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Objective: To evaluate the associations between dipeptidyl peptidase IV (DPP4) single-nucleotide polymorphism (SNP) and clinicopathological characteristics of oral cancer., Methods: Four loci of DPP4 SNPs (rs7608798 A/G, rs3788979 C/T, rs2268889 T/C, and rs6741949 G/C) were genotyped by using the TaqMan allelic discrimination in 1238 oral cancers patients and 1197 non-cancer individuals., Results: The percentage of DPP4 SNP rs2268889 TC + CC was significantly higher in the oral cancer participants compared to the control group (odds ratio [OR]: 1.178, 95% confidence interval (CI): 1.004-1.382, p = 0.045). Among 1676 smokers, DPP4 polymorphisms carriers with betel quid chewing were found to have an 8.785- to 10.903-fold risk to have oral cancer compared to DPP4 wild-type carriers without betel quid chewing. Similar trend was found in individuals with alcohol consumption. Moreover, the oral cancer individuals without cigarette smoking history with at least one varied C allele of DPP4 rs2268889 had a significantly higher percentage of large tumor size with the wild-type TT homozygote (p = 0.011)., Conclusions: The DPP4 SNP may correlate to the development of oral cancer in those with cigarette smoking and alcohol consumption. Besides, the DPP4 SNP rs2268889 could relate to worse clinical course of oral cancer in non-smokers., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The aim of the present study was to investigate the awareness of oral cancer among adults in Jakarta, Indonesia, and explore the factors influencing it., Methods: A previously-tested questionnaire on 1000 adults in Jakarta was used in the present study. The data included sociodemographic factors and answers to assess the awareness of oral cancer, early signs and symptoms, risks factors, lifestyles, and history of dental visits., Results: Only 53.2% of participants were aware of oral cancer. The level of awareness significantly differed by level of education, occupation, and experience of dental visits. Only 30% of patients had been asked about their tobacco and alcohol habits, and had been informed about the hazards of these by their dentists. All of the smokers knew that tobacco increased the risk for oral cancer. However, only a few participants considered alcohol, betel quid chewing, UV light exposure, poor diet, and genetics to play role in the development of oral cancer. Health warnings were the main source of information about oral cancer; the role of health professionals is still quite low and needs to be emphasized., Conclusion: Oral cancer awareness is still low among adults in Jakarta; this finding was consistent with other studies conducted in Asia. Educational material suited to particular communities is warranted., (© 2018 John Wiley & Sons Australia, Ltd.)

Oral submucous fibrosis (OSMF) is a debilitating condition of oral cavity which has significant potential for malignant transformation. In spite of over 20 years of research, the pathogenesis of the condition is still obscure and no single management modality is effective. Many OSMF treatment protocols have been proposed to alleviate the signs and symptoms of the disorder and there is overwhelming evidence that as areca nut is primary cause, stopping its use may have a considerable effect on symptoms rather than reversing pre-existing fibrosis. We present a review of the current protocols for managing OSMF., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Limited mouth opening (LMO) in oral submucous fibrosis (OSF) has been attributed to both the submucosal and muscle fibrosis (MF). While reflectory trismus was proposed before as an auxiliary mechanism by another group, the stretch-mediated muscle damage (MSD), histopathological changes in blood vessels (such as endothelial dysfunction, endothelial hypertrophy, and endarteritis obliterans), and upregulated anaerobic isoforms of lactate dehydrogenase (LDH) have been proposed by us as complementary events leading to MF. Additionally, the amount of hypoxia-mediated upregulation of anaerobic isoforms of LDH determines the extent of MF. Radiotherapy (RT)-mediated release of reactive oxygen species causes vascular damage thereby worsening hypoxia. While the alteration in LDH levels secondary to hypoxia enhances fibrosis, RT worsens it. Oral squamous cell carcinoma occurring in the background of OSF is an absolute contraindication for RT as it augurs unfavorable prognosis. An algorithm to demonstrate this with evidence is clearly depicted. The role of HIF-1α in the progression of OSF and its malignant transformation, and the consideration of hyperbaric oxygen therapy as a therapeutic remedy in OSF are underscored., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Over the last 40 years, many theories linking oral submucous fibrosis (OSMF) to various risk factors have been proposed. Spicy, pungent foods and irritants such as supari (areca nut), paan (betel leaves), tobacco (through chewing or smoking)-the common Asian habits of chewing the aforementioned agents-have all been incriminated as causative agents. Systemic factors such as nutritional deficiency, genetic predisposition and autoimmunity have also been proposed in the pathogenesis of OSMF. However, the precise aetiology of OSMF is still unknown, and no conclusive evidence has been found despite many extensive investigations on implicated factors. Most of the ideas proposed have been derived from the existing clinical and epidemiological data. We present a comprehensive review of the various theories regarding the pathogenesis of the condition, but have not concentrated on malignant transformation in this article., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Oral submucous fibrosis (OSMF) is a potentially malignant condition associated with areca nut chewing. Formerly confined to the Indian subcontinent, it is now often seen in Asian populations of the United Kingdom, USA and other developed countries, and is therefore a serious problem for global health. What makes it more sinister is the malignant transformation rate, which has been reported to be around 7.6% over a 17-year period. In this concise article, we review the current trends in the pathophysiology of malignant transformation of OSMF., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Oral submucous fibrosis (OSF) is a chronic progressive disease of the oral cavity that is considered a common potentially malignant disorder in South Asia. Areca nut chewing is the main etiological factor, but its carcinogenic mechanism has yet to be proven. The purpose of this study was to identify the useful biomarkers in predicting high-risk patients with OSF., Methods: Thirty-six cases of OSF and six cases of normal oral mucosa (NOM) were used for this study. Immunohistochemical staining was performed for Ki67, cyclin D1, p16, p53, β-catenin, c-Jun, c-Met, and insulin-like growth factor II mRNA-binding protein 3 (IMP3). The expression patterns of NOM served as guidelines for the scoring system., Results: The expression of Ki67, cyclin D1, c-Met, IMP3, and β-catenin showed a significant difference between OSF and NOM samples. The combined biomarkers of Ki67 and p16 showed significantly different expression between the transformation and non-transformation groups. With discriminant analysis, we proposed a noble formula and cutoff value for predicting high-risk patients with OSF., Conclusion: The notable biomarkers in our present study were Ki67 and p16 showing significantly different expression levels between the transformation and non-transformation groups. With the identification of high-risk patients with OSF, we can expect to develop more intensive treatment modalities, leading to the reduction in cancer transformation rate from OSF., (© 2016 The Authors. Journal of Oral Pathology & Medicine Published by John Wiley & Sons Ltd.)

Background: Oral submucous fibrosis (OSF) is a chronic debilitating disease and a premalignant condition of the oral cavity. It is well known for its impervious nature to medical therapy. Omega-3 polyunsaturated fatty acids have been reported to have anti-inflammatory properties. However, its role in OSF is still not known. This preliminary study assessed the efficacy of systemic omega 3 in this disease., Methods: A randomized single-blinded controlled trial was designed, and a total of 10 clinically confirmed adult patients with OSF were included in the study. Group A was given biweekly intralesional injections of dexamethasone 1.5 ml and hyaluronidase 1500 IU mixed with lignocaine for 6 weeks and a placebo for 3 months. Group B was also given similar intralesional injections but with 1 gm of omega 3 three times daily continuously for 3 months. Patients were followed every month for 3 months and then after 6 months., Results: Significant improvement was noted among all clinical parameters (interincisal distance, tongue protrusion, cheek flexibility, and visual analogue scale) in both the groups. Intergroup comparison showed significant reduction in burning sensation in group B; that is, P value was 0.005, while improvement in rest of the three clinical features was not statistically significant., Conclusion: Omega 3 can be used as an adjunctive treatment option in patients with OSF to reduce subjective symptoms. More studies should be conducted with a larger sample size to study the effect of omega 3 in patients with OSF., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Monocyte chemoattractant protein-1 (CCL2) is a major profibrotic mediator with a proven role in fibrosis of different organs of the body. Recently, increased fibrosis in oral submucous fibrosis (OSMF) is linked with betel quid-related chronic irritation and myofibroblast. Hence, this study is designed to investigate expression of CCL2 in OSMF and its correlation with myofibroblasts., Materials and Methods: Paraffin-embedded specimens of 30 OSMF and 10 tissues of normal buccal mucosa were subjected to immunohistochemical analysis for CCL2 and alpha-smooth muscle actin (α-SMA) expression., Results: CCL2 expression in basal cells (CCL2-B) and connective tissue (CCL2-CT), and α-SMA showed significantly increased expression in advanced OSMF as compared with early OSMF and controls. Significant differences were observed in the expression of CCL2-B between control vs. OSMF (P = 0.002), control vs. advanced OSMF (P = 0.005), and early vs. advanced OSMF (P = 0.0377). Similarly, differences in the CCL2-CT expression were statistically significant between control vs. OSMF (P = 0.00086), control vs. early OSMF (P = 0.02914), and control vs. advanced OSMF (P = 0.0006). For α-SMA expression, significant differences were observed between control vs. OSMF (P = 0.0003), control vs. early OSMF (P = 0.036), control vs. advanced OSMF (P = 0.00008), and early vs. advanced OSMF (P = 0.0009). In OSMF group, a significant correlation was observed between CCL2-B and CCL2-CT (P < 0.00001), CCL2-B and α-SMA (P < 0.00001), and CCL2-CT and α-SMA (P < 0.00001)., Conclusion: CCL2 could be responsible for pathogenesis of OSMF by recruiting myofibroblasts., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The aim of this study was to compare the clinicopathological features of oral squamous cell carcinoma in the background of oral submucous fibrosis (OSCC-OSMF) and oral squamous cell carcinoma (OSCC)., Methods: A total of 217 cases of OSCC were retrieved from achieves for the analysis. OSCC-OSMF cases were segregated on the basis of history and clinicopathological parameters., Results: The study included 217 patients of which 112 had OSCC and 105 OSCC-OSMF. OSCC-OSMFs were younger compared with OSCC. Overall oral cancer was noted predominantly in males compared to females. The number of OSCC-OSMF was more in clinical TNM stage I and stage II as compared to OSCC, whereas the number of OSCC was more in stage III and stage IV compared to OSCC-OSMF. Histological presentation of well-differentiated squamous cell carcinoma was significantly more in OSCC-OSMF compared to OSCC, whereas moderately differentiated squamous cell carcinoma was significantly more in OSCC compared to OSCC-OSMF. Regional lymph node metastasis was significantly higher in OSCC compared to OSCC-OSMF. Three-year disease-free survival rate was significantly higher in OSCC-OSMF compared to OSCC., Conclusion: The OSCC-OSMF was found to be a clinicopathologically distinct entity with a better grade of tumor differentiation, less incidence of nodal metastases, and early detection (early clinical TNM stage) compared to OSCC. All these factors probably contribute to a better prognosis and increased 3-year disease-free survival in OSCC-OSMF patients., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The aim of this study was to assess the prevalence and risk indicators of betel quid oral lichenoid lesions in chewers., Methods: A total of 1209 chewers were identified and categorized into three main groups based on the type of lesion: betel quid oral lichenoid lesions only, betel quid oral lichenoid lesions in association with quid-induced other oral mucosal lesions, and no lesions. Multinomial regression analyses were used to determine associations between dependent and independent variables., Results: Betel quid oral lichenoid lesions were more common in individuals who chewed quid comprising both tobacco and areca nut, and in those who chewed it two to three, or greater than three, times a day. Betel quid oral lichenoid lesions + quid-induced other oral mucosal lesions were more likely to occur in females, and in individuals who chewed quid containing both tobacco and areca nut, in their processed and unprocessed forms, and greater than three times a day., Conclusion: The prevalence of betel quid oral lichenoid lesions was higher than that reported in previous studies conducted in India. Increase in the frequency and duration of quid chewing was associated with increased likelihood of developing these oral lichenoid lesions., (© 2015 Wiley Publishing Asia Pty Ltd.)

Background: Oral squamous cell carcinoma (OSCC) is the sixth most prevalent malignancy worldwide and the third most common cancer in developing nation. Most OSCC patients relapse within months after receiving treatment. Therefore, searching the biomarkers of recurrence is urgently required to improve OSCC patient survival., Methods: We set out to explore whether expression of ZEB1 could be triggered in oral epithelial cells (SG and FaDu) by arecoline in vitro. Control and ZEB1-knockdown arecoline-stimulated SG and FaDu were subjected to migration/invasiveness/anchorage-independent growth assay. Primary and recurrent OSCC tissues from areca quid chewers were analyzed using real-time RT-PCR analysis for ZEB1 expression., Results: Arecoline led to dose-dependent elevation of ZEB1 expression in SG and FaDu cells. Downregulation of ZEB1 by lentiviral infection significantly reversed arecoline-induced oncogenicity including migration ability, cell invasiveness, and anchorage-independent growth in SG and FaDu cells. Clinically, the level of ZEB1 expression was higher in recurrent OSCC tumor samples but lower in primary lesions., Conclusions: Targeting ZEB1 might offer a new strategy for the treatment of OSCC patients. ZEB1 can serve as a progression and relapse marker in OSCC patients., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In modern times, potent dietary carcinogens are key contributors for neoplastic development. For oral squamous cell carcinoma (OSCC), one of the leading cancer types in developing countries, main oncogenic inducers/enhancers, including areca nut chewing, tobacco smoking, and alcohol consumption, were shown to promote cancer initiation/progression. Over decades, studies from different laboratories have identified underlying cellular and molecular mechanisms for carcinogen-induced OSCC. In this review, we will give an overview of where we are in understanding potential oral carcinogenic factors stimulated OSCC tumorigenesis, especially those associated with areca nut chewing in Asians, aiming to provide future scope of possible interception., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Oral submucous fibrosis (OSF) is a premalignant and fibrosing disease, which is closely associated with the habit of chewing areca nut. Panax notoginseng Buck F. H. Chen is an often used antifibrotic and antitumor agent. To treat areca nut-induced OSF, we have developed a chewable tablet, in which one of the major medicines is total Panax notoginseng saponins (PNS). In this study, we have investigated the antifibrotic effect and mechanism of PNS on areca nut-induced OSF in vitro., Methods: Through human procollagen gene promoter luciferase reporter plasmid, hydroxyproline assay, gelatin zymography, qRT-PCR, ELISA, and Western blot, the influences of PNS on areca nut extract (ANE)-induced cell growth, collagen accumulation, procollagen gene transcription, MMP-2/-9 activity, MMP-1/-13 and TIMP-1/-2 expression, cytokine secretion, and the activation of PI3K/AKT, ERK/JNK/p38 MAPK, and TGFβ/Smads pathways were detected., Results: Panax notoginseng saponins could inhibit the ANE-induced abnormal growth and collagen accumulation of oral mucosal fibroblasts in a concentration-dependent manner. PNS (25 μg/ml) could significantly inhibit the ANE-induced expression of Col1A1 and Col3A1, augment the ANE-induced decrease of MMP-2/-9 activity, inhibit the ANE-induced increase of TIMP-1/-2 expression, and decrease the ANE-induced transcription and release of CTGF, TGFβ1, IL-6, and TNFα. PNS (25 μg/ml) also significantly inhibited the ANE-induced activation of AKT and ERK/JNK/p38 MAPK pathways in oral mucosal fibroblasts and the ANE-induced activation of TGFβ/smad pathway in HaCaT cells., Conclusion: Panax notoginseng saponins possess excellent anti-OSF activity, and its mechanism may be related to its ability to inhibit the ANE-induced activation of PI3K/AKT, ERK/JNK/p38 MAPK, and TGFβ/smad pathways., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Oral cancer in the form of squamous cell carcinoma (OSCC) is typically detected in advanced stages when treatment is complex and may not be curative. The need for surgical biopsy may contribute to delays in diagnosis and impede early detection. Multiple studies of RNA from surgically obtained tumor samples have revealed many genes differentially expressed with this disease. We sought to determine whether the identified mRNAs could be used as markers by a non-invasive detection system for OSCC using RNA from brush cytology., Methods: Levels of mRNAs from 21 genes known to be differentially expressed in head and neck squamous cell carcinoma surgical samples, compared with controls, were shown to be quantifiable in oral brush cytology samples. These mRNAs were quantified in a training set of 14 tumor and 20 non-malignant brush cytology samples from tobacco/betel nut users. With the measurement of two additional mRNAs and analysis using support vector machines algorithm for class prediction of these cancers was produced., Results: This OSCC classifier based on the levels of 5 mRNAs in RNA from brush cytology initially showed 0.93 sensitivity and 0.91 specificity in differentiating OSCC from benign oral mucosal lesions based on leave-one-out cross-validation. When used on a test set of 19 samples from 6 OSCCs and 13 non-malignant oral lesions, we found misclassification of only one OSCC and one benign lesion., Conclusions: This shows the promise of using RNA from brush cytology for early OSCC detection and the potential for clinical usage of this non-invasive classifier., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Betel quid (BQ) and areca nut chewing is widely prevalent in many parts of Asia and Asian-migrant communities throughout the world. Global reports estimate 600 million users. Sufficient evidence of carcinogenicity has been found for BQ and its main ingredient, areca nut. BQ areca nut users have an increased risk of potentially malignant disorders. Among chewers, BQ remains in contact with the oral mucosa for prolonged periods. This review examines the clinical and pathological aspects of lichenoid lesions caused by areca nut and BQ, a condition that has received little attention in the published literature., (© 2012 Blackwell Publishing Asia Pty Ltd.)

Background: Arecanut and smokeless tobacco usage is a major cause for oral submucous fibrosis (OSF) and its subsequent development to oral squamous cell carcinoma in South-east Asian population. Polymorphisms at N-acetyltransferase 2 locus, coding for an enzyme catalyzing acetylation of aromatic amines, might cause DNA adduct formation because of improper acetylation of these polyaromatic hydrocarbons. DNA repair enzymes remove these adduct to prevent malignancy., Methods: In this hospital-based study, 100 controls and 88 OSF patients were genotyped at four polymorphic sites on NAT2 481 (C > T; silent), 590 (G > A; Arg197 > Gln), 803 (A > G; Lys268 > Arg), 857 (G > A; Gly286 > Glu) and two on XRCC1 18067 (C > T Arg 194 > Trp), 28152 (G > A Arg 399 > Gln), and one of XRCC3 26304 (C > T Thr 241 > Met) loci by PCR-RFLP to determine the risk of the disease., Results: Heterozygous XRCC3 codon 241 [OR 2.07 (1.05-4.06)], homozygous variant of NAT C481T [OR 2.81 (1.09-7.21)], and both heterozygous and homozygous variants of NAT codon 268 and 286 [OR 2.31 (1.20-4.45) and 4.98 (1.87-13.14), and 6.12 (2.75-13.62) and 2.65 (1.04-6.72)] individually influenced susceptibility to OSF in the population., Conclusion: Gene-gene interaction analysis by multifactor dimensionality reduction (MDR) revealed that XRCC3 Thr 241 Met had the largest univariate effect followed by XRCC3 Thr 241 Met - NAT2 A857G in men that presents a highly synergistic interaction as one of the potential combinations of single nucleotide polymorphisms (SNPs) to increase the risk of OSF in men if exposed to arecanut or smokeless tobacco usage. These observations can speculate the impact of the studied SNPs on the etiology of OSF., (© 2011 John Wiley & Sons A/S.)

Background:  Recognition of how risk factors affect the age when cancers are first diagnosed may help to establish more appropriate cancer screening and preventive strategies., Methods:  To investigate the independent and synergistic effects of alcohol, tobacco-free betel-quid (TF-BQ), and cigarette use on diagnosis age and dissemination of upper aerodigestive tract squamous cell carcinoma (UADT-SCC), we recruited pathology-proven 1522 patients with UADT-SCC for study., Results:  A 49-, 53-, 57-, and 62-year-old stepwise older median age at carcinoma diagnosis was, respectively, found among patients with oral, pharyngeal, esophageal, and laryngeal cancer. Oral cavity (53.2%) and larynx (11.6%) were separately the dominant and recessive sites where the UADT-SCC occurred. Although alcohol and tobacco bestowed increased risks of earlier tumor occurrence only for oral/pharyngeal and oral cancers, respectively, TF-BQ was consistently observed to confer elevated age-associated risks for each UADT-SCC [adjusted hazard ratio (aHR) = 1.6-2.3]. Alcohol and TF-BQ joint consumers experienced a stepwise increased cumulative risk (CR) of contracting carcinomas of the larynx (46.2%), esophagus (47.5%), pharynx (53.5%), and oral cavity (60.5-71.0%), with >68% of CRs found among drinkers who started chewing before age 20. Alcohol + Betel + Cigarette and Alcohol + Betel users exhibited earlier diagnosis ages than non-users: 10 years ahead for oral cancer, 7, 17, and 12 years earlier for pharyngeal, esophageal, and laryngeal cancers. Noticeably, higher cumulative cancer risks regarding earlier tumor occurrence were correspondingly identified for these users aged 43, 49, 43, and 44 upward., Conclusions:  Tobacco-free betel-quid, in conjunction with alcohol and/or tobacco consumption, impacts early cancer occurrence for specific UADT-SCC and influences tumor site incidence pattern of these neoplasms., (© 2011 John Wiley & Sons A/S.)

Background: Heat shock protein 47 (HSP47) is a product of CBP2 gene located at chromosome 11q13.5, a region frequently amplified in human cancers. Areca quid chewing is a major risk factor of oral squamous cell carcinoma (OSCC). The aim of this study was to compare HSP47 expression in normal human oral epithelium and OSCC and further to explore the potential mechanisms that may lead to induce HSP47 expression., Methods: Thirty-two OSCC specimens and ten normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The oral epithelial cell line OC2 cells were challenged with arecoline, a major areca nut alkaloid, by using Western blot analysis. Furthermore, glutathione precursor N-acetyl-l-cysteine (NAC), extracellular signal-regulated protein kinase (ERK) inhibitor PD98059, phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, cyclooxygenase-2 inhibitor NS-398, and tyrosine kinase inhibitor herbimycin A were added to find the possible regulatory mechanisms., Results: HSP47 expression was significantly higher in OSCC specimens than normal epithelium (P<0.05). No significant difference in HSP47 expression was observed with respect to age, sex, T category, stage, and differentiation (P>0.05). The lower HSP47 expression was associated with lymph node metastasis (P=0.015). Arecoline was found to elevate HSP47 expression in a dose- and time-dependent manner (P<0.05). The addition of NAC, PD98059, LY294002, NS398, and herbimycin A markedly inhibited the arecoline-induced HSP47 expression (P<0.05)., Conclusion:   Our findings demonstrated that HSP47 expression is significantly upregulated in areca quid chewing-associated OSCCs. HSP47 could be used clinically as a marker for lymph node metastasis of oral carcinogenesis. In addition, arecoline-induced HSP47 expression was downregulated by NAC, PD98059, LY294002, NS398, and herbimycin A., (© 2010 John Wiley & Sons A/S.)

Background: Oral submucous fibrosis (OSF) is a chronic oral mucosal condition with pre-malignant potential. The association between psychiatric morbidity and OSF has been sparsely studied., Methods: This cross-sectional study included 33 consecutive subjects clinically diagnosed with OSF who attended an academic tertiary care dental centre. General Health Questionnaire-28 was administered to assess the psychological morbidity. Dependence to areca products was assessed using the ICD-10 criteria. Patient group was compared with an age and gender matched control group (n=33) from the same hospital that comprised patients who had dental diseases other than OSF and had no areca/tobacco habit., Results: Total mean scores (SD) of GHQ-28 for study group and control group respectively were 48.2 (18.1) vs. 24.2 (6.5) (P<0.001). Among the patient group, the mean total GHQ scores were significantly higher in those with functional stage C (those with worst functional staging) of OSF 63.4 (15.2) when compared with those with stage B 54 (14.2) and stage A 38.7 (17) (d.f.=2; P=0.005). 22 (66.7%) of patients met ICD-10 criteria for dependence to areca products., Conclusions: OSF may be associated with considerable psychological morbidity. This morbidity may be significantly more in patients with worst functional staging. It is difficult to determine whether this is the cause or effect of the disease. Further systematic studies are urgently needed to address this issue., (© 2010 John Wiley & Sons A/S.)

Background: Because of delays in diagnosis, oral cancer usually presents for therapy at a late stage. Patients are unaware of having lesions as they are mostly asymptomatic and physicians generally do not examine the mouth sufficiently. People in rural areas or are underserved may not frequently visit the dentist who can easily pick up these lesions early. Screening programs are useful in that regard. Such programs in general are conducted by either inviting people to come to a screening center or by health care workers visiting the individual households. However, those who work during the day may not visit screening centers or be at home during the day of the screening by a visiting health care worker. Workplace screening overcomes these challenges., Methods: To assess the feasibility of a screening program to detect potentially pre-malignant oral disorders in a workplace in India, clinically visible mucosal lesions were compared with the clinical photographs of the same lesions assessed by an expert. Role of smoking, alcohol, and chewing betel quid and tobacco in the etiology of those lesions were assessed., Results: Sixty-nine percent of the eligible subjects participated in the screening (n=1613). Prevalence of leukoplakia was 5%. Bidi (OR=35.6), and cigarette smoking (OR=22.8), alcohol (OR=17.6), and tobacco and areca nut chewing (OR=7.5), were significantly associated with leukoplakia and erythroplakia (all P< 0.05)., Conclusions: Conduction of a screening program by valid visual inspection to detect potentially malignant oral disorders within a workplace is not only feasible but also effective., (© 2010 John Wiley & Sons A/S.)

Background: Oral submucous fibrosis (OSMF) is a widely prevalent, potentially malignant disorder of the oral cavity in the Indian subcontinent. Areca nut has been incriminated as the main causative factor. However, other factors, including viruses may also play a role in the initiation/development of these lesions. This study was designed to assess the correlation of addictive factors, human papilloma virus infection and histopathology of OSMF., Methods: One hundred and thirteen cases of OSMF were studied. Demographic information of each patient, including the patient's age, sex, addiction habits and histopathological grading was obtained. Presence of high-risk human papilloma virus (HR-HPV) DNA was detected using the Hybrid Capture II assay., Results: Of 105 cases finally included in the study, 33 (31.4%) patients were found to be positive for HR-HPV, while 72 (68.6%) were negative. A total of 52/105 (49.5%) patients chewed areca nut, of whom 18 (34.6%) patients were found to be positive and 34 (63.5%) were negative (P = 0.08). A total of 18/105 (17.1%) patients were addicted to smoking, of whom five (27.7%) were positive (0.69). Only one (11.1%) patient, who was only habituated to alcohol, was positive (1.08). Of the 105 patients 26 (24.7%) chewed as well as smoked tobacco, of whom, nine (34.6%) were positive and 17(65.3%) were negative (P = 0.67). Thus, there was no significant association between the various addiction habits and the presence of HR-HPV. On correlating the various histopathological grades of the disease with HR-HPV positivity a Pearson correlation of 0.053 was obtained (P = 0.588). Thus, again no significant correlation was observed between the different histopathological grades and HR-HPV positivity., Conclusion: In conclusion, it was found that there is neither significant correlation between HR-HPV infection and the various addiction habits nor with the different histopathological grades of the disease. To the best of our knowledge, a study of these different factors has never been attempted before in patients with OSMF.

Background: Oral verrucous hyperplasia (OVH) is a premalignant lesion that may transform into an oral cancer., Methods: Sixty consecutive OVH cases were collected from 2003 to 2004. Clinicopathological features and the 5-year malignant transformation rate of these 60 OVH lesions were evaluated and analyzed., Results: We found that 84% of OVH lesions occurred in patients between 40 and 69 years of age. The most common site for OVH lesions was the buccal mucosa (48%), followed by the tongue (20%), palate (18%), gingiva (7%), and labial mucosa (7%). Approximately 91% of OVH patients were areca quid chewers and 89% were smokers. When 60 OVH lesions were classified into 30 plaque-typed and 30 mass-typed OVH lesions, the mass-typed OVH lesions had a higher malignant transformation rate of 17% (5/30) than the plaque-typed OVH lesions (3%, 1/30) during a mean follow-up period of 59 +/- 7 months. The mean time for malignant transformation was 22 +/- 11 months. Of the 6 OVH lesions with malignant transformation, 2 underwent total surgical excision and 4 did not receive any form of therapy., Conclusions: We conclude that OVH lesions occur more commonly on the buccal mucosa and are highly associated with the areca quid chewing and cigarette smoking habits. The overall 5-year malignant transformation rate of 60 OVH lesions was 10%. The mass-typed OVH lesions had a higher malignant transformation rate than the plaque-typed OVH lesions and thus should receive an immediate treatment, such as total surgical excision or photodynamic therapy, after the histopathologic diagnosis.

Background and Objective: Areca (betel) chewing is associated with an increase in the incidence of periodontal diseases. Aberrations in matrix metalloproteinase (MMP) expression have been reported to be associated with periodontal disease. This study investigated the effects of areca nut extract on MMP activity and the phenotype of human gingival epithelial cells., Material and Methods: Reverse transcription-polymerase chain reaction, western blotting and gelatin zymography were used to assay MMPs. Cell viability, mobility and detachment assays were performed to characterize the phenotypic impact. Confocal microscopy was employed to evaluate cell aggregation and the distribution of E-cadherin and F-actin., Results: Treatment of gingival epithelial cells with 10 microg/mL of areca nut extract reduced its cell viability. Treatment with 5 and 10 microg/mL of areca nut extract for 24 h activated MMP-9 but not MMP-2 in gingival epithelial cells. This activation could be nuclear factor-kappaB dependent and was abrogated by 10 microM curcumin. Areca nut extract also reduced the migration and detachment of gingival epithelial cells. The differentiated cell-cell contact of gingival epithelial cells was markedly impaired by areca nut extract. This was accompanied by a disruption of distribution of E-cadherin and F-actin., Conclusion: The areca nut extract-mediated activation of MMP-9 in gingival epithelial cells could signify a potential periodontal pathogenesis in areca chewers. The areca nut extract-mediated inhibition of cell viability and migration, together with the changed aggregation in gingival epithelial cells, suggests that impairment of the re-epithelization underlies the process and this, in turn, might exacerbate gingival inflammation.

Background: Betel quid chewing (BQC) in Vietnam is still prevalent, however, no detailed information about its association with oral cancer and pre-cancer are available in the English literature. Respective online searches (PubMed, Medline) were negative., Methods: Relevant publications in Vietnamese were collected by the authors and translated. Visits to cancer centres and institutes of odontology (Ho Chi Minh City, Hanoi) were made and seminars with respective scientists were held. Field excursions to local markets and interviews with betel quid vendors and individual BQ chewers gave further insights., Results: Generally, BQC is on the decline in Vietnam. 6.7% of the female population still seems to indulge in this habit. In an earlier study, a prevalence of 0.06% of oral cancer was reported. In a study of 1084 cases of oral cancer, the male:female ratio was 1.05:1 (1997). The age group between 60 and 75 years is most often affected by oral cancer. In BQ chewing women, the buccal mucosa (27.9%), tongue (23.1%) and lips (22.4%) are most often affected. Verrucous carcinoma is seen in the age group 70-79 years with women most often being affected (male:female ratio 1:3.4). The most important risk factor for oral cancer in women is BQC compared with men where smoking, alcohol drinking or combined smoking and drinking habits are the most common risk factors. Oral leukoplakia in BQ chewers is observed in 3.8%, oral submucous fibrosis in 13%., Conclusions: BQC in Vietnam is on the decline. Association between BQC and oral cancer in elderly women is still of importance. Eventually, the BQC habit will vanish and only play a role in socio-ritual contexts.

Background: Oral squamous cell carcinoma and the most common oral pre-malignancies appear to be related to the habit of betel-quid chewing in Sri Lanka. Although hypermethylation of the tumour suppressor genes in oral cancer have been well documented, little information has been available concerning hypermethylation in oral pre-cancerous lesions. In the present study, we investigated the hypermethylation of p14, p15 and p16 in pre-cancerous lesions including epithelial dysplasia and submucous fibrosis., Methods: All samples were obtained from patients with a betel-quid chewing habit in Sri Lanka. Sixty-four patients were clinically diagnosed with leukoplakia, and histopathologically diagnosed with mild or severe dysplasia. Ten patients were diagnosed with submucous fibrosis without epithelial dysplasia. CpG island hypermethylation was assessed by a methylation-specific PCR method. Immunohistochemical staining was performed using anti-p53 antibodies., Results: A high frequency of hypermethylation of p14, p15 and p16 was detected in the pre-cancerous lesions, although no hypermethylation was found in normal epithelium. The frequency of hypermethylation was higher than that of positive staining for p53 mutation except in the case of p16 in mild dysplasia. No significant correlation was observed between p53-positive reactions and hypermethylation in any lesions. The hypermethylation was highly detectable even in p53-negative lesions, suggesting that hypermethylation of p14, p15 and p16 occur regardless of whether the lesions have p53 mutations or not., Conclusions: The present study indicates that hypermethylation may be involved in the pathogenesis of oral pre-cancerous lesions associated with betel-quid chewing in Sri Lanka.

Background: To report on Areca chewing (AC) in Xiangtan, Hunan province, China, and to test the knowledge of chewers related to side effects of the habit., Methods: Interviews with 276 individuals were performed. A questionnaire including general data, chewing habits, educational level and knowledge about side effects were used. Data were analysed using SPSS. Chi-square test was used at a significance level of P < 0.05., Results: Around 257 individuals were chewers (male: 54.1%; female: 45.9%) and 19 were former chewers (male: 31.6%; female: 68.4%). Mean age of chewers was 36.1 years. Around 42.4% of chewers smoked; 58.0% had a drinking habit. Average period of chewing was 11.2 years. Around 88.3% of chewers did not include the nut (seed). Around 79.0% considered AC habits negative for general health and 85.2% for oral health., Conclusions: Most respondents did not know that AC may induce oral submucous fibrosis and oral cancer. The 'betel quid' chewed in Xiangtan usually does not contain Areca 'nut' (seed, endosperm), but consists of the husk. As no studies on the chemical composition of the Areca husk have been published such investigations are urgently needed.

Background: Although the effect of betel quid chewing and smoking on oral cancer has been well documented, both influences, dose and duration during life time, on multistate progression of oral pre-malignancy are hardly addressed., Methods: By recruiting a group of male chewers from different occupation groups, we modeled the effects of both duration and quantity of betel quid chewing and smoking on annual incidence rate of developing leukoplakia and average dwelling times (ADTs) staying in leukoplakia and erythroleukoplakia., Results: The annual incidence rate (per year) of leukoplakia was estimated as 0.35% (95% CI: 0.22-0.48%). The ADTs were 24 years for leukoplakia and 7 years for erythroleukoplakia. Annual incidence rate of leukoplakia with high consumption and long duration of betel quid and smoking was higher. Both quantity and duration of smoking and betel quid chewing play minor roles in the influence of ADT. The risks of developing oral cancer after 20 years of follow-up were 42.2% for leukoplakia and 95.0% for erythroleukoplakia., Conclusion: The effects of betel quid chewing and smoking on multistate progressions between oral pre-malignancies were elucidated. These results can be applied to predict long-term risk of malignant transformation varying with different duration and quantity of betel quid and cigarette.

Aim: To determine the relationship between betel quid chewing additives and established periodontitis in Bangladeshi subjects., Material and Methods: A total of 864 subjects participated in this study. Among them, 140 pairs of sex- and age-matched case subjects and control subjects were selected. A case was defined as a person who had at least two sites with a clinical attachment level (CAL)> or =6 mm and at least one site with probing depth (PD)> or =5 mm. Subjects who did not fulfill these criteria were considered as controls. Information on sociodemographic variables, psychological stress, dental health behaviour, smoking and betel quid chewing habits was obtained., Results: Multiple logistic regression analysis showed that current betel quid chewers had greater probabilities of having established periodontal disease than did non-chewers (odds ratio=3.97, p<0.05). Mean PD, mean CAL, mean percentage of bleeding on probing and number of missing teeth were significantly higher in chewers of betel quid with tobacco and masala than in chewers of betel quid without such additives adjusting for age, sex, smoking habit, body mass index, dental visit pattern, stress and plaque index. Higher frequency and longer duration of betel quid chewing showed a significant relation to an increase in periodontal parameters., Conclusion: The results indicate that betel quid additives might significantly enhance periodontitis in the population studied.

At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Pre-cancer in the UK issues related to potentially malignant disorders of the oral cavity were discussed by an expert group. The consensus views of the Working Group are presented in a series of papers. In this report we review the literature on the epidemiology and natural history of potentially malignant disorders (PMD), detailing those characteristics of the patients and lesions thought to be associated with future development of oral squamous cell carcinoma (OSCC). Older patients, particularly females are more at risk than younger patients; the duration of PMD may be important. Those who have never used tobacco seem at greater risk than smokers. OSCC is more likely with PMD on the lateral and ventral tongue, floor of mouth and retromolar/soft palate complex than with those elsewhere. The vast majority of PMD in which OSCC develop are non-homogenous although 5% of homogenous PMD will develop carcinoma. Large lesions covering several intraoral subsites also appear more at risk.

Background: Circulating matrix metalloproteinase-9 (MMP-9) is a prognostic factor for gastric cancer and vascular diseases, and has been associated with head and neck cancers. The -1562 C-to-T polymorphism in MMP-9 promoter (abbreviated MMP-9 -1562 C>T polymorphism) leads to differential transcription, and is associated with increased susceptibility to neoplastic and vascular diseases. Thus, our aim was to determine whether a functional MMP-9 polymorphism might also influence the risk or affect the progression of areca-associated oral cancers., Methods: Genomic DNAs were obtained from peripheral blood cells of male subjects with areca-associated oral squamous cell carcinoma (OSCC) (n = 192), oral submucosal fibrosis (OSF) (n = 73), and non-diseased areca users (n = 191). The PCR-based restriction fragment length polymorphism analysis was performed for MMP-9 genotyping., Results: MMP-9 -1562 C>T polymorphism was not associated with the risk of OSCC or OSF. However, when subjects were stratified by the median age, an association with the risk of OSCC was found in younger patients (P = 0.029). The T allele frequency was significantly higher in the subset of older patients with buccal mucosa OSCC than older patients with OSCC in counterpart locations. The joint MMP-9 -1562 C>T and MMP-3 -1171 5A>6A functional polymorphisms were not associated with OSCC risk or patient survival., Conclusion: Aberrant MMP-9 expression is closely related to tumor invasiveness and the prognosis of head and neck cancers. However, functional MMP-9 -1562 C>T polymorphism is associated with OSCC risk only in younger areca chewers. The impact of aging or areca-related effect on this functional polymorphism should be elucidated.

Background: Epidemiological data have shown an association of areca nut chewing with oral submucous fibrosis (OSF). Experimental evidence to confirm this has been limited. Fibrosis-promoting activity of areca nut was tested in an animal model., Method: Buccal mucosa of a group of 20 female BALB/c strain mice, 10-12 weeks of age, was treated twice daily 6 days per week with topical application of aqueous areca nut extracts for 300-600 days. A control group (n = 20) was treated with 50 mM NaCl. The influence of areca nut on the oral epithelium and connective tissue was recorded semiquantitatively by light microscopy., Results: The areca nut-treated oral epithelium showed progressive changes in epithelial thickness leading to atrophy, increased cellularity of fibroblasts, fibrosis of connective tissue, focal infiltration of inflammatory cells and muscle atrophy. On killing after 600 days of treatment, the scores on cellularity, inflammation and muscle atrophy were significantly different to the control group (P = 0.03)., Conclusion: The study provides further evidence that areca nut contributes to the development of OSF in treated animals. The model has the potential to test synergism of areca nut with other carcinogens and any therapeutic interventions.

Objectives: Because most screening was done by dentists, the purpose of this prospective cohort study was to evaluate the effectiveness of oral visual screening by otolaryngologists. In addition, we wanted to determine which group of enrolled patients was at potential risk of contracting oral cancer., Methods: All male patients age > or =18 years who visited our clinic received oral mucosal screening. Basic data, including personal habits, were also obtained. A multivariate logistic regression model was devised to determine relevant risk factors for developing oral cancer., Results: A total of 5,825 patients were enrolled in this study. Positive findings were found in 226 patients (3.9%). One hundred seventy-two patients received biopsy and 131 patients were proven to have oral cancer (sensitivity rate: 76.2%). The results showed that those who smoked, consumed alcohol, and chewed betel quid on a regular basis were most likely to contract oral cancer (odds ratio = 49.81, 95% confidence interval = 29.38-84.42)., Conclusions: The otolaryngologists involved in this study successfully performed the oral screening. The sensitivity and specificity rates were both satisfactory. We suggest that those who are habitual cigarette smokers, alcohol consumers, and betel quid chewers should receive oral mucosal screening regularly so that potential oral cancer can be detected as early as possible.

Background: The concentration of MICA in serum seems be a good candidate marker in cancer. Previous studies from our laboratory have shown that the polymorphic MIC gene may confer a risk for oral squamous cell carcinoma (OSCC). The study investigated the expression levels of MICA and MICB of OSCC patients and cancer cell lines., Material and Methods: We used RT-PCR to analyze the mRNA expression of MICA and MICB in four oral cancer cell lines compared with three normal human oral keratinocyte (NHOK) cell lines and in tissues from 36 patients with OSCC comparing tumor tissue with non-cancerous matched tissue (NCMT)., Results: Endogenous MICB mRNA expression in OSCC cell lines was significantly higher than that in NHOK (1.40 +/- 0.27 vs. 0.40 +/- 0.16; P = 0.04). In 20 of 36 sets of tissue from patients with OSCC, MICB mRNA expression was higher in the cancerous tissue than in the NCMT. The mean MICB mRNA expression in OSCC tissues was significantly higher than in NCMT (0.39 +/- 0.08 vs. 0.14 +/- 0.03, P = 0.009, paired t-test). A significantly lower MICA mRNA was found in patients who chewed areca nut compared with those who did not use areca (P = 0.001) and in patients with well-differentiated tumors compared with those with less well-differentiated tumors (P = 0.02)., Conclusion: MICA and MICB mRNA expression may be increased in OSCC but there appears to be individual variation.

Background: Very few reports have been published on the gender specificity of oral submucous fibrosis (OSF) in relation to habit patterns and the severity of disease in the world literature. The purpose of the study was to ascertain the gender specificity for different habits and severity of OSF., Methods: A hospital-based cross-sectional study on various habit patterns associated with OSF was performed in Nagpur over a 5-year period. A total of 1000 OSF cases from 266,418 out patients comprised the study sample., Results: The male-to-female ratio of OSF was 4.9:1. Occurrence of OSF was at a significant younger age group (<30 years) among men when compared with women (OR = 4.62, 3.22-6.63, P = 0.0001). Reduced mouth opening, altered salivation and altered taste sensation were found to be significantly more prevalent in women when compared with men. Exclusive areca nut chewing habit was significantly more prevalent in women (OR = 44.5, 25.4-79.8, P = 0.0001). Whereas significant increase for Gutkha (Areca quid with tobacco) (OR = 2.33, 1.56-3.54, P = 0.0001) and kharra/Mawa (crude combination of areca nut and tobacco) (OR = 6.8, 4.36-11.06, P = 0.0001) chewing was found in men when compared with women., Conclusions: There is a marked difference in literacy, socioeconomic status, areca nut chewing habits, symptoms and disease severity in women when compared with men in the central Indian population.

This report describes the 'Skull from Bangkok', collected by Rudolf Virchow (Berlin, Germany) in the late 19th century. The skull is part of an extensive anthropological collection of skeletons and skulls from all over the world. The skull was probably brought to Berlin during the years 1882-1883. An inscription on the frontal bone gives the name of the skull: 'Skull from Bangkok'. The few remaining teeth of the maxilla show brown black stains because of betel quid chewing. In the collection, there is an extensive number of skulls from South- and Southeast Asia with similar betel stains. Virchow himself was aware of this habit and has described some of the skulls in detail often mentioning the black stains because of betel quid chewing. The Skull from Bangkok is a proof that betel quid chewing was prevalent in Siam of the late 19th century.

Cancer in Myanmar is one of the 10 leading causes of morbidity and mortality. In 1974, the Yangon Cancer Registry was established. From 1974 to 2001 a total of 85 298 cancer cases were registered. From 1963 to 1972 the average annual incidence rate of oral cancer was calculated to be 363 per 100 000 population. The tongue was mostly affected (31.2%). In one study, the prevalence of oral leukoplakia was 1.7%, erythroplakia 0.1%, and submucous fibrosis 0.1%. No epidemiologic studies of the prevalence of betel quid chewing (BQC) in Myanmar have been performed. One study showed that among 773 individuals over the age of 6 years, 46.4% were habitual smokers. A recent symposium on oral health stressed the necessity to introduce concepts of prevention, focusing on BQC habits and smoking as high-risk factors for oral cancer and pre-cancer in Myanmar.

Background: Oral submucous fibrosis (OSMF) is a chronic, insidious, disabling potentially malignant condition of the oral mucosa seen predominantly in south and Southeast Asia. No reports are hitherto available on the aetiological factors of OSMF based on Sri Lankan patients., Methods: A total of 74 patients with OSMF and 74 controls who consecutively attended the Oral Medicine clinic at the Dental Hospital (Teaching) Faculty of Dental Sciences, University of Peradeniya, Sri Lanka were included in the study. Binary logistic regression analyses were performed to model the influence of betel chewing, smoking and alcohol use and to determine the effects of different combinations of chewing habits on OSMF., Results: Betel chewing was the only significantly associated factor in the aetiology of OSMF (OR = 171.83, 95% CI: 36.35-812.25). There were no interaction effects of chewing, smoking and alcohol consumption in the causation of OSMF., Conclusion: The present study has shown a strong association of betel quid chewing (including tobacco as an ingredient) with the causation of OSMF.

Background: Insertion/deletion (-1171 5A-->6A) polymorphisms in the promoter region of matrix metalloproteinase 3 (MMP3) gene result in different transcriptional activities. MMP3 is able to degrade collagens types II, V, IX, and X, and other extracellular matrix. The functional promoter polymorphism of MMP3 has been related to the susceptibility in some inflammatory diseases and metastasis of cancers., Methods: Oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC) are prevalent among Asian areca users. In this study, genomic DNA obtained from the blood of OSCC (n = 150), OSF (n = 71), and control non-diseased areca user (n = 98) in male were subjected to polymerase chain reaction (PCR)-based genotyping of MMP3., Results: The 5A genotype in MMP3 promoter was observed more frequently in OSF group than in control group (P = 0.01). No significant difference was noted between OSCC and control groups on the 5A genotype frequency (P = 0.18). No association was found between 5A genotype in MMP3 promoter and site or lymph node metastasis and stage of OSCC., Conclusion: The results indicated that the 5A genotype of MMP3 promoter was associated with the risk of OSF but not OSCC.

Background: In a previous article, we reported the prevalence rates of oral mucosal lesions in an aboriginal community from an epidemiological survey of oral pre-cancerous lesions., Methods: Since 1997, the authors have started regular follow-up of the study population originally investigated. Thus, it has been possible to obtain incidence rates for the various oral pre-cancerous lesions and conditions., Results: There were 194 persons without any oral lesion in the 1997 screening. During the clinical follow-up investigation and during the analysis of biopsies from pre-cancerous lesions, we discovered six new lesions (including cancer and pre-cancerous lesions) from five participants. All of the five persons were areca/betel quid chewers, and only one mixed areca/betel quid chewing with cigarette smoking habit. The age-standardized incidence rates for quid lesion, oral submucous fibrosis (OSF) and squamous cell carcinoma (SCC) were 267.0, 374.1 and 146.2 per 100,000 person-years, respectively, for areca/betel quid chewers., Conclusions: As compared with the rates from India and the general Taiwanese population, the study community encountered a serious problem of oral lesions.

Objective: To investigate the prevalence and the associated risk factors of oral precancerous disorders in southern Taiwan., Methods: We conducted a cross-sectional community survey interviewing 1075 adult subjects, 15 years of age and over, gathered from randomly selected 591 households, and spanning five villages in southern Taiwan. The study protocol included a visual oral soft tissue examination and a questionnaire-based interview. The chi-square test was used to test the differences in prevalence of oral precancerous lesions and conditions by different "life styles" relating to current risk habits of current areca quid chewing, smoking, and alcohol drinking. To control for possible confounding, a logistic regression model was used to estimate the Odds Ratios (OR) for leukoplakia and oral submucous fibrosis (OSF)., Results: 136 precancerous lesions and conditions were detected among 1075 subjects (12.7%). The analysis of the spectrum of oral precancerous disorders detected, leukoplakia (n = 80), OSF (n = 17) and verrucous lesions (n = 9), demonstrated an association with gender (P < 0.001). There were statistically significant associations among leukoplakia (P < 0.01), OSF (P < 0.0001), and verrucous lesions (P < 0.0001) and the life style of current areca quid chewing, smoking, and alcohol drinking. The synergistic effect of smoking and areca quid chewing habit on leukoplakia and OSF was demonstrated., Conclusion: This study reinforces the association of current areca quid chewing without tobacco, cigarette smoking, and alcohol drinking to leukoplakia, OSF, and verrucous lesions in Taiwan.

Aim: No long-term studies have reported on risk factors for tooth loss in subjects without home or professional dental care. The purpose of this report is to identify potential risk factors for tooth loss among male Sri Lankan tea labourers who participated in a 20-year investigation of the natural history of periodontal disease., Material and Methods: Data for this report were obtained from the 455 subjects who participated in multiple examinations over the 20-year period from 1970 to 1990. Analyses included data from interim examinations in 1971, 1973, 1977, 1982 and 1985. Oral health assessments included the following: (1) attachment levels in millimetres on all mesial and mesio-buccal surfaces, excluding third molars; (2) plaque index; (3) gingival index; (4) calculus index; (5) caries index; and (6) missing teeth. Other variables included age, history of smoking and betel nut use. Statistical analyses included descriptive statistics and multivariate repeated-measures modelling with generalized estimating equations., Results: Tooth loss was significantly dependent upon interactions between the mean attachment loss and betel nut use (Z=3.40; p=0.0007) and history of missing teeth (Z=-3.70; p=0.0002). The effect of attachment loss on tooth loss was increased in the presence of betel nut and diminished when teeth were already missing at baseline., Conclusion: History of missing teeth, betel nut use and increasing attachment loss were significant predictors of tooth loss over time. Betel nut use increased the effect of attachment loss on loss of teeth, while history of missing teeth diminished the effect of attachment loss on tooth loss.

Background: Environment-gene interaction in oral carcinogenesis is well demonstrated by phase I and II enzymes that are involved in the metabolism of carcinogens. This study investigated the association of glutathione S-transferase (GST)T1 and GSTM1 genotypes of phase II enzyme genes with risk for, age of onset, and neck lymph node metastasis (LNM) in areca-associated oral squamous cell carcinoma (OSCC)., Methods: A total of 114 OSCC male patients and 100 male controls were recruited. All subjects were areca users and tobacco smokers. DNA was obtained from peripheral blood samples. Genotyping of GSTT1 (non-null/null) and GSTM1 (non-null/null) was determined by polymerase chain reaction (PCR) analysis using specific primers that only amplify non-null alleles., Results: No association was found between GST genotype and the risk of OSCC based on case-controls. Patients with the GSTT1 null genotype were older at onset (P = 0.03). Those with the GSTM1 null genotype had a higher incidence of neck LNM than those with the GSTM1 non-null genotype (P = 0.01). Patients with the GSTM1/GSTT1 null genotype appeared to have later onset and a higher incidence of neck LNM than those carrying the opposite genotype., Conclusion: The GST genotypes may be important markers for the age of onset and risk of metastasis in OSCC. The data also suggest that the various GST isoforms may be differentially involved in development or progression of OSCC.

Oral submucous fibrosis (OSF) is a chronic debilitating disease and a premalignant condition of the oral cavity. It is characterized by a generalized submucosal fibrosis. The pathogenesis of the disease is not well established. Epidemiological evidences strongly indicate the association of the betel quid (BQ) habit and OSF. Various findings indicate the disease to be a consequence of disturbances in the homeostatic equilibrium between synthesis and degradation of extracellular matrix (ECM), wherein collagen forms a major component, thus can be considered as a collagen-metabolic disorder. Transforming growth factor-beta (TGF-beta) is a potent stimulator of production and deposition of the ECM. The objectives of this review are to highlight the molecular events involved in the overproduction of insoluble collagen and decreased degradation of collagen occurring via exposure to BQ and stimulation of the TGF-beta pathway, and elucidate the cell signaling that is involved in the etiopathogenesis of the disease process.

Background: Betel-chewing, a risk factor for oral carcinoma, is a common habit of elderly Vietnamese females, but concomitant habits of tobacco and alcohol are uncommon., Methods: In the present study, 36 paraffin-embedded betel-associated oral carcinoma samples including 27 squamous cell carcinoma (SCC) and nine verrucous carcinomas (VC) were analyzed for the hypermethylation of tumor suppressor genes (TSGs) and loss of heterozygosity (LOH) of important TSG loci. Methylation-specific polymerase chain reaction (MSP) was used to identify promoter hypermethylation of p16INK4a and RASSF1A. For LOH analysis, 39 microsatellite markers at 12 chromosomal arms were examined by p olymerase chain reaction (PCR)-based microsatellite assay., Results: Hypermethylation of p16IKN4a was detected in 63% of SCC and 67% of VC. In addition, LOH at 9p21 (locus for p16INK4a) was 58% for SCC and 22% for VC, and hypermethylation of RASSF1A was 93% for SCC and 100% for VC. LOH at 3p21.3-3p22.1 (where RASSF1A is located) was detected in only 12% of SCC and 0% of VC. LOH of other chromosomal arms were infrequent., Conclusion: As LOH for chromosomes other than 9p was uncommon, epigenetic silencing of RASSF1A and p16INK4a gene expression by promoter hypermethylation may play a critical role in betel-associated oral carcinogenesis.

Background: Buccal squamous cell carcinoma (BSCC) is the most frequently occurring oral cancer in Asians due to the popularity of areca use in this area. The aim of the present study was to evaluate the survival of areca-associated BSCC associated with multiple molecular markers., Methods: Using immunohistochemistry, we evaluated the survival of a cohort of 55 patients with BSCC being followed long term, as correlated to the expression of variable markers., Results: We found that p53, p21, Rb, cyclin D1 (CCD1), MDM2, and gamma-catenin were positive in 81, 60, 70, 31, 88, and 44% of patients, respectively. Subjects with -ve immunoreactivity for CCD1, and +ve immunoreactivity for MDM2 and gamma-catenin had significantly better survival than subjects with the opposite immunoreactive pattern. KAPLAN-meier survival curves confirmed this association., Conclusion: The data indicate that expression of CCD1, MDM2, and gamma-catenin might serve as potential prognostic markers for BSCC in areca-using patients.

Background: Oral submucous fibrosis (OSF) is a pre-cancerous condition caused by the use of areca nut in various forms. There are very few published reports on areca nut use and OSF from Chennai, South India., Methods: A hospital-based case-control study on habits and OSF was performed in Chennai over a 3-year period. A total of 185 consecutive patients with OSF were matched with age- and sex-matched controls. History was recorded in a pre-determined format by qualified dental surgeons., Results: The male to female ratio of OSF cases was 9.9 : 1. All areca nut products were associated with OSF, with the risk being greatest for pan masala. The duration of the habit was more significant than the frequency of the chewing habit., Conclusion: The present study confirms the strong association between areca nut use and OSF and the increasing use of pan masala.