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The present investigation aimed to assess the safety of photobiomodulation (PBM) on the oral carcinogenesis process induced by 4NQO, focusing on cell proliferation and apoptosis. Sixty-six Wistar rats received systemic 4NQO for 12 (n = 33) and 20 weeks (n = 33), divided into Control group, PBM 0.3 J, and PBM 1 J. Applications for PBM occurred three times a week. At weeks 12 and 20, the animals were euthanized. The immunoreactivity for anti-ROS1 and anti-p53 antibodies was also assessed. Statistical analysis was assessed by multiple t-tests, Kruskal-Wallis, and Spearman's correlation. At 12 weeks, PBM 1 J group had nodular lesions, distinct from control and PBM 0.3 J groups (p = 0.005). At 20 weeks, nodular lesions were common in control and PBM 0.3 J groups. Histopathological characteristics did not significantly differ between groups at 12 (p = 0.30) and 20 weeks (p = 0.58). Epithelial dysplasia (n = 21) was common at 12 weeks. After 20 weeks, most of the cases revealed squamous cell carcinoma (n = 24). No differences were observed in the immunostaining of p53 and ROS1 among the control and experimental groups and there was no correlation of these proteins with clinicopathological data. During the carcinogenesis process, the PBM did not modify the development of oral lesions and the expression of proliferative and apoptosis proteins. [ABSTRACT FROM AUTHOR]

Oral leukoplakia (OL) has an inherent disposition to develop oral cancer. OL with epithelial dysplasia (OED) is significantly likely to undergo malignant transformation; however, routine OED assessment is invasive and challenging. This study investigated whether a deep learning (DL) model can predict dysplasia probability among patients with leukoplakia using oral photographs. In addition, we assessed the performance of the DL model in comparison with clinicians' ratings and in providing decision support on dysplasia assessment. Retrospective images of leukoplakia taken before biopsy/histopathology were obtained to construct the DL model (n = 2,073). OED status following histopathology was used as the gold standard for all images. We first developed, fine-tuned, and internally validated a DL architecture with an EfficientNet-B2 backbone that outputs the predicted probability of OED, OED status, and regions-of-interest heat maps. Then, we tested the performance of the DL model on a temporal cohort before geographical validation. We also assessed the model's performance at external validation with opinions provided by human raters on OED status. Performance evaluation included discrimination, calibration, and potential net benefit. The DL model achieved good Brier scores, areas under the curve, and balanced accuracies of 0.124 (0.079–0.169), 0.882 (0.838–0.926), and 81.8% (76.5–87.1) at testing and 0.146 (0.112–0.18), 0.828 (0.792–0.864), and 76.4% (72.3–80.5) at external validation, respectively. In addition, the model had a higher potential net benefit in selecting patients with OL for biopsy/histopathology during OED assessment than when biopsies were performed for all patients. External validation also showed that the DL model had better accuracy than 92.3% (24/26) of human raters in classifying the OED status of leukoplakia from oral images (balanced accuracy: 54.8%–79.7%). Overall, the photograph-based intelligent model can predict OED probability and status in leukoplakia with good calibration and discrimination, which shows potential for decision support to select patients for biopsy/histopathology, obviate unnecessary biopsy, and assist in patient self-monitoring. [ABSTRACT FROM AUTHOR]

Background: India bears the highest global burden of oral cancer, despite having an operational tobacco cessation framework. Occupational groups like solid waste management personnel face significant health challenges due to prevalent tobacco use, leading to oral potentially malignant lesions and oral cancer. Enhanced tobacco control strategies are essential for these groups. Methods: A pre-post interventional, community-based study enrolled 1200 municipal workers in Varanasi, India, from July 2022 to August 2023. 858 tobacco users underwent screening and were randomly assigned to one of three interventions: Very Brief Advice, Individual Behavioral Counseling, or Group Behavioral Therapy. Follow-up was conducted one year after the baseline interventions Effectiveness was measured by nicotine dependence reduction using the Fagerstrom Test for Nicotine Dependence (FTND) scores and cessation rates defined as at least 6-month abstinence. Appropriate statistical tests assessed the burden of tobacco use, oral potentially malignant lesions, and pre-post differences in FTND scores within and between groups. A p-value of < 0.05 was considered statistically significant. Results: Municipal workers exhibited a high prevalence (71.5%) of smokeless tobacco (SLT) use. One-third (32.9%) of the participants screened positive for oral potentially malignant lesions and oral cancer. Leukoplakia was the most common lesion. Screened positivity correlated with significant nicotine dependence. Among 494 follow-up participants, 47.1% reported a significant reduction in nicotine dependence across all intervention groups. Quade's ANCOVA indicated significant differences in post-test FTND scores, with individual behavioral counselling showing the greatest reduction. However, no cessation was achieved in any group despite the significant decline in dependence. Conclusion: Solid waste management personnel in Varanasi show heightened SLT use and associated oral potentially malignant lesions. The persistent tobacco use in these high-risk occupational populations undermines government tobacco control efforts and highlights the need for robust policy and implementation strategies. The study demonstrated a significant reduction in nicotine dependence following interventions, though tobacco cessation was not achieved. More frequent interventions and addressing quitting barriers—such as cultural norms, lack of awareness, easy accessibility, and adverse working conditions—are crucial. Developing a tailored workplace model to tackle tobacco use in occupational settings may facilitate cessation. Clinical trial registration number: Trial registration Clinical Trials Registry India CTRI/2020/07/026479. Date of registration 10/07/2020. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Key points Plain language summary Proliferative verrucous leukoplakia (PVL) is a rare and refractory form of oral leukoplakia. The etiology of PVL remains unknown. The lesion is characterized by a high rate of malignant transformation. There is no definitive treatment for PVL.This case study presents a patient diagnosed in 2000 with a localized hyperkeratinized/verrucous lesion involving the facial gingivae of teeth #6–#8. Over the next 24 years, the lesion was biopsied five times. Further, two attempts to ablate the lesion with a CO2 laser (10.6 µm wavelength) were performed. Both ablation treatments were unsuccessful as the lesion recurred and progressed to involve more areas of gingival tissue. To date, biopsy has not revealed transformation into verrucous or squamous cell carcinoma (SCCA).This case study demonstrates that two attempts at ablation of PVL using a CO2 laser had no short‐ or long‐term benefit. The patient eventually lost all maxillary teeth due to root caries and inability to maintain adequate oral hygiene. The PVL lesion currently involves the entire maxillary edentulous ridge, extending from the 2nd molar site to the opposite corresponding site. During the 24 years encompassed by this report, the patient has not experienced a malignant transformation.The results of CO2 laser ablation of the PVL lesion in this case provided no short‐ or long‐term benefit. Given the potential for a sinister outcome, PVL patients require frequent clinical evaluation and biopsy for early detection of a malignant transformation into oral verrucous or SCCA. Proliferative verrucous leukoplakia (PVL) is a clinical diagnosis and represents a refractory form of multifocal oral mucosal leukoplakia of unknown origin. Currently, there is no reliable and successful treatment for PVL. PVL may undergo transformation to a verrucous or squamous cell carcinoma, thereby necessitating frequent oral examination and biopsy of sinister‐appearing mucosal sites. Proliferative verrucous leukoplakia (PVL) is a clinical diagnosis and represents a refractory form of multifocal oral mucosal leukoplakia of unknown origin.Currently, there is no reliable and successful treatment for PVL.PVL may undergo transformation to a verrucous or squamous cell carcinoma, thereby necessitating frequent oral examination and biopsy of sinister‐appearing mucosal sites.Proliferative verrucous leukoplakia (PVL) is a rare disorder that affects the gum tissue around the teeth. PVL is a pre‐cancerous disorder for which the cause is unknown and there is no treatment that yields a consistently successful result. This case study presents a patient diagnosed in 2000 with PVL involving the facial gum tissue of the upper right cuspid, lateral, and central incisor teeth. Over the next 24 years, the lesion was biopsied five times and two attempts to irradicate the lesion with a CO2 laser were performed. All attempts at treatment were unsuccessful and the lesion slowly progressed to involve more areas of gum tissue. The last biopsy taken in February 2024 did not reveal any areas of developing cancer. During the 24 years covered in this report, the patient did not develop oral cancer. However, treatment with the CO2 laser afforded no measurable benefit. Given the potential for developing cancer of the gum tissues, PVL patients should receive frequent oral exams and periodic biopsies for the detection of early cancer. [ABSTRACT FROM AUTHOR]

Objectives Materials and Methods Results Conclusions To update the current evidence on the malignant transformation of oral leukoplakia (OL), including all studies published worldwide on the subject, selected with the maximum rigor regarding eligibility.MEDLINE, Embase, Web of Science and Scopus were searched for studies published before June‐2024, with no lower date limit. The risk of bias was analyzed using the Joanna Briggs Institute tool for meta‐analyses of proportions. We carried out meta‐analyses, explored heterogeneity across subgroups and identified risk factors with potential prognostic value.Fifty‐five studies (41,231 with OL) were included. The pooled malignant transformation proportion for OL was 6.64% (95% CI = 5.21–8.21). The malignant transformation did not significantly vary by time periods (p = 0.75), 5.35% prior to 1978, 7.06% from 1979 to 2007 and 6.97% during more recent times. The risk factors that significantly had a higher impact on malignant transformation were the non‐homogeneous leukoplakias (RR = 4.23, 95% CI = 3.31–5.39, p < 0.001), the larger size (RR = 2.08, 1.45–2.96, p < 0.001), leukoplakia located on the lateral border of tongue (malignant transformation = 12.71%; RR = 2.09, 95% CI = 1.48–2.95, p < 0.001), smoking (RR = 1.64, 95% CI = 1.25–2.15, p < 0.001), and the presence of epithelial dysplasia (RR = 2.75, 95% CI = 2.26–3.35, p < 0.001).OL presents a considerable malignant transformation probability that is especially increased in large non‐homogeneous lesions in smokers, located on the lateral border of the tongue, with epithelial dysplasia. [ABSTRACT FROM AUTHOR]

Background: Oral cancers, which include tumors of the oral cavity, salivary glands, and pharynx, are becoming increasingly prevalent worldwide. Squamous cell carcinoma accounts for over 90% of malignant oral lesions, with oral squamous cell carcinoma (OSCC) being notably common in the Indian subcontinent and other regions of Asia. This is especially true in South-Central Asia, including Sri Lanka, where it is particularly prevalent among men. This study aims to evaluate the levels of Vascular Endothelial Growth Factor-A (VEGF-A) and Cytokeratin-19 (CK-19) mRNAs in whole blood as a potential method for the early detection of OSCC. Methods: The study included 40 patients (each from OSCC, Oral Submucous Fibrosis (OSF), Oral Leukoplakia (OLK), Oral Lichen Planus (OLP), and 10 healthy controls. The expression levels of VEGF-A and CK-19 mRNAs were measured from extracellular RNA extracted from whole blood samples using real-time reverse transcription polymerase chain reaction (RT-PCR) with sequence-specific primers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of these biomarkers in detecting OSCC. Results: The results demonstrated a significant increase in blood transcripts of the candidate mRNAs CK-19 and VEGF-A in patients with OSCC, OSF, OLK, and OLP. The Wilcoxon signed-rank test revealed a p-value of 0.002 for each specific comparison between diseased patients and healthy controls (i.e., OSCC vs. HC, OSF vs. HC, OLP vs. HC, OLK vs. HC) for both CK-19 and VEGF-A. When these two biomarkers were used together, they provided a 60% predictive probability for patients with OSCC (p = 0.023). Conclusion: This study highlights the efficacy of blood mRNA transcriptome diagnostics in detecting OSCC. This innovative clinical approach has the potential to be a robust, efficient, and reliable tool for early cancer detection. Blood-based transcriptomes could be further explored for their effectiveness in various health contexts and for routine health monitoring. [ABSTRACT FROM AUTHOR]

Objective: To identify potential salivary biomarkers for the diagnosis and monitoring of disease progression in oral squamous cell carcinoma and oral leukoplakia. Materials and Methods: An advance search from PubMed and Hindawi was performed with keywords; oral leukoplakia/oral squamous cell carcinoma, salivary biomarker and diagnosis/prognosis. An additional search of articles was done through a manual search from the Google Scholar database. Results: Twenty studies involving salivary biomarkers as diagnostic tools for oral squamous cell carcinoma and/or oral leukoplakia were identified. A narrative review was carried out. Conclusion: Single or multiple salivary biomarkers reported by most studies have shown great potential as diagnostic tools for oral squamous cell carcinoma and oral leukoplakia. However, the validation of sensitivity and specificity should be carried out to ensure the accuracy of the biomarkers. Furthermore, a standardised method for saliva collection should be established to prevent variability in the expression of biomarkers. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to assess the effectiveness of the best performing interpretable machine learning models in the diagnoses of leukoplakia and oral squamous cell carcinoma (OSCC). Methods: A total of 237 patient cases were analysed that included information about patient demographics, lesion characteristics, and lifestyle factors, such as age, gender, tobacco use, and lesion size. The dataset was preprocessed and normalised, and then separated into training and testing sets. The following models were tested: K-Nearest Neighbours (KNN), Logistic Regression, Naive Bayes, Support Vector Machine (SVM), and Random Forest. The overall accuracy, Kappa score, class-specific precision, recall, and F1 score were used to assess performance. SHAP (SHapley Additive ExPlanations) was used to interpret the Random Forest model and determine the contribution of each feature to the predictions. Results: The Random Forest model had the best overall accuracy (93%) and Kappa score (0.90). For OSCC, it had a precision of 0.91, a recall of 1.00, and an F1 score of 0.95. The model had a precision of 1.00, recall of 0.78, and F1 score of 0.88 for leukoplakia without dysplasia. The precision for leukoplakia with dysplasia was 0.91, the recall was 1.00, and the F1 score was 0.95. The top three features influencing the prediction of leukoplakia with dysplasia are buccal mucosa localisation, ages greater than 60 years, and larger lesions. For leukoplakia without dysplasia, the key features are gingival localisation, larger lesions, and tongue localisation. In the case of OSCC, gingival localisation, floor-of-mouth localisation, and buccal mucosa localisation are the most influential features. Conclusions: The Random Forest model outperformed the other machine learning models in diagnosing oral cancer and potentially malignant oral lesions with higher accuracy and interpretability. The machine learning models struggled to identify dysplastic changes. Using SHAP improves the understanding of the importance of features, facilitating early diagnosis and possibly reducing mortality rates. The model notably indicated that lesions on the floor of the mouth were highly unlikely to be dysplastic, instead showing one of the highest probabilities for being OSCC. [ABSTRACT FROM AUTHOR]

Background: We aimed to construct an artificial intelligence‐based model for detecting oral cancer and dysplastic leukoplakia using oral cavity images captured with a single‐lens reflex camera. Subjects and methods: We used 1043 images of lesions from 424 patients with oral squamous cell carcinoma (OSCC), leukoplakia, and other oral mucosal diseases. An object detection model was constructed using a Single Shot Multibox Detector to detect oral diseases and their locations using images. The model was trained using 523 images of oral cancer, and its performance was evaluated using images of oral cancer (n = 66), leukoplakia (n = 49), and other oral diseases (n = 405). Results: For the detection of only OSCC versus OSCC and leukoplakia, the model demonstrated a sensitivity of 93.9% versus 83.7%, a negative predictive value of 98.8% versus 94.5%, and a specificity of 81.2% versus 81.2%. Conclusions: Our proposed model is a potential diagnostic tool for oral diseases. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) comprises more than 90% of oral cavity cancer and remains the leading cause of death in oral disease. Limited studies have been conducted to evaluate cellular histomorphometry changes in OSCC compared to premalignant lesions such as Dysplastic leukoplakia (DL), Nondysplastic leukoplakia (NDL), and normal epithelial. This cross-sectional descriptive-analytical study was conducted on total 72 samples, including superficial areas of squamous cell carcinoma (SCCSF), Invasive Front of Squamous Cell Carcinoma (SCCIF), Apparently Normal Adjacent Oral Mucosa (SCCANM) or normal margin, Dysplastic leukoplakia (DL), Nondysplastic leukoplakia (NDL), and normal oral mucosa tissue (NOM) (N = 12 per group). ANOVA was used to compare the nucleus-to-cytoplasm ratio (N/C), nucleus area (NA), and cellular area (CA) of the stained hematoxylin and eosin (H&E) samples in the studied groups. A P value less than 0.05 was considered to be a significant level. There was a significant increase in the CA, NA, and N/C in the basal and parabasal layers from normal epithelium to dysplastic epithelium and OSCC. The highest NA, CA, and N/C were in the SCCIF and SCCSF groups, respectively, and the lowest was observed in NOM. In addition, SCCANM basal and parabasal layer cells had a significant difference in N/C compared to NOM, which indicates a high risk of SCCANM transformation into malignancy. Cell histomorphometry changes were observed from normal tissue to premalignant lesions and OSCC. These parameters can be used as indicators of the potential for transformation into malignancy in premalignant lesions. [ABSTRACT FROM AUTHOR]

Background and Objectives: The present study attempts to evaluate and assess the presence of Fusobacterium, Leptotrichia, and Campylobacter among patients manifesting oral leukoplakia and healthy individuals. The aim is to compare variations in the presence of total microbiomes in the oral cavity of patients manifesting oral leukoplakia and healthy individuals. Methods: This study comprised 55 male subjects, 27 with a history of tobacco smoking (leukoplakia patients) and 28 healthy individuals (nonsmokers) within the age range of 30 years and above. Mucosal swabs were collected from the oral sites of the subjects, and the microbial counts were assessed in the laboratory. Comparative evaluation of Fusobacterium, Leptotrichia, and the total microbiome of oral leukoplakia patients and healthy individuals was statistically analyzed using SPSS version 22.0. Results: The culture analysis of the study subject samples indicated a higher value of total microbial flora count, Fusobacterium, and Leptotrichia when compared to that of control subjects. Conclusions: This study suggests Fusobacterium and Leptotrichia may have a major influence in the malignant transformation of leukoplakia.

Aim: To estimate and compare the level of serum immunoglobulin A in patients of oral submucous fibrosis (OSMF), leukoplakia, and control group. Introduction: OSMF is a well‑recognized potentially malignant condition in the oral cavity, and a transformation rate as high as 7.6% over a period of 10 years has been reported from India. Leukoplakia has evolved as a clinico‑pathologic concept over many years, with the current clinical designation being accepted worldwide. Materials and Methods: Quantia IgA is a turbidometric immunoassay for the detection of IgA in human serum and is based on the principle of agglutination reaction. The test specimen is mixed with the activation buffer (R1) and then with antihuman IgA reagent (R2) and allowed to react. For the estimation of serum IgA, 500 μl of Quantia IgA activation buffer R1 is taken in a clean test tube. Serum sample is diluted in the ratio of 1:5 with normal saline. Ten microliters of diluted serum sample are added to R1. After incubation for 10 min, 50 μl of R2 is added, which is Quantia IgA antihuman IgA reagent to the sample, and the reading is recorded at wavelength 340 nm at 37°C. The level of IgA will be estimated by a semi‑automatic biochemical analyzer machine and then data analysis will be done. Results: The immunologic alterations observed by us in OSMF and leukoplakia are almost similar or nearer to the alterations observed in oral cancer, so it is reasonable to assume that OSMF and leukoplakia can be an intermediate stage in the transformation process of a normal cell to oral malignancy. Conclusion: Prevention and early detection is the best way to reduce the incidence and mortality of premalignant disorders and oral cancer. There are many ways and methods of early detection of premalignant disorders and oral cancer, and the immunological method is one of them. [ABSTRACT FROM AUTHOR]

Objectives: This study assessed the validity of nomograms for predicting malignant transformation (MT) among patients with oral leukoplakia (OL) and oral lichen planus (OLP). Materials and Methods: Two nomograms were identified following a systematic search. Variables to interrogate both nomograms were obtained for a retrospective OL/OLP cohort. Then, the nomograms were applied to estimate MT probabilities twice and their average was used to calculate the discriminatory performance, calibration, and potential net benefit of the models. Subgroup analyses were performed for patients with OL, OLP, and oral epithelial dysplasia. Results: Predicted probabilities were mostly significantly higher among OL/OLP patients who developed MT compared to those who did not (p = <0.001–0.034). AUC values and Brier scores of the nomograms were 0.644–0.844 and 0.040–0.088 among OL patients and 0.580–0.743 and 0.008–0.072 among OLP patients. Decision curve analysis suggested that the nomograms had some net benefit for risk stratification. However, the models did not best binary dysplasia grading in discriminatory validity and net benefit among patients with OL and oral epithelial dysplasia. Conclusion: Nomograms for predicting MT may have satisfactory validity among patients with OL than OLP, but they do not outperform binary dysplasia grading in risk stratification of OL. [ABSTRACT FROM AUTHOR]

Objectives: Evaluate whether regular follow‐up of oral leukoplakia (OL) resulted in early detection of malignant transformation (MT). Method: Two hundred and twenty‐two consecutive patients with OL (147 females, 75 males); median follow‐up period of 64 months (range: 12–300). Three groups were distinguished: group A (n = 92) follow‐up at the hospital; group B (n = 84) follow‐up by their dentist; group C (n = 46) lost to follow‐up. Results: OLs in group B compared to group A, were smaller in size (<2 cm; p < 0.001), showed more hyperkeratosis (p < 0.001) and less moderate/severe dysplasia (p < 0.001). MT occurred in 45 (20%) patients: 32 (35%) in group A, five (6%) in group B and eight (17%) in group C. There was no significant difference in clinical tumour size between group A (median: 15 mm, range: 1–40) and group B (median: 10 mm, range: 3–25; p = 0.496). Tumour size was smaller for patients in groups A and B (median: 10 mm, range 1–40) compared to group C (median: 33 mm, range: 3–100; p = 0.003). There was a positive correlation between tumour size and interval between the last visit in all patients (p = 0.022). Conclusion: Regular follow‐up of OL resulted in early detection of MT. If properly selected, follow‐up of OL performed by the dentist seems feasible. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of oral squamous cell carcinoma (OSCC) associated or not with oral potentially malignant disorders (OPMD), and the epidemiological profile and traditional risk factors in Latin America. Methods: A retrospective observational study was conducted in 17 Latin American centres. There were included cases of OSCC, analysing age, gender, OSCC and their association with previous OPMD. Clinicopathological variables were retrieved. The condition of sequential‐OSCC versus OSCC‐de novo (OSCC‐dn) was analysed concerning the aforementioned variables. Quantitative variables were analysed using Student's t‐test, and qualitative variables with chi‐square. Results: In total, 2705 OSCC were included with a mean age of 62.8 years old. 55.8% were men. 53.75% of the patients were smokers and 38% were common drinkers. The lateral tongue border was the most affected site (24.65%). There were regional variations in OPMD, being leukoplakia the most frequent. Of the overall 2705 OSCC cases, 81.4% corresponded to OSCC‐dn, while s‐OSCC were 18.6%. Regarding lip vermillion SCC, 35.7% corresponded to de novo lip SCC and 64.3% were associated with previous OPMD. Conclusions: In Latin America, OSCC‐dn seems to be more frequent with regional variations of some clinical and histopathological features. Further prospective studies are needed to analyse this phenomenon. [ABSTRACT FROM AUTHOR]

Objective: DNA methylation data can be used to derive mitotic indices from complex tissues. Here, we assessed if the DNA methylation‐derived mitotic ageing indices are associated with oral squamous cell carcinoma (OSCC) development and recurrence‐free survival (RFS). Methods: DNA methylation‐based mitotic indices (MitoticAge, TNSC and hypoSC) were derived using algorithms "MitoticAge" and "epiTOC2" for the discovery [non‐malignant (n = 22), premalignant (n = 22) and OSCC (n = 68) tissues] and validation datasets (GSE87053, GSE136704 and TCGA‐HNSCC). Differences in mitotic indices between non‐malignant, premalignant and OSCC tissues were assessed. Finally, the association between estimated mitotic indices and RFS was evaluated in OSCCs. Results: In the discovery and validation datasets, increased mitotic ageing was observed in OSCC compared to non‐malignant and premalignant oral tissues. HPV‐positive HNSCCs had higher mitotic index TNSC. Mitotic age index hypoSC was associated with RFS in OSCC (p = 0.011, HR 2.61, 95% CI 1.24–5.48). Conclusions: DNA methylation‐derived mitotic indices are associated with OSCC development and RFS. Thus, DNA methylation‐derived mitotic indices may be a valuable research tool to reliably estimate the cumulative number of stem cell divisions in malignant and non‐malignant oral tissues. Future research utilizing mitotic indices for predicting clinical outcomes in OSCC is warranted. [ABSTRACT FROM AUTHOR]

Background: This study aims to compare the efficacy between conventional exfoliative cytology (EC) and centrifuged liquid-based cytology (CLBC) in control, leukoplakia, and oral squamous cell carcinoma (OSCC) patients. Oral leukoplakia and oral cancer require an early definitive diagnosis for better prognostic outcome. Oral EC, a minimally invasive technique that involves the examination of desquamated cells from the tissue surfaces used as a method of early diagnosis. CLBC is a modified technique that is used to achieve improved quality of the cytology findings. Materials and Methods: A comparative study was done in 30 subjects, of which, 10 cases from control group, 10 oral leukoplakia, and 10 OSCC cases. These subjects were selected according to the appropriate inclusion and exclusion criteria. The cases in each group underwent conventional as well as CLBC. The comparison was carried out between these groups with respect to the cellular and background stromal factors. Appropriate qualitative evaluation of the samples was collected and statistical analysis was done using the Chi-squared test. The significance level of value was P < 0.05. Results: Significant results were obtained for certain parameters such as cellular overlap clear background, uniform distribution in control, leukoplakia, and OSCC with a P = 0.004**, P = 0.001**, P = 0.006** using CLBC. Conclusion: CLBC is better and give clearer vision as compared to conventional cytology and can be used in the early diagnosis. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions Oral leukoplakia (OL) is one of the most common and investigated oral potentially malignant disorders (OPMD). Preventing OSCC occurrence should be the primary outcome in the clinical management of OL. Surgical removal of OL is performed by most clinicians, although its effectiveness in reducing OSCC onset has still not been established by randomized controlled trials (RCT). Wait and see approach is characterized by frequent clinical examinations and periodical biopsies of OL, avoiding unnecessary surgical procedures.This is the first multicenter RCT in literature aiming at comparing the effectiveness of surgical removal and the “wait and see” approach in preventing OSCC onset in patients affected by dysplastic and non‐dysplastic OL.Two Italian referral care centres for oral diseases were involved in this multicenter two‐arm RCT comparing the surgical removal of OL (group A) and the “wait and see” approach (group B), with the aim of reducing oral cancer onset.This report shows preliminary data on the first 161 patients, with a mean follow‐up of 19.14 ± 11.25 months. Eight cases of OSCC occurred (6 out 8 involving the tongue): one case in group A and seven cases in group B. Moreover, OL recurred in 13 (20%) cases after surgical excision.Within the limitations of this preliminary report, these initial data underline the increased risk of OSCC onset in the case of OL of the tongue in the presence of epithelial dysplasia in group B (“wait and see”) compared to group A (surgery). This RCT is currently ongoing at the same clinical departments, with the aim of enrolling 310 patients and collecting data at 5‐year follow‐up, in order to achieve conclusive results, in an evidence‐based medicine approach. [ABSTRACT FROM AUTHOR]

Oral cancer represents a significant global public health challenge, contributing substantially to the incidence and mortality of cancer. Despite established risk factors such as tobacco use and alcohol consumption, early detection remains crucial for effective treatment. This study introduces a novel approach using a transistor-based biosensor system for detecting the P90 (CIP2A) protein. We tested the presence of CIP2A in human leukoplakia samples, which can undergo malignant conversion into aggressive oral squamous cell carcinoma. The method used commercially available glucose test strips functionalized with P90 antibodies, providing high sensitivity and a low limit of detection which was five orders lower than that of commercial ELISA kits. A specially designed printed circuit board (PCB) facilitated accurate measurements, and the device's performance was optimized through characteristic tests. Human sample testing validated the biosensor's effectiveness in distinguishing samples after cell lysis. This study contributes to advancing accurate and cost-effective diagnostic approaches for oral pre-cancer and cancer tissues. [ABSTRACT FROM AUTHOR]

Objective: Proliferative verrucous leukoplakia (PVL) has high rates of malignant transformation into oral squamous cell carcinoma (OSCC), but the clinical and evolutionary pattern of OSCC from PVL (PVL‐OSCC) is more favorable than that of OSCC not preceded by PVL (OSCC). Here, we aimed to explore the pathophysiologic differences between PVL‐OSCC and OSCC through transcriptomic and DNA methylation analyses. Materials and methods: In this case‐control study, oral biopsies from 8 PVL‐OSCC and 10 OSCC patients were obtained for global sequencing using RNAseq and a genome‐wide DNA methylation analysis via the Infinium EPIC Platform (graphical abstract). Results: One hundred and thirty‐three differentially expressed genes (DEGs) were detected, 94 of them upregulated in OSCC. Most of these genes were previously described in cancer and associated with prognosis. The integrative analysis revealed 26 DEGs, corresponding to 37 CpGs, whose promoters were regulated by DNA methylation. Twenty‐nine of the CpGs were found as hypermethylated in PVL‐OSCC. Only 5 of the genes that were aberrantly methylated and differentially expressed were upregulated in PVL‐OSCC patients, whereas 21 were underexpressed. Conclusions: PVL‐OSCC patients presented lower expression of cancer‐related genes. Hypermethylation of the promoter region of many genes was also noticed, indicating that DNA methylation could be a regulatory mechanism. [ABSTRACT FROM AUTHOR]

The term dermatoglyphics was first used in 1926 by anatomist Cummins. Dermatoglyphic is a term that refers to “a skin carving.” The unique carve present on the skin surface of humans and other living beings is referred to as dermatoglyphics. This research was conducted to understand the variations in patterns and assess the usefulness of dermatoglyphics among individuals diagnosed with potentially malignant diseases and mouth cancer. Three hundred subjects were selected. The study consisted of three groups. Patients were divided into the following groups: Group I: oral submucous fibrosis (OSMF) (100), Group II: ORAL LEUKOPLAKIA (100), and Group III: Healthy Individuals (100). Our research study indicates a difference in dermatoglyphic patterns between patients and healthy individuals. Specifically, there is a lower percentage of loop patterns and an increase in arch patterns in OSMF and leukoplakia patients. These findings suggest that dermatoglyphics may have relevance in understanding or identifying certain health conditions. [ABSTRACT FROM AUTHOR]

Background: Oral leukoplakia, a potentially precancerous lesion primarily attributed to tobacco use, poses a significant health concern worldwide. Identifying reliable prognostic markers for predicting the malignant transformation of oral leukoplakia is essential for early intervention and improved patient outcomes. This study explores the use of tissue p53 expression as a potential prognostic marker for assessing the risk of malignant transformation in individuals with tobacco-induced oral leukoplakia. Materials and Methods: In this retrospective cohort study, tissue samples from 150 patients with tobacco-induced oral leukoplakia were collected and analyzed for p53 expression using immunohistochemistry. Clinical data, including age, gender, tobacco consumption history, and follow-up information, were also gathered. Patients were categorized into two groups based on p53 expression: high p53 and low p53. The follow-up period ranged from 2 to 5 years. Results: Among the 150 patients, 65 (43.3%) exhibited high p53 expression in their oral leukoplakia tissue samples, while the remaining 85 (56.7%) had low p53 expression. During the follow-up period, 20 out of 65 patients (30.8%) with high p53 expression experienced malignant transformation, whereas only 8 out of 85 patients (9.4%) with low p53 expression developed malignancies. The odds ratio for malignant transformation in the high p53 group compared to the low p53 group was 4.12 (95% CI: 1.79-9.47, p < 0.001). Conclusion: This study demonstrates that tissue p53 expression is a valuable prognostic marker for assessing the risk of malignant transformation in individuals with tobacco-induced oral leukoplakia. Patients with high p53 expression in their oral lesions are significantly more likely to experience malignant transformation compared to those with low p53 expression. These findings underscore the importance of regular monitoring and early intervention for individuals with high p53 expression to reduce the risk of oral cancer development. [ABSTRACT FROM AUTHOR]

Early detection of oral cancer is essential for improving patient survival rates and leads to higher chances of successful treatment, reduced cost of complex treatments,and improved quality of life of patients. Oral cancer often arises from oral potentially malignant disorders (OPMDs), among which leukoplakia is the most common. Numerous chairside diagnostic aids and imaging modalities have been reviewed for screening detection of OPMDs and oral cancer, but these techniques have limitations. Novel optical diagnostic modalities work on the assumption that neoplastic and dysplastic tissues have different absorbance and reflectance properties when exposed to specific wavelengths of light. Optical coherence tomography (OCT) imaging is a promising new technology in the field of oral oncology. The ability of OCT to provide real-time, nondestructive, high-resolution, radiation-free images makes it an ideal modality for screening and detection of neoplastic changes in the oral mucosa, but interpretation of OCT images requires training and expertise. To overcome this incilimitation, artificial intelligence-based diagnostic algorithms are being combined with OCT imaging to assist professionals in achieving high-accuracy interpretation of OCT images. This review highlights the applications and scope of artificial intelligence in OCT imaging for the screening and detection of early-stage oral cancer. [ABSTRACT FROM AUTHOR]

Introduction: Inflammation plays an important role in the process of carcinogenesis. It is associated with initiation, progression as well as metastasis of cancer. C-reactive protein (CRP) is a reliable marker for inflammation. Aim: The present study is designed to determine and compare the serum CRP levels in Oral Submucous Fibrosis (OSMF), Oral Leukoplakia (OL), Oral Cancer (OC) and Healthy Controls (HC) in order to assess its possible role in carcinogenesis. Materials and Methods: A total of 40 participants were equally divided in four groups i.e. OSMF, OL, OC and HC. From each participant, 5 ml of blood was obtained from antecubital vein. The serum was analysed for CRP levels using nephelometric analysis method. Results: There were total 29 males and 11 females, who were between 16 to 77 years of age, with a mean age of 44.45 ± 7.45 years. The serum CRP levels were significantly increased in OSMF, OL and OC groups as compared to HC group (p<0.05). Conclusion: Serum CRP levels can be used as diagnostic and prognostic marker for oral premalignant and malignant lesions. [ABSTRACT FROM AUTHOR]

Simple Summary: In Sri Lanka, the authors are encouraging a cost-effective way to reduce the number of people developing oral cancer, which is a common cancer among men. The authors wanted to find out how well dentists can find signs of oral cancer and potential problems in their patients, and they did this by asking dentists questions in an online survey. Surprisingly, most of the dentists thought it would be better to only check people who are at a higher risk for oral cancer instead of checking everyone. Only about two thirds of the dentists regularly look for signs of oral cancer when people come for dental check-ups. The authors found that these dentists, on average, had noticed about 34 patients with concerning signs in the past year. Almost all the dentists believed that they needed more training to spot these problems. So, while opportunistic screening at the dentist's office is good, dental professionals also need to focus on other ways to prevent oral cancer, like checking high-risk groups and giving dentists more confidence to spot potential issues. In Sri Lanka, opportunistic screening is encouraged as a cost-effective tool to bring down the prevalence of oral cancer, which is the most common cancer among males. The objectives of the study were to determine the practices, attitudes, and level of competency of dental surgeons regarding the early detection of oral cancer and oral potentially malignant disorders (OPMDs) through opportunistic screening. A prospective study was conducted online via a Google form using a pretested, self-administered questionnaire of 22 close-ended questions and 3 open-ended questions. Out of the 137 dental surgeons who responded, 88% (121/137) of the participants believed that screening high-risk target groups would be more effective in the early detection of oral cancer rather than opportunistic screening. Only 64% (88/137) of the participants frequently check for oral cancer and OPMDs when patients visit for dental treatment. Participants recalled an average of 34 patients (4628/137) with clinically suspicious lesions being diagnosed during examination at general dental practice during the past year, and 98% (134/137) of the participants believed that they should receive additional training in order to identify and diagnose clinically suspicious OPMDs and oral cancer. Opportunistic screening in general dental practice as an oral-cancer prevention strategy is appreciable, but due emphasis should be given to other prevention strategies such as population screening and screening high-risk target groups. The level of confidence of general dental practitioners in the early detection of oral cancer has to be raised in order to achieve higher standards in oral cancer prevention through opportunistic screening. [ABSTRACT FROM AUTHOR]

CD44 and SALL4 are markers of stemness and expressed in cancer stem cells (CSCs). Their deregulated expression was seen in various tumors and has been correlated with clinical severity. We evaluated immunohistochemical expression of CD44 and SALL4 in leukoplakia and oral squamous cell carcinoma (OSCC). CD44 was expressed in all the cases of leukoplakia and Its expression correlated with severity of the dysplasia in leukoplakia but varied with differentiation in OSCC. SALL4 did not express in leukoplakia. Its expression was varied in OSCC cases. We opine that CD44 expression is consistent with the progression of dysplasia in leukoplakia and differentiation in OSCC. [ABSTRACT FROM AUTHOR]

Abstract Background The rising cancer incidence in patients with oral leukoplakia (OL) highlights the importance of identifying potential biomarkers for high‐risk individuals and lesions because these biomarkers are useful in developing personalized management strategies for OL patients. This study systematically searched and analyzed the literature on potential saliva and serum biomarkers for OL malignant transformation. Methods PubMed and Scopus were searched for studies published up to April 2022. The primary outcome of this study was the difference in biomarker concentrations in saliva or serum samples from healthy control (HC), OL and oral cancer (OC) populations. Cohen's d with 95% credible interval was calculated and pooled using the inverse variance heterogeneity method. Results A total of seven saliva biomarkers were analyzed in this paper, including interleukin‐1alpha, interleukin‐6 (IL‐6), interleukin‐6‐8, tumor necrosis factor alpha (TNF‐α), copper, zinc, and lactate dehydrogenase. IL‐6 and TNF‐α exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. A total of 13 serum biomarkers were analyzed, including IL‐6, TNF‐α, C‐reactive protein, total cholesterol, triglycerides, high‐density lipoproteins, low‐density lipoproteins, albumin, protein, β2‐microglobulin, fucose, lipid‐bound sialic acid (LSA), and total sialic acid (TSA). LSA and TSA exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. Conclusion IL‐6 and TNF‐α in saliva have strong predictive values for OL deterioration, and LSA and TSA concentration levels in serum also have the potential to serve as biomarkers for OL deterioration.

Oral leukoplakia is the most frequent and potentially malignant lesion of the oral cavity. Although dysplasia grading remains the main factor for risk assessment, challenges persist in determining the exact risk of transformation, and the literature has focused on studying alternative biomarkers. The interaction between dysplastic epithelial cells and the microenvironment starts early, and the communication is mainly mediated by lymphocytes, inflammatory factors, fibroblasts, and the extracellular matrix, leading to dysplastic progression. Leukoplakia-infiltrating leukocytes (LILs) and leukoplakia-associated fibroblasts (LAFs) play crucial roles in the dysplastic microenvironment. The immune response is related to intraepithelial T lymphocyte infiltration, mechanisms of immunosuppression coordinated by regulatory T cells, M2 macrophage polarization, and increased numbers of Langerhans cells; in contrast, fibroblastic and extracellular matrix factors are associated with increased numbers of pro-tumorigenic myofibroblasts, increased expression of metalloproteinases vs. decreased expression of TIMPs, and increased expression of chemokines and other inflammatory mediators. The microenvironment offers insights into the progression of leukoplakia to carcinoma, and understanding the complexity of the oral microenvironment in potentially malignant diseases aids in determining the risk of malignant transformation and proposing new therapeutic alternatives.

Frequent forms of malignancy localized to the oral cavity are considered a major health problem, especially in developing countries. Research on the experimental oral carcinogenesis inhibition using topical beta-carotene has led to the observation that beta-carotene significantly inhibits the formation of DMBA (7,12-dimethylbenz anthracene) and hamster squamous cell carcinomainduced oral pouch when used topically daily. In another study, 13-CIS-retinoic acid was used in the oral leukoplakia treatment where the efficacy of vitamin A in the oral leukoplakia treatment was highlighted. The efficacy of a mixture of ascorbic acid, glutathione, α-tocopherol, and β-carotene has shown that α-tocopherol and β-carotene can act synergistically to inhibit the growth of oral cancer. Analyzing the delay in oral cancer development using topical vitamin E demonstrated a significant delay in tumor formation compared to the animals from the control group. Extensive research has been conducted in experimental animals to indicate the anticancer activity of tocopherol, carotenoids, and retinoids on oral precancerous leukoplakia and oral cancer. The anticancer attributes of these micronutrients have been investigated in experiments on carcinogenesis inhibition, the prevention of oral cancer development, and oral carcinoma regression. Synergism has been shown in the anticancer activity of alpha-tocopherol and betacarotene. Synergism has been shown between anticancer alkylating agents such as cyclophosphamide, melphalan, and beta-carotene. In conclusion, antioxidant micronutrients such as beta-carotene are oral carcinogenesis inhibitors; vitamin E and beta-carotene can induce oral leukoplakia clinical regression, a premalignant lesion of oral cancer. [ABSTRACT FROM AUTHOR]

Background: Oral leukoplakia (OLK) is the most studied oral potentially malignant disorders in the scientific literature. Its malignant transformation (MT) rate varies between 1.1% and 40.8%, depending on the type of study and population group studied. There is no universal agreement to treat or manage these lesions, so it is up to each clinician’s experience and expertise in how he/she manages these patients. Objectives: The aim of this retrospective study was to assess the clinical aspects and pattern of evolution of OLK in 30 patients five years or more after the initial diagnosis. Materials and methods: We selected 30 OLK patients from our database. Demographic, clinical and evolutive data was retrieved from the medical files. The following variables were analysed: age and sex, smoking habits, clinical features (form, dimension, site of the lesion), result of mycological examination, treatment and outcomes of the lesions over a follow-up of more than five years. Results: For a follow-up of 119.63 months, we detected a value of 0.2% MT rate per year. Outcomes varied from the complete disappearance of the lesion to recurrence and malignant transformation with a variety of treatment methods applied. Conclusion: Despite the low MT rate for a long follow-up, it is hard to say which treatment method is the best, due to the heterogeneity of the clinical aspects of the lesions and because there is no standardised test method, either genetic testing or immunohistochemical testing. We recommend a varied approach, suitable for each patient's needs and medical context, always when possible histopathological confirmation for grading epithelial dysplasia, which remains the most reliable method of checking the process of malignant transformation. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the expression of the senescence markers, Decoy Receptor 2 (DcR2) and Differentiated Embryo-Chondrocyte expressed gen 1 (DEC1), in oral potentially malignant disorders (OPMDs) to ascertain their possible association with oral cancer risk. The immunohistochemical analysis of DcR2 and DEC1 expression (along with p16 and Ki67 expression) was carried out in 60 patients with clinically diagnosed oral leukoplakia. Fifteen cases (25%) subsequently developed an invasive carcinoma. Correlations between protein marker expression, histological grade and oral cancer risk were assessed. DcR2, DEC1 and Ki67 protein expressions were found to correlate significantly with increased oral cancer risk, and also with an increased grade of dysplasia. Multivariate analysis demonstrated that DcR2 and Ki67 expression are independent predictors of oral cancer development. Our results evidence for the first time the potential of DcR2 as an early biomarker to assess oral cancer risk in patients with oral leukoplakia (HR = 59.7, p = 0.015), showing a superior predictive value to histology (HR = 4.225, p = 0.08). These findings reveal that the increased expression of DcR2 and DEC1 occurred frequently in OPMDs. In addition, DcR2 expression emerges as a powerful biomarker for oral cancer risk assessment in patients with oral leukoplakia. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of methylene blue-mediated photodynamic therapy (MB-PDT) for the treatment of oral leukoplakia (OL) and compare it to systemic Vitamin A therapy. Materials and Methods: Forty clinically and histopathologically confirmed cases of OL were included. They were divided into two groups: 20 were given systemic Vitamin A therapy and on the other group MB-PDT for 30 days. Pre- and posttreatment assessment of size of lesion and clinical appearance were done and followed up for 1 year to check for recurrence and delayed side effects. Results: The reduction in size of lesion pre- and posttreatment was statistically nonsignificant in the Vitamin A Group, but statistically highly significant in the PDT group according to unpaired t-test with no immediate or delayed side effects seen in both the groups. Conclusion: Both the treatment methods showed response in terms of reduction of size of lesion, but MB-PDT was a better treatment option for OL. Clinical Relevance: Oral cancer is often preceded by various premalignancies, OL being the most common among them. Early diagnosis and intervention will prevent malignant transformation thereby reducing the cost, side effect and mortality associated with oral cancer. Considering the prevalence, symptomless nature of OL, an effective, well-accepted mode of treatment with minimal side effects is of utmost need. [ABSTRACT FROM AUTHOR]

Approximately 1 in 60 men and 1 in 141 women will develop oral and oropharyngeal cancer in the US. This article presents the risk factors, pathogenesis, clinical presentation, and management of patients with oral and oropharyngeal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: Evidence confirms that the use of Optical Coherence Tomography (OCT) in oral medicine can be a reliable aid for the diagnosis and management of Oral Potentially Malignant Disorders (OPMDs). Several authors described the ability of this system to detect the structural changes of the epithelia involved by the OPMDs. The purpose of this case series is to provide a suggestion for interpretation of OCT images from different OPMDs, compared to OCT images of healthy tissues. Methods: A sample of 11 OPMDs patients was recruited and analyzed with OCT. The images obtained were then compared with an OCT repertoire image. In this work the reflectance degree was considered, together with the analysis of the increased/decreased thicknesses of the various layers. Keratin Layer (KL), Epithelial Layer (EP), Lamina Propria (LP), Basal Membrane (BM) assessment, for each lesion, was performed. Results: OCT measurements of KL, EP and LP layers, together with BM assessing, should aid the physicians to recognize and describe different oral lesions, relating them to the corresponding oral pathology. Conclusion: More studies like this, on larger samples, are needed to validate the results and provide, in the future, a kind of manual that could guide clinicians to correctly interpret the OCT images in relation to the causing pathologies. Trial registration: The present trial has been registered with ISRCTN (#17,893,224). [ABSTRACT FROM AUTHOR]

Background: The rising cancer incidence in patients with oral leukoplakia (OL) highlights the importance of identifying potential biomarkers for high‐risk individuals and lesions because these biomarkers are useful in developing personalized management strategies for OL patients. This study systematically searched and analyzed the literature on potential saliva and serum biomarkers for OL malignant transformation. Methods: PubMed and Scopus were searched for studies published up to April 2022. The primary outcome of this study was the difference in biomarker concentrations in saliva or serum samples from healthy control (HC), OL and oral cancer (OC) populations. Cohen's d with 95% credible interval was calculated and pooled using the inverse variance heterogeneity method. Results: A total of seven saliva biomarkers were analyzed in this paper, including interleukin‐1alpha, interleukin‐6 (IL‐6), interleukin‐6‐8, tumor necrosis factor alpha (TNF‐α), copper, zinc, and lactate dehydrogenase. IL‐6 and TNF‐α exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. A total of 13 serum biomarkers were analyzed, including IL‐6, TNF‐α, C‐reactive protein, total cholesterol, triglycerides, high‐density lipoproteins, low‐density lipoproteins, albumin, protein, β2‐microglobulin, fucose, lipid‐bound sialic acid (LSA), and total sialic acid (TSA). LSA and TSA exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. Conclusion: IL‐6 and TNF‐α in saliva have strong predictive values for OL deterioration, and LSA and TSA concentration levels in serum also have the potential to serve as biomarkers for OL deterioration. [ABSTRACT FROM AUTHOR]

Introduction: Chemerin is a multifunctional chemoattractant cytokine, encoded by RARRES2 gene. Its role in oral carcinogenesis is largely unexplored. Study was undertaken to evaluate the role of salivary chemerin as a potential biomarker in the early diagnosis of oral cancer and to elucidate the clinicopathologic and prognostic significance of chemerin in different grades of Oral Squamous Cell Carcinoma (OSCC) and oral leukoplakia. Materials and Methods: The study comprised 96 subjects, divided into 3 groups, each consisting of 32 subjects. These groups were clinically and histopathologically diagnosed with OSCC, oral leukoplakia, and healthy controls, respectively. The whole unstimulated saliva (1.5 mL) was collected from the subjects using passive drool technique and immediately centrifuged at 3000 rpm for 10 minutes. The salivary chemerin level was estimated using the competitive sandwich enzyme-linked immunosorbent assay method. The statistical analysis was performed using R software EZR version 1.32. Independent t-tests, analysis of variance tests, and Scheffe Multiple Comparisons were carried out to compare quantitative parameters. A receiver operating characteristic (ROC) curve was plotted to assess diagnostic accuracy of salivary chemerin. Results: Significantly higher levels of salivary chemerin were observed in OSCC and oral leukoplakia patients compared to healthy controls (P < 0.05). The study further established an increase in salivary chemerin concentration in different histological grades of OSCC and oral leukoplakia. ROC curve analysis suggested that salivary chemerin is a highly sensitive and specific indicator for early screening and detection of oral leukoplakia and OSCC. Conclusion: Salivary chemerin can be considered as a reliable and specific indicator for the early screening and detection of oral leukoplakia and OSCC and a highly sensitive biomarker which may aid in detection of malignant transformation of oral leukoplakia. [ABSTRACT FROM AUTHOR]

Oral and oropharyngeal cancers have been recognized as a major global health problem and are the sixth most common cancers in the world, with increasing rates of incidence and mortality. Dentists have an important role and responsibility in the early diagnosis of oral cancer. This study aimed to assess knowledge, awareness, and attitudes regarding oral cancer among dentists in North Cyprus. This study was conducted via a questionnaire that was distributed to the dentists in different provinces of Northern Cyprus. The questionnaire comprised 19 main items about the demographic information, dentist's oral cancer knowledge, attitude, opinions, and practices. The study consisted of 120 dentists and an overall response rate of 81.6% (98) was achieved. Nearly, all respondents were knowledgeable about tobacco use (98%) and previous oral cancer history (98%). The percentage of correct answers to questions concerning knowledge about risk factors of oral cancer ranged from 4.1% (family history of cancer) to 98%. Two-thirds of the participants pointed out correctly that the tongue and floor of the mouth are the most affected sites for oral cancers and leukoplakia and erythroplakia are two lesions most commonly correlated with oral cancer. However, 47% of participants were able to identify squamous cell carcinoma as the most frequent form of oral cancer. In conclusion, dental faculty curriculums and continuing education programs should aim at managing oral cancer need to address not only increase the knowledge and awareness about oral cancers but also include the clinical cases and practices. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoke releases free radicles that have deleterious effects on the oral mucosa including potentially malignant disorders and oral cancer. In response to cigarette smoking, salivary flow rate increases as a defense activity along with a rise in alpha-amylase levels. Aim: To estimate salivary alpha-amylase levels in smokers with and without leukoplakia and oral cancer cases. Methods: This comparative study was carried out on 120 subjects; 30 subjects each in four groups which include non-smokers, smokers without oral lesions, smokers with leukoplakia, and smokers with oral squamous cell carcinoma (OSCC). Five microliters of unstimulated saliva were collected from the subjects by the spitting method. Alpha-amylase salivary levels were determined by spectrophotometric assay. Data collected were analyzed using a one-way ANOVA test. Results: No significant difference between alpha-amylase values was observed among smokers without oral lesions and smokers with leukoplakia groups when compared with non-smokers, but a significant difference was seen in the OSCC group in comparison with all three groups (smokers without oral lesions group vs OSCC group – P = 0.0045; leukoplakia group vs OSCC group P = 0.0326). Conclusion: Salivary alpha-amylase levels increased in smokers without any lesion and smokers with leukoplakia when compared with nonsmokers, although it was statistically not significant. Salivary alpha-amylase levels in oral cancer were significantly higher when compared with non-smokers, and smokers with and without leukoplakia. Smoking induced a change in salivary antioxidant levels. Changes in antioxidant levels can influence the deleterious effects of smoking on oral mucosa as well as systemic health.

Leukoplakia, a potentially malignant oral condition, manifests as a nonremovable white lesion that is often linked to risk factors such as smoking, alcohol, and HPV. Pegylated liposomal doxorubicin (PLD), which is used in cancer treatment, has been associated with secondary oral cancers, particularly in patients with leukoplakia. A case study revealed the development of squamous cell carcinoma (SCC) on the tongue following PLD treatment, suggesting a potential link between the drug and malignant transformation. Despite the benefits of PLD in reducing cardiac toxicity, long-term oral monitoring is essential due to the persistent risk of oral cancer posttreatment. [ABSTRACT FROM AUTHOR]

Objectives: To assess the clinicopathological characteristics of a cohort of patients with oral leukoplakia (OL) managed in a Romanian dental hospital and to evaluate the risk of malignant transformation (MT). Materials and methods: We conducted a hospital‐based retrospective study using the clinical charts of patients diagnosed with OL that had complete clinical and histopathological evaluation followed up for 1–16 years. Results: From 120 included patients, 68 (56.7%) were females, and 71 (59.2%) were current smokers. The homogeneous form was present in 60% of cases; the buccal mucosa was the most frequently involved site. MT was observed in 9 cases, which was more common in females and in those with dysplastic leukoplakia. A significant statistical association was found between MT and dysplasia grade (χ2 test: p = 0.007). MT occurred during a mean interval of time 75 months in both treated and non‐treated patients. Conclusions: In this leukoplakia cohort, most of the lesions encountered were in smokers, clinically homogeneous and 62.5% proved histologically benign. But despite the clinically benign appearance of leukoplakia, tissue diagnosis of some cases was carcinoma. The results of the current study advocate the necessity for biopsy even in apparently homogeneous, clinically benign lesions. The malignization rate was 7.5%; two‐thirds were nonhomogeneous lesions. [ABSTRACT FROM AUTHOR]

Background: Establishing the risk of malignant transformation (MT) in oral leukoplakia is usually based on grading oral epithelial dysplasia (OED) on biopsy tissue, for which two systems are proposed: a 3‐tier and a binary system. Only very few actuarial studies have tested the accuracy of such methods in predicting MT, especially for the binary system. This study aimed to assess the accuracy of the two grading systems in predicting MT in a cohort of oral leukoplakia (OL) from Brazil, with follow‐up data. Methods: The sample comprised 878 individuals diagnosed with OL from 2005 to 2018. Follow‐up data were obtained both locally and from the regional cancer registry. All lesions were graded using both the 3‐tier and the binary systems. Kaplan–Meier curves (Log‐rank Mantel‐Cox) were used to assess risk and kappa to assess interobserver agreement. Results: Thirty‐five individuals underwent MT (4%). Both systems demonstrated prognostic value, though the 3‐tier system proved superior, with OR 9.23 (3.42–23.69), PPV 0.152, NPV 0.98, compared to binary OR 3.49 (1.79–6.79), PPV 0.079, NPV 0.976. Interobserver agreement was also superior in the 3‐tier system (0.47, p < 0.05) compared to the binary system (0.139, p = 0.39). Combining the two systems enhanced prognostic values (OR 14.28, PPV 0.217, NPV 0.981). Conclusion: The 3‐tier system presented superior prognostic value to the binary system. Combining both systems to double‐grade intermediate lesions might enhance risk assessment. [ABSTRACT FROM AUTHOR]

Betel quid and areca nut are complex mixture carcinogens, but little is known about whether their derived single-agent arecoline or arecoline N-oxide (ANO) is carcinogenic, and the underlying mechanisms remain unclear. In this systematic review, we analyzed recent studies on the roles of arecoline and ANO in cancer and strategies to block carcinogenesis. In the oral cavity, flavin-containing monooxygenase 3 oxidizes arecoline to ANO, and both alkaloids conjugate with N-acetylcysteine to form mercapturic acid compounds, which are excreted in urine, reducing arecoline and ANO toxicity. However, detoxification may not be complete. Arecoline and ANO upregulated protein expression in oral cancer tissue from areca nut users compared to expression levels in adjacent normal tissue, suggesting a causal relationship between these compounds and oral cancer. Sublingual fibrosis, hyperplasia, and oral leukoplakia were diagnosed in mice subjected to oral mucosal smearing of ANO. ANO is more cytotoxic and genotoxic than arecoline. During carcinogenesis and metastasis, these compounds increase the expression of epithelial–mesenchymal transition (EMT) inducers such as reactive oxygen species, transforming growth factor-β1, Notch receptor-1, and inflammatory cytokines, and they activate EMT-related proteins. Arecoline-induced epigenetic markers such as sirtuin-1 hypermethylation, low protein expression of miR-22, and miR-886-3-p accelerate oral cancer progression. Antioxidants and targeted inhibitors of the EMT inducers used reduce the risk of oral cancer development and progression. Our review findings substantiate the association of arecoline and ANO with oral cancer. Both of these single compounds are likely carcinogenic to humans, and their mechanisms and pathways of carcinogenesis are useful indicators for cancer therapy and prognosis. [ABSTRACT FROM AUTHOR]

Oral cancer may arise from oral leukoplakia and oral lichenoid mucositis (oral lichen planus and oral lichenoid lesions) subtypes of oral potentially malignant disorders. As not all patients will develop oral cancer in their lifetime, the availability of malignant transformation predictive platforms would assist in the individualized treatment planning and formulation of optimal follow-up regimens for these patients. Therefore, this study aims to compare and select optimal machine learning (ML)-based models for stratifying the malignant transformation status of patients with oral leukoplakia and oral lichenoid mucositis. One thousand one hundred and eighty-seven patients with oral leukoplakia and oral lichenoid mucositis treated at three tertiary health institutions in Hong Kong, Newcastle UK, and Lagos Nigeria were included in the study. Demographic, clinical, pathological, and treatment-based factors obtained at diagnosis and during follow-up were used to populate and compare forty-six machine learning-based models. These were implemented as a set of twenty-six predictors for centers with substantial data quantity and fifteen predictors for centers with insufficient data. Two best models were selected according to the number of variables. We found that the optimal ML-based risk models with twenty-six and fifteen predictors achieved an accuracy of 97% and 94% respectively following model testing. Upon external validation, both models achieved a sensitivity, specificity, and F1-score of 1, 0.88, and 0.67 on consecutive patients treated after the construction of the models. Furthermore, the 15-predictor ML model for centers with reduced data achieved a higher sensitivity for identifying oral leukoplakia and oral lichenoid mucositis patients that developed malignancies in other treatment settings compared to the binary oral epithelial dysplasia system for risk stratification (0.96 vs 0.82). These findings suggest that machine learning-based models could be useful potentially to stratify patients with oral leukoplakia and oral lichenoid mucositis according to their risk of malignant transformation in different settings. [ABSTRACT FROM AUTHOR]

Background: Oral leukoplakia (OL) is one of the most prevalent oral potentially malignant disorders (OPMD). Although there is emerging evidence that quality of life (QoL) is impaired in subjects with OL; studies to date are based on single and heterogenous point‐in‐time assessments. The aim of this study was to ascertain if QoL scores change over time in individuals diagnosed with OL. Methods: Forty‐one individuals with OL were administered the Short Generic Health Questionnaire (SF‐12) and the discipline‐specific Oral Potentially Malignant Disorder Questionnaire (OPMDQ) at four points in time: at the time of clinical diagnosis, at the post‐biopsy review (confirmed diagnosis), and at 3‐ and 6‐month follow‐up appointments. Responses were compared between the four time points. Results: No significant differences were observed in the SF‐12 questionnaire scores over time. However, a general improvement in the participants' life quality was evident over the 6‐month period under investigation in the domains of psychological and social well‐being (p = 0.0027) and effect of treatment on daily life (p = 0.0317) as well as in the total score (p = 0.0005) of the OPMDQ. Age, gender, medical status, tobacco/alcohol use, lesion site, size, the presence of dysplasia and treatment did not impact QoL scores over time. Conclusions: QoL scores of OL subjects may improve with time. Our results suggest that studies examining QoL in individuals with OL should be controlled for time at which the participants are surveyed. [ABSTRACT FROM AUTHOR]

Purpose: The difficulty in risk assessing oral leukoplakia (OL) for malignant transformation has recently been reduced as novel strategies based on DNA content measurements have been providing consistent and reproducible predictive values, with a major advantage of using archived material. Regrettably, most such approaches are based on costly equipment and human resources that are not widely available, especially in populations with limited access to dedicated technology. The aim of this study was to investigate DNA content as a predictive marker of malignant transformation adapting novel image-based cytometry advances to a conventional flow cytometry context. Patient and methods: Nuclei isolation was performed enzymatically on thick sections from paraffin embedded tissue from 97 cases, 18 that progressed to oral carcinoma and 79 that did not. Flow cytometry was used to establish DNA content based on propidium iodide fluorescent labeling of nuclear suspensions. Multiple logistic regression was used to establish DNA content thresholds for DNA content parameters (G1, S-phase, G2, 4cER) to facilitate risk classification criteria. The predictive values of each marker were calculated from Kaplan-Meier and the Log-rank tests (p

The tongue and floor of the mouth are high-risk sites for oral squamous cell carcinoma (OSCC), while smoking is its most significant risk factor. Recently, questions have been raised as to the role of the oral microbiome in OSCC because of a wealth of evidence demonstrating that the microbiome of OSCC differs from that of healthy mucosa. However, oral site and smoking also have a significant impact on oral microbial communities, and to date, the role these factors play in influencing the dysbiotic microbial communities of OSCC and precursor lesions has not been considered. This review aims to examine the influence of site and smoking on the oral microbiome and, in turn, whether these microbiome changes could be involved in oral carcinogenesis.

The role of dysbiosis in the development and progression of oral potentially malignant disorders (OPMDs) remains largely unknown. Here, we aim to characterize and compare the oral microbiome of homogeneous leucoplakia (HL), proliferative verrucous leukoplakia (PVL), oral squamous cell carcinoma (OSCC), and OSCC preceded by PVL (PVL-OSCC). Fifty oral biopsies from HL (n = 9), PVL (n = 12), OSCC (n = 10), PVL-OSCC (n = 8), and healthy (n = 11) donors were obtained. The sequence of the V3–V4 region of the 16S rRNA gene was used to analyze the composition and diversity of bacterial populations. In the cancer patients, the number of observed amplicon sequence variants (ASVs) was lower and Fusobacteriota constituted more than 30% of the microbiome. PVL and PVL-OSCC patients had a higher abundance of Campilobacterota and lower Proteobacteria than any other group analyzed. A penalized regression was performed to determine which species were able to distinguish groups. HL is enriched in Streptococcus parasanguinis, Streptococcus salivarius, Fusobacterium periodonticum, Prevotella histicola, Porphyromonas pasteri, and Megasphaera micronuciformis; PVL is enriched in Prevotella salivae, Campylobacter concisus, Dialister pneumosintes, and Schaalia odontolytica; OSCC is enriched in Capnocytophaga leadbetteri, Capnocytophaga sputigena, Capnocytophaga gingivalis, Campylobacter showae, Metamycoplasma salivarium, and Prevotella nanceiensis; and PVL-OSCC is enriched in Lachnospiraceae bacterium, Selenomonas sputigena, and Prevotella shahii. There is differential dysbiosis in patients suffering from OPMDs and cancer. To the best of our knowledge, this is the first study comparing the oral microbiome alterations in these groups; thus, additional studies are needed. [ABSTRACT FROM AUTHOR]