patients with oral cancer and patients with oropharyngeal cancer. CONCLUSIONS: ABC habits, particularly betel nut chewing, are significantly associated with diminished survival rates in patients with HNC. Accordingly, the implementation of an integrated campaign targeting the prevention of betel nut chewing would be one of the effective public health strategies for improving outcomes for HNC patients.

Duration and frequency of betel quid chewing affects periodontitis severity and life quality of people in Tanini Village, Kupang, Indonesia.

BACKGROUND: Chewing betel nuts can increase the risk of periodontal disease severity and potentially become malignant in the oral cavity. OBJECTIVE: This study aimed to investigate the effect of the duration and frequency of betel quid chewing behaviour on periodontitis severity and the life quality of people in Tanini Village, Kupang Regency, Indonesia. METHODS: The type of this study was an analytic observational study with a cross-sectional design. We used a questionnaire to obtain sociodemographic data. Oral Health Survey Basic Methods were used to measure debris index, plaque index, bleeding on probing, loss of attachment, and pocket depth. Behaviour and quality of life were measured by questionnaire and WHOQOL-BREF method as well. RESULTS: The largest number of respondents were male. Duration of chewing had a significant relationship with the frequency of chewing and periodontal status. Periodontitis was higher compared to all categories. The lifestyle of the community greatly influenced their behaviour in betel nut chewing and also affected the severity of their periodontitis and OHIs significantly. CONCLUSION: The lifestyle of betel nut chewing of the people in Tanini Village, greatly influences their behaviour. Prolonged and excessive use of betel nut induced significant adverse effects on human health. The longer and more often chew betel or areca nut, the higher the incidence of periodontitis, which significantly affects the quality of life as there is a possibility of the development of carcinogenesis, particularly in the oral cavity.

The Association between Betel Quid Chewing and Metabolic Syndrome Among Urban Adults in Mandalay District of Myanmar.

Background: As the prevalence of metabolic syndrome, obesity and diabetes increase worldwide, the need to identify modifiable lifestyle risk factors also increases, especially those that may be relatively unique to a specific population. To explore a possible association between betel quid chewing and metabolic syndrome, a community-based cross-sectional study was conducted. Methodology: Three hundred ninety-one (391) adults were interviewed and the following parameters were measured: triglycerides, HDL-cholesterol, glucose, waist circumference, body mass index and blood pressure. Multiple logistic regression was used to determine the association between betel quid chewing and metabolic syndrome while controlling for confounders. Results: The prevalence of metabolic syndrome was similar in chewers and non-chewers, 50% and 49%, respectively. After controlling for other factors, development of metabolic syndrome was positively associated with number of betel quids chewed per day, age greater than 40 years, and a positive family history of hypertension and diabetes. Regarding the duration of betel chewing, when analyzed by sex, the risk was doubled in men compared to non-chewers (OR 2.15; 95% CI = 1.21, 3.84). As a result, a man chewing more than 10 pieces (OR 2.49; 95% CI = 1.36, 4.57) of betel quids per day for more than 10 years had a two-fold increased chance of developing the metabolic syndrome. Conclusions: Frequency and duration of betel quid chewing may represent a behavioral lifestyle target for approaches to reduce the incidence of metabolic syndrome.

Guideline for the Diagnosis and Clinical Management of Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is a chronic, progressive and potentially malignant oral mucosal disease. Patients often have a habit of chewing betel nuts. Areca catechu has been listed as a Class 1 carcinogen by the International Agency for Research on Cancer (IARC), and its main active component, arecoline, is classified as a Group 2B carcinogen by the IARC. The World Health Organization (WHO) categorises OSF as an oral potentially malignant disorder (OPMD). The present guideline describes the risk factors, clinical symptoms and clinical signs of OSF. Clinical staging, auxiliary examination methods, basis for diagnosis and differential diagnosis and the need to improve bad lifestyle habits are proposed and addressed, and local treatment drugs, therapies, dosage and course of treatment, possible adverse reactions, and oral treatment drugs, dosage and course of treatment are proposed. The guideline also addresses the indications for surgical treatment, alternative non-drug treatment methods, selection of treatment plans for different clinical stages, criteria for efficacy evaluation, and preventive measures.

The association between alcohol, betel nut, and cigarette use with hepatitis C virus infection in Taiwan.

Hepatitis C virus (HCV) infection may cause chronic liver disease, liver cirrhosis, and liver cancer. It has been reported to associate with habits including alcohol, betel nut and cigarette use. We aimed to investigate the association between alcohol, betel nut, and cigarette use with HCV infection in Taiwan and to explore their effects. A total of 121,421 participants were enrolled from the Taiwan Biobank. They were stratified into two groups according to whether they had (n = 2750; 2.3%) or did not have (n = 118,671; 97.7%) HCV infection. All participants were also classified into four groups according to the number of habits, including a history of alcohol drinking, betel nut chewing, and cigarette smoking. There were 85,406 (no habit), 24,299 (one habit), 8659 (two habits), and 3057 (three habits) participants in the four groups, respectively. Multivariable analysis showed that the participants who had an alcohol drinking history (odds ratio [OR] 1.568; 95% confidence interval [CI] 1.388-1.773; p < 0.001), betel nut chewing history (OR 1.664; 95% CI 1.445-1.917; p < 0.001), cigarette smoking history (OR 1.387; 95% CI 1.254-1.535; p < 0.001), were significantly associated with HCV infection. Furthermore, the participants were classified into four groups according to the number of habits as follows: 85,406 (no habit), 24,299 (one habit), 8659 (two habits), and 3057 (three habits). The HCV infection rates in these four groups were 2.11%, 2.14%, 3.23%, and 4.78%, respectively. Compared to the participants with no or one habit, those with two habits had a higher HCV infection rate (all p < 0.001). In addition, compared to the participants who had no, one or two habits, those who had three habits also had higher HCV infection rates (all p < 0.001). The participants who had three habits had the highest prevalence of HCV infection. In an era when most HCV can be cured, understanding the epidemiology link between habits and HCV may help the case finding.

Aversive Reaction Between Disulfiram and Betel Quid Among Inpatients With Alcohol Use Disorder in Bhutan: A Preliminary Study.

Betel quid (BQ) is commonly used in the Asia-Pacific region. Disulfiram is prescribed for people with alcohol use disorders (PwAUDs) after the completion of detoxification as an alternative to rehabilitation. This prospective observational study reported the aversive reactions and common symptoms of disulfiram and BQ in PwAUDs. Participants included PwAUDs admitted to the psychiatric ward at the Jigme Dorji Wangchuck National Referral Hospital for detoxification, who were on Disulfiram and using BQ at the same time. Aversive reactions between disulfiram and BQ were observed for 100 patients over a year. Twenty participants showed aversive reactions between BQ and disulfiram. Common symptoms included sweating, diarrhea, dizziness, tremors, palpitations, shortness of breath, nausea and vomiting, and headache. Since PwAUDs in Bhutan are inducted on disulfiram after detoxification, and most use BQ simultaneously, this study will help inform health care providers to educate people about the aversive reactions of disulfiram and BQ.

Statin use and its association with decreased risk of esophageal squamous cell carcinoma in betel nut chewers.

BACKGROUND: Betel nut chewing involves the chewing of areca nuts or betel quid (areca nuts wrapped in betel leaves), which is associated with an increased risk of esophageal squamous cell carcinoma (ESCC). Statins have anticancer properties. We investigated the association between statin use and ESCC risk in betel nut chewers. METHODS: The study included 105 387 betel nut chewers matched statin users and nonusers. Statin use was defined as the use of ≥28 cumulative defined daily doses (cDDDs) of statin. The primary outcome was incidence of ESCC. RESULTS: The incidence rate of ESCC was significantly lower in statin users than in nonusers (2.03 vs. 3.02 per 100 000 person-years). Statin users had a lower incidence rate ratio of 0.66 for ESCC (95% confidence interval [CI]: 0.43-0.85) relative to nonusers. After potential confounders were adjusted for, statin use was determined to be associated with a reduced risk of ESCC (adjusted hazard ratio [aHR], 0.68; 95% CI: 0.51-0.91). A dose-response relationship was observed between statin use and ESCC risk; the aHRs for statin use at 28-182 cDDDs, 183-488 cDDDs, 489-1043 cDDDs, and > 1043 cDDDs were 0.92, 0.89, 0.66, and 0.64, respectively. CONCLUSION: Statin use was revealed to be associated with a reduced risk of ESCC in betel nut chewers.

Presence of Candida and its associated factors in participants attending oral cancer screening in the lower northeastern area of Thailand.

BACKGROUND: Certain evidence indicated high prevalence of Candida in oral potentially malignant disorders (OPMDs) and oral cancer (OC). This study was aimed to investigate the presence of Candida and its associated factors in participants who attended the oral cancer screening program in the lower northeastern districts of Thailand. METHODS: Convenient participants residing in the lower northeastern districts of Thailand who attended the oral cancer screening were enrolled. A questionnaire retrieving demographic characteristics, risk factors of oral cancer, and risk of having Candida was completed. Oral examination was performed by oral medicine specialists or oral surgeons. The participants were categorized into 4 groups according to their clinical diagnosis, namely normal oral mucosa (NOM), OPMDs/OC, non-OPMDs/OC and clinically suspected oral candidiasis (CSOC). Stimulated saliva flow rate was measured. Dip-slide test was performed in each participant to evaluate the presence of Candida. The levels of Candida were categorized into high and low levels according to the score received from the dip-slide test. Factors associated with high levels of Candida were identified using multivariate logistic regression analysis. RESULTS: A total of 577 participants were recruited. High levels of Candida were found in 31.3%, 24.7%, 25.9% and 18.1% in the OPMDs/OC, the non-OPMDs/OC, the CSOC and the NOM groups, respectively. According to multivariate logistic regression analysis, age above 60 years, female gender, betel quid chewing habit, use of denture, hyposalivation, and being in the CSOC group were found to be significantly associated with high levels of Candida. CONCLUSION: Higher number of participants in the OPMDs/OC group was found to have high levels of Candida. Increasing age, female gender, betel quid chewing habit, use of denture, hyposalivation and having CSOC lesions were associated with high levels of Candida.

Effectiveness of health promotion intervention on the knowledge and selected practices related with oral cancer among a group of vulnerable youth in Sri Lanka.

BACKGROUND: There has been a noticeable trend of younger people being diagnosed with oral cancer, particularly among those from low socio-economic backgrounds. Poor knowledge on risk factors toward oral cancer and the growing fashion of using tobacco also identified among younger generation. Present study aimed to assess the effectiveness of a health promotion intervention to improve the knowledge and encourage positive practices associated with oral cancer among a group of vulnerable youth in Sri Lanka. METHODS: The study was a community based quasi experimental study, conducted in urban slums in the district of Colombo, Sri Lanka. Sample size for one group was 120 youth participants aged between 15 and 24 years. Health promotion intervention was implemented to the intervention group and follow up period was 6 months. The control group did not receive the intervention. Awareness of oral cancer and oral potentially malignant disorders, tobacco chewing practice (betel quid chewing and commercially prepared tobacco and areca nut packet (CPTAP) chewing) and self-mouth examination practice were assessed at the beginning and after 6 months in both groups using an interviewer administered questionnaire. Changes in the knowledge, self-mouth examination practice, quit rate and fresh up take rate were computed to determine the effectiveness. RESULTS: There was no loss to follow up. No significant difference was observed between the groups in pre intervention assessment regarding the knowledge, tobacco chewing and self-mouth examination practices. Knowledge score was significantly differed between the groups P = 0.000 in the post intervention assessment as well as among females P = 0.001. Quit rate of the tobacco chewing practice, betel chewing practice and CPTAP chewing practice among intervention group was 33%, 70%, and 13% respectively while control group did not have any quitters, P = 0.001. Fresh up take rate of tobacco chewing in the intervention group was 6.7% compared to the 37.5% in the control group, P = 0.001. Practicing self-mouth examination was significantly higher in intervention group in post intervention assessment, P = 0.000. CONCLUSION: Multicomponent health promotion intervention (Advocacy, Interactive discussions, IEC materials and Community mobilization) was significantly effective in enhancing the knowledge, increasing self-mouth examination practice, and reducing tobacco chewing practice among a vulnerable group of youth in Sri Lanka.

The association of severely worn dentition resulting from betel nut chewing with temporomandibular disorders: a cross-sectional study.

BACKGROUND: Most studies support parafunctions play an important role in temporomandibular disorders (TMD), whereas the association between tooth wear and TMD remains controversial. Betel nut chewing as a parafunction is popular in South and Southeast Asia. We therefore investigated the association of severely worn dentition resulting from betel nut chewing with TMD. METHODS: A cross-sectional analysis of 408 control participants (male: 380, female: 28, 43.62 ± 9.54 years) and 408 participants with betel nut chewing related severely worn dentition (male: 380, female: 28, 43.73 ± 8.93 years) who received dental and TMD checkup according to Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) in Health Management Center, Xiangya Hospital was performed. Betel nut chewing related severely worn dentition meant all the natural teeth had moderate to severe tooth wear [Tooth Wear Index (TWI) ≥ 2)] including ≥ 2 severe wear teeth (TWI ≥ 3) due to betel nut chewing. Multivariable logistic regression analysis was used. RESULTS: After adjusting for age, gender, betel nut chewing related severely worn dentition, oral submucosal fibrosis, number of missing teeth, number of dental quadrants with missing teeth, visible third molar and orthodontic history, variables of age, gender and betel nut chewing related severely worn dentition were significant for overall TMD. Multivariable analysis showed betel nut chewing related severely worn dentition was significantly associated with intra-articular TMD [odds ratio and 95% confidence intervals: 1.689 (1.271-2.244), P = 0.001] in a betel nut chewing dose-dependent manner. CONCLUSION: Betel nut chewing related severely worn dentition was associated with intra-articular TMD.

Prevalence and determinants of oral potentially malignant disorders in rural areas of South India.

Purpose: Oral potentially malignant disorders are associated with a risk of undergoing malignant transformation and a concomitant increase in morbidity and mortality. Moreover, epidemiological studies, especially from rural areas, are important in assessing their prevalence and the identification of determinants of these disorders so that preventive strategies can be employed in tackling them. Methods: Cross-sectional descriptive study was conducted based on guidelines of the World Health Organization's Guide Epidemiology and Diagnosis of Oral Mucosal Disease and Conditions 1995 in rural areas of south India. Results: Prevalence of oral potentially malignant disorders (OPMDs) in the studied population was 13.28%, with oral submucous fibrosis (OSMF) accounting to 6.21% and erythroplakia at 1.3%. Regression analysis revealed, age 40-54 years (odds ratio [OR] = 3.8, confidence interval [CI] at 95%-1.5-4.0, P < 0.05), lower socioeconomic groups (OR = 2.1, CI at 95%-1.4-3.1, P < 0.05), habits (OR = 3.2, CI at 95%-1.9-3.8, P < 0.05), smoke form of tobacco-beedi (OR = 2.5, CI at 95%-1.6-2.8, P < 0.05), smokeless form of tobacco-areca nut lime and leaf and tobacco (OR = 3.1, CI at 95%-1.9-3.4, P < 0.05) to be the possible determinants for OPMDs. Conclusions: The overall prevalence of OPMDs in the studied population was 13.28%. The most common OPMDs were OSMF. Identified determinants were age, socioeconomic group, ethnicity, diet, body mass index, and associated harmful habits.

The Controversial Roles of Areca Nut: Medicine or Toxin?

Areca nut (AN) is used for traditional herbal medicine and social activities in several countries. It was used as early as about A.D. 25-220 as a remedy. Traditionally, AN was applied for several medicinal functions. However, it was also reported to have toxicological effects. In this review article, we updated recent trends of research in addition to acquire new knowledge about AN. First, the history of AN usage from ancient years was described. Then, the chemical components of AN and their biological functions was compared; arecoline is an especially important compound in AN. AN extract has different effects caused by different components. Thus, the dual effects of AN with pharmacological and toxicological effects were summarized. Finally, we described perspectives, trends and challenges of AN. It will provide the insight of removing or modifying the toxic compounds of AN extractions for enhancing their pharmacological activity to treat several diseases in future applications.

Prognostic stratification of oropharyngeal cancer patients in a betel nut chewing and low HPV area.

BACKGROUND: This study aimed to establish a simple predictive model for oropharyngeal cancer (OPC) in an area with a relatively low prevalence of human papillomavirus (HPV) and frequent betel nut chewing. METHODS: A total of 116 patients with OPC were recruited from the clinical research database of a referral cancer center between 2013 and 2018. Patient characteristics-including age, gender, tumor stage, differentiation, and treatment modality-were extracted from the database. Patients diagnosed after 2018 were staged using the 7th AJCC staging system to explore the impact of extra-nodal tumor extension (ENE) on survival. Immunohistochemical analysis was performed for p16, epidermal growth factor receptor (EGFR), p53, and programmed cell death ligand 1 (PD-L1). ENE status was evaluated by pathological analysis or radiological features. Primary outcome was disease-specific overall survival (OS). Univariate and multivariate Cox regression were used to establish a predictive model. RESULTS: Mean age was 57.3 ± 9.9 years; 103 patients (88.8%) were male. P16 positive OPC was positively associated with higher PD-L1 and a tonsillar sub-site and negatively associated with betel nut chewing and cigarette smoking. In Cox regression, age, p16 status, EGFR, cT4, ENE, and cigarette smoking were significantly associated with OS. In survival tree analysis, cT stage was the most important risk stratification parameter, followed by EGFR expression and p16 status. Patients with cT4 stage or high EGFR were classified as the high-risk group and had poorest OS. CONCLUSIONS: Due to the low prevalence of HPV and popularity of betel nut chewing in Asia, the relative importance of prognostic predictors for OPC are not identical to Western countries. Identification of significant prognostic biomarkers may improve treatment. Trial registration This study was registered and approved by the Institutional Review Board (IRB) of Kaohsiung Veterans General Hospital (VGHKS19-CT9-07; date of approval: Aug 9, 2019).

The effect of statin medication on the incidence of oral squamous cell carcinoma among betel-nut chewers.

BACKGROUND: This study examines the relationship between statin use and oral cancer squamous cell carcinoma (OCSCC) risk in a cohort of 47 942 betel nut chewers. METHODS: The study used individual 1:1 matching and propensity score matching to compare statin users and nonusers. RESULTS: The incidence rate of OCSCC was significantly lower in statin users compared to nonusers (17.12 vs. 26.75 per 10 000 person-years), yielding an incidence rate ratio of 0.64. After adjusting for confounders, statin use was associated with a reduced risk of OCSCC (adjusted hazard ratio: 0.61; 95% confidence interval: 0.52-0.71). A dose-response relationship was observed, with a significant reduction in OCSCC incidence when the cumulative defined daily dose of statin use was equal to or greater than Q3. The risk of OCSCC was lower among users of both hydrophilic and lipophilic statins. CONCLUSION: This study provides evidence that statin use is associated with a reduced risk of OCSCC in betel nut chewers.