Betel Nut Chewing Research Articles

Influence of betel nut chewing on oral microbiome in Papua New Guinea

Abstract Background and objectives For thousands of years, betel nut has been used as a psychoactive agent in Asian and Oceanian populations. Betel nut chewing was associated with the alteration of human oral microbiome and with diseases such as oral cancer and periodontitis, but only in populations of Asian cultural background. We studied the influence of betel nut chewing on the oral microbiome in Papua New Guinea, where half of the population uses betel nut and the prevalence of these diseases is one of the highest in the world. Methodology We characterised the oral microbiomes of 100 Papua New Guineans. We defined two cohorts of betel chewers (n=50) and non-chewers (n=50) based on a genetic approach to identify the presence of betel nut in saliva. We statistically compared the alpha and beta microbial diversities between the two cohorts. We performed linear discriminant analyses to identify bacterial species more prevalent in each cohort. Results We found that oral microbial diversity is significantly different between betel chewers and non-chewers. The dysbiosis observed in betel chewers, led to an increase of pathogenic bacterial species including Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, known to be in the aetiology of periodontal diseases. Conclusions and implications Our study strongly supports the alteration of human oral microbiome by betel nut use, potentially leading to periodontal diseases. It also shows the need to consider local specificities (e.g. different habits, betel nut types, and oral microbial diversities) to better characterise the impact of betel nut chewing on health.

MIAT promotes myofibroblastic activities and transformation in oral submucous fibrosis through sponging the miR-342-3p/SOX6 axis.

Oral submucous fibrosis (OSF) is an oral potentially malignant disorder that is closely related to the habit of areca nut chewing. Long non-coding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) has been identified as an essential regulator in the fibrosis progression. However, the role of MIAT in the development of OSF remains unknown. The transcriptomic profile showed that MIAT is significantly overexpressed in the OSF cohort, with a positive correlation to fibrotic markers. The silencing of MIAT expression in primary buccal mucosal fibroblasts (BMFs) markedly inhibited arecoline-induced myofibroblast transformation. Mechanistically, MIAT functioned as a miR-342-3p sponge and suppressed the inhibitory effect of miR-342-3p on SOX6 mRNA, thereby reinstating SOX6 expression. Subsequent RNA expression rescue experiments confirmed that MIAT enhanced resistance to apoptosis and facilitated myofibroblastic properties such as cell mobility and collagen gel contraction by regulating the miR-342-3p/SOX6 axis. Taken together, these results suggest that the abnormal upregulation of MIAT is important in contributing persistent activation of myofibroblasts in fibrotic tissue, which may result from prolonged exposure to the constituents of areca nut. Furthermore, our findings demonstrated that therapeutic avenues that target the MIAT/miR-342-3p/SOX6 axis may be a promising approach for OSF treatments.

Sweetened Areca Nut, A Risk in Dental Caries among Adolescents in Pune, Maharashtra? A Case-Control Study

Abstract Introduction: Smokeless tobacco (SLT) causes dental caries and so does chewing of areca nut (sweetened supari) due to the presence of sugar. Since conflicting views exist about whether areca nut causes dental caries or not, and since studies are undertaken in adults and data on adolescents are not available, this study was carried out. Since those were cross-sectional or longitudinal studies, this case-control study was undertaken to understand if flavored/sweetened areca nut is a risk factor for dental caries. Material and Method: This unmatched case-control study was conducted among the male students of 8th to 10th standard in the age group of 12–16 of four Madhyamik Vidyalaya’s (MVs) in Pimpri–Chinchwad (urban area), Pune. A directed acyclic graph (DAG) was drawn to determine the independent variables to be selected for the study and minimal variables to be adjusted during data analysis. Selection of cases was based on diagnostic and eligibility criteria. The data on the use of sweetened areca nuts and the presence of caries were collected through oral examination and a semistructured questionnaire administered by the principal investigator on a one-to-one basis between August 2022 and October 2022. Data were analyzed using epiinfoTM 7.2.5.0. Results: This study of 146 males in the age group of 13 to 16 years had 61 students as cases and 85 as controls. No significant difference was observed between the group with (cases) and without (controls) dental caries for areca nut use (pack years) whether consumed daily or less frequently for 1 year or more. While the exposure rate to areca nut among cases was 44.26%, for the control group it was 36.47%. The odds ratio of sweetened areca nut as being the risk factor for dental caries was 1.38 at 95% CI (0.70–2.71) with P = 0.44. Conclusion: This study revealed that the adolescent users of sweetened areca nuts studying in government schools had a higher exposure odds ratio for dental caries. However, it was not significant statistically. Information bias including recall may have influenced the outcome.

Comprehensive analysis of clinicopathological characteristics in oral squamous cell carcinoma arising from oral submucous fibrosis: a retrospective study

BackgroundOral squamous cell carcinoma arising from oral submucous fibrosis is recognized as a clinicopathologically distinct disease. This study aims to summarize and compare the population and clinicopathologic characteristics of OSCC-OSF with other OSCC in Hunan Province, China. The objective is to formulate treatment strategies more in line with regional characteristics.MethodsA retrospective review of OSCC cases recruited from the Second Xiangya Hospital from 2010 to 2020 was conducted. A total of 1,413 OSCC patients were selected, including 481 patients with OSCC-OSF and 932 were other OSCC. Population characteristics, risk factors and clinicopathological manifestations were explored in OSCC-OSF and other OSCC, as well as thinprep cytologic test and DNA quantification.ResultsWe found that OSCC-OSF patients were younger than those with other OSCC. Both types of disease were predominantly observed in males compared to females. Tumor biopsy analysis indicated that tumor cells within OSCC-OSF patients were more likely to be well differentiated and showed a higher frequency of lymph node metastases. Clinicopathological factors, such as the chewing betel nuts habit and smoking, were more prevalent in OSCC-OSF patients in contrast to other OSCC. DNA quantification revealed that the number of DNA aneuploid cells was higher in OSCC-OSF compared to other OSCCs.ConclusionIn this study, OSCC-OSF is considered a clinicopathologically distinct disease. Compared with other OSCC, OSCC-OSF patients have a higher incidence of nodal metastases, an early clinical TNM stage, and a lower three-year survival rate. Therefore, early diagnosis and treatment are crucial to improving the prognosis of OSCC-OSF.

Clinicopathological risk factors of oral second primary tumours

BackgroundOral second primary tumours (SPTs) have a poor prognosis due to late-stage diagnosis. This study evaluates the demographic and clinicopathological risk predictors of SPTs. MethodsPatients with oral squamous cell carcinoma, carcinoma in situ, or severe dysplasia were accrued into the Oral Cancer Prediction Longitudinal study within one year post-curative treatment. Data on demographics, risk habits, and primary tumour characteristics were collected. Clinical follow-up included assessing the presence of second oral premalignant lesions (SOPLs), clinicopathological features, and the results from toluidine blue staining and fluorescence visualization. ResultsAmong 296 patients, 23 (8 %) developed SPTs. Older age at primary cancer diagnosis (P = 0.008) and a history of chewing tobacco or betel nut (P = 0.043) increased the risk of SPTs. Patients with primary tumours located at low-risk sites had an increased risk of SPTs (P = 0.004), which often presented at high-risk sites. The presence of SOPLs (P < 0.001), and multiple lesions (P = 0.017) significantly increased the risk of SPTs. Positive toluidine blue staining indicated a trend toward higher risk of SPTs, whereas fluorescence visualization did not. The median time to SPT diagnosis was 3.25 years post-treatment. ConclusionsIdentifying second or multiple oral premalignant lesions is critical for predicting the risk of SPTs regardless of their clinical or histological characteristics. Routine biopsy of these lesions should be prioritized to ensure timely diagnosis. Incorporating these risk predictors into clinical follow-up can enhance early cancer detection and improve patient outcomes.

A novel nomogram for predicting overall survival in patients with tongue squamous cell carcinoma using clinical features and MRI radiomics data: a pilot study

ObjectiveTongue squamous cell carcinoma (TSCC) accounts for 43.4% of oral cancers in China and has a poor prognosis. This study aimed to explore whether radiomics features extracted from preoperative magnetic resonance imaging (MRI) could predict overall survival (OS) in patients with TSCC.MethodsThe clinical imaging data of 232 patients with pathologically confirmed TSCC at Xiangyang No. 1 People’s Hospital were retrospectively analyzed from February 2010 to October 2022. Based on 2–10 years of follow-up, patients were categorized into two groups: control (healthy survival, n = 148) and research (adverse events: recurrence or metastasis-related death, n = 84). A training and a test set were established using a 7:3 ratio and a time node. Radiomics features were extracted from axial T2-weighted imaging, contrast-enhanced T1-weighted imaging, and diffusion-weighted imaging (DWI) sequences. The corresponding radiomics scores were generated using the least absolute shrinkage and selection operator algorithm. Kaplan–Meier and multivariate Cox regression analyses were used to screen for independent factors affecting adverse events in patients with TSCC using clinical and pathological results. A novel nomogram was established to predict the probability of adverse events and OS in patients with TSCC.ResultsThe incidence of adverse events within 2–10 years after surgery was 36.21%. Kaplan–Meier analysis revealed that hot pot consumption, betel nut chewing, platelet–lymphocyte ratio, drug use, neutrophil–lymphocyte ratio, Radscore, and other factors impacted TSCC survival. Multivariate Cox regression analysis revealed that the clinical stage (P < 0.001), hot pot consumption (P < 0.001), Radscore 1 (P = 0.01), and Radscore 2 (P < 0.001) were independent factors affecting TSCC-OS. The same result was validated by the XGBoost algorithm. The nomogram based on the aforementioned factors exhibited good discrimination (C-index 0.86/0.81) and calibration (P > 0.05) in the training and test sets, accurately predicting the risk of adverse events and survival.ConclusionThe nomogram constructed using clinical data and MRI radiomics parameters may accurately predict TSCC-OS noninvasively, thereby assisting clinicians in promptly modifying treatment strategies to improve patient prognosis.

Knowledge, Attitudes, and Practices of University Students Regarding the Impact of Smokeless Tobacco, Areca Nut, E-cigarette Use on Oral Health.

The prevalence of smokeless tobacco, areca nut, and e-cigarette use among university students has raised concerns regarding their potential impact on oral health. Assessing students' knowledge, attitudes, and practices toward these substances is necessary. Understanding these factors can inform targeted interventions and policies promoting oral health among this population. This study aims to investigate the awareness levels, attitudes, and behaviors of university students regarding smokeless tobacco, areca nut, and e-cigarette use and their potential effects on oral health. Identifying gaps in knowledge and misconceptions will help guide educational initiatives and public health interventions tailored to the needs of university students. The study employed a designed questionnaire, comprising 20 closed-ended queries, administered via the Google Forms platform. This survey was disseminated among college students in Chennai to gather insights for the study. Of the 500 college students included in the study, almost 85.5% (427) were aware of the harmful effects of smokeless tobacco on oral health. Additionally, 74.6% (373) recognized that chewing areca nut contributes to poor oral health, while 59.8% (299) acknowledged the negative impact of e-cigarette use. The present study concluded that 11.1% (6) used smokeless tobacco, 18.9% (94) chewed areca nut, and 1.9% (10) used areca nut along with tobacco. Regarding e-cigarettes, 3.9% (19) indulged in vaping as a substitute for smoking regular cigarettes and 12.1% (61) used it along with tobacco cigarettes. It was also noted that 27.8% (139) were trying to quit and 12.6% (63) have tried but could not succeed. Therefore, although there was awareness of the ill effects of these deleterious habits on oral health and the increased risk of oral cancer, there remains a need to educate individuals and provide support for quitting these habits. Our study will provide insights into the present scenario of the awareness of the association between oral health and tobacco/areca nut consumption among college students in Chennai city.

Substances use and risk of hypertension before midlife in military young adults: CHIEF cohort study, 2014–2020

BackgroundThe use of substances, e.g., tobacco and betel nut, are prevalent among military personnel in Taiwan, whereas some specific substances such as alcohol use are forbidden in military base. There were inconsistent findings for the incidence of hypertension with habitual substances use in diverse populations, while no studies were carried out in the military. MethodsA total of 2419 Taiwanese military personnel, aged 18–39 years, who were not taking any antihypertensive agents and did not have a baseline systolic blood pressure (SBP) ≥130 mmHg and/or diastolic blood pressure (DBP) ≥80 mmHg were followed for incidence of hypertension from baseline (2014) through the end of 2020. Alcohol, tobacco and betel nut use status (active vs. former/never) were self-reported by each participant at baseline. New-onset hypertension of each participant was defined by an average of two resting BP measurements in the annual health examinations (2015–2020). Multivariable Cox regression analysis with adjustments for baseline BP and other potential covariates were performed to determine the risk of incident hypertension with each substance use. Five-year absolute changes in BP level with specific substance use were compared using analysis of covariance (ANCOVA). ResultsThere were 867 active smokers (35.8 %), 237 active betel nut chewers (9.8 %) and 961 active alcohol consumers (39.7 %) at baseline. During a median follow-up of 5.8 years, 911 new-onset hypertension events (37.7 %) were observed. While compared to those without any substances use, merely active holiday alcohol users had a significantly lower risk of incident hypertension [hazard ratio (HR) and 95 % confidence interval: 0.72 (0.58–0.89)]. The 5-year diastolic BP increase (mmHg) was borderline significantly lower in active alcohol users on holidays as compared to former/never alcohol users (4.02 (standard deviation =9.01) and 4.76 (9.42), p = 0.07). The risk of incident hypertension was not significant in active smokers and active betel nut users, while the 5-year BP increase level was significantly greater in active smokers than former/never smokers (5.60 (9.96) vs. 4.42 (9.22), p = 0.03). ConclusionOur findings suggest that military young personnel consuming alcohol only allowed on holidays had a lower incidence of new-onset hypertension. On the contrary, the 5-year BP change may increase greater with habitual smoking, though the risk of new-onset hypertension was not affected.

Prevalence of oral submucous fibrosis linking with Areca Nut usage among Indians.

The prevalence of oral submucous fibrosis amongst population of Southern Rajasthan is of interest to dentists. Hence, a cross sectional study had been conducted on 3548 patients from 18-60 years age group who visited the Department of the Oral Medicine and Radiology, Pacific Dental College and Research Centre, Bedla, Udaipur was completed. They were subjected to thorough case history related to quid habit in arecanut (Areca catechu L.) form and to diagnose OSMF clinically. 1645 processed form of arecanut users were identified. The prevalence of arecanut chewers in study population has been reported to be 46.36%. The prevalence of OSMF in study population has been reported to be 458 (12.9%). Exact component associated and the mechanism involved in the occurrence of OSMF is still not available in literature and research is going on regarding unveiling this mysterious lesion.

Transforming Hospital Housekeeping: The Kayakalp Journey.

The Kayakalp guidelines for public healthcare facilities under the Swachh Bharat Abhiyan (Clean India Mission) focus on improving sanitation, cleanliness, and infection control at public hospitals in India. This study was conducted in a 960-bed tertiary-level teaching hospital in eastern India. Housekeeping has been a challenge in public institutions, with factors like overcrowding and resource constraints. Tobacco and betel nut chewing, spitting, poor sanitation practices, and open urination are major challenges in ensuring sanitation at the hospital. The research objective was to study the implementation of the Kayakalp guidelines for quality improvement in housekeeping services at the institution. A pre- and post-interventional study was conducted using the Plan-Do-Check-Act (PDCA) quality tool. Plan phases included the gap assessment using the Kayakalp checklist with numerical scoring. Necessary interventions were done under three headings: structure, processes, and outcomes in the "Do" phase. The "Check" phase included monitoring of the activities followed by the "Act" phase, which included a review of the action plan. External experts nominated by the government conducted the final assessments and recommended it as one of the cleanest hospitals. A 360-degree improvement was observed in hospital services, with assessment score improvement from 73.68% to 95.0%. The institution received the first prize in 2020 and 2021 and runners-up Kayakalp National Award under category "B" (Institute of National Importance) Hospitals in 2019. The implementation of Kayakalp guidelines of the Government of India proved to be efficient in the improvement of housekeeping and infection control practices in the institution.

MiRNA genetic variations associated with the predisposition of oral squamous cell carcinoma in central Indian population

The disease burden of Oral Squamous Cell Carcinoma (OSCC) is rising day-by-day and is expected to rise 62 % through 2035. The chewing of tobacco, areca nut, and betel leaf, poor oral hygiene, and chronic infection are common risk factors of OSCC, but genetic and epigenetic factors also contribute equally. MicroRNAs (miRNAs) are comprised of small, non-coding endogenous RNA that regulate a plethora of biological activities by targeting messenger RNA through degradation or inhibition. Single Nucleotide Polymorphisms (SNPs) in miRNA genes can regulate the development and progression of OSCC. The present study aimed to determine the association between SNPs in miRNA genes (miRSNPs) with the risk of OSCC. A case-control study involving 225 histo-pathologically confirmed OSCC cases and 225 healthy controls was conducted, where 25 miRSNPs were analyzed by iPLEX MassArray analysis. A SNP rs12220909 in MIR4293 showed a highly protective effect (CC vs GG, OR = 0.0431, 95%CI = 0.005–0.323, p = 3e-6). Whereas three SNPs, namely, rs4705342 in MIR143 (CC vs TT, OR = 2.25, 95%CI = 2.00–2.53, p = 0.0008), rs531564 in MIR124 (CC vs GG, OR = 24.18, 95%CI = 3.22–181.37, p = 3e-6), and rs3746444 in MIR499 (AA vs GG, OR = 2.01, 95%CI = 1.32–3.05, p = 0.001) were significantly associated with a higher risk of OSCC. Additionally, NanoString-based nCounter miRNA expression profiling revealed that miR-499a (Log2FC = −1.07), and miR-143 (Log2FC = −1.56) were aberrantly expressed in OSCC tissue. Taken together, the above miSNPs may contribute to the high incidence of OSCC in central India. However, further studies with large cohorts and ethnic stratification are required to validate our findings.

Urban–rural health disparity among patients with chronic kidney disease: a cross-sectional community-based study from 2012 to 2019

ObjectivesThe incidence of chronic kidney disease (CKD) is increasing owing to the ageing population, resulting in an increased demand for dialysis and kidney transplantation, which can be costly. Current research...

Association of oral cancer site with addiction and sociodemographic characteristics: A cross-sectional study conducted at a tertiary health centre

Abstract Introduction: In contemporary epidemic scenarios, oral cancer ranks the top 3 cancer types afflicting the Indian population. The primary risk factors include alcohol consumption, tobacco usage in various forms, such as cigarettes and smokeless tobacco, betelnut chewing, and infection with the human papillomavirus. This article submitted in preprint in medRxiv on 20 February 2024. Materials and Methods: This study, conducted at a tertiary healthcare center, adopted a hospital-based cross-sectional approach involving 233 oral cancer patients who sought medical care from January 1 to December 31, 2017. Results: The findings indicate that males above the age of 60 (40.11%) and females aged between 41 and 50 years (45.45%) were the most affected groups. A statistically significant association (P &lt; 0.05) was found. The primary sites for oral cancer were the cheek (40.36%) and tongue (31.78%). Remarkably, the majority of male patients exhibited a combination of addictions, including tobacco chewing, smoking, and alcohol use, whereas most female patients were exclusively involved in tobacco chewing. Conclusion: To curb the increasing prevalence of oral cancer in India, it is imperative to implement comprehensive public education initiatives and health promotion strategies aimed at reducing both smoking and alcohol consumption.

Evaluation of the Role of Trace Elements in Malignant Transformation of Oral Submucous Fibrosis: A Study in the Population of Krishna District, Andhra Pradesh, India.

Oral submucous fibrosis (OSMF) is a chronic, potentially malignant disorder linked predominantly to areca nut chewing. This study investigates the role of serum trace elements (Cu, Fe, Zn, Se) in the progression and malignant transformation of OSMF. A community-based cross-sectional study involved 80 participants from the Government Dental College, Vijayawada, Krishna District, AP. Participants were divided into four groups: areca nut users without OSMF, areca nut users with OSMF, areca nut users with malignant-transformed OSMF, and healthy controls. Blood samples were analyzed for serum iron, copper, zinc, and selenium levels. Significant differences were found in serum copper(P=0.032) and zinc levels (P=0.006), with elevated levels observed in the malignant-transformed OSMF group compared to controls. No significant differences were observed in serum iron (P=0.542) and selenium levels(P=0.062) across the groups. Elevated serum copper levels can serve as a reliable diagnostic marker for malignant transformation in OSMF. Future research should explore the potential therapeutic benefits of copper chelation in OSMF management.

Exploring the therapeutic mechanisms of resveratrol for treating arecoline-induced malignant transformation in oral epithelial cells: insights into hub targets.

Betel nut chewing is a significant risk factor for oral cancer due to arecoline, its primary active component. Resveratrol, a non-flavonoid polyphenol, possesses anti-cancer properties. It has been shown to inhibit arecoline-induced oral malignant cells in preliminary experiments but the underlying mechanism remains unclear. This research therefore aimed to explore the potential therapeutic targets of resveratrol in treating arecoline-induced oral cancer. Data mining identified common targets and hub targets of resveratrol in arecoline-induced oral cancer. Gene set variation analysis (GSVA) was used to score and validate the expression and clinical significance of these hub targets in head and neck cancer (HNC) tissues. Molecular docking analysis was conducted on the hub targets. The effect of resveratrol intervention on hub targets was verified by experiments. Sixty-one common targets and 15 hub targets were identified. Hub targets were highly expressed in HNC and were associated with unfavorable prognoses. They played a role in HNC metastasis, epithelial-mesenchymal transition, and invasion. Their expression also affected immune cell infiltration and correlated negatively with sensitivity to chemotherapeutic agents such as bleomycin and docetaxel. Experiments demonstrated that resveratrol down-regulated the expression of the hub targets, inhibited their proliferation and invasion, and induced apoptosis. Resveratrol inhibits the arecoline-induced malignant phenotype of oral epithelial cells by regulating the expression of some target genes, suggesting that resveratrol may be used not only as an adjuvant treatment for oral cancer, but also as an adjuvant for oral cancer prevention due to its low toxicity and high efficacy. © 2024 Society of Chemical Industry.

Expression profile of diagnostic genes in oral submucous fibrosis

Oral Submucous Fibrosis (OSMF) is a chronic precancerous disorder of the oral mucosa caused by chewing of areca nut and its other variants. Chewing of areca nuts leads to dysregulated expression of specific genes, leading to various premalignant or malignant disorders. This study aimed to determine the differential expression of the diagnostic genes (MYH6, TNNT3, MYL1, and TPM2) in healthy controls and OSMF patients using saliva and tissue samples, determining the histopathological grade of the clinical samples. A total of 20 patients were included in the study and were divided into two groups: Group I consisted of 10 healthy patients (control group) and Group II consisted of 10 OSMF patients. Unstimulated whole saliva samples were collected from both groups, and the tissue samples were divided into two parts: one for RT-qPCR analysis and the other for histopathological assay. The expression profile of genes concerning OSMF saliva and tissue samples was significantly upregulated compared to the healthy control, and all the clinical samples of the study were categorized into histopathological grade 1. The findings of this study concluded that these genes can be referred to as diagnostic genes for OSMF in early and very early clinical samples, and saliva can be used as a promising diagnostic tool for early OSMF studies.

Oropharyngeal stenosis in patient with oral submucous fibrosis: a case report with 8-year follow-up

Oral submucous fibrosis (OSF) is a chronic, progressive condition affecting the oral mucosa associated with areca nut consumption. It leads to restricted tongue movement, loss of papillae, blanching and stiffening of the mucosa, difficulty in opening the mouth, and challenges in eating due to inflammation and fibrosis. This report presents a rare case of oropharyngeal stenosis secondary to OSF in a 43-year-old male with a history of chewing betel nut. A surgical procedure similar to Uvulopalatopharyngoplasty was performed to excise the submucous oropharyngeal stenosis and to reconstruct the uvula, palatoglossal arch, and palatopharyngeal arch. At 8 years postoperatively, the patient exhibited a normal mouth opening and oropharyngeal aperture.

Substance use and incidence of metabolic syndrome before midlife among military adults: the CHIEF cohort study.

Habitual substance use, i. e., alcohol, tobacco and betel nut, has been found with an increased risk of metabolic syndrome (MetS) in the general population, whereas the association remains unclear in physically fit military personnel. This study aimed to investigate the combination of these substances use and their associations with new-onset MetS in the military. A total of 2,890 military men and women, aged 18-39 years, without MetS were obtained from the cardiorespiratory fitness and health in eastern armed forces study (CHIEF) in Taiwan and followed for incident MetS from baseline (2014) through the end of 2020. Incident MetS event was defined by the International Diabetes Federation guideline and confirmed in the annual health examinations. A self-report was used to assess the alcohol, tobacco and betel nut use status (active vs. former/never). Multivariable Cox regression model was performed to determine the association with adjustments for sex, age, body mass index and physical activity at baseline. At baseline, there were 279 active betel nut chewers (9.7%), 991 active smokers (34.3%) and 1,159 active alcohol consumers (40.1%). During a mean follow-up of 6.0 years, 673 incident MetS (23.3%) were observed. As compared to no substance users, only one substance, and two and three substances users had a greater risk of incident MetS [hazard ratios (HRs) and 95% confidence intervals: 1.27 (1.06-1.54), 1.38 (1.12-1.69) and 1.78 (1.37-2.32), respectively]. In subgroup analyses, the risk of incident MetS in two and three substances users was significantly greater in those free of baseline low high-density lipoprotein [HRs: 1.54 (1.21-1.95) and 2.57 (1.92-3.46), respectively], as compared to their counterparts (both p for interactions <0.05). A dose-response association of more substances use for new-onset MetS was noted in military personnel. This finding suggests that the combined alcohol, tobacco and betel nut use may play a role in the development of MetS. Further study is required to establish causation and to investigate the potential benefits of substance use cessation in reducing the risk of MetS.

Analysis of PD-L1 expression in locally advanced head and neck squamous cell carcinoma and its correlation with the efficacy of neoadjuvant immunotherapy + chemotherapy: A retrospective real-world study.

6074 Background: The incidence rate of HNSCC in Hunan China are notably higher than in other regions, likely due to the high prevalence of betel nut chewing. Therefore, we conducted a study to examine the PD-L1 expression in newly diagnosed locally advanced (stage III-IVB) HNSCC patients. Methods: 1. We conducted a retrospective analysis of the PD-L1 expression (represented as CPS) in pre-treatment biopsy tissues from locally advanced HNSCC. 2. 57 patients received neoadjuvant treatment consisting of nab-paclitaxel+ cisplatin+ pembrolizumab. The efficacy of the treatment was evaluated using pathology assessments. Results: 1. A total of 373 patients were included. The top five primary sites of the tumors were the tongue(32.17%), Buccal oris (20.91%), oropharynx (10.19%), hypopharynx(9.92%), and gingiva(7.77%). The proportion of patients with PD-L1 CPS≥20 (55.23%) was significantly higher than the 43.20% reported in the KEYNOTE-048 study. Furthermore, the subgroup was even higher in the buccal oris (70.51%) and gingiva (72.41%). 2. A total of 57 patients were tested for PD-L1 CPS and received neoadjuvant treatment.After surgery, 22/57 (38.60%) achieved pathological complete response (pCR) or major pathological response (MPR), 29/57 (50.88%) achieved partial pathological response (pPR), resulting in an overall response rate (ORR) of 89.47%. In the PD-L1 CPS ≥20 group, the ORR was as high as 91.89% (34/37). 3. Among the 57 patients, 36 patients had lymph node metastasis. After treatment, 15/36 patients (41.67%) achieved pCR/MPR in lymph nodes, 7/36 patients (19.44%) achieved pPR, resulting in an ORR was 61.11% (22/36). Conclusions: 1. The oral cavity is the most common primary in HNSCC in Hunan,China. In the locally advanced , the proportion of PD-L1 CPS ≥20 is higher than reported in other studies. 2. Regardless of PD-L1 expression, neoadjuvant treatment with nab-paclitaxel+ cisplatin+ pembrolizumab has shown a high rate of local disease control in newly diagnosed HNSCC patients. Additionally, the use of neoadjuvant therapy has improved the delineation of surgical safety margins, leading to 100% R0 resections in all 57 patients. 3. The response of the primary lesion in patients treated with neoadjuvant therapy is better than that of the lymph node. Patients with a well-responding primary lesion but multiple lymph node metastases should be closely monitored for the possibility of short-term systemic metastasis. [Table: see text]

Pattern of Occurrence and Severity of Oral Submucous Fibrosis Among Habitual Gutkha, Areca Nut and Pan Chewers

Oral submucous fibrosis (OSF) is a complex, insidious and precancerous disease of the oral cavity. The high use of addictive substances in our local setting merits to be worked on finding out the resultant prevalence of OSF. Objective: To determine the frequency of occurrence and severity of OSF among habitual gutkha, areca nut and pan chewers. Methods: A total of 183 patients with presenting complaints of burning in mouth, difficulty in chewing and cheek biting and who are habitual chewer of areca nut, gutkha or pan for over 6 months with minimum frequency of 1 pack per day were recruited in this study at Oral and Maxillofacial Surgery Department of Liaquat University of Medical and Health Sciences Jamshoro, Pakistan. Severity of OSF was assessed as per clinical staging and findings was reported. Results: The average age of the patients was 34.57±9.98 years. Frequency of occurrence of OSF among habitual gutkha, areca nut and pan chewers was 100%. Regarding severity of OSF among habitual gutkha, areca nut and pan chewers was observed and found 31.15% stage 1, 51.91% stage 2 and 16.94% stage 3. Severity of stages were not statistically significant in all type of addiction. Conclusions: It was concluded that dose-dependent association between the frequency and length of daily use of commercially accessible areca nut and tobacco products and the increased risk of disease.