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Oral squamous cell carcinoma (OSCC) is a malignancy associated with high morbidity and mortality, yet treatment options are limited. In addition to genetic alterations, aberrant gene expression contributes to the pathology of malignant diseases. In the present study, we identified 629 genes consistently dysregulated between OSCC and normal oral mucosa across nine public gene expression datasets. Among them, mitosis‐related genes were significantly enriched, including spindle and kinetochore‐associated complex subunit 1 (SKA1), whose roles in OSCC had been studied only to a very limited extent. We show that SKA1 promoted proliferation and colony formation in 2D and 3D, shortened the duration of metaphase, and increased the migration of OSCC cell lines. In addition, high SKA1 expression enhanced radioresistance, a previously unknown effect of this gene, which was accompanied by a reduction of radiation‐induced senescence. SKA1 was also upregulated in a subset of advanced oral premalignancies and promoted tumor‐relevant properties in a corresponding cell line. Gene expression patterns evoked by SKA1 overexpression confirmed that this gene is able to advance properties required for both early and advanced stages of tumorigenesis. In summary, our data show that SKA1 contributes to malignant progression in OSCC and may be a useful marker of radioresistance in this disease. [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]

Statement of the Problem: Squamous cell carcinomas (SCCs) and premalignant disorders such as leukoplakia are common oral cavity lesions. Although these lesions are epithelial in nature, they are also associated with juxta-epithelial chronic inflammation. Mast cells play a significant role in inflammation initiation and propagation. Purpose: Previous studies have yielded conflicting results in this field. Therefore, this research aimed to assess the number of mast cells in oral SCC and dysplastic leukoplakia and explore their possible role in these lesions. Materials and Method: In this retrospective cross-sectional study, sixty-three archival cases, including 22 OSCCs, 28 dysplastic leukoplakias as epithelial dysplasia (ED), and 13 normal oral mucosal tissues, were examined for mast cells, using toluidine blue staining. Hotspot areas were identified at 10× magnification and mast cells were counted in 5 fields at 40× magnification. The average cell numbers were calculated, and the severity of inflammation was scored. Statistical analysis was performed using SPSS statistical software 20, including One-way ANOVA, Two-way ANOVA, paired-t test, and independent t-test. p Value < 0.05 was considered significant. Results: Among the 51 pathologic lesions, 54.9% were males and 45.1% were females, with a mean age of 56.34±15.35 years. The most common locations were the tongue and buccal mucosa. The mast cell count was significantly lower in SCC compared to ED (p= 0.009). There was no correlation between mast cell count and inflammation score (p= 0.345). Conclusion: In this study, the mast cell count was higher in ED compared to OSCC, suggesting an increase in these cells during the pre-malignant stages. However, the number of mast cells decreased after connective tissue invasion and microenvironmental changes occurred. [ABSTRACT FROM AUTHOR]

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]

To explore diagnostic and prognostic biomarkers in the progression of oral squamous cell carcinoma (OSCC) and to reveal their regulatory mechanisms in key pathways. A RayBiotech protein chip was used to screen differentially expressed serum proteins in OSCC, oral leukoplakia (OLK), and healthy participants. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to determine the pathways enriched by characteristic differential proteins. Immunohistochemical analysis and western blotting were used to verify the expression of characteristic differential proteins and key regulatory factors in human tissues and in a nude mouse model. Fibroblast growth factor 6 (FGF6) was identified as a key differential protein and was weakly expressed in OSCC tissues. The mitogen-activated protein kinases (MAPK) and PI3K-AKT pathways were identified as key signaling pathways. The results showed that pERK, Cyclin D1, pAKT, and BCL2 were highly expressed in OSCC, Caspase9 was lowly expressed in OSCC. With an increase in FGF6 expression in nude mice, the expression of FGFR4, pERK, Cyclin D1, pAKT, BCL2, GPX4, and ACSL4 increased, and the expression of Caspase9 decreased. FGF6 may change the expression of apoptosis-related proteins and proliferation factors by binding to FGFR4 in the PI3K-AKT/MAPK pathway and may inhibit the ferroptosis of OSCC, thereby possibly participating in the process of inhibiting OSCC. [ABSTRACT FROM AUTHOR]

Proliferative verrucous leukoplakia (PVL) is a rare, but relentless, form of leukoplakia, with a high recurrence rate and a tendency to become malignant, either as an oral squamous cell carcinoma (OSCC) or verrucous carcinoma (VC). Its aetiology is mainly unknown, and there is uncertainty around its management owing to its resistance to most treatments with a high rate of recurrence. CPD/Clinical Relevance: Understanding PVL is key to making prompt diagnosis and referral for improved outcome of treatment due to its high malignancy transformation rate. [ABSTRACT FROM AUTHOR]

Oral leukoplakia (OLK) is the most representative oral potentially malignant disorder, with a high risk of malignant transformation and unclear mechanisms of occurrence. Recently, photodynamic therapy (PDT) has exhibited great potential in the treatment of OLK. However, the efficacy of PDT is difficult to predict and varies from person to person. Ferroptosis-related pathways are upregulated in many cancers, and ferroptosis induction is considered to be a potential synergistic strategy for various antitumor therapies, but its role in OLK treatment remains unclear. This study aimed to determine whether ferroptosis induction can enhance the efficacy of PDT in OLK treatment. Our study revealed that solute carrier family 7 member 11 (SLC7A11), a component of a crucial amino acid transporter and a key negative regulator of ferroptosis, was found to be highly expressed in OLK patients with no response to PDT. 5-Aminolevulinic acid (ALA)-PDT is known to cause apoptosis and necrosis, but ferroptosis also occurred under ALA-PDT in OLK cells in our study. Using erastin to induce ferroptosis enhanced the efficacy of ALA-PDT on OLK cells by disrupting the antioxidant system and further elevating intracellular reactive oxygen species levels, leading to increased apoptosis. Furthermore, this combined modality also enhanced the efficacy of ALA-PDT on 4-nitroquinoline-1-oxide (4NQO)–induced OLK lesions in mice. In summary, ferroptosis induction may serve as a potential strategy to enhance the efficacy of ALA-PDT for OLK treatment. [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]

ABSTRACT Objective Materials and Methods Results Conclusion Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder. Forms that affect only one tissue are poorly studied, especially the exclusively gingival PVL (gPVL), which may have a more increased malignant transformation potential. The aim of the present study was to characterise the gPVL and its risk of malignant transformation to better raise awareness of this specific disorder.The systematic review was performed on PubMed, Scopus, Web of Science and Google Scholar. Only articles reporting primary studies, case reports and case series were included. The meta‐analysis was performed for the cancer prevalence, proportion of smokers, age and sex ratio, recurrences of gPVL and mortality.A total of 1298 studies were assessed for eligibility by reading titles and abstracts. Fourteen original articles were included with a total of 58 patients. The malignant transformation rate of gPVL was 47.75%. The mortality was 5.84%. The mean follow‐up duration before malignant transformation was 3 years.gPVL seems to have a faster malignant transformation rate than the other forms of PVL. Finding anatomo‐pathological or genetic markers could be a line of research to predict gPVL malignant transformation and improve its diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Oral leukoplakia (OL) is the most common potentially malignant disease of the oral cavity. In recent years, studies have identified a correlation between the gut microbiota (GM) and oral cancer, in addition, inflammation-related proteins have been reported to play an important role in the development of OL. However, the causal relationship between gut microbiota and OL, as well as whether cytokines play a mediating role, remain unclear. Methods: In this Mendelian randomization (MR) study, the genome-wide association studies (GWAS) (n=18340) of the MiBioGen consortium microbiome was used as exposure data. Genetic variation data related to OL were extracted from the Finngen R9 project (513 cases of OL and 411668 controls). The 91 inflammation-related proteins obtained in the literature serve as potential mediators. Two-sample Mendelian randomization analysis was applied to infer causality using Inverse Variance Weighted (IVW), MR Egger, weighted media, simple mode and weighted mode method. Subsequently, sensitivity analysis was conducted to ensure the robustness of the MR results. In addition, we conducted reverse MR analysis to alleviate reverse causality. Finally, we used mediation analysis to determine the pathway mediated by inflammation-related proteins from the gut microbiota to OL. Results: The five bacterial taxa in the gut microbiota indicate a potential causal relationship with the development of OL. Notably, family Clostridiaceae1 was negatively correlated with the risk of OL development, while genus Dorea, genus Ruminococcus1, genus Senegalimasilia and genus Veillonella were positively associated with the risk of OL development. In addition, this study identified a potential causal relationship between interleukin-10 receptor subunit alpha (IL-10RA), interleukin-18 receptor 1(IL18-R1) and the occurrence of OL. In addition, intermediary analysis indicates that IL18-R1 mediated the pathway between the gut microbiota genus Senegalimasilia and OL. Conclusions: In summary, our research emphasize the complex relationship between gut microbiota, inflammation-related proteins and OL. The identified associations and mediating effects provide new insights into potential therapeutic approaches for targeting the gut microbiota in the management of OL, and contribute to its prevention, diagnosis and treatment. [ABSTRACT FROM AUTHOR]

The article presents interim trial results comparing the effectiveness of diode laser (DL) and traditional scalpel (TS) in treating oral leukoplakia (OL) concerning recurrence and malignant transformation (MT). Topics discussed include the surgical techniques employed, the rates of recurrence and malignancy observed in each treatment group, and the statistical analysis conducted to evaluate the outcomes of the two methods.

Background: Oral Potentially Malignant Disorders (OPMDs) can lead to Oral Squamous Cell Carcinoma (OSCC). The sixth most common cancer in the world is OSCC. This study aimed to describe the demographical and clinical characteristics of OPMD patients and their risk factors registered at the Oral Medicine Department of Shahid Beheshti Dental School in 2019-2021. Methods: The observational-analytical study was conducted using the dental records of 96 consecutive patients using a web-based registration software (OPMDs registry). Information including demographics and clinical features, the type of OPMD, and risk factors were extracted. Data were analyzed using the Chi-square test, T-test, and Fisher’s exact test with SPSS version 21. Results: In this study, 96 patients (average age: 52.41±14.87) including 52 women and 44 men, participated. The most common OPMDs comprised 69 Oral Lichen Planus (OLP) and 15 leukoplakia. The most common location of lesions was the buccal mucosa (74%) with erosions and plaques being the most common morphology types. Most patients with leukoplakia were male, however, majority of the patients with OLP were female (p=0.001). In patients with leukoplakia, 66.5% were smokers; hence, a significant relationship between smoking and OPMD was observed (p=0.001). Patients with OLP commonly presented with burning symptoms, while patients with leukoplakia were mostly asymptomatic (p=0.004). Conclusion: A significant relationship was observed between gender, clinical symptoms, location of lesions, morphology, and type of OPMDs. Most patients with OPMDs were women with OLP in their buccal mucosa, suffering from burning sensation. [ABSTRACT FROM AUTHOR]

The management of oral leukoplakia (OL) is challenging because of a high risk for recurrence and malignant transformation (MT), and recurrent OL is associated with a higher risk of MT than nonrecurrent OL. The present meta-analysis aimed to examine the association between OL recurrence and surgical techniques used for their management as well as their clinicopathological factors. Electronic searches were conducted in EMBASE, PubMed, Scopus, and Web of Science to retrieve studies reporting OL recurrence after surgery. The pooled proportion of OL recurrence after surgical excision was estimated. Subgroup analyses were conducted based on the surgical technique, data type, grades of epithelial dysplasia, anatomical subsites, clinical type and size of the lesion, surgical margin, and risk habits. Meta-regression analyses were conducted to identify the association between age, sex, and follow-up duration and OL recurrence. The risk of MT based on the recurrence status was also estimated. A network meta-analysis was performed to determine the surgical modality associated with the least OL recurrence. Eighty studies with a total of 7,614 samples and various surgical modalities (laser-based techniques, conventional scalpel surgery, cryosurgery, and photodynamic therapy) were included in the meta-analysis. A pooled proportion of recurrence of 22% was observed. Laser-based surgeries resulted in fewer OL recurrences than other surgical modalities, and the combination of laser excision and vaporization was identified to be the best treatment approach. OL in the retromolar area and multiple sites, nonhomogeneous OL, advanced age, female sex, inadequate surgical margin, retrospective data, and betel quid chewing habit were significantly associated with higher OL recurrence. Recurrent OL showed a 7.39 times higher risk of MT than nonrecurrent OL. These results suggest that the combination of laser excision and vaporization might reduce OL recurrence. Furthermore, OL in older patients, females, and nonhomogeneous OL need close monitoring after any surgical therapy. [ABSTRACT FROM AUTHOR]

Background: Both smoked and smokeless tobaccos play crucial roles in forming potentially malignant oral disorders. Studies are scant in India, particularly among vulnerable tribal populations. Odisha, with the highest number of tribes in India, stands at the top in smokeless tobacco use among major states. The present study explores tobacco use status among Indian tribes by evaluating the OPMD risks.. Methods: A cross-sectional study was carried out among the tribal populations in Odisha. Data was collected pertaining to sociodemographic profile, tobacco use and prevalence of oral potentially malignant disorders (OPMD). The Fagerstrom Test for Nicotine Dependence (FTND) scale was used to evaluate tobacco dependency.. Results: The findings revealed that 75.2% of people are tobacco consumers. Half of the studied population consumes Dukuta and Khaini. Maximum people, including 54.2% of youth, fall in the high nicotine dependence category. Additionally, 45.2% of the participants reported mouth lesions, and 27.1% with potentially malignant disorders (PMD). The incidence of tobacco pouches in the studied population is 22.9%, followed by 12.4% leukoplakia lesions. Conclusion: A health policy for community-level intervention toward tobacco cessation and early diagnosis of previously undiagnosed OML (oral malignant lesion) and OPMD would be a positive strategy. [ABSTRACT FROM AUTHOR]

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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.

Objective·To explore the correlation between the quantitative results of autofluorescence imaging under computer assistance and the grade of epithelial dysplasia in oral leukoplakia.Methods·From April 2016 to January 2024, 357 patients with oral leukoplakia who visited the Department of Oral Mucosal Diseases at Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, were included. Autofluorescence images of the lesions were obtained using a handheld autofluorescence device. These images were converted to grayscale images to obtain quantitative metrics. An ordered multinomial Logistic regression model was fitted in Python, and cumulative probability plots were generated. The dataset was divided into training and testing sets, and a decision tree was generated. Different hyperparameters were adjusted to achieve optimal model performance. Accuracy, precision, and F1 scores were calculated. The model performance was visualized using a confusion matrix.Results·As the degree of epithelial dysplasia increased, the relative mean color level showed a declining trend. In the binary classification of epithelial dysplasia, there was no overlap between the cumulative probability curves of different categories. In the four-category classification, only severe epithelial dysplasia overlapped with other category curves, indicating good discriminative ability of the model. In binary pathological grading, when the training and testing set ratio was 4∶1 and the maximum depth was 2, the accuracy, precision, and F1 scores were 0.792, 0.801, and 0.795, respectively. In the four-category pathological grading, when the training and testing set ratio was 9∶1 and the maximum depth was 4, the accuracy, precision, and F1 scores were 0.611, 0.537, and 0.569, respectively.Conclusion·Computer-assisted quantitative analysis of autofluorescence images can be used by oral mucosal specialists as a reference to predict the degree of epithelial dysplasia in patients with oral leukoplakia and to monitor their risk of cancer.

Abstract 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.

Abstract 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.

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]

ABSTRACT 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. [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]

Telomere biology disorders (TBD) are a complex set of inherited illnesses characterized by short telomeres. Dyskeratosis congenita (DC), which is now considered a severe TBD phenotype, is characterized by reticulated pigmentary changes, nail dystrophy, premalignant oral leukoplakia, and systemic involvement. This case describes a 2‐year‐old female with reticulated pigmentary changes and Terry's nails who was found to have a TERT variant and short telomeres; she lacked other mucocutaneous and systemic features of TBD. This report describes a unique clinical presentation of TBD and highlights the importance of upholding suspicion for TBD in individuals with limited or subtle features of classic DC. [ABSTRACT FROM AUTHOR]

Objective·To explore the correlation between the quantitative results of autofluorescence imaging under computer assistance and the grade of epithelial dysplasia in oral leukoplakia. Methods·From April 2016 to January 2024, 357 patients with oral leukoplakia who visited the Department of Oral Mucosal Diseases at Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, were included. Autofluorescence images of the lesions were obtained using a handheld autofluorescence device. These images were converted to grayscale images to obtain quantitative metrics. An ordered multinomial Logistic regression model was fitted in Python, and cumulative probability plots were generated. The dataset was divided into training and testing sets, and a decision tree was generated. Different hyperparameters were adjusted to achieve optimal model performance. Accuracy, precision, and F1 scores were calculated. The model performance was visualized using a confusion matrix. Results·As the degree of epithelial dysplasia increased, the relative mean color level showed a declining trend. In the binary classification of epithelial dysplasia, there was no overlap between the cumulative probability curves of different categories. In the four-category classification, only severe epithelial dysplasia overlapped with other category curves, indicating good discriminative ability of the model. In binary pathological grading, when the training and testing set ratio was 4∶1 and the maximum depth was 2, the accuracy, precision, and F1 scores were 0.792, 0.801, and 0.795, respectively. In the four-category pathological grading, when the training and testing set ratio was 9∶1 and the maximum depth was 4, the accuracy, precision, and F1 scores were 0.611, 0.537, and 0.569, respectively. Conclusion·Computer-assisted quantitative analysis of autofluorescence images can be used by oral mucosal specialists as a reference to predict the degree of epithelial dysplasia in patients with oral leukoplakia and to monitor their risk of cancer. [ABSTRACT FROM AUTHOR]

Oral lichen planus is a frequent, chronic autoimmune disease that affects the oral mucosa and is characterized as an oral potentially malignant disorder. The aim of our study is to examine the presence of CSCs bearing CD147 (a marker related to local inflammation and associated with various cancers) through immunohistochemistry in oral lichen planus (OLP) compared to oral leukoplakia (OL) and healthy tissues. These findings could contribute to clinical practice by providing a marker for the prognostic assessment of OLP lesions with regards to their potentially malignant nature. The study sample consisted of paraffin-embedded oral mucosa specimens from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece during the period 2009–2019. The study sample contained 24 cases of OLP (14 erosive and 10 reticular) and 30 cases of oral leukoplakia, which were compared to 5 normal oral epithelium samples derived from healthy epithelium adjacent to fibromas from other cases. Cell membrane staining of CD147 was observed mostly in the basal and parabasal cell layer. The statistically significantly higher expression of CD147 in the erosive lichen planus subgroup than in the moderately and severely dysplastic leukoplakia subgroup (p = 0.01) constituted the most important finding of this study. The characteristic expression of CD147 in erosive OLP suggests the presence of epithelial cells with CSC characteristics, but its lower expression in oral leukoplakias suggests a more intense relation of the CD147 marker with inflammation rather than with oral dysplastic progression. [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]

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. [ABSTRACT FROM AUTHOR]

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 twosample 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. [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]

Objective Materials and Methods Results Conclusion 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.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.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.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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Oral leukoplakia (OLK) is themost 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. [ABSTRACT FROM AUTHOR]

Proliferative verrucous leukoplakia (PVL) is a non-homogenous type of oral leukoplakia, characterized by multifocal white plaques, propensity to recur after treatment, with strong tendency towards malignant transformation. Interestingly, some studies show that, at initial stages, PVL may resemble oral lichen planus (OLP), potentially leading to misdiagnosis. A 52-year-old woman, with a previous OLP diagnosis, was referred to our service for implant installation and follow-up of OLP lesions. After clinicopathological re-evaluation, a diagnosis of PVL (early stage) was made, and a maxillary full-arch implant-supported prosthesis supported by implants was installed. After 6 years of follow-up, the patient developed squamous cell carcinoma around the implants. The current case emphasizes that PVL patients with oral lesions suggesting peri-implantitis or peri-implant mucositis deserve a more meticulous investigation. [ABSTRACT FROM AUTHOR]

Hypoxia is a key trigger in the transformation of oral leukoplakia into oral cancer. However, it is still too early to determine the role of hypoxia in the development of oral leukoplakia. Prx1, an antioxidant protein, upregulated by hypoxia, regulates cellular autophagy in leukoplakia. This study aimed to understand the mechanisms by which hypoxia induces Prx1 expression during autophagy in oral leukoplakia. We used an experimental model of tongue epithelial hyperplasia induced by 4-nitroquinoline-1-oxide (4NQO) and dysplastic oral keratinocytes. Prx1 knockdown DOK cells, Leuk-1 cells and control cells were harvested, and cell proliferation was assayed using the Cell Counting Kit-8. Several hypoxia and autophagy-related proteins were examined using quantitative real-time polymerase chain reaction, immunohistochemistry, immunofluorescence, and western blotting in cells and mouse tongue tissues. In addition, the ultrastructure of the cells was observed by transmission electron microscopy. Hypoxia induces cell proliferation, autophagic vesicles and the expression of Prx1, BNIP3, LC3II/I and Beclin-1 in DOK and Leuk-1 cells. However, these effects were all attenuated by Prx1 knockdown. Histologically, 4NQO induced epithelial hyperplasia in the tongue mucosa. The expression of proliferation marker PCNA, autophagy-related proteins LC3B and Beclin-1, as well as HIF-1α/BNIP3 was significantly lower in the tongue tissues of Prx1flox/flox:Cre+ mice compared with Prx1flox/flox mice. In Prx1flox/flox:Cre+ mice, an increased expression of HIF-1α/BNIP3, LC3B and Beclin-1 was detected in epithelial hyperplasia tongue tissues compared to normal tissues. The current study suggests that Prx1 may promotes cell proliferation and autophagy in oral leukoplakia cells via the HIF-1α/BNIP3 pathway. [ABSTRACT FROM AUTHOR]

Introduction: Dyskeratosis congenita is a rare genetic disorder characterized by abnormalities of the skin, nails, and oral mucosa. Retinal involvement in this condition is uncommon. Here, we present a case of a young male patient diagnosed with presumptive cytomegalovirus retinitis, ultimately found to be concomitant with dyskeratosis congenita. Case Presentation: A non-HIV-infected young male with recurrent infections, including aspergillus pneumonia and pneumocystis pneumonia, presented with presumptive cytomegalovirus retinitis in both eyes. Systemic manifestations included cutaneous hyperpigmentation, nail dystrophy, and oral mucosal leukoplakia. Genetic testing revealed a mutation in the DKC1 gene. The final diagnosis was dyskeratosis congenita complicated by presumptive cytomegalovirus retinitis. Conclusion: Cytomegalovirus retinitis can serve as an ocular complication of dyskeratosis congenita. When a patient presents with cytomegalovirus retinitis, a comprehensive systematic examination should be conducted as it indicates severe immunodeficiency. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion We aimed to assess the effectiveness of the use of topical imiquimod for the management of oral leukoplakia (OL).This was a retrospective study. Medical chart reviews were conducted to identify patients with biopsy‐proven OL treated with topical 5% imiquimod. Data included OL characteristics, histopathological diagnosis, treatment outcome, and adverse events (AEs). Treatment response was assessed by measuring the percentage reduction in the size of OL lesions.33 patients (51.5% females; median age: 65 years) with 38 lesions were included. OLs were either localized (23.7%) or multifocal lesions (76.3%), with the majority on the gingiva (86.8%). Pretreatment histopathological diagnoses were dysplasia in 84.2% and nonreactive hyperkeratosis in 15.8%. Most regimens consisted of 60‐minute applications, 5‐days‐a‐week, for 6 weeks. At the end of treatment, 81.6% of 38 lesions showed a reduction in size with 68.4% exhibiting ≥50% reduction in size, and 42.1% exhibiting complete resolution. Application site reactions were the most common with pain/soreness/sensitivity occurring in 86.8%. Fatigue was the most frequently reported systemic AE (28.9%).Two‐thirds of OL lesions had ≥50% reduction in size. Most AEs were temporary and resolved upon treatment discontinuation. Prospective studies are needed to further assess Imiquimod's effectiveness in OL management. [ABSTRACT FROM AUTHOR]

Introduction: Oral Leukoplakia (ol) is a Potentially Malignant Oral Disorder (pmod) that can transform into Oral Squamous Cell Carcinoma (oscc). Defined as "a white plaque of questionable risk," ol necessitates the exclusion of other known diseases or disorders that do not carry an increased cancer risk. Case Presentation: A 65-year-old female, i'tidal hussein mohammed, presented to the diagnostic clinic at cairo university in 2017, seeking denture fabrication after being edentulous for five years. An intraoral examination revealed a non-symptomatic white lesion on the left lower ridge, raising suspicion for leukoplakia. Conclusion: Regular dental check-ups and thorough examinations are crucial, particularly in asymptomatic edentulous patients. Early diagnosis, monitoring, and patient education on routine dental visits can significantly mitigate the risk of malignant transformation in potentially malignant lesions. [ABSTRACT FROM AUTHOR]

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: This study explored associations between histological features of dysplasia and malignant transformation, as well as genomic copy number alterations. Materials and Methods: Overall, 201 samples were collected from patients of oral leukoplakia. The associations of dysplastic features with malignant transformation and copy number alterations were investigated by Cox proportional hazards regression analysis and the Mann–Whitney U‐test. Results: Eight individual histological features, such as irregular epithelial stratification (p = 0.001), mitoses high in epithelium (p = 0.033), extension of changes along minor gland ducts (p < 0.001), etc., were associated with greater risk of malignant transformation. A model including histological features and age showed good performance for predicting malignant transformation (area under receiver operating characteristic curve: 0.806). Irregular epithelial stratification (p = 0.007), abnormal nuclear shape (p = 0.005), abnormal cell size (p = 0.004), etc. were associated with greater genomic instability. Conclusions: A Cox proportional hazards model using eight histological features and patient age reliably predicted the malignant potential of oral epithelial dysplasia. Identification of these histological features closely related to malignant transformation may aid the management of oral potentially malignant disorders and early detection of oral squamous cell carcinoma. [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]

Objectives: The objective of this retrospective study was to evaluate clinicopathologic profile and collagen type I expression in oral leukoplakia and oral squamous cell carcinoma to elucidate stromal alterations in malignant transformation. Material and Methods: The sample consisted of 40 cases, of which 20 oral leukoplakia (OL) were classified according to World Health Organization and binary systems for grading oral epithelial dysplasia (OED) as well as 20 oral squamous cell carcinoma (OSCC), moderately or poorly differentiated. Type I collagen was analysed by immunohistochemistry, Fisher's exact test and chi-square test evaluated the clinical data. One-way ANOVA and Tukey's test were applied to analyse type I collagen expression between groups. Associations between data were analysed by two-way ANOVA with Sidak's multiple comparison test. Results: Men were most affected with OSCC (90%) and 60% of OL were in women (P = 0.0022). Type I collagen expression was higher in mild (P = 0.04) and moderate (P = 0.03) OED than moderately differentiated OSCC. Severe OED had a lower expression when compared with moderate OED (P = 0.01) and well differentiated OSCC (P = 0.02). The binary system showed that low-risk had more collagen expression than high-risk (P = 0.03) and severe OED (P = 0.03). Conclusions: The binary system allows more effective correlations to be established between stromal changes and oral epithelial dysplasia. The higher expression of collagen in the benign lesions may represent changes in the microenvironment that will favour the process of epithelial transformation and the establishment of a more aggressive disease. [ABSTRACT FROM AUTHOR]

Introduction and aim. Oral squamous cell carcinoma (OSCC) and premalignant disorders (PMDs) are becoming common in India as the use of tobacco in different forms is increasing from a young age, and the prevalence of this disease is becoming more common in middle age. Identifying disease at earlier stages is an important measure for limiting disease incidence and improving patient prognosis. The micronuclei count can be a valid biomarker for screening suspected patients and can be helpful in educating patients about the discontinuation of treatment, diagnosing the disease in its early stages and planning a treatment for a better prognosis. Different stains that are nuclear specific can be used to identify micronuclei. The aim was to establish diagnostic efficacy of various staining techniques in OSCC and potentially malignant disorders on oral brush cytology smears with observation of micronuclei as a valid biomarker for evaluation of the disease. Material and methods. Exfoliative cytology was done with oral brush and smears are obtained from 25 oral squamous cell carcinoma, 25 leukoplakia, 25 lichen planus, 25 oral sub mucous fibrosis patients and 15 samples with no disease. Each smear was stained with five different stains Papanicolaou (PAP), hematoxylin and eosin (H&E), toluidine blue, Leishman and Giemsa (LG) cocktail and Feulgen and observed for staining efficacy of micronuclei and cellular structures. Results. The best stain to observe DNA content as micronuclei is Feulgen which gives clear and crisp details of micronuclei without giving any false count as it is nuclear specific stain. PAP can be the second choice stain. Micronuclei count is definitely increased in OSCC and PMDs compared to samples without disease confirming its use as biomarker. Conclusion. Micronuclei count in oral brush cytology smears is a valid biomarker for evaluation of premalignant disorders and OSCC and can be used for detection of disease in individuals and for screening purposes of large populations at risk. Feulgen stain is best to study DNA content as micronuclei, on the other hand PAP can be used in large sampling investigations where there is lack of armamentarium. [ABSTRACT FROM AUTHOR]