An Atypical Presentation of Dyskeratosis Congenita in a Child With a Familial RTEL1 Mutation.

Dyskeratosis congenita (DC) is a rare inherited bone marrow disease that classically presents with the triad of oral leukoplakia, nail dystrophy, and reticular hyperpigmentation. It is most commonly caused by a defect in the DKC1 gene involved in telomere stability. Malignant progression of oral leukoplakia to squamous cell carcinoma (SCC) is rare in DC, especially in younger patients, and cutaneous SCC is only reported in 1.5% of cases of DC. Here we report a case of a 12-year-old female with a familial heterozygous RTEL1 (regulator of telomere elongation helicase 1) gene mutation associated with a severe phenotype of DC characterized by multiple cutaneous SCCs.

Applying Deep Learning with Convolutional Neural Networks to Laryngoscopic Imaging for Automated Segmentation and Classification of Vocal Cord Leukoplakia.

Objectives: Vocal cord leukoplakia is clinically described as a white plaque or patch on the vocal cords observed during macroscopic examination, which does not take into account histological features or prognosis. A clinical challenge in managing vocal cord leukoplakia is to assess the potential malignant transformation of the lesion. This study aims to investigate the potential of deep learning (DL) for the simultaneous segmentation and classification of vocal cord leukoplakia using narrow band imaging (NBI) and white light imaging (WLI). The primary objective is to assess the model's accuracy in detecting and classifying lesions, comparing its performance in WLI and NBI. Methods: We applied DL to segment and classify NBI and WLI of vocal cord leukoplakia, and used pathological diagnosis as the gold standard. Results: The DL model autonomously detected lesions with an average intersection-over-union (IoU) >70%. In classification tasks, the model differentiated between lesions in the surgical group with a sensitivity of 93% and a specificity of 94% for WLI, and a sensitivity of 99% and a specificity of 97% for NBI. In addition, the model achieved a mean average precision of 81% in WLI and 92% in NBI, with an IoU threshold >0.5. Conclusions: The model proposed by us is helpful in assisting in accurate diagnosis of vocal cord leukoplakia from NBI and WLI.

A hyaluronic acid-based dissolving microneedle patch loaded with 5-aminolevulinic acid for improved oral leukoplakia treatment.

INTRODUCTION: A local microneedle patch loaded with 5-aminolevulinic acid (ALA) was constructed to improve the efficiency of ALA photodynamic treatment of oral leukoplakia, reduce local photosensitivity reactions, and promote the healing of lesions. METHODS: The microneedle patch loaded with ALA was constructed with the hyaluronic acid (HA) solution (ALA-HAMN), and its morphology, strength, mucosal penetration, and biocompatibility were tested. RESULTS: In vivo safety and permeability tests confirmed that ALA-HAMN had good biocompatibility and could penetrate the mucosal barrier and quickly dissolve and release ALA for in situ transdermal administration. The 4-nitroquinoline oxide (NQO) rat model experiment showed that ALA-HAMN can significantly improve photodynamic therapy (PDT) efficiency and has no damage to mucosal tissue compared with the commonly used ALA cotton ball dressing. CONCLUSIONS: The ALA-loaded microneedle patch was successfully constructed for the photodynamic treatment of oral leukoplakia, and the photodynamic efficiency and comfort of oral leukoplakia were improved, which provided an effective delivery mode to improve clinical ALA-PDT treatment of oral leukoplakia (OLK).

Association between 35 blood and urine biomarkers and oral leukoplakia: a two-sample Mendelian randomization study.

Background: Several existing studies have shown a correlation between some of the blood and urine biomarkers and oral leukoplakia (OLK). However, the causality of this relationship remains uncertain. Thus, this study aimed to examine the causal association between 35 blood and urine biomarkers and OLK. Methods: Single nucleotide polymorphisms (SNPs) associated with 35 blood and urine biomarkers were selected as instrumental variables (IVs) using a two-sample Mendelian randomization(MR) study to assess the causal relationship between the biomarkers and the risk of oral leukoplakia. We used the inverse variance weighted (IVW) method as the main analysis. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability. Results: Based on the selection criteria of the Inverse Variance Weighted (IVW) method, the analysis found that 5 blood and urine biomarkers were significantly associated with the development of leukoplakia, of which the results of IVW showed that abnormalities of Apolipoprotein B (Apo B), Cholesterol, Low-density Lipoprotein (LDL), Triglycerides (TG) promoted the development of oral leukoplakia, and Non Albumin Protein (NAP) had a protective effect on the development of oral leukoplakia. We then performed a Bonferroni correction for these results, and after correction Apo B was still causally associated with the development of oral leukoplakia (IVW P<0.0007), whereas the other four biomarkers could only provide some evidence of predisposition. Conclusion: Our two-sample Mendelian randomization study supports the existence of a causal relationship between these five blood and urine biomarkers and the occurrence of oral leukoplakia, and provides evidence for a number of risk and protective factors for the development of oral leukoplakia; however, the definitive mechanisms for the occurrence and development of oral leukoplakia still remain to be elucidated, and further studies on these relevant mechanisms are still needed.

Single-cell RNA sequencing highlights the immunosuppression of IDO1+ macrophages in the malignant transformation of oral leukoplakia.

Rationale: Immunosuppressive tumor microenvironment (iTME) plays an important role in carcinogenesis, and some macrophage subsets are associated with iTME generation. However, the sub-population characterization of macrophages in oral carcinogenesis remains largely unclear. Here, we investigated the immunosuppressive status with focus on function of a macrophage subset that expressed indoleamine 2,3 dioxygenase 1 (Macro-IDO1) in oral carcinogenesis. Methods: We built a single cell transcriptome atlas from 3 patients simultaneously containing oral squamous cell carcinoma (OSCC), precancerous oral leukoplakia (preca-OLK) and paracancerous tissue (PCA). Through single-cell RNA sequencing and further validation using multicolor immunofluorescence staining and the in vitro/in vivo experiments, the immunosuppressive cell profiles were built and the role of a macrophage subset that expressed indoleamine 2,3 dioxygenase 1 (Macro-IDO1) in the malignant transformation of oral leukoplakia was evaluated. Results: The iTME formed at preca-OLK stage, as evidenced by increased exhausted T cells, Tregs and some special subsets of macrophages and fibroblasts. Macro-IDO1 was predominantly enriched in preca-OLK and OSCC, distributed near exhausted T cells and possessed tumor associated macrophage transformation potentials. Functional analysis revealed the established immunosuppressive role of Macro-IDO1 in preca-OLK and OSCC: enriching the immunosuppression related genes; having an established level of immune checkpoint score; exerting strong immunosuppressive interaction with T cells; positively correlating with the CD8-exhausted. The immunosuppression related gene expression of macrophages also increased in preca-OLK/OSCC compared to PCA. The use of the IDO1 inhibitor reduced 4NQO induced oral carcinogenesis in mice. Mechanistically, IFN-γ-JAK-STAT pathway was associated with IDO1 upregulation in OLK and OSCC. Conclusions: These results highlight that Macro-IDO1-enriched in preca-OLK possesses a strong immunosuppressive role and contributes to oral carcinogenesis, providing a potential target for preventing precancerous legions from transformation into OSCC.

Differences in the landscape of colonized microorganisms in different oral potentially malignant disorders and squamous cell carcinoma: a multi-group comparative study.

BACKGROUND: The role of microbes in diseases, especially cancer, has garnered significant attention. However, research on the oral microbiota in oral potentially malignant disorders (OPMDs) remains limited. Our study investigates microbial communities in OPMDs. MATERIALS AND METHODS: Oral biopsies from19 oral leukoplakia (OLK) patients, 19 proliferative verrucous leukoplakia (PVL) patients, 19 oral lichen planus (OLP) patients, and 19 oral lichenoid lesions (OLL) patients were obtained. 15 SCC specimens were also collected from PVL patients. Healthy individuals served as controls, and DNA was extracted from their paraffin-embedded tissues. 2bRAD-M sequencing generated taxonomic profiles. Alpha and beta diversity analyses, along with Linear Discriminant Analysis effect size analysis, were conducted. RESULTS: Our results showed the microbial richness and diversity were significantly different among groups, with PVL-SCC resembling controls, while OLK exhibited the highest richness. Each disease group displayed unique microbial compositions, with distinct dominant bacterial species. Noteworthy alterations during PVL-SCC progression included a decline in Fusobacterium periodonticum and an elevation in Prevotella oris. CONCLUSIONS: Different disease groups exhibited distinct dominant bacterial species and microbial compositions. These findings offer promise in elucidating the underlying mechanisms of this disease.

Is long-term administration of PLD-pegylated liposomal doxorubicin able to induce oral cancer?

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.

Optimal Pathological Prediction of Vocal Fold Leukoplakia Based on IPCLs and Morphology.

OBJECTIVES: To establish a combined classification based on intrapapillary capillary loops (IPCLs) and morphological characteristics to improve the accuracy of pathological prediction of vocal fold leukoplakia (VFL). MATERIAL AND METHODS: A prospective research was conducted of VFL patients diagnosed by IPCLs and morphology. The VFL cases were classified as Type I-III based on IPCLs and morphological characteristics. Type I referred to VFL with dendritic vessels but not IPCLs. Type II defined VFL without any IPCLs or vessels and classified by morphology into two subtypes as non-rough Type IIa and rough Type IIb. Type III referred to VFL with IPCLs and classified into two subtypes as Type IIIa with small IPCLs and Type IIIb with large IPCLs or vascular distortion in or around lesions. Predicting pathology accuracy was analyzed. RESULTS: 182 eligible patients were recruited. The prediction accuracy rates of VFL pathology were 81.5% according to the 2019 Ni classification. The combined classification includes 4 cases of Type I, 28 Type IIa, 35 Type IIb, 56 Type IIIa, and 59 Type IIIb VFLs. The prediction accuracy rate of combined classification ranged from 95.1% to 97.3% in three observers. The average sensitivity, specificity, positive predictive value, negative predictive value was 97.8%, 86.2%, 97.4%, 88.2%, respectively. The inter-observer agreement varied from 84.1% to 94.0%, and mean area under curve of receiver-operating curve analysis was 0.954. CONCLUSIONS AND SIGNIFICANCE: The new combined classification based on IPCLs and morphological characteristics could predict pathology of VFL accurately. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

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.

Neglected area of oral cancer: A word about the International Agency for Research on Cancer (IARC) "Handbook of Oral Cancer Prevention".

The International Agency for Research on Cancer (IARC) "Handbook of Oral Cancer Prevention", vol. 19, provides a thorough and comprehensive evidence-based evaluation of primary and secondary prevention interventions for oral cancer.

Effects of artemisinin and cisplatin on the malignant progression of oral leukoplakia. In vitro and in vivo study.

OBJECTIVES: Chemoprevention can be a treatment for potentially malignant lesions (PMLs). We aimed to evaluate whether artemisinin (ART) and cisplatin (CSP) are associated with apoptosis and immunogenic cell death (ICD) in vitro, using oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) cell lines, and whether these compounds prevent OL progression in vivo. METHODS: Normal keratinocytes (HaCat), Dysplastic oral cells (DOK), and oral squamous cell carcinoma (SCC-180) cell lines were treated with ART, CSP, and ART + CSP to analyze cytotoxicity, genotoxicity, cell migration, and increased expression of proteins related to apoptosis and ICD. Additionally, 41 mice were induced with OL using 4NQO, treated with ART and CSP, and their tongues were histologically analyzed. RESULTS: In vitro, CSP and CSP + ART showed dose-dependent cytotoxicity and reduced SCC-180 migration. No treatment was genotoxic, and none induced expression of proteins related to apoptosis and ICD; CSP considerably reduced High-mobility group box-1 (HMGB-1) protein expression in SCC-180. In vivo, there was a delay in OL progression with ART and CSP treatment; however, by the 16th week, only CSP prevented progression to OSCC. CONCLUSION: Expression of proteins related to ICD and apoptosis did not increase with treatments, and CSP was shown to reduce immunogenic pathways in SCC-180, while reducing cell migration. ART did not prevent the malignant progression of OL in vivo; CSP did despite significant adverse effects.

Surgical protocols for oral leukoplakia and precancerous lesions across three different anatomic sites.

OBJECTIVE: This systematic review and meta-analysis aimed to compare the risk of recurrence and cancer progression after surgical treatment for oral potentially malignant disorders (OPMD) and precancerous lesions in different anatomical sites. MATERIALS AND METHODS: A comprehensive search was conducted in nine databases and grey literature. We included randomized controlled trials assessing surgical treatment efficacy for OPMD and precancerous lesions of cervical, vaginal, anal, and penile sites. Excision or ablation surgical treatments were considered. RESULTS: Overall, 12 studies met the eligibility criteria for oral leukoplakia (OL), proliferative verrucous leukoplakia, cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia, and anal intraepithelial neoplasia (AIN). In qualitative analysis of surgical protocols, the lack of margin description impacts the clinical outcomes of OL and AIN, and the ablative protocols were heterogeneous in both OPMD and precancerous lesions. No significant difference in OL (risk ratio 0.82 [95% CI: 0.59-1.15]) and CIN (risk ratio 0.31 [95% CI: 0.09-1.09]) for recurrence was observed when cold-knife was compared with ablative protocols. OL exhibited higher recurrence and cancer progression rates compared to CIN and AIN. CONCLUSION: There is no difference in recurrence risk post-surgical treatment for OL and CIN. Surgical protocols for oral leukoplakia and CIN/AIN lack standardized approaches.

Potential of Photodynamic Therapy as a Minimally Invasive Treatment for Oral Verrucous Carcinoma.

Oral verrucous carcinoma (OVC) and proliferative verrucous leukoplakia (PVL) share similar histological characteristics and may have a common origin. When they appear simultaneously, the risk of malignant transformation in PVL increases. In elderly patients with both conditions, a safe, effective, simple, and minimally invasive treatment is preferable. Photodynamic therapy (PDT), a non-invasive treatment, utilizes specific wavelengths of light to activate photosensitizers, generating reactive oxygen species that selectively target malignant tissues with cytotoxic effects. This case report describes an elderly patient with coexisting extensive leukoplakia, PVL, and OVC, who achieved complete remission with no recurrence at 10 months following PDT. The treatment resulted in a satisfactory clinical outcome, preserving both the appearance and function of the oral cavity.

Prevalence and Malignant Transformation Rate of Oral Erythroplakia Worldwide - A Systematic Review.

Background: To determine the characteristics of oral erythroplakia (OE) on a global scale, it is important to analyse and evaluate findings from various studies conducted across multiple geographical locations. Objectives: This review was conducted to determine the prevalence and malignant transformation rate (MTR) of OE. Data Sources: A systematic search was performed to identify studies reporting the prevalence and MTR of OE across various databases - PubMed, Web of Science, Google Scholar, Elsevier and ScienceDirect without any restriction for the time of publication. Study Eligibility Criteria: This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines, and the protocol was registered in the PROSPERO database (ID: CD42023395215). Results: The prevalence rate of OE reported across the studies ranged from 0.04% to 1.14% with a mean of 0.25 + 0.002%. The MTRs reported across the studies included ranged from 2.6% to 65% with a mean of 30 ± 0.2%. Limitations and Conclusions: Based on the findings from the present review, it can be concluded that while the range of MTRs of OE varies widely across different geographical locations, the average rate can be considered 30%. The review also identified a need for conducting more studies on the prevalence rates as well as longitudinal studies assessing the MTR across different regions.

NBI Classification Optimization With Morphological Characteristics in Vocal Fold Leukoplakia.

Objectives: To investigate the pathological contribution of vocal fold leukoplakia (VFL) of type II in narrow-band imaging (NBI) classification and morphological characteristics to improve pathological prediction. Material and Methods: The 59 VFL patients with type II in 2019 Ni classification in NBI were included. The pathological reports were collected and divided following 2005 WHO Blue Book. Low-risk VFL contained non-, mild, moderate dysplasia, high-risk VFL included severe dysplasia. The morphological classification and laryngoscopic scoring system were employed to evaluate leukoplakia for pathological prediction. Results: The pathologies contained 1 case of leukoplakia with non-dysplasia, 12 of mild dysplasia, 15 of moderate dysplasia, 8 of severe dysplasia, and 23 of carcinoma. The 30 smooth VFL contained 1 non-dysplasia, 12 mild dysplasia, 14 moderate dysplasia, 2 severe dysplasia, and 1 carcinoma. The 29 rough cases included 1 moderate dysplasia, 6 severe dysplasia, and 22 carcinomas. Laryngoscopic scoring system revealed irregular texture, large size, and thick lesion as factors in relationship with high-risk leukoplakia in univariate (P = .002, <.001, <.001) and multivariate (P = .025, .002, .016) analysis, irregular texture was the most accurate predictor of high-risk VFL pathology. Conclusions and Significance: The pathologies of VFL with type II in NBI classification were hard to be predicted. Morphological irregular/rough texture contributed to predict high-risk pathology in leukoplakia.

Comparative study of conventional exfoliative cytology and centrifuged liquid-based cytology in oral leukoplakia and oral squamous cell carcinoma patients.

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.

Estimation of depression, anxiety and serum cortisol in patients with oral lichen planus, leukoplakia and oral submucous fibrosis.

Stress and anxiety may be found in patients with oral submucous fibrosis (OSMF), oral leukoplakia (OL) and oral lichen planus (OLP). Cortisol, sometimes referred to as the "stress hormone," has been employed as a stress predictor. Therefore, it is of interest to estimate the levels of depression, anxiety and serum cortisol and establish correlation between them in patients with OL. OLP and OSMF. There were 240 patients, aged 20 years to 45 years, who were divided into four categories (OL, OSMF, OLP and control) of 60 patients apiece. In the supervision of a psychiatrist, the Hamilton Depression Rating Scale (HAM D) and Hamilton Anxiety Rating Scale (HAM (A) questionnaires were filled out. Five millilitres of venous blood were extracted using standard aseptic technique, and all of the samples were examined for serum cortisol level. Anxiety and depression was found in subjects of OL, OSMF and OLP at advanced stages. It was inferred that serum cortisol level was statistically correlated with depression and anxiety in patients with OL, OSMF and OLP.

Serum iron, zinc and copper among Indian patients with leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma.

The serum levels of iron, zinc and copper in patients with leukoplakia, oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC) and compare them with normal subjects is of interest to dentists. The effort was to determine a parameter that will aid the initial diagnosis, a more efficient therapy plan, and ultimately a better prognosis. Participants in the study comprised 40 healthy normal volunteers, 60 patients diagnosed with leukoplakia, 60 patients diagnosed with OSCC, and 60 patients diagnosed with OSMF. After fasting for the whole night, blood samples were taken from each participant. There was analysis by inductively coupled plasma-optical emission spectrometry (ICP-OES) for the determination of trace elements; iron, copper, and zinc. The serum levels of iron and zinc in normal subjects was greater as compared to patients with leukoplakia, OSMF and OSCC. There was increase in serum copper levels in patients with oral leukoplakia, OSMF and OSCC as compared with normal subjects.

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.

Quantitative Assessment of Receptors of Advanced Glycation End Products Expression in Tissue Samples from Patients with oral Submucous Fibrosis, Leukoplakia, and Oral Squamous Cell Carcinoma.

Background and Aim: Oxidative stress markers have been firmly established as elevated in oral squamous cell carcinomas (OSCCs). These markers play a crucial role in the pathogenic mechanism underlying the accumulation of advanced glycation end products (AGEs) and their respective receptors. The primary objective of this study is to discern and compare the levels of receptors of AGEs (RAGEs) within tissue samples from patients diagnosed with oral submucous fibrosis (OSMF) at varying stages, oral leukoplakia at various stages, and OSCC. Materials and Methods: A cross-sectional investigation was conducted, enrolling a total of 49 patients, distributed across three distinct groups. Tissue samples were meticulously collected from the aforementioned patient groups. Subsequently, these samples underwent a process of homogenization and centrifugation. The supernatant obtained was subjected to enzyme-linked immunosorbent assay analysis to precisely determine the concentration of RAGE. Results: The concentration of RAGEs was found to be significantly higher at various stages of OSMF when compared to the reference group of OSCC (P < 0.05). This difference was statistically significant, indicating a substantial association. In contrast, the levels of RAGE in patients with hyperkeratosis accompanied by epithelial dysplasia at various stages were observed to be lower than those in the OSCC group, with the difference in concentration being statistically insignificant (P > 0.05). Conclusion: This comprehensive study has provided compelling evidence demonstrating the heightened levels of RAGE in OSMF when compared to OSCC. These findings collectively suggest the potential utility of anti-RAGE interventions as a promising avenue for novel therapeutic strategies in potentially malignant disorders such as OSMF.