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.

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.

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.

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.

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.

[Papillomavirus in the genesis of oral leukoplakia].

Immunohistochemical examination of the proliferative activity of cells was made investigating the expression of Ki-67 protein and the location of proteins associated with epithelial cell papillomavirus infection involving P16(INK4a) and HPV16 proteins in different cell areas of the intact mucosa, in leukoplakia with the signs of hyperplasia and dysplasia, and in squamous cell carcinoma. There was a positive correlation between the proliferative activity of cells in the parabasal cell areas and the expression of P16(INK4a) protein in oral leukoplakia with the signs of hyperplasia (r(s)=0.397; p=0.018). In oral leukoplakia with dysplastic changes, there was a positive correlation between the proliferation of cells in the parabasal and prickle cell layers and the location of HPV type 16 antigens (r(s)=0.515; p=0.041 and r(s)=0.651; p=0.006). Detection of papillomavirus infection in leukoplakia can solve not only the problems with its genesis, but this is also a morphological basis for the effective prevention and treatment of this common oral mucosal disease.

Cancer Precursor Syndromes and Their Detection in the Head and Neck.

This article explores the multifaceted landscape of oral cancer precursor syndromes. Hereditary disorders like dyskeratosis congenita and Fanconi anemia increase the risk of malignancy. Oral potentially malignant disorders, notably leukoplakia, are discussed as precursors influenced by genetic and immunologic facets. Molecular insights delve into genetic mutations, allelic imbalances, and immune modulation as key players in precancerous progression, suggesting potential therapeutic targets. The article navigates the controversial terrain of management strategies of leukoplakia, encompassing surgical resection, chemoprevention, and immune modulation, while emphasizing the ongoing challenges in developing effective, evidence-based preventive approaches.

Urban legends series: oral leukoplakia.

To date, the term oral leukoplakia (OL) should be used to recognize 'predominantly white plaques of questionable risk, having excluded (other) known diseases or disorders that carry no increased risk of cancer'. In this review, we addressed four controversial topics regarding oral leukoplakias (OLs): (i) Do tobacco and alcohol cause OLs?, (ii) What percentage of OLs transform into oral squamous cell carcinoma (OSCC)?, (iii) Can we distinguish between premalignant and innocent OLs?, and (iv) Is proliferative verrucous leukoplakia (PVL) a specific entity or just a form of multifocal leukoplakia? Results of extensive literature search suggest that (i) no definitive evidence for direct causal relationship between smoked tobacco and alcohol as causative factors of OLs, (ii and iii) the vast majority of OLs follow a benign course and do not progress into a cancer, and no widely accepted and/or validated clinical and/or biological factors can predict malignant transformation, and (iv) the distinction between multifocal/multiple leukoplakias and PVL in their early presentation is impossible; the temporal clinical progression and the high rate of recurrences and development of cancer of PVL are the most reliable features for diagnosis.

The prevalence of HIV associated oral lesions among adults in the era of HAART.

INTRODUCTION: The overall prevalence of HIV associated oral lesions among adults has decreased since the advent of highly active anti-retroviral therapy (HAART). AIMS AND OBJECTIVES: This study describes the prevalence and types of oral mucosal lesions in adults, who accepted a dedicated oral and dental programme for HIV-infected patients. The incidence of oral lesions and the CD4 cell counts on those patients, were related to cases receiving HAART and to those who were not. DESIGN: This was a retrospective, descriptive cross-sectional study. METHODS: Patients were interviewed, using a structured questionnaire to obtain information regarding medical history, current medications and demographic details. Data relating to CD4 cell counts were extracted from clinical medical records of the patent. In each case, the oral cavity of the sitting patient was examined under artificial light, by a clinician using a mouth mirror. Oral lesions were categorised in accordance with EC-Clearinghouse diagnostic criteria. RESULTS: The prevalence of HIV-associated oral lesions was significantly reduced (p < 0.001) in patients receiving HAART. There was, however, no significant difference (p = 0.29) in mean CD4 counts between patients receiving HAART and those not receiving HAART. The presence of oral lesions was statistically significantly, associated with both CD4 counts of < 200 cells/mm3 (p < 0.001) and the absence of HAART (p = 0.033). CONCLUSIONS: The study confirmed that the incidence of oral lesions and of pseudo-membranous candidiasis in particular, were statistically significantly reduced in patients receiving HAART.

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.

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.

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.

Two stem cell markers, ATP-binding cassette, G2 subfamily (ABCG2) and BMI-1, predict the transformation of oral leukoplakia to cancer: a long-term follow-up study.

BACKGROUND: Although oral leukoplakia (OL) is the best-known potentially malignant disorder, the risk of OL malignant transformation is difficult to assess. ATP-binding cassette, G2 subfamily (ABCG2) and BMI-1 are stem cell markers that have been found to be associated with head and neck tumorigenesis. The objective of the current study was to evaluate the usefulness of ABCG2 and BMI-1 in predicting OL transformation. METHODS: In a retrospective cohort of 135 patients with OL from the study institution who had a mean follow-up of 5.5 years, 32 developed cancer between 1985 and 2008. The expression of ABCG2 and BMI-1 was determined using immunohistochemistry in samples from these patients, and included untransformed OL (n = 103) and malignant-transformed OL (n = 32). The association between protein expression and clinicopathological parameters and transformation was analyzed. RESULTS: Expression of ABCG2 and BMI-1 was observed in 58 (43.0%) and 44 (32.6%) of 135 patients, respectively. The correlation between ABCG2 and BMI-1 expression was significant (P = .024). Kaplan-Meier analysis revealed that 37.9% of patients with ABCG2 positivity developed cancer compared with 13.0% of patients with ABCG2 negativity (P = .014, log-rank test). Approximately 40.9% of patients with BMI-1 positivity developed cancer compared with 15.4% of patients with BMI-1 negativity (P = .029, log-rank test). Multivariate analysis revealed that ABCG2 and BMI-1 expression was associated with a 3.24-fold (95% confidence interval [95% CI], 1.31-7.98; P = .011) and 4.03-fold (95% CI, 1.59-10.26; P = .003) increased the risk of transformation, respectively. CONCLUSIONS: ABCG2 and BMI-1 expression was found to be associated with the development of oral cancer in a large cohort of patients with OL for whom long-term follow-up was available, which suggests that ABCG2 and BMI-1 may be used as predictors of OL transformation.

CO2 laser of oral dysplasia: clinicopathological features of recurrence and malignant transformation.

The use of the CO(2) laser in the management of oral dysplastic lesions has become a more common practice. Very few studies have evaluated recurrence, residual disease malignant transformation, and overall outcome in patients undergoing such a procedure. In this prospective study, a total of 123 oral dysplastic lesions from 77 consecutive patients were treated with the CO(2) laser (resection and/or ablation). The average age was 58 ± 4.8 years. The patients' recovery was uneventful and no complications were reported. Comparisons with the clinical and histopathological features and rate of recurrence as well as malignant transformation were made. The patients were followed-up for a mean of 6.4 years, and biopsies taken in case of changes suggestive of malignant development. Homogenous leukoplakias were identified in 31 patients, non-homogenous leukoplakias in 34 patients, whereas 12 patients had erythroplakias. Ex- and life-long smokers formed 88.3% of the recruited patients. While people who currently smoke and drink formed 55.8% of the cohort. Erythroplakias were solely identified in heavy life-long smokers. The most common identified primary anatomical locations were the lateral border of tongue, floor of mouth, and buccal mucosa. Moderate dysplasia was identified in 42 patients while 18 patients had severe dysplasia. Laser resection margins in selected cases (68 patients) were clear in 53 and showed mild-moderate dysplasia in the involved margins. The rate of recurrence had no significant association with the location but the severity of epithelial dysplasia. The rate of first recurrence after laser surgery was approximately 19.5%. Malignant transformation was observed in eight patients (10.4%), in the tongue and the floor of mouth. Recurrence and malignant transformation was mainly identified in erythroplakias and non-homogenous leukoplakias. Laser resection/ablation is recommended for oral dysplasia to prevent not only recurrence and malignant transformation but also postoperative oral dysfunction encountered by other conventional modalities.

Effect of methylxanthines (coffee/tea consumers) on oral precancer and oral cancer patients with smoking and smokeless tobacco habits.

AIM: To study, whether the consumption of regular tea/coffee (methylxanthines) increases the risk of oral cancer in patients with smoking and smokeless tobacco habits. MATERIALS AND METHODS: This study was conducted on a total of 90 oral cancer and precancerous patients, from western Maharashtra (India) males in the age group of 20 to 45 years who were with smoking and smokeless tobacco habits; also regular tea/coffee consumers were subjected to biochemical parameters such as aspartate transaminase (AST) and alanine transaminase (ALT) from saliva and serum of patients with oral precancer (submucous fibrosis, leukoplakia) and oral cancer patients and compared with 90-age and sex-matched controls. Individuals consent was taken to measure their biochemical parameters, by using Hafkenscheid method in whole saliva and serum. Statistical analysis of variance (ANOVA) with Tukey's correction for multiple group comparisons was performed using Student t-test. RESULTS: Results show, that a statistically significant increase in value (p < 0.05) in ALT, AST in both saliva and serum was observed in precancerous and oral cancer patients among the study group as compared to the control group. CONCLUSION: In the present study, there was increase in the levels of ALT, AST enzymes in both saliva and serum levels in the study group as compared to the control group which was statistically significant (p < 0.05) suggesting that long-term exposure of methylxanthines results in impairment of salivary gland antioxidant system which may affect the anticarcinogenic action of saliva. CLINICAL SIGNIFICANCE: Oral fluids may be utilized effectively to study the variations in the biochemical constituents of saliva of leukoplakia, submucous fibrosis and oral cancer patients.

Evidence for a possible anatomical subsite-mediated effect of tobacco in oral potentially malignant disorders and carcinoma.

PURPOSE: To test the hypothesis that cigarette smokers develop oral potentially malignant disorders or carcinomas in preferential anatomical subsites. METHODS: The association of smoking habit with the presence of oral lesions in specific anatomical subsites was assessed in 123 patients using the odds ratio analysis. RESULTS: When compared to all the other subsites, the relative frequency of smokers with lesions was higher in the buccal mucosa and in the floor of the mouth (FOM) (P=0.002 and P=0.005), while it was lower in the tongue (P<0.0005). Smokers were about 7 years younger than non-smokers (P=0.008). CONCLUSIONS: The association of smoking and age suggests that smoking may contribute to generate a field of injury that leads to lesions in shorter periods than other causes. The stronger relationship of smoking with lesions in the buccal mucosa and FOM than in the tongue suggests that tissue characteristics mediate the effects of tobacco.

Oral premalignant lesions: from a clinical perspective.

In this review article, the clinical and histopathological characteristics of oral premalignant lesions, and primarily oral leukoplakia, are noted and the risk factors for malignant transformation of oral leukoplakia are discussed. Malignant transformation rates of oral leukoplakia range from 0.13 to 17.5%. The risk factors of malignant transformation in the buccal mucosa and labial commissure are male gender with chewing tobacco or smoking in some countries such as India, or older age and/or being a non-smoking female in other countries. Some authors have reported that leukoplakia on the tongue or the floor of the mouth showed a high risk of malignant transformation, although others have found no oral subsites at high risk. In concurrence with some authors, the authors of this review view epithelial dysplasia as an important risk factor in malignant transformation; however, there are conflicting reports in the literature. Many authors believe that nonhomogeneous leukoplakia is a high risk factor without exception, although different terms have been used to describe those conditions. The large size of lesions and widespread leukoplakia are also reported risk factors. According to some studies, surgical treatment decreased the rate of malignant transformation; however, many review articles state that no definitive treatment including surgery can decrease the malignant transformation rate of oral leukoplakia because of the lack of randomized control trials of treatment. Tobacco chewing and smoking may be causative agents for cancerization of oral leukoplakia in some groups, and evidence for a role of human papilloma virus in the malignant transformation of oral leukoplakia is inconsistent. Further research to clarify its role in malignant transformation is warranted.

Significance of cannabis use to dental practice.

The illicit use of the three main forms of cannabis-marijuana, hash, hash oil-pose certain obstacles and challenges to the dental professional. There are a number of systemic, as well as oral/head and neck manifestations, associated with cannabis use. Dentists need to be aware of these manifestations in order to take whatever precautions and/or modifications to the proposed treatment that might be necessary.

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.