The mechanism of low molecular weight fucoidan-incorporated nanofiber scaffolds inhibiting oral leukoplakia via SR-A/Wnt signal axis.

Oral leukoplakia (OLK) is the most common oral precancerous lesion, and 3%-17% of OLK patients progress to oral squamous cell carcinoma. OLK is susceptible to recurrence and has no effective treatment. However, conventional drugs have significant side effects and limitations. Therefore, it is important to identify drugs that target OLK. In this study, scavenger receptor A (SR-A) was found to be abnormally highly expressed in the oral mucosal epithelial cells of OLK patients, whereas molecular biology studies revealed that low molecular weight fucoidan (LMWF) promoted apoptosis of dysplastic oral keratinocytes (DOK) and inhibited the growth and migration of DOK, and the inhibitory effect of LMWF on OLK was achieved by regulating the SR-A/Wnt signaling axis and related genes. Based on the above results and the special situation of the oral environment, we constructed LMWF/poly(caprolactone-co-lactide) nanofiber membranes with different structures for the in-situ treatment of OLK using electrospinning technology. The results showed that the nanofiber membranes with a shell-core structure had the best physicochemical properties, biocompatibility, and therapeutic effect, which optimized the LMWF drug delivery and ensured the effective concentration of the drug at the target point, thus achieving precise treatment of local lesions in the oral cavity. This has potential application value in inhibiting the development of OLK.

Oriented cellulose hydrogel: Directed tissue regeneration for reducing corneal leukoplakia and managing fungal corneal ulcers.

Fungal corneal ulcer is one of the leading causes of corneal blindness in developing countries. Corneal scars such as leukoplakia are formed due to inflammation, oxidative stress and non-directed repair, which seriously affect the patients' subsequent visual and life quality. In this study, drawing inspiration from the oriented structure of collagen fibers within the corneal stroma, we first proposed the directional arrangement of CuTA-CMHT hydrogel system at micro and macro scales based on the 3D printing extrusion method combined with secondary patterning. It played an antifungal role and induced oriented repair in therapy of fungal corneal ulcer. The results showed that it effectively inhibited Candida albicans, Aspergillus Niger, Fusarium sapropelum, which mainly affects TNF, NF-kappa B, and HIF-1 signaling pathways, achieving effective antifungal functions. More importantly, the fibroblasts interacted with extracellular matrix (ECM) of corneal stroma through formation of focal adhesions, promoted the proliferation and directional migration of cells in vitro, induced the directional alignment of collagen fibers and corneal stromal orthogonally oriented repair in vivo. This process is mainly associated with MYLK, MYL9, and ITGA3 molecules. Furthermore, the downregulation the growth factors TGF-ß and PDGF-ß inhibits myofibroblast development and reduces scar-type ECM production, thereby reducing corneal leukoplakia. It also activates the PI3K-AKT signaling pathway, promoting corneal healing. In conclusion, the oriented CuTA-CMHT hydrogel system mimics the orthogonal arrangement of collagen fibers, inhibits inflammation, eliminates reactive oxygen species, and reduces corneal leukoplakia, which is of great significance in the treatment of fungal corneal ulcer and is expected to write a new chapter in corneal tissue engineering.

Epidemiological Trends and Clinicopathological Characteristics of Oral Leukoplakia: A Retrospective Analysis From a Single Institution in Chennai, Tamil Nadu, India.

Background India has a high prevalence of oral potentially malignant disorders and malignant transformation. Cases of oral leukoplakia are not commonly encountered, and only a small cohort of patients undergo biopsies for the same. This study aims to assess the various etiological factors causing leukoplakia, the clinical features, histopathological findings, and treatment received by the patients who were histopathologically diagnosed with oral leukoplakia. Methodology Oral leukoplakia cases were included in this study from total biopsy samples received in the oral pathology department. Details were collected from the Dental Information Archival Software of our institution. The period analyzed was from January 1, 2021, to December 31, 2023. Relevant clinical and histopathological details were retrieved and tabulated. Statistical analysis (chi-square test) was used to assess the association between the clinicopathological parameters using SPSS software version 21.0 (IBM Corp., Armonk, NY, USA) with a significance level set at a p-value <0.05. Results A total of 76 oral leukoplakia cases were retrieved from 2,600 biopsy samples. The prevalence of oral leukoplakia was 3.1% to 3.4% for the three years. Leukoplakia was commonly observed in those aged 51 to 60 years (33%). Overall, 21% of the patients with leukoplakia showed severe epithelial dysplasia, 22% showed mild epithelial dysplasia, and 39% showed moderate epithelial dysplasia. Moreover, 30% of the patients presented with leukoplakia and oral submucous fibrosis and showed varying degrees of epithelial dysplasia. Finally, 45% of the patients were managed conservatively using pharmacotherapy. Conclusions Severe epithelial dysplasia was commonly associated with oral leukoplakia. Oral submucous fibrosis was also found to be associated with leukoplakia and showed epithelial dysplasia. None of our proliferative verrucous leukoplakia cases showed any association with oral submucous fibrosis. Surgical management was the preferred treatment.

Assessing DNA methylation of ATG 5 and MAP1LC3Av1 gene in oral squamous cell carcinoma and oral leukoplakia- a cross sectional study.

Background: The progression and pathogenesis of oral cancer is greatly impacted by epigenetic modifications, such as DNA methylation. Autophagy, is an adaptive mechanism used to maintain the survival and integrity of cells. Oral squamous cell carcinoma is linked to a number of autophagy indicators, although it is yet unknown if DNA methylation of autophagy-related genes promotes the development of oral leukoplakia (OL), oral squamous cell carcinoma (OSCC). Aim: Our study was aimed to assess, compare and evaluate the DNA methylation of ATG5 and MAP1LC3Av1 genes in oral leukoplakia, oral squamous cell carcinoma. Materials and methods: This cross-sectional study was designed with sample size of 48 tissues which was clinically and histopathologically diagnosed as OL, OSCC and normal tissue. The samples were divided into three groups (Group A, Group B, and Group C; (n = 16 each). Following histopathological confirmation, the tissue was stored in the RNA reagent, then subjected to DNA extraction, methylation-sensitive polymerase chain reaction (MS-PCR). DNA methylation of the ATG5 and MAP1LC3Av1 genes were assessed. Results: Shapiro-Wilk and Kolmogorov-Smirnov tests showed that the values were normally distributed. Both the ATG5 and MAP1LC3Av1 genes were methylated in OSCC, OL tissues compared to normal tissues. A statistically significant results was seen among the three study groups. Conclusion: A significant difference was noted in the hypermethylation status of the promoter regions of the ATG5 and MAP1LC3Av1 genes. This provides some insight into their crucial role in the development of tumors. Future research with larger sample is needed to assess its potential clinical implications in oral carcinoma.

Treatment outcomes of oral leukoplakia on the irradiated or nonirradiated mucosa among survivors of head and neck cancer in the papulation where practice of betel nut chewing and cigarette smoking are widespread.

BACKGROUND: Radiotherapy (RT) has numerous effects on the oral mucosa, primarily genetic alterations and changes in the microenvironment. The characteristics of oral leukoplakia (OL) may differ between patients who have received previous head and neck cancer (HNC) treatment with radiation therapy and those who have not. Due to a lack of data on this scenario, we aimed to investigate the surgical outcomes of OL by comparing these two patient groups. METHODS: This retrospective cohort study enrolled a total of 224 OL lesions in 124 patients who underwent carbon dioxide laser (CO2 laser) surgery from July 2002 to Aug 2021. All patients had received previous treatments for HNC, with 59 patients undergoing only surgical approach, 65 patients undergoing RT, and 46 patients undergoing concurrent chemotherapy during RT. The analysis was performed on a per-lesion basis, not a per-capita basis. We investigated the associations of clinicopathological characteristics and treatment outcomes of OL lesions that developed from irradiated or nonirradiated oral mucosa. RESULTS: The median follow-up time was 5.87 years. Postoperative recurrence of OL occurred in 30 patients. Malignant transformation occurred in 17 patients with the incidence rate 4.19% annually and 13.7% cumulatively. The average time for OL transforming into squamous cell carcinoma was 3.27 ± 3.26 years (median 1.82, range 0.11 - 11.90). In univariate analysis, non-homogeneous morphology (P = 0.042), moderate to high-grade dysplasia (P = 0.041), and nonirradiated oral mucosa (P = 0.0047) were predictors for malignant transformation. However, in the Cox proportional hazard model, only nonirradiated oral mucosa remained an independent prognostic factor related to postoperative malignant transformation of OL (P = 0.031, HR 5.08, CI95 1.16 - 22.25). CONCLUSION: In the population whose OL is strongly aetiologically linked to environmental carcinogens such as betel nut and tobacco, OL lesions that develop on previously irradiated oral mucosa have a lower risk for postoperative malignant transformation compared to those that develop on nonirradiated mucosa. This finding highlights the potential impacts of radiation on OL. Further research is needed to confirm this observation and elucidate the underlying mechanism.

Investigation of the Vascular-Endothelial Pattern of Expression of DAPK-1 in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders Through Immunohistochemistry.

Introduction Potentially malignant disorders, like oral lichen planus (OLP) and oral leukoplakia (OL) of several degrees of dysplasia, manifest a significant potential of malignant transformation being a precursor of oral squamous cell carcinoma (OSCC). The role of microvascularization in carcinogenesis is critical; therefore, microvascularization constitutes a major therapeutic target. DAPK-1 constitutes a possible cancer marker, with proven implications in other human cancers, and there isn't any study on its vascular endothelial expression in the oral cavity, particularly in oral cancer and oral potentially malignant diseases. The present study aims to investigate the vascular endothelial expression of the DAPK-1 in paraffin-embedded tissue samples of oral leukoplakia, oral squamous cell carcinoma, and oral lichen planus. Materials and methods The study focuses on the immunohistochemical, vascular-endothelial, expression pattern of biomarker DAPK-1 (NBP2-38468, Novus Biologicals, Centennial, CO, US). Tissue samples were obtained from six cases of oral lichen planus (OLP) (3 of reticular and 3 of erosive form), 30 cases of oral leukoplakia (OL) (10 with no dysplasia, 10 with mild dysplasia, and 10 with moderate/severe dysplasia), 22 cases of OSCC (2 well-differentiated, 17 moderately differentiated, and 3 poorly differentiated), as well as 5 cases of normal oral epithelium. The tissue samples were retrieved from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, as well as from St Lukas Hospital of Thessaloniki, Greece, from 2004-2019. In accordance with the Research and Ethics Committee guidelines of the Aristotle University, School of Dentistry, and the Helsinki II declaration, the study was conducted. The primary inclusion criteria for the study focused on the presence of sufficient precancerous or cancerous tissue. Conversely, inadequate tissue served as the exclusion criteria. The staining was evaluated exclusively in a quantitative manner. The vascular endothelial staining was evaluated as either positive or negative. If at least one endothelial cell exhibited positive staining, the section was classified as positive. Statistical analysis was carried out using SPSS Statistics v25.0 (IBM Corp., Armonk, NY, US) utilizing Pearson's chi-square or Fisher's exact test, depending on the sample size, to compare OLP to OL, OLP to OSCC, OLP to normal, OL to OSCC, OL to normal, and OSCC to normal. The significance level was established at 0.05 (p=0.05). Results A prevalence of positive OL cases may be noticed. The comparison between OLP and OL yielded Fisher's exact test of p>0.999, OLP and OSCC p=0.389, OLP and normal oral epithelium p>0.999, OL and OSCC p=0.226, OL and normal oral epithelium p>0.999, as well as OSCC and normal oral epithelium p=0.342. Conclusions The role of DAPK in tumorigenesis is already supported by limited literature. However, its implication in the development of OSCC and oral potentially malignant disorders (OPMDs) has yet to be elucidated. Its elevated expression in OL suggests a role in affecting the microenvironment, the vessels, in particular, surrounding oral potentially malignant lesions, possibly assisting their transition into cancer. The evaluation of the vascular-endothelial immunohistochemical profile of DAPK-1 in OL, OLP, and OSCC requires further studies in more tissue samples to illustrate its possible implications.

Unraveling the Keratin Expression in Oral Leukoplakia: A Scoping Review.

Intermediate filaments are one of three polymeric structures that form the cytoskeleton of epithelial cells. In the epithelium, these filaments are made up of a variety of keratin proteins. Intermediate filaments complete a wide range of functions in keratinocytes, including maintaining cell structure, cell growth, cell proliferation, cell migration, and more. Given that these functions are intimately associated with the carcinogenic process, and that hyperkeratinization is a quintessential feature of oral leukoplakias, the utility of keratins in oral leukoplakia is yet to be fully explored. This scoping review aims to outline the current knowledge founded on original studies on human tissues regarding the expression and utility of keratins as diagnostic, prognostic, and predictive biomarkers in oral leukoplakias. After using a search strategy developed for several scientific databases, namely, PubMed, Scopus, Web of Science, and OVID, 42 papers met the inclusion and exclusion criteria. One more article was added when it was identified through manually searching the list of references. The included papers were published between 1989 and 2024. Keratins 1-20 were investigated in the 43 included studies, and their expression was assessed in oral leukoplakia and dysplasia cases. Only five studies investigated the prognostic role of keratins in relation to malignant transformation. No studies evaluated keratins as a diagnostic adjunct or predictive tool. Evidence supports the idea that dysplasia disrupts the terminal differentiation pathway of primary keratins. Gain of keratin 17 expression and loss of keratin 13 were significantly observed in differentiated epithelial dysplasia. Also, the keratin 19 extension into suprabasal cells has been associated with the evolving features of dysplasia. The loss of keratin1/keratin 10 has been significantly associated with high-grade dysplasia. The prognostic value of cytokeratins has shown conflicting results, and further studies are required to ascertain their role in predicting the malignant transformation of oral leukoplakia.

Proliferative verrucous and homogeneous Leukoplakias exhibit differential methylation patterns.

OBJECTIVE: Proliferative verrucous leukoplakia (PVL) is considered a clinically distinct entity from other oral leucoplakias (OLs) due to its clinical presentation and evolution. However, molecular differences between them remain unclear. We aimed to determine whether there are methylation differences between PVL and other forms of OLs. MATERIALS AND METHODS: Oral biopsies from 12 patients with PVL, eight patients with homogeneous leucoplakia (HL), and 10 healthy individuals were obtained for a genome-wide DNA methylation analysis via the Infinium EPIC Platform. RESULTS: A total of 1815 differentially methylated CpGs were found between PVL and HL, with a prominent state of hypermethylation in HL patients. CpGs covered 813 genes with distinct roles, including cell adhesion, extracellular matrix organization, and cell and synaptic signaling. 43% of these genes had been previously described in cancer and associated with prognosis. We developed a multinomial logistic regression model able to differentiate HL, PVL, and control samples. The model had a cross-validated estimate of 73% and included differentially methylated cancer-related genes between the pathological conditions and the healthy donors, including ADNP, BRCA2, CDK13, GNB1, NIN, NUMB, PIK3C2B, PTK2, SHISA4, THSD7B, WWP1, and ZNF292. It also included CpGs covering differentially methylated genes in HL (MEN1 and TNRC6B) and PVL (ACOXL, ADH1B, CAMTA1, CBFA2T3, CPXM2, LRFN2, SORCS2, and SPN). CONCLUSIONS: PVL and HL present differential methylation patterns that could be linked to their differential clinical behavior. Our findings show the potential of methylation markers and suggest novel diagnostic biomarkers.

Oral Squamous Cell Carcinoma of the Right Buccal Mucosa: A Case Report.

Oral squamous cell carcinoma (OSCC) is indeed one of the most common types of oral cancer, typically affecting individuals over the age of 50. It primarily originates from the squamous epithelial cells lining the oral cavity. While it is relatively rare in individuals under 40 years old, it can still occur, albeit less frequently in that age group. Risk factors for developing OSCC include tobacco use (smoking or chewing), excessive alcohol consumption, chronic irritation (such as from poorly fitting dentures), human papillomavirus (HPV), infection, and certain dietary foods. Early detection and treatment are crucial for improving outcomes and reducing the mortality associated with this type of cancer. This report describes a case of OSCC, staged T2 N0 M0, involving the right buccal mucosa of a 51-year-old male patient. The patient reported intense pain in an ulcer on the right side of his cheek. This report focuses on the etiological factors and a brief literature review of squamous cell carcinoma.

New Model and Public Online Prediction Platform for Risk Stratification of Vocal Cord Leukoplakia.

OBJECTIVE: To extract texture features from vocal cord leukoplakia (VCL) images and establish a VCL risk stratification prediction model using machine learning (ML) techniques. METHODS: A total of 462 patients with pathologically confirmed VCL were retrospectively collected and divided into low-risk and high-risk groups. We use a 5-fold cross validation method to ensure the generalization ability of the model built using the included dataset and avoid overfitting. Totally 504 texture features were extracted from each laryngoscope image. After feature selection, 10 ML classifiers were utilized to construct the model. The SHapley Additive exPlanations (SHAP) was employed for feature analysis. To evaluate the model, accuracy, sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC) were utilized. In addition, the model was transformed into an online application for public use and further tested in an independent dataset with 52 cases of VCL. RESULTS: A total of 12 features were finally selected, random forest (RF) achieved the best model performance, the mean accuracy, sensitivity, specificity, and AUC of the 5-fold cross validation were 92.2 ± 4.1%, 95.6 ± 4.0%, 85.8 ± 5.8%, and 90.7 ± 4.9%, respectively. The result is much higher than the clinicians (AUC between 63.1% and 75.2%). The SHAP algorithm ranks the importance of 12 texture features to the model. The test results of the additional independent datasets were 92.3%, 95.7%, 90.0%, and 93.3%, respectively. CONCLUSION: The proposed VCL risk stratification prediction model, which has been developed into a public online prediction platform, may be applied in practical clinical work. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Evaluation of the Role of C-reactive Protein as a Prognostic Indicator in Oral Pre-malignant and Malignant Lesions.

Biopsy is the gold standard in the diagnosis of oral pre-malignant and malignant cases. In borderline cases, false-positive or false-negative results can grossly affect treatment planning, leading to a bad prognosis. C-reactive protein (CRP) has been linked to poorer outcomes for patients with oral pre-malignant and malignant lesions. To validate the histopathological finding and ultimately direct treatment, the study aims to correlate pre-treatment levels of CRP in oral pre-malignant and malignant lesions. This will provide a biomarker to assess the prognosis in such cases. Our study investigated 53 patients, out of whom 35 were males and 18 were females. A CRP analysis was performed on each patient. The automated immunoturbidimetric method was utilized to quantify CRP levels. The CRP values of pre-malignant lesions ranged from 2.46±1.79 mg/L, while the malignant group's levels ranged from 7.90±3.18 mg/L. The findings imply that plasma CRP levels may be a potential indicator of elevated cancer risk and that pre-diagnostic CRP concentrations are linked to the later development of oral cancer.

Clinical and mycological analysis of colonization by Candida spp. in oral leukoplakia and oral lichen planus.

OBJECTIVE: This study aims to analyze the prevalence of Candida spp. colonization in oral leukoplakia and oral lichen planus lesions, verify the influence of systemic and local factors, besides identify and determine the in vitro antifungal susceptibility profile of Candida species. MATERIALS AND METHODS: Samples were collected by swabbing from oral lesions and healthy mucosa and cultured on Sabouraud Dextrose and CHROMagar® Candida plates. Species identification was confirmed with MALDI-TOF MS analysis. RESULTS: Candida spp. was found in 36.8% of cases of oral leukoplakia and 18.2% of cases of oral lichen planus. Candida albicans was the only species found in oral lichen planus lesions (n = 2, 100%) and the most prevalent in oral leukoplakia (n = 5, 76.4%). Among the non-albicans Candida species found in oral leukoplakia were C. parapsilosis (n = 2, 25.5%) and C. tropicalis (n = 1, 14.1%). Candida isolates were susceptible to all antifungals tested. CONCLUSION: C. albicans was the most commonly found species in the studied lesions. No correlation was found between systemic and local factors with positive cases of oral lichen planus. However, smoking and alcohol consumption may be associated with positive cases of oral leukoplakia, especially the non-homogeneous clinical form. In addition, there is a possible predisposition to associated Candida colonization in cases of epithelial dysplasia found in oral leukoplakia. The antifungal medications tested showed excellent efficacy against isolates.

Expression of CD44 and SALL4 in Leukoplakia and Oral Squamous Cell Carcinoma.

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.

Prx1/PHB2 axis mediates mitophagy in oral leukoplakia cellular senescence.

BACKGROUND: Oral leukoplakia (OLK) is the most common oral potentially malignant disorder (OPMD), which can be malignantly transformed into oral squamous cell carcinoma (OSCC). Peroxiredoxin1(Prx1) has been predicted to bind to Prohibitin2 (PHB2), which confers to affect OLK progression; however, the mechanism of Prx1/PHB2 mediated mitophagy involved in OLK remains unclear. METHODS: This study aimed to explore the mechanism of the Prx1/PHB2 axis on senescence in OLK through mediating mitophagy. The positive rate of Ki67 and the expression of p21, p16, PHB2, and LC3 in human normal, OLK, and OSCC tissues were detected by immunohistochemical staining. The mitophagy and mitochondrial function changes were then analyzed in Prx1 knockdown and Prx1C52S mutations in dysplastic oral keratinocyte (DOK) cells treated with H2O2. In situ Proximity Ligation Assay combined with co-immunoprecipitation was used to detect the interaction between Prx1 and PHB2. RESULTS: Clinically, the positive rate of Ki67 progressively increased from normal to OLK, OLK with dysplasia, and OSCC. Higher p21, p16, PHB2, and LC3 expression levels were observed in OLK with dysplasia than in normal and OSCC tissues. In vitro, PHB2 and LC3II expression gradually increased with the degree of DOK cell senescence. Prx1/PHB2 regulated mitophagy and affected senescence in H2O2-induced DOK cells. Furthermore, Prx1C52S mutation specifically reduced interaction between Prx1 and PHB2. Prx1Cys52 is associated with mitochondrial reactive oxygen species (ROS) accumulated and cell cycle arrest. CONCLUSION: Prx1Cys52 functions as a redox sensor that binds to PHB2 and regulates mitophagy in the senescence of OLK, suggesting its potential as a clinical target.

Prediction of the short-term efficacy and recurrence of photodynamic therapy in the treatment of oral leukoplakia based on deep learning.

BACKGROUND: The treatment of oral leukoplakia (OLK) with aminolaevulinic acid photodynamic therapy (ALA-PDT) is widespread. Nonetheless, there is variation in efficacy. Therefore, this study constructed a model for predicting the short-term efficacy and recurrence of OLK after ALA-PDT. METHODS: The short-term efficacy and recurrence of ALA-PDT were calculated by statistical analysis, and the relevant influencing factors were analyzed by Logistic regression and COX regression model. Finally, prediction models for total response (TR) rate, complete response (CR) rate and recurrence in OLK patients after ALA-PDT treatment were established. Features from pathology sections were extracted using deep learning autoencoder and combined with clinical variables to improve prediction performance of the model. RESULTS: The logistic regression analysis showed that the non-homogeneous (OR: 4.911, P: 0.023) OLK and lesions with moderate to severe epithelial dysplasia (OR: 4.288, P: 0.042) had better short-term efficacy. The area under receiver operating characteristic curve (AUC) of CR, TR and recurrence predict models after the ALA-PDT treatment of OLK patients is 0.872, 0.718, and 0.564, respectively. Feature extraction revealed an association between inflammatory cell infiltration in the lamina propria and recurrence after PDT. Combining clinical variables and deep learning improved the performance of recurrence model by more than 30 %. CONCLUSIONS: ALA-PDT has excellent short-term efficacy in the management of OLK but the recurrence rate was high. Prediction model based on clinicopathological characteristics has excellent predictive effect for short-term efficacy but limited effect for recurrence. The use of deep learning and pathology images greatly improves predictive value of the models.

Utilizing deep learning for automated detection of oral lesions: A multicenter study.

OBJECTIVES: We aim to develop a YOLOX-based convolutional neural network model for the precise detection of multiple oral lesions, including OLP, OLK, and OSCC, in patient photos. MATERIALS AND METHODS: We collected 1419 photos for model development and evaluation, conducting both a comparative analysis to gauge the model's capabilities and a multicenter evaluation to assess its diagnostic aid, where 24 participants from 14 centers across the nation were invited. We further integrated this model into a mobile application for rapid and accurate diagnostics. RESULTS: In the comparative analysis, our model overperformed the senior group (comprising three most experienced experts with more than 10 years of experience) in macro-average recall (85 % vs 77.5 %), precision (87.02 % vs 80.29 %), and specificity (95 % vs 92.5 %). In the multicenter model-assisted diagnosis evaluation, the dental, general, and community hospital groups showed significant improvement when aided by the model, reaching a level comparable to the senior group, with all macro-average metrics closely aligning or even surpassing with those of the latter (recall of 78.67 %, 74.72 %, 83.54 % vs 77.5 %, precision of 80.56 %, 76.42 %, 85.15 % vs 80.29 %, specificity of 92.89 %, 91.57 %, 94.51 % vs 92.5 %). CONCLUSION: Our model exhibited a high proficiency in detection of oral lesions, surpassing the performance of highly experienced specialists. The model can also help specialists and general dentists from dental and community hospitals in diagnosing oral lesions, reaching the level of highly experienced specialists. Moreover, our model's integration into a mobile application facilitated swift and precise diagnostic procedures.

Surgical treatment compared with "wait and see" in patients affected by oral leukoplakia to prevent oral cancer: Preliminary data from a multicenter randomized controlled trial.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.