The potential roles of cigarette smoke-induced extracellular vesicles in oral leukoplakia.

BACKGROUND: The onset of oral leukoplakia (OLK), the most common oral lesion with a high risk of malignant transformation, is closely associated with the exposure of cigarette smoke. Cigarette smoke is a complicated mixture of more than 4500 different chemicals including various oxidants and free radical, which contributes to the onset of immune and inflammatory response or even carcinogenesis. Recent studies have proved that the exposure of cigarette smoke leads to the onset and aggravation of many diseases via significantly changed the production and components of extracellular vesicles. The extracellular vesicles are membrane-enclosed nanosized particles secreted by diverse cells and involved in cell-cell communication because of their ability to deliver a number of bioactive molecules including proteins, lipids, DNAs and RNAs. Getting insight into the mechanisms of extracellular vesicles in regulating OLK upon cigarette smoke stimulation contributes to unravel the pathophysiology of OLK in-depth. However, evidence done on the role of extracellular vesicles in cigarette smoke-induced OLK is still in its infancy. MATERIALS AND METHODS: Relevant literatures on cigarette smoke, oral leukoplakia and extracellular vesicles were searched in PubMed database. CONCLUSIONS: In this review, we summarize the recent findings about the function of extracellular vesicles in the pathogenesis of cigarette smoke-induced diseases, and to infer their potential utilizations as diagnostic biomarkers, prognostic evaluation, and therapeutic targets of OLK in the future.

Deep learning-based pathology image analysis predicts cancer progression risk in patients with oral leukoplakia.

BACKGROUND: Oral leukoplakia (OL) is associated with an increased risk for oral cancer (OC) development. Prediction of OL cancer progression may contribute to decreased OC morbidity and mortality by favoring early intervention. Current OL progression risk assessment approaches face large interobserver variability and is weakly prognostic. We hypothesized that convolutional neural networks (CNN)-based histology image analyses could accelerate the discovery of better OC progression risk models. METHODS: Our CNN-based oral mucosa risk stratification model (OMRS) was trained to classify a set of nondysplastic oral mucosa (OM) and a set of OC H&E slides. As a result, the OMRS model could identify abnormal morphological features of the oral epithelium. By applying this model to OL slides, we hypothesized that the extent of OC-like features identified in the OL epithelium would correlate with its progression risk. The OMRS model scored and categorized the OL cohort (n = 62) into high- and low-risk groups. RESULTS: OL patients classified as high-risk (n = 31) were 3.98 (95% CI 1.36-11.7) times more likely to develop OC than low-risk ones (n = 31). Time-to-progression significantly differed between high- and low-risk groups (p = 0.003). The 5-year OC development probability was 21.3% for low-risk and 52.5% for high-risk patients. The predictive power of the OMRS model was sustained even after adjustment for age, OL site, and OL dysplasia grading (HR = 4.52, 1.5-13.7). CONCLUSION: The ORMS model successfully identified OL patients with a high risk of OC development and can potentially benefit OC early diagnosis and prevention policies.

Clinical roles of autophagy-related proteins Beclin-1 and mTOR in smoking and non-smoking patients with oral leukoplakia.

Background: To study the expressions of autophagy-related proteins Beclin-1 and mammalian target of rapamycin (mTOR) in smoking and non-smoking patients with oral leukoplakia (OLK). Methods: A total of 240 patients diagnosed as OLK from January 2017 to December 2017 were enrolled. Beclin-1 and mTOR expressions were detected by immunohistochemistry. Their clinical data were collected. The correlations of smoking with Beclin-1 and mTOR expressions as well as clinical factors were explored by Spearman's analysis. Results: There were significant differences in gender ratio, age, lesion location, severity and malignancy between smoking and non-smoking OLK patients (P<0.05). The positive expression rate of Beclin-1 in OLK patients with simple hyperplasia and abnormal hyperplasia in the smoking group was significantly lower than that of the non-smoking group (P<0.05). In the abnormal hyperplasia group, the number of cigarettes daily was significantly positively correlated with mTOR expression (r=0.843, P=0.042). After the simple hyperplasia group was included, there was a positive correlation between smoking age and positive expression rate of mTOR (r=0.942, P=0.012). For number of cigarettes and smoking age, the positive expression rates of Beclin-1 and mTOR showed significant negative correlations (r=-0.952, P=0.003, r=-0.953, P=0.002). Conclusion: Autophagy-related proteins Beclin-1 and mTOR may be involved in the smoking-induced pathogenesis of OLK.

Clinicopathological Evaluation of Tobacco-related Oral Mucosal Lesions.

AIM: To clinically evaluate the nature of precancerous and cancerous lesions associated with tobacco consumption habit and to correlate clinical profile with the histopathological findings of clinically suspected precancerous and cancerous lesions. MATERIALS AND METHODS: These included the examination of patients who visited the outpatient department (OPD) of the institute that includes 1,500 patients who had tobacco chewing habits were classified into the following two groups according to their characteristics. The study group comprised 270 patients, of which 170 gave consent for biopsy and 100 patients who not gave consent were counseled for tobacco cessation. RESULTS: Among 270 patients, the highest number of patients, 146 (54.07%) patients, were found to be smokeless tobacco consumers followed by 65 (24.07%) patients who were smoked tobacco consumers while 59 (21.85%) patients were found to have both the habits. Wide variation was noted in duration and frequency of habit. Most prevalent site was the buccal mucosa affected in 138 (51.11%) patients who consumed both smoked as well as smokeless tobacco. And on clinical examination, 138 (51%) patients had leukoplakia followed by 54 (20%) patients with oral squamous cell carcinoma and 40 (15%) patients with oral submucous fibrosis (OSMF). Other patients were tobacco pouch keratosis 17 (6%), smoker's melanosis 8 (3%), smoker's palate 7 (3%), and erythroplakia 6 (2%). The patients who gave consent (170 patients) were evaluated histopathologically to correlate with clinical findings. CONCLUSION: Tobacco-related oral lesions are also high, which brings an alarming signal toward the development of cancer. Our contribution as healthcare providers can be made by conducting more oral health education programs and educating the general population about the adverse effects of tobacco. The appropriate clinical assessment and categorization of all these lesions aided us in motivating patients to undergo necessary treatments and also to discontinue their habits in order to prevent deterioration of their conditions. CLINICAL SIGNIFICANCE: Set up de-addiction centers in dental colleges and help tobacco users in discontinuing their habits. Interestingly, this study also served as a mirror for those patients who were unaware of the lesions they were giving abode to in their oral cavities.

Management of oral leukoplakia by ablative fractional laser-assisted photodynamic therapy: A 3-year retrospective study of 48 patients.

OBJECTIVES: This study aimed to review the results of oral leucoplakia (OL) using ablative fractional laser-assisted photodynamic therapy (AFL-PDT) and to further evaluate the risk factors for recurrence and malignant transformation. MATERIALS AND METHODS: Forty-eight patients diagnosed with OL using histopathology were enrolled in this study. All patients received one session of AFL-PDT. Therapeutic efficacy was evaluated 1 month posttreatment. Follow-up was scheduled every 3 months in the first year and every 6 months thereafter. RESULTS: An overall positive response rate of 87.5% (42/48) was achieved, including 62.5% (30/48) complete responses and 25.0% (12/48) partial responses. During the 3-year follow-up period, the recurrence and malignant transformation rates were 37.5% (18/48) and 8.3% (4/48), respectively. Lesions on gingiva/palate seemed to be associated with recurrence (p < 0.001; odds ratio [OR]: 1.64, 95% confidence interval [CI]: 1.13-2.37). The severity of epithelial dysplasia (p = 0.02; OR: 2.93, 95% CI: 1.96-4.42) and recurrence (p = 0.016; OR: 3.14, 95% CI: 2.04-4.84) were associated with a predisposition to malignant transformation. CONCLUSIONS: AFL-PDT is an effective management of OL, but requires close follow-up. OL lesions on the gingiva/palate are predisposed to recurrence. OLs that recur with moderate/severe epithelial dysplasia have a higher risk of transforming into oral squamous cell carcinoma.

Oral Potentially Malignant Disorders (OPMD): What is the clinical utility of dysplasia grade?

INTRODUCTION: Oral epithelial dysplasia is considered a potential histologic precursor of subsequent squamous cell cancer. As standard clinical practice, pathologists grade dysplasia to assess risk for progression to malignancy. Except for the most advanced grade, severe dysplasia, dysplasia grading has failed to correlate well with the risk to develop invasive cancer. The questions of what process dysplasia grading best represents and what clinical utility dysplasia grading may have are explored. AREAS COVERED: This narrative review is based on PubMed search with emphasis on papers since 2010. Epithelial dysplasia as a precursor lesion of cancer and dysplasia grading as a risk assessment tool for progression to cancer are discussed. The close clinical association of dysplasia with known carcinogens, alcohol, and tobacco products is presented. EXPERT OPINION: Oral epithelial dysplasia is often, associated with prolonged exposure to tobacco and alcohol products. With reduction of carcinogen exposure, dysplasia is known to regress in some cases. It is proposed that histologic dysplasia grade together with macroscopic images of dysplastic clinical lesions be used as an educational tool to incentivize patients to reduce their known carcinogen exposure. This strategy has the potential to reduce lesion progression thereby reducing the disease burden of oral cancer.

Chewing tobacco may act as a risk factor for dysplastic transformation of squamous cells in Oral leukoplakia- A cytochemistry based approach.

The use of chewing tobacco is a severe risk factor for oral mucosa related diseases including cancer in India as well as USA, although its relationship with Oral Leukoplakia (OL) or related carcinogenicity is still not clear. This work chose two oncogenic pathway proteins- the Epidermal Growth Factor Receptor and the WNT pathway among leukoplakia patients and established their correlation with the individuals' tobacco chewing habit. 89 fresh patients with OL were selected for the work. The samples were classified based on the individual's tobacco chewing habit. The divided samples were then immunostained with antibodies for both of the EGFR as well as WNT pathway proteins. The samples were further classified based on their proliferation status and the expression of these oncoproteins was also observed. In order to compare the cytological data with histological data, 30 OL patients undergoing biopsy were chosen and immunohistological analysis was performed for the same pathways. Results showed overexpressing EGFR and WNT pathway proteins in all OL samples. Structurally atypic cells had a tendency to overexpress these oncoproteins. However the immunocytochemistry data could not confirm any positive effect of chewing tobacco on the OL's proliferative state. Statistical data from the immunfluorescence finally revealed the overexpression of both EGFR and WNT pathway proteins on the proliferative population establishing chewing tobacco as a positive risk factor for the onset of OL. Data from biopsy samples followed the same trend of protein expression seen in the cytological samples. Dysplastic zones showed huge overexpression of EGFR and WNT pathway proteins among tobacco chewers. In conclusion, this is the first time report showing the effect of chewing tobacco on the EGFR and WNT pathway in OL and its possible role as a potential risk factor for its proliferative type.

Recurrence rates after surgical removal of oral leukoplakia-A prospective longitudinal multi-centre study.

Oral leukoplakia (OL) is a potentially malignant oral disorder. The Gold Standard treatment is to remove surgically the OL. Despite optimal surgery, the recurrence rates are estimated to be 30%. The reason for this is unknown. The aim of this study was to investigate the clinical factors that correlate with recurrence after surgical removal of OL. In a prospective study data were collected from 226 patients with OL. Forty-six patients were excluded due to incomplete records or concomitant presence of other oral mucosal diseases. Overall, 180 patients proceeded to analysis (94 women and 86 men; mean age, 62 years; age range, 28-92 years). Clinical data, such as gender, diagnosis (homogeneous/non-homogeneous leukoplakia), location, size, tobacco and alcohol use, verified histopathological diagnosis, and clinical photograph, were obtained. In patients who were eligible for surgery, the OL was surgically removed with a margin. To establish recurrence, a healthy mucosa between the surgery and recurrence had to be confirmed in the records or clinical photographs. Statistical analysis was performed with the level of significance set at P<0.05. Of the 180 patients diagnosed with OL, 57% (N = 103) underwent surgical removal in toto. Recurrence was observed in 43 OL. The cumulative incidence of recurrence of OL was 45% after 4 years and 49% after 5 years. Fifty-six percent (N = 23) of the non-homogeneous type recurred. Among snuff-users 73% (N = 8) cases of OL recurred. A non-homogeneous type of OL and the use of snuff were significantly associated with recurrence after surgical excision (P = 0.021 and P = 0.003, respectively). Recurrence was also significantly associated with cancer transformation (P<0.001). No significant differences were found between recurrence and any of the following: dysplasia, site of lesion, size, multiple vs. solitary OL, gender, age, use of alcohol or smoking. In conclusion, clinical factors that predict recurrence of OL are non-homogeneous type and use of snuff.

Oral keratosis of unknown significance shares genomic overlap with oral dysplasia.

OBJECTIVES: To identify molecular characteristics of keratosis of unknown significance and to nominate pathways of molecular progression to oral cancer. Our work could provide a rationale for monitoring and treating these lesions definitively. METHODS: Patients with oral leukoplakia were eligible for our prospective observational study. We correlated alterations in cancer-associated genes with clinical and histopathologic variables (keratosis of unknown significance vs. moderate-to-severe dysplasia) and compared these alterations to a previously molecularly characterized oral cancer population. RESULTS: Of 20 enrolled patients, 13 (65%) had evidence of keratosis of unknown significance, while seven (35%) had dysplasia. Nine patients (45%) developed oral cancer (4/13 with keratosis of unknown significance, 5/7 with dysplasia). At a median follow-up of 67 (range 22-144) months, median overall survival was significantly shorter for patients with dysplasia (hazard ratio 0.11, p = .02). KMT2C and TP53 alterations were most frequent (75% and 35%, respectively). There were molecular similarities between keratosis of unknown significance and dysplasia patients, with no significant differences in mutational frequency among genes with ≥15% rate of alteration. CONCLUSIONS: Among patients with leukoplakia, both patients with keratosis of unknown significance and patients with dysplasia developed oral cancer. Molecular alterations between these two groups were similar at this sample size.

A correlation between oral mucosal lesions and various quid-chewing habit patterns: A cross-sectional study.

BACKGROUND AND OBJECTIVES: Quid-chewing habit is a common and old tradition in India. It causes various potentially malignant disorders. Therefore, a study was undertaken to analyze the association of various quid-chewing habit patterns and different oromucosal lesions. MATERIALS AND METHODS: A cross-sectional study was conducted on 150 cases, where all the individuals selected were having quid-chewing habit and oromucosal lesions. Detailed habit history was taken through preformed questionnaire, clinical examination was done, and the lesion was subjected to incisional biopsy and confirmed histopathologically. RESULTS: The male to female ratio of various quid-chewing habit and oromucosal lesions was 9:1. The middle aged were more commonly involved. Of the various types of quids chewed, a combination of processed betel and processed tobacco which is commercially available was used by majority of the individuals. Oral submucous fibrosis (OSMF) was seen in majority of the cases. INTERPRETATION AND CONCLUSION: The present study confirms the association between betel, tobacco, and various lesions such as OSMF, leukoplakia, chewer's mucosa, lichenoid reaction, and chemical burn. It also confirms the strong association of betel to OSMF and tobacco to leukoplakia.

Prevalence of oromucosal lesions in relation to tobacco habit among a Western Maharashtra population.

OBJECTIVES: This study was conducted to determine the number and types of oromucosal lesions (OMLs) in relation to tobacco habits in patients who attended the outpatient department. METHODOLOGY: A total of 1730 patients visiting the Department of Oral Medicine and Radiology were interviewed and screened for tobacco habits (smoking and smokeless). Clinical oral examination was conducted with diagnostic instruments using the Color Atlas of Common Oral Diseases as a guide for diagnosis. When clinical features were not diagnostic, a biopsy was done. RESULTS: Of the 1730 outpatients, 975 (56.3% ) individuals used tobacco in one or other forms and 687 (70.4%) of these had OMLs. CONCLUSION: The results of this study provide important information on the prevalence of OMLs in patients seeking dental care. This provides baseline data for future studies on the prevalence of oral lesions in the general population.

Variants in FAT1 and COL9A1 genes in male population with or without substance use to assess the risk factors for oral malignancy.

A number of genetic variants were suggested to be associated with oral malignancy, few variants can be replicated. The aim of this study was to identify significant variants that enhanced personal risk prediction for oral malignancy. A total of 360 patients diagnosed with oral squamous cell carcinoma, 486 controls and 17 newly diagnosed patients with OPMD including leukoplakia or oral submucous fibrosis were recruited. Fifteen tagSNPs which were derived from somatic mutations were genotyped and examined in associations with the occurrence of oral malignancy. Environmental variables along with the SNPs data were used to developed risk predictive models for oral malignancy occurrence. The stepwise model analysis was conducted to fit the best model in an economically efficient way. Two tagSNPs, rs28647489 in FAT1 gene and rs550675 in COL9A1 gene, were significantly associated with the risk of oral malignancy. The sensitivity and specificity were 85.7% and 85.5%, respectively (area under the receiver operating characteristic curve (AUC) was 0.91) for predicting oral squamous cell carcinoma occurrence with the combined genetic variants, betel-quid, alcohol and age. The AUC for OPMD was only 0.69. The predictive probability of squamous cell carcinoma occurrence for genetic risk score without substance use increased from 10% up to 43%; with substance use increased from 73% up to 92%. Genetic variants with or without substance use may enhance risk prediction for oral malignancy occurrence in male population. The prediction model may be useful as a clinical index for oral malignancy occurrence and its risk assessments.

Malignant transformation to oral cancer by subtype of oral potentially malignant disorder: A prospective cohort study of Taiwanese nationwide oral cancer screening program.

OBJECTIVES: To elucidate the risk of malignant transformation to invasive oral cancer by subtypes of oral potentially malignant disorders (OPMD) and to examine the independent effects of risk factors, particularly alcohol drinking, by subtype based on a nationwide oral cancer screening program targeting at general population with habits of smoking and/or betel quids chewing. MATERIALS AND METHODS: The total of 8501 subjects diagnosed as different subtypes of OPMDs from the Taiwanese screening program between 2004 and 2009 were followed up over time to ascertain the occurrence of invasive oral cancer. The hazard ratios of malignant transformation were estimated by using Cox proportional hazards regression model. RESULTS: The overall malignant rate (per 1000 person-years) to oral cancer was 8.4 (407 incident cases with an average of 5.7 years of follow-up). The highest rate was noted in exophytic verrucous hyperplasia (33), followed by erythroplakia (11.8), erythroleukoplakia (10.7), oral submucous fibrosis (OSF) (8.6), and leukoplakia (5.4). After adjusting for confounders, exophytic verrucous hyperplasia still had a 5.69 (4.47-7.24) times risk compared with leukoplakia. The corresponding figures for erythroplakia, erythroleukoplakia, and OSF were 2.25 (1.31-3.89), 2.00 (1.13-3.53), and 1.63 (1.29-2.06), respectively. Alcohol drinking elevated the overall risk of malignant transformation by 23% (1-52% and also triggered a higher risk in OSF (aHR = 1.62 (1.06-2.47)). The higher risk attributed to betel quids chewing was noted for exophytic verrucous hyperplasia (aHR = 4.23 (1.55-11.55)). CONCLUSIONS: The risk of malignant transformation to oral cancer varied with the subtypes of OPMD and was elevated in OSF and verrucous hyperplasia attributed to alcohol drinking and betel quids, respectively.

Harmful consequences of specific substances on the oral health.

Numerous substances may have an adverse influence on the oral region by virtue of their potentially harmful effects. Dental practitioners are often the first to see these effects in the head and neck region. Knowledge of the damaging consequences of agents such as alcohol, tobacco, areca nut, medications, alcohol-containing mouthwashes, dental devices and materials can assist the practitioners in clinical decision-making and accurate diagnosis of associated lesions. More importantly, timely diagnosis and prompt reporting of such harmful effects improve the quality of care. Such knowledge may also help in patient's education for the avoidance of associated adverse effects (AEs). Consequently, a thorough acquaintance of AEs will consolidate the distinct role of medical and oral health practitioners in safeguarding the patients' oral and systemic well-being. This article was planned to review the harmful consequences of specific substances on the oral health. Traditionally, the emphasis of review articles has been on reviewing the harmful effects of a single entity on oral health. This review is unique in the sense that it comprehensively and collectively focussed on the harmful effects on the oral health of addictive and illicit substances (alcohol, betel nut), medications, alcohol-containing mouthwashes, medications and dental materials.

Oral mucosal lesions in electronic cigarettes consumers versus former smokers.

OBJECTIVES: Electronic cigarettes (ECs) have become very popular in recent years. However, many uncertainties remain about their side effects. This study aims to evaluate the prevalence and characteristics of oral mucosal lesions (OMLs) in former smokers compared to ECs consumers. METHODS: A prospective case-control study was carried out. Outpatients for dental consultation were consecutively enrolled into two groups based on their habits, i.e. former smokers and ECs consumers. Each patient was examined to detect possible oral lesions and, if needed, a swab or biopsy of the lesion was taken for diagnosis. Data was entered into a spreadsheet and analyzed. RESULTS: A total of 90 patients were examined, 45 were former smokers (group A) and 45 were ECs consumers (group B). OMLs were detected in 55 cases, of which 19/55 (34.6%) belonged to group A and 36/55 (65.4%) to group B. Nicotine stomatitis, a hairy tongue and angular cheilitis resulted to be significantly more common among EC consumers. CONCLUSIONS: We found no statistically significant differences in terms of total prevalence of OMLs between former smokers and ECs consumers. An increased prevalence of three specific types of OMLs was detected among ECs consumers.

Proliferative verrucous leukoplakia: diagnosis, management and current advances / Leucoplasia verrucosa proliferativa: diagnóstico, conduta e avanços atuais

Abstract Introduction: Proliferative verrucous leukoplakia is a multifocal and progressive lesion of the oral mucosa, with unknown etiology, and commonly resistant to all therapy attempts with frequent recurrences. It is characterized by a high rate of oral squamous cell carcinoma and verrucou carcinoma transformations. Objective: To analyze the studies about Proliferative verrucous leukoplakia and develop a concise update. Methods: A Pubmed search identifying studies (laboratory research, case series and reviews of literature) that examined patients with Proliferative verrucous leukoplakia was realized. Results: There are not enough studies about Proliferative verrucous leukoplakia in the literature. The few found studies not present a consensus about its etiology and diagnosis criteria. Although several treatment strategies have been proposed, most of them still show a high recurrence rate. Conclusion: More research about Proliferative verrucous leukoplakia is necessary to understand and treat this disease.

Resumo Introdução: Leucoplasia verrucosa proliferativa (LVP) é uma lesão multifocal e progressiva da mucosa oral, com etiologia desconhecida e comumente resistente a todas as tentativas terapêuticas, com recorrências frequentes. É caracterizada por uma alta taxa de transformação em carcinoma de células escamosas e carcinoma verrucoso da cavidade oral. Objetivo: Analisar os estudos sobre LVP e elaborar uma atualização resumida. Método: Foi realizada uma pesquisa na base de dados Pubmed que identificou estudos (pesquisas laboratoriais, séries de casos e revisões de literatura) que avaliaram pacientes com LVP. Resultados e discussão: Não há estudos suficientes sobre LVP na literatura. Os poucos estudos encontrados não apresentam consenso quanto aos critérios de etiologia e diagnóstico. Embora várias estratégias de tratamento tenham sido propostas, a maioria ainda apresenta alta taxa de recorrência. Conclusão: Mais pesquisas sobre LVP são necessárias para entender e tratar essa doença.

Environmental heavy metal as a potential risk factor for the progression of oral potentially malignant disorders in central Taiwan.

OBJECTIVE: Oral cancer (OC) is a leading cause of death from cancer in men between the ages of 25 and 44 years in Taiwan. The overall 5-year survival rates for the four OC stages (I-IV) in Taiwan are approximately 70%, 30%, 20%, and 10%, respectively, indicating the importance of the early diagnosis of oral potentially malignant disorders (OPMDs). Previous studies indicated an association between the OC incidence and certain environmental heavy metal concentrations. If these associations do exist for OC, they may also be observed for OPMD. The purpose of this study is to explore the association between the development of OPMD to OC and environmental heavy metals. Oral submucous fibrosis (OSF) and oral leukoplakia (OL) are two major types of OPMD in Taiwan. MATERIALS AND METHODS: A retrospective cohort study was conducted by Changhua Christian Hospital, the sole medical center in Changhua County, where 2725 male adult patients diagnosed with either OSF or OL between 2000 and 2014 were recruited. Data were analyzed by Cox regression and adjusted for smoking and betel-quid chewing. RESULTS AND DISCUSSION: OPMD patients who resided in areas with high nickel concentrations (polluted levels) exhibited hazard ratios of 1.8-2 for OC relative to those who lived in areas with low nickel levels (P<0.01). Meanwhile, smokers with OPMDs had a hazard ratio of 2.8-2.9 relative to non-smokers. Betel-quid chewers had a 2.2-2.3 hazard ratio relative to non-chewers. Smoking, betel-quid chewing, and environmental nickel exposure are associated with an increased risk of OC development in OPMD patients. This study provides valuable findings on the environmental effects of heavy metals on human health. Enhanced surveillance of the condition of OPMD patients who have been exposed to high nickel concentrations may be crucial for OC prevention.

Proliferative verrucous leukoplakia: diagnosis, management and current advances.

INTRODUCTION: Proliferative verrucous leukoplakia is a multifocal and progressive lesion of the oral mucosa, with unknown etiology, and commonly resistant to all therapy attempts with frequent recurrences. It is characterized by a high rate of oral squamous cell carcinoma and verrucou carcinoma transformations. OBJECTIVE: To analyze the studies about Proliferative verrucous leukoplakia and develop a concise update. METHODS: A Pubmed search identifying studies (laboratory research, case series and reviews of literature) that examined patients with Proliferative verrucous leukoplakia was realized. RESULTS: There are not enough studies about Proliferative verrucous leukoplakia in the literature. The few found studies not present a consensus about its etiology and diagnosis criteria. Although several treatment strategies have been proposed, most of them still show a high recurrence rate. CONCLUSION: More research about Proliferative verrucous leukoplakia is necessary to understand and treat this disease.

Association between smoking, glycaemia, blood lipoproteins and risk of oral leukoplakia.

BACKGROUND: Among potentially malignant disorders, oral leukoplakia is the most common in clinical practice. The aim of this study was to assess risk factors associated with oral leukoplakia. METHODS: This retrospective study included 142 patients diagnosed with oral leukoplakia according to World Health Organization clinical and histopathological criteria and a control group of healthy subjects matched for age and gender. Sociodemographic data were registered for each patient: age, gender, smoking and alcohol consumption. Leukoplakia characteristics were also registered: size, position, clinical form, and presence or absence of dysplasia; all cases of leukoplakia were classified systematically according to clinicopathological stage. Blood lipid component levels of total cholesterol, high-density lipoproteins, low-density lipoproteins and triglycerides were compared between groups. RESULTS: Smoking had a significant effect on the risk of leukoplakia (P = 0.01, odds ratio (OR) = 8.33). High glucose levels also increased the probability of leukoplakia (P = 0.03, OR = 6.35), as did low-density lipoproteins (P = 0.049, OR = 5.65). The risk of dysplasia increased among patients presenting the non-homogeneous form of leukoplakia (P = 0.039, OR = 9.06) and among smokers (P = 0.044, OR = 28.33). CONCLUSIONS: Smoking, increased glucose and low-density lipoproteins in the blood are associated with a risk of oral leukoplakia.