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Abstract Type VII collagen (Col7) is a major component of anchoring fibrils. Col7 plays a role in tumor development and aggressiveness of cutaneous squamous cell carcinoma of recessive dystrophic epidermolysis bullosa. However, the role of Col7 in oral squamous cell carcinoma (OSCC) and oral leukoplakia (OL) remains largely unknown. Objective To elucidate the role of Col7 and its diagnostic potential during oral carcinogenesis. Methodology Col7 expression was immunohistochemically studied in 254 samples, including normal oral mucosa (NM), OL without dysplasia, OL with dysplasia, and OSCC. The correlation between Col7 expression and clinicopathologic parameters of OSCC was also determined. Results Col7 was present as a linear deposit at the basement membrane of NM, OL without dysplasia and OL with dysplasia, and at the tumor-stromal junction around tumor islands in OSCC. Discontinuity of expression was frequently observed in OL with dysplasia and OSCC. OSCC had the significantly lowest Col7 expression (p

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

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

Oral squamous cell carcinoma (OSCC) is the most common cause of morbidity and mortality in India. Buccal mucosa is the most common site because of tobacco quid. Several parameters for the assessment of OSCC have been studied like lymph node metastasis, tumor stage, grade, and perineural invasion. Tumor-associated tissue eosinophilia is another parameter, on which several studies have been done because of its favorable and unfavorable prognosis. The aim of our study is to study quantitative and qualitative eosinophilia in premalignant and malignant lesions of squamous origin in oral cavity with respect to tumor-associated blood eosinophilia. A retrospective study was done at Tertiary care hospital between January 2016 and December 2016. A total of 150 cases of premalignant (oral leukoplakia and dysplasia) and malignant oral squamous cell carcinoma (of various grades) along with blood pictures were evaluated. [ABSTRACT FROM AUTHOR]

Background: Fibroblast growth factor receptor 1 is a potential prognostic factor for tongue squamous cell carcinoma and is associated with oral epithelial dysplasia grade in oral leukoplakia. Methods: Thirty cases of tongue squamous cell carcinoma and 30 cases of oral leukoplakia were analyzed. Fibroblast growth factor receptor 1 and phosphorylated Akt protein expression were analyzed by immunohistochemistry and quantified using a digital algorithm. Fibroblast growth factor receptor 1 gene amplification was analyzed by fluorescent in situ hybridization in the tongue squamous cell carcinoma cases. Results: Clinical appearance and dysplasia grade were correlated with oral leukoplakia malignant transformation. Oral leukoplakia cases presenting high fibroblast growth factor receptor 1 expression showed a higher risk of malignant transformation (p = 0.016, HR: 7.3, 95% CI: 1.4–37.4). Phosphorylated Akt showed faint to no expression in oral leukoplakia, which did not correlate with dysplasia grade or malignant transformation. High expression of fibroblast growth factor receptor 1 and phosohorylated Akt were associated with poor overall survival and disease‐free survival in tongue squamous cell carcinoma, although only fibroblast growth factor receptor 1 expression was significantly associated with poor overall survival (p = 0.024; HR: 4.9, 95% CI: 1.2–19.9). Cases presenting double fibroblast growth factor receptor 1/phosphorylated Akt overexpression (n = 8) showed markedly impaired overall survival (p = 0.020; HR: 6.4, 95% CI: 1.3–31.1) and disease‐free survival (p = 0.001, HR: 13.0, 95% CI: 3.0–55.7). Fibroblast growth factor receptor 1 amplification was observed in 16.6% of tongue squamous cell carcinoma cases, being correlated with vascular and neural invasion (p = 0.001 and 0.017, respectively), but not with fibroblast growth factor receptor 1 protein expression, overall survival, or disease‐free survival. Conclusion: Fibroblast growth factor receptor 1 protein expression is an important prognostic factor in oral leukoplakia and tongue squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next‐generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high‐risk individuals. Noninvasive genetic screening can be employed to screen high‐risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient. [ABSTRACT FROM AUTHOR]

Copyright of Revista de Ciencias Médicas de Pinar del Río is the property of Editorial Ciencias Medicas and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: To assess histopathological characteristics of oral leukoplakia among snuff users and non-users. Material and Methods: The descriptive cross-sectional study was conducted at different hospitals in Khyber Pakhtunkhwa. The study consisted of 60 cases of oral leukoplakia of which 30 were snuff users and 30 were non-users and histopathological features were assessed in both groups. SPSS 20 was used for the evaluation and analysis of the data. Results: The observed mean age of the cases was 50.3 years. In snuff users, the mean age was 56.97 (SD+14.71) while in non-users the mean age was 47.43 (SD+13.44). In snuff users, dysplasia 9/30 (30%) was the most common histopathological feature. The relationship between dysplasia in snuff users and non-users was found to be statistically significant with a p-value of 0.04. Conclusion: It is concluded from the present study that oral leukoplakia showed a wide range of histopathological features and these variants exist even among snuff users however the cases of dysplasia are high in snuff users than non-users which shows a greater potential for conversion of oral leukoplakia into malignancy in snuff users. [ABSTRACT FROM AUTHOR]

Oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) are oral potentially malignant disorders (OPMDs) that microscopically show no or varying degrees of dysplasia. Even sharing clinical and microscopic aspects, PVL shows a more aggressive clinical behaviour, with a malignant transformation rate greater than 40%. Inflammatory infiltrate associated with dysplastic lesions may favour malignant transformation of OPMDs. This study aimed to evaluate the density of T cells and cytokines in dysplastic lesions from OL and PVL patients. Additionally, we evaluated whether soluble products produced in vitro by dysplastic keratinocytes are capable of modulating apoptosis rates and Th phenotype (Th1, Th2, Th17 and Treg) of peripheral blood mononuclear cells. The density of CD3, CD4 and CD8 T cells was assessed by immunohistochemistry. Cytokines and chemokines profile from frozen tissue samples were analysed using the LUMINEX system. Apoptosis rates and Th phenotype modulation were evaluated by flow cytometry. Our results showed an increase in the number of CD8 T cell in the subepithelial region from PVL dysplastic lesions in relation to OL samples. PVL showed increased levels of IL‐5 and a decrease in IL‐1β and IFN‐γ levels compared to OL. Soluble products of PVL and oral carcinoma cell cultures were able to reduce apoptosis rate and promote an imbalance of Th1/Th2 and Th17/Treg. The high‐subepithelial density of CD8 T cells and immune imbalance of T lymphocytes subsets probably play an important role in the pathogenesis of PVL and may explain its more aggressive behaviour in relation to OL. [ABSTRACT FROM AUTHOR]

Copyright of Revista de Ciencias Médicas de Pinar del Río is the property of Editorial Ciencias Medicas and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has a serious impact on HIV-infected individuals due to limited access to treatment services. This report aimed to describe four cases of oral lesions in HIV-infected antiretroviral-naive patients found during the COVID-19 pandemic. Case: Four patients, males, with an age ranged from 29 to 53 years, came to Oral Medicine Department with chief complaints of lesions on their mouth. They had postponed their visit to healthcare services due to limited access during pandemic. Three patients had just been diagnosed with HIV and had not yet received anti-retrovirus, while 1 patient had not yet been detected with HIV. From the clinical examination and laboratory findings, we diagnosed the lesions with mucous patches, chronic atrophic candidiasis, angular cheilitis, necrotizing ulcerative gingivitis, linear gingival erythema, cytomegalovirus-associated ulcers, and oral hairy leukoplakia. Case Management: We gave chlorhexidine gluconate 0.2% mouthwash for mucous patches, nystatin oral suspension for chronic atrophic candidiasis, miconazole cream 2% for angular cheilitis, debridement with hydrogen peroxide 1.5% and rinsed with normal saline for necrotizing ulcerative gingivitis, and diphenhydramine hydrochloride and 0.2% chlorhexidine gluconate for CMV ulcers. All patients showed good clinical improvement after the treatments. Conclusion: Oral lesions are still commonly found in HIV-infected patients during COVID-19 pandemic. Dentists remain to have a crucial role in the early diagnosis and treatment of HIV-associated oral lesions during COVID-19 pandemic that will have an impact on HIV treatments, also in implementing the Bali Declaration on oral health in HIV/AIDS 2019 to support UNAIDS goal to end AIDS by 2030. [ABSTRACT FROM AUTHOR]

Oral leukoplakia (OL), an oral potentially malignant disorder, begins with a hyperplastic/hyperkeratotic stage at which no genome-scale somatic single nucleotide variant profiles have been described so far. We performed exome sequencing of five cases at this stage with no evidence of dysplasia to identify genetic alterations (exon-level copy number alterations, indels, and single nucleotide variants), their association with transcript levels, and relationship with oral cancer susceptibility. Pathway enrichment analysis of genes associated with tobacco chewing and age-related mutation signatures, transcripts with variants predicted to be functionally damaging and those with significantly altered levels all indicated the involvement of focal adhesion, ECM-receptor interactions, regulation of cytoskeleton, and DNA repair. Two novel mutations identified in FAT1 tumor suppressor gene were associated with decreased transcript levels. In addition, 16 expressed cancer driver genes contained functionally damaging variants. Many of the affected genes were also reported in dysplastic OL lesions. The presence of variants in cancer driver genes and those shared with oral dysplasias possibly provides a basis for further progression and increased susceptibility to oral cancer. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is an alternative microinvasive approach with satisfying results in the treatment of oral leukoplakia (OL). PDT combined with laser irradiation shows promise, safety and efficacy in treating OL. The efficacy of waterlase (YSGG) combined with PDT was studied by brush and tissue biopsy. Seventy-one patients with histologically diagnosed OL were enrolled, including patients with mild to moderate dysplasia, severe dysplasia and various dysplastic tissues. Patients were evaluated at baseline (t0), the end of treatment (t1) and 1 year later (t2). At t1, PDT showed a significant therapeutic effect on OL with mild to moderate dysplasia. Clinical and histological examinations revealed 60 cases (84.51%) of complete remission and 11 cases (15.49%) of partial remission. On brush biopsy, all PDT-treated patients showed reduced aneuploidy and normal histological findings. Unfortunately, at t2, 9 patients relapsed with OL, which may be related to continued smoking and betel nut chewing. At t2, 5 patients developed new severe epithelial dysplasia and even carcinoma in situ in other areas, mostly the tongue. ALA-mediated PDT combined with YSGG is effective in treating OL, particularly that with mild to moderate dysplasia. However, severe dysplasia may present undesirable effects, and the mechanism remains to be further investigated. ALA-mediated PDT combined with YSGG provides a new method for OL treatment. [ABSTRACT FROM AUTHOR]

Oral white lesions are quite common clinical conditions in clinical dental practice. They can be an expression of different diseases, so it is crucial to achieve a correct diagnosis to start an adequate treatment. However, differential diagnosis is not always easy because the clinical appearance of oral white lesions is often similar and non-pathognomonic. We report on a 42-year-old Caucasian woman who complained of a chronic white patch on the left border of her tongue. A provisional diagnosis of oral hairy leukoplakia was made, but the patient was HIV-negative and not immunocompromised. A patch test was performed to exclude an allergic reaction, which resulted negative. Two large amalgam fillings were removed, and the lesion regressed after two weeks, suggesting a diagnosis of oral lichenoid lesions. Amalgam-associated oral lichenoid lesions could be mistaken for hairy leukoplakia when located on the lateral border of the tongue. Patch tests for dental metal series are only sometimes helpful for a diagnosis of oral lichenoid lesions. Patients should follow a careful follow-up to monitor any neoplastic derailment of the lichenoid lesions. [ABSTRACT FROM AUTHOR]

Introduction: Lactate dehydrogenase (LDH) is an enzyme seen within every cell during their normal metabolic function. It is always confined within the cell cytoplasm and it becomes extracellular only when a cell dies. The extracellular presence of LDH is related to cell necrosis and tissue breakdown. Therefore, we designed a study to estimate and compare LDH levels in the saliva of patients with oral cancer, oral leukoplakia (OL), and smokers without lesions and in controls. Materials and Methods: A total of 81 subjects of both genders, between the ages of 20 and 70 years, were included in the study. The study group was divided into four: group I-controls (n = 20), Group II-smokers (n = 20), Group III-subjects with OL (n = 20), and Group IV-subjects with oral squamous cell carcinoma (OSCC) (n = 21). Five milliliters of unstimulated salivary sample was collected from each participant, and salivary LDH level was measured. The obtained values were tabulated and statistically analyzed. P < 0.05 was considered to be statistically significant. Results: The difference in LDH levels among the four groups was found to "BE" statistically significant. LDH values showed a marked increase in the leukoplakia group (49.79 ± 19.88 IU/L) and OSCC group (106.97 ± 32.75 IU/L) when compared to controls and smokers. Conclusion: We found that salivary LDH was increased in patients with leukoplakia and OSCC. Smoking alone did not produce any alterations in salivary LDH. It is possible that salivary LDH could be a potential biomarker to identify early premalignant or malignant changes in smokers. [ABSTRACT FROM AUTHOR]

Oral leukoplakia (OL) and oral submucosal fibrosis (OSMF) are precancerous conditions with common etiologies but with different risks for oral cancer (OC) progression. In rare cases, both conditions occur in the same patient and provide an opportunity for understanding the common and distinctive variants upon exposure of genetically identical normal cells to the same carcinogen(s). We performed exome sequencing of a patient with OL (hyperplasia, but no dysplasia) and OSMF (grade II) in the opposite cheeks using blood DNA as the reference genome. The overall somatic variant burden was higher in OSMF than OL, but opposite in the case of copy number alterations. OL-specific variants were enriched in genes associated with DNA repair, cell division/cell cycle checkpoint pathways, whereas in OSMF, extracellular matrix-receptor interaction was mainly affected. The proportions of variants in cancer driver genes and cancer driver mutations were similar in both cases indicating no difference in the potential risk associated with the two conditions at the stages sampled. Future studies on rare cases similar to the one described in this report will help in understanding the molecular basis of differences associated with OL and OSMF and shared processes accompanying OC progression. [ABSTRACT FROM AUTHOR]

Objective: To detect promoter hypermethylation status of tumor suppressor genes of DAPK and TIG1 in oral leukoplakia (OLK) and explore its potential roles in oral carcinogenesis. Methods: DAPK and TIG1 hypermethylation were evaluated in 77 OLK, 32 oral squamous cell carcinomas (OSCC) and 40 normal tissues by quantitative methylation-specific PCR (QMSP). Results: It was found that DAPK were hypermethylated in OSCC. The frequency (46.9%) and the quantity (0.0728± 0.1617) of DAPK hypermethylation in OSCC was significant higher than those in OLK and normal tissues (OLK: 19.5%, 0.0070 ± 0.0172; normal tissues: 18.8%, 0.0021± 0.0050, P<0.05). Furthermore, DAPK hypermethylation was significantly correlated with epithelial dysplasia. Compared with the low malignant potential group of OLK patients(LMP), the high malignant potential group (HMP) was more likely to express increased gene hypermethylation of DAPK (OR, 1.013; 95% CI: 1.004-1.023; P=0.004). No hypermethylation of TIG1 was found in normal tissues. The frequency (OSCC: 28.1%; OLK: 27.3%) and the quantity (OSCC: 0.0174± 0.0440; OLK: 0.0035± 0.0076) of TIG1 hypermethylation were both higher than those in normal tissues (P<0.05). Conclusion: Our data suggested that DAPK and TIG1 hypermethylations were associated with oral precancer and may be useful as early detection markers for oral cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: The study was the first to screen seven genes and identify the set of genes using twelve machine learning algorithms that predict the progression from oral leukoplakia to oral squamous cell carcinoma. We verified these genes by RT-qPCR experiments and speculated on the possible molecular mechanisms through the results. These genes could be used as biomarkers for early diagnosis and predicting patients with a high risk of malignant transformation. This will aid in early intervention, improve the patient prognosis, and reduce the incidences of oral squamous cell carcinoma. The aim of the study is to identify key genes during the progression from oral leukoplakia (OL) to oral squamous cell carcinoma (OSCC) and predict effective diagnoses. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were performed to identify seven genes associated with the progression from OL to OSCC. Twelve machine learning algorithms including k-nearest neighbor (KNN), neural network (NNet), and extreme gradient boosting (XGBoost) were used to construct multi-gene models, which revealed that each model had good diagnostic efficacy. The functional mechanism or the pathways associated with these genes were evaluated using enrichment analysis, subtype clustering, and immune infiltration analysis. The enrichment analysis revealed that the genes enriched were associated with the cell cycle, cell division, and intracellular energy metabolism. The immunoassay results revealed that the genes primarily affected the infiltration of proliferating T cells and macrophage polarization. Finally, a nomogram and Kaplan–Meier survival analysis were used to predict the prognostic efficacy of key genes in OSCC patients. The results showed that genes could predict the prognosis of the patients, and patients in the high-risk group had a poor prognosis. Our study identified that the seven key genes, including DHX9, BCL2L12, RAD51, MELK, CDC6, ANLN, and KIF4A, were associated with the progression from OL to OSCC. These genes had good diagnostic efficacy and could be used as potential biomarkers for the prognosis of OSCC patients. [ABSTRACT FROM AUTHOR]

Dysregulation of the cell cycle is an important factor in a potentially malignant oral disorder. There have not been many studies on the role of the cell cycle regulator p27 in oral non-homogenous leukoplakia. The aim of our study was to characterise the p27 protein in homogenous and non-homogenous oral leukoplakias (OL), in comparison with healthy mucosa and squamous cell carcinoma tissues. The current study included 25 patients with OL, 15 cases with oral squamous cell carcinoma, and 15 samples of healthy oral mucosa, both as comparison groups. Immunohistochemical p27 antigen expression was determined by a standard EnView imaging system. The expression level of p27 in nodular and verrucous leukoplakia was lower than in homogenous OL but higher than in erythroleukoplakia. There was a statistically significant difference (p < 0.05) between the expression of p27 in healthy mucosa and homogenous OL. There was a significantly lower amount of p27 positive cells in oral cancer than in OL (p < 0.0001); however, its intracytoplasmic presence was diagnosed. Our study proved the instability of p27 protein and its dual nature in non-homogenous OL and OSCC, and therefore, it can be used as a predictive marker for the clinical course of these conditions. [ABSTRACT FROM AUTHOR]

Introduction: Oral cancer has become one of the leading causes of death and disease globally as well as in India. Tobacco consumption is responsible for nearly half of all cancers in men and nearly one-fourth of cancers in women in India and more than two-third of oral cancers are directly attributable to tobacco use. Early detection of precancerous lesions and tobacco cessation activities, if conducted together can have high impact on reducing incidence of oral cancer. Aim: To study prevalence of oral precancerous lesions in tobacco and areca nut habituated patients in Barpeta district, Assam, India. Materials and Methods: The present observational, crosssectional, hospital-based study was conducted on Outpatient Department (OPD) patients of Dentistry Department of Fakhruddin Ali Ahmed Government Medical College. College, Barpeta, Assam, India, from June 2021 to June 2022. Patients with tobacco and areca nut chewing habits were selected as study participants. Total number of study participants were 404. Oral cavity screening was done to detect oral precancerous lesion. History of tobacco and areca nut chewing habits were recorded in terms of gender, age, form of tobacco, duration and frequency. Chi-square test was used for statistical analysis. Results: Prevalence of oral precancerous lesions in tobacco consuming patients was 3.46% in smoke form and 9.9% in smokeless form. Premalignant lesions had been seen predominantly in male. Among the premalignant lesions prevalence of oral leukoplakia was highest (22.27%) followed by erythroplakia (4.46%). Overall, prevalence of precancerous lesions in tobacco and areca nut habituated patient in the present study was 37.62%. The association between prevalence of oral precancerous lesion with frequency and duration of habits was statistically insignificant (2=7.167, p-value=1.000). Conclusion: In the present study, prevalence of oral precancerous lesion in tobacco and areca nut consuming patients in Barpeta district was quite high. The findings from this present study can be used to design cohort study to further understand the relation between precancerous lesions in tobacco and areca nut habituated patients. [ABSTRACT FROM AUTHOR]

Recently, the possibility that oral microbiomes is associated with oral squamous cell carcinoma (OSCC) initiation and progression has attracted attention; however, this association is still unclear. Here, we comprehensively analyze the microbiome profiles of saliva samples using next-generation sequencing followed by determining the association between oral microbiome profiles and OSCC. Microbiome profiles in saliva samples from patients with OSCC, oral leukoplakia (OLK), and postoperative OSCC (Post) were analyzed. Candidate OSCC-associated bacteria were identified by comparing the bacterial diversity and relative abundance of each group based on these microbiome profiles, and their applicability as OSCC detection tools were evaluated. There were significant differences in genus abundances (Streptococcus, Aggregatibacter, and Alloprevotella) among the groups from saliva samples. In the OSCC group, compared with the OLK and Post groups, abundances of the genus Fusobacterium, phylum Fusobacteria and phylum Bacteroidetes were markedly increased and that of the genus Streptococcus and phylum Firmicutes were decreased. The results suggested a strong association of these bacteria with OSCC. Especially, phylum Fusobacterium was significantly associated with early recurrence of OSCC. Thus, oral microbiome analysis may have a potential of novel OSCC detection and prognostic tool. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the expression of nuclear EGFR (nEGFR) and the stem cell marker ABCG2 in oral leukoplakia (OL) and oral erythroplakia (OE) and to assess their significance as prognostic biomarkers for malignant transformation. Methods: In this study we included 50 patients with oral potentially malignant disorders (OPMD), 31 with OL and 19 with OE, in whom we examined the expression of nEGFR and ABCG2 by immunohistochemical methods. Results: Twenty‐one (42%) of 50 patients with OL and OE developed oral squamous cell carcinoma (OSCC). The malignant transformation was increased 12,84‐fold (95% CI, 2.15–76.44, p = 0.005) in OPMD expressing both ABCG2 and nEGFR. Expression of nEGFR is a strong indicator of malignant transformation, unlike ABCG2 expression, respectively. Conclusions: Determining the co‐expression of the biomarkers nEGFR and ABCG2 in OPMD may serve us to determine the risk of malignant transformation in OSCC. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is often preceded by a white patch on a surface of the mouth, called oral leukoplakia (OL). As accelerated telomere length (TL) shortening in dividing epithelial cells may lead to oncogenic transformation, telomere length measurement could serve as a predictive biomarker in OL. However, due to high variability and lack of a universal reference, there has been a limited translational application. Here, we describe an approach of evaluating TL using paired peripheral blood mononuclear cells (PBMC) as an internal reference and demonstrate its translational relevance. Oral brush biopsy and paired venous blood were collected from 50 male OL patients and 44 male healthy controls (HC). Relative TL was measured by quantitative PCR. TL of each OL or healthy sample was normalized to the paired PBMC sample (TL ratio). In OL patients, the mean TL ratio was significantly smaller not only in the patch but also in distal normal oral tissue, relative to healthy controls without a high‐risk oral habit. Dysplasia was frequently associated with a subgroup that showed a normal TL ratio at the patch but significantly smaller TL ratio at a paired normal distal site. Our data suggest that evaluation of TL attrition using a paired PBMC sample eliminates the requirement of external reference DNA, makes data universally comparable and provides a useful marker to define high‐risk OL groups for follow‐up programs. Larger studies will further validate the approach and its broader application in other premalignant conditions.

Abstract Oral leukoplakia (OLK) has gained extensive attention because of the potential risk for malignant transformation. Photosensitizers (PSs) played an indispensable role in the photodynamic therapy (PDT) of OLK, but the poor light sensitivity greatly hampered its clinical application. Herein, a novel organic photosensitive ITIC-Th nanoparticles (ITIC-Th NPs) were developed for OLK photodynamic/photothermal therapy (PTT). ITIC-Th NPs present both high photothermal conversion efficiency (~ 38%) and suitable reactive oxygen species (ROS) generation ability under 660 nm laser irradiation, making them possess excellent PDT and PTT capability. In 4-nitroquinoline 1-oxide (4NQO)-induced oral precancerous animal models, ITIC-Th NPs effectively suppress the OLK's cancerization without apparent topical or systemic toxicity in vivo. This study offers a promising therapeutic strategy for PDT and PTT in OLK treatment, and this study is the first interdisciplinary research in the field of multimodal therapy for OLK. Graphical Abstract

• A complete course of PDT can reduce the risk of malignant transformation of OLK. • The protective effect of completing PDT is more significant in high-risk patients. • PDT has considerable application value in the treatment of OLK. Photodynamic therapy (PDT) has shown good short-term efficacy in the treatment of oral leukoplakia (OLK). However, the malignant transformation of OLK was seldom evaluated in most PDT studies. Therefore, this study evaluated the effect of PDT on the risk of malignant transformation of OLK. Kaplan-Meier survival analysis, COX regression, and sensitivity analysis were used to evaluate the effects of PDT on the risk of malignant transformation of OLK. Subgroup analyses were performed to explore the role of PDT in OLK patients with different clinical characteristics. OLK patients with older age (HR=1.032, P = 0.018) and non-homogeneous lesion (HR=2.104, P = 0.044) had higher risk of malignant transformation. Patients who had finished a complete course of PDT (HR=0.305, P = 0.006) had a significant lower risk of malignant transformation, while those who hadn't finished a complete course of PDT (HR=0.692, P = 0.352) cannot be considered to have such a protective effect. In the subgroup analyses, complete PDT course showed a significant protective effect on malignant transformation of OLK in patients with female sex, no smoking or drinking habits, non-homogeneous lesions, lesions on oral mucosa outside the dangerous region, and any grade of epithelial dysplasia. A complete course of PDT could significantly reduce the risk of malignant transformation of OLK, especially in those patients with risk factors of malignant transformation. [ABSTRACT FROM AUTHOR]

• Utilizing deep learning for automated detection of oral lesions. • Detection of Oral Lichen Planus (OLP), Oral Leukoplakia (OLK), and OSCC. • Analysis of clinical photographs to enhance targeted accuracy for OSCC detection. • Accurately identify oral lesions and support healthcare professionals. [ABSTRACT FROM AUTHOR]

Smoking is a well-established risk factor for several oral diseases, including oral cancer, oral leukoplakia and periodontitis, primarily related to reactive oxygen species (ROS). SS-31, a mitochondria-targeting tetrapeptide, has exhibited demonstrable efficacy in medical conditions by attenuating mitochondrial ROS production. However, its potential in the treatment of oral diseases remains underexplored. The aim of this study was to investigate the therapeutic potential of SS-31 in mitigating smoking-induced oral epithelial injury. Through in vitro experiments, our results indicate that SS-31 plays a protective role against cigarette smoke extract (CSE) by reducing oxidative stress, attenuating inflammatory response, and restoring mitochondrial function. Furthermore, we found that mitophagy, regulated by PINK1 (PTEN-induced putative kinase 1)/Parkin (Parkin RBR E3 ubiquitin–protein ligase), was critical for the protective role of SS-31. Our findings offer valuable insights into SS-31's therapeutic potential in mitigating CSE-induced oxidative stress, inflammatory response, and mitochondrial dysfunction in oral epithelial cells. This study provides novel intervention targets for smoking-related oral diseases. [Display omitted] • Smoking-induced ROS and oxidative stress contribute to several oral diseases. • SS-31 attenuated smoking-induced oxidative stress, inflammatory response, and mitochondrial dysfunction. • SS-31 promoted PINK1-mediated mitophagy in oral epithelial cells. • SS-31 may have therapeutic potential for smoking-related oral diseases. [ABSTRACT FROM AUTHOR]

Context and Aim: Oral leukoplakia has recently been re-defined as “a predominantly white lesion of the oral mucosa that cannot be characterised as any other definable lesion”. Superoxide dismutase (SOD) is one of the enzymatic anti-oxidants which form the first line of defence in the cell. There are very limited data available on the analysis of SOD in leukoplakia patients. Therefore, the present study was planned to analyse anti-oxidant SOD levels in leukoplakia patients. Methods and Material: The study group consisted of 29 subjects of oral leukoplakia, and the control group consisted of 25 healthy individuals. All the subjects were evaluated for SOD enzyme in plasma. Statistical Analysis Used: The results for each determinant were calculated using one-way ANOVA test, Student 't' test, Pearson Chi square test, and 't' test for equality of means wherever applicable. Results: The study revealed that among the different clinical entities of oral leukoplakia, the enzymatic anti-oxidant SOD is shown to have decreased in all forms of oral leukoplakia, but without any statistical significance. A statistically highly significant decrease (at P < 0.0001) of SOD in oral leukoplakia patients compared to normal healthy patients was observed in the present study. Conclusions: The study revealed a difference in the free-radical activity and oxidative stress in blood of leukoplakia patients compared to healthy patients, which is reflected by the variation in the levels of blood SOD, thus showing vulnerability to cellular damage and tendency towards further malignant changes.

Background: Galectin 3 (Gal-3) has diverse functions critical in cancer biology including cell proliferation, apoptosis, evasion of immune responses and angiogenesis. The expression of Gal-3 is heterogeneous in normal and neoplastic tissues. In oral squamous cell carcinoma (OSCC) and oral leukoplakia (OL), both increased and decreased expressions of Gal-3 were elicited in numerous studies. Aims: To evaluate, compare and correlate the immunohistochemical expression of Gal-3 in OSCC, OL and normal oral mucosa. Settings and Design: The study was conducted at the Department of Oral Pathology and Microbiology at PMS College of Dental Science and Research, Vattapara, Thiruvananthapuram. This is a retrospective analytical study. Methods and Material: Clinically diagnosed and histopathologically confirmed cases of OSCC (n = 21), OL (n = 21), and normal oral mucosa (n = 21) were included in the study. Paraffin-embedded tissues were subjected to immunohistochemical analysis for Gal-3 expression. Gal-3 staining expression, staining distribution and cellular localisation were evaluated. All sampled categories were compared using immunohistochemical scoring analysis such as the H-score, labelling index (LI), immunoreactive score (IRS) and staining intensity (SI). Statistical Analysis: The results were statistically analysed using multivariate analysis of variance (MANOVA) within and among the groups. Results and Conclusion: The statistical inferences obtained found that the H-score could be used as a guideline for better differentiation between the groups and among the groups. The P value obtained was < 0.0125 and was found to be significant. The observation in our study shows that the immunohistochemical expression of Gal-3 gradually decreased from normal oral mucosa to OL to OSCC.

Context: The concept of field cancerization necessitates substantiation of clinical assessment and histopathological examination by molecular markers. Molecular tumor biomarkers such as p53 protein overexpression aid in assessing the malignant transformation of such potentially malignant oral lesions. Aim: To identify the molecular changes in oral leukoplakia by studying the immunoexpression of tissue p53 and correlating it with the clinical and histological findings to establish an appropriate treatment plan. Methods and Material: Biopsy samples taken from 25 oral leukoplakia cases were subjected to histopathological and immunohistochemical analysis to determine the percentage positivity of p53 expression. Histopathological grading was based on dysplastic features and level of epithelial involvement. Dysplasia grading in IHC sections was estimated by p53% positivity in the cells. The obtained data were subjected to statistical analysis. Results: 24 samples were considered for statistical analysis due to the loss of epithelium in the IHC section of one sample. The results showed a statistically significant association between histopathological and IHC grading of dysplasia with a P value less than 0.05 in Fisher Exact test. Conclusion: Increased expressions of p53 in potentially malignant oral lesions are proportional to the risk of malignancy. The gold standard histopathological result does not reveal the molecular abnormality associated with a potentially malignant oral lesion. Therefore molecular analysis of such lesions will aid in the effective prevention of oral cancer.

The search for biomarkers associated with oral leukoplakia malignant transformation is critical for early diagnosis and improved prognosis of oral cancer patients. This systematic review and meta-analysis aimed to assess protein-based markers potentially associated with malignant transformation of oral leukoplakia. Five database and the grey literature were searched. In total, 142 studies were included for qualitative synthesis, where 173 proteins were investigated due to their potential role in malignant progression from oral leukoplakia (OL) to oral squamous cell carcinoma (OSCC). The abundance of these proteins was analyzed in fixed tissues and/or biofluid samples, mainly by immunohistochemistry and ELISA, and 12 were shared by both samples. Enrichment analysis revealed that the differential abundant proteins are mostly involved with regulation of cell death, regulation of cell proliferation, and regulation of apoptotic process. Also, these proteins are mainly expressed in the extracellular region (55.5%), cell surface (24.8%), and vesicles (49.1%). The meta-analysis revealed that the proteins related to tumor progression, PD-L1, Mdm2, and Mucin-4 were significantly associated with greater abundance in OSCC patients, with an Odds Ratio (OR) of 0.12 (95% CI: 0.04–0.40), 0.44 (95% CI: 0.24–0.81), and 0.18 (95% CI: 0.04–0.86), respectively, with a moderate certainty of evidence. The results indicate a set of proteins that have been investigated across OSCC initiation and progression, and whose transcriptional expression is associated with clinical characteristics relevant to the prognosis and aggressiveness. Further verification and validation of this biomarkers set are strongly recommended for future clinical application.

Introduction: Oral cancer has become one of the leading causes of death and disease globally as well as in India. Tobacco consumption is responsible for nearly half of all cancers in men and nearly one-fourth of cancers in women in India and more than two-third of oral cancers are directly attributable to tobacco use. Early detection of precancerous lesions and tobacco cessation activities, if conducted together can have high impact on reducing incidence of oral cancer. Aim: To study prevalence of oral precancerous lesions in tobacco and areca nut habituated patients in Barpeta district, Assam, India. Materials and Methods: The present observational, cross-sectional, hospital-based study was conducted on Outpatient Department (OPD) patients of Dentistry Department of Fakhruddin Ali Ahmed Government Medical College. College, Barpeta, Assam, India, from June 2021 to June 2022. Patients with tobacco and areca nut chewing habits were selected as study participants. Total number of study participants were 404. Oral cavity screening was done to detect oral precancerous lesion. History of tobacco and areca nut chewing habits were recorded in terms of gender, age, form of tobacco, duration and frequency. Chi-square test was used for statistical analysis. Results: Prevalence of oral precancerous lesions in tobacco consuming patients was 3.46% in smoke form and 9.9% in smokeless form. Premalignant lesions had been seen predominantly in male. Among the premalignant lesions prevalence of oral leukoplakia was highest (22.27%) followed by erythroplakia (4.46%). Overall, prevalence of precancerous lesions in tobacco and areca nut habituated patient in the present study was 37.62%. The association between prevalence of oral precancerous lesion with frequency and duration of habits was statistically insignificant (χ2=7.167, p-value=1.000). Conclusion: In the present study, prevalence of oral precancerous lesion in tobacco and areca nut consuming patients in Barpeta district was quite high. The findings from this present study can be used to design cohort study to further understand the relation between precancerous lesions in tobacco and areca nut habituated patients.

Objective Recently, the possibility that oral microbiomes is associated with oral squamous cell carcinoma (OSCC) initiation and progression has attracted attention; however, this association is still unclear. Here, we comprehensively analyze the microbiome profiles of saliva samples using next-generation sequencing followed by determining the association between oral microbiome profiles and OSCC.Materials and Methods Microbiome profiles in saliva samples from patients with OSCC, oral leukoplakia (OLK), and postoperative OSCC (Post) were analyzed. Candidate OSCC-associated bacteria were identified by comparing the bacterial diversity and relative abundance of each group based on these microbiome profiles, and their applicability as OSCC detection tools were evaluated.Results There were significant differences in genus abundances (Streptococcus, Aggregatibacter, and Alloprevotella) among the groups from saliva samples. In the OSCC group, compared with the OLK and Post groups, abundances of the genus Fusobacterium, phylum Fusobacteria and phylum Bacteroidetes were markedly increased and that of the genus Streptococcus and phylum Firmicutes were decreased.Conclusion The results suggested a strong association of these bacteria with OSCC. Especially, phylum Fusobacterium was significantly associated with early recurrence of OSCC. Thus, oral microbiome analysis may have a potential of novel OSCC detection and prognostic tool.

Photodynamic therapy (PDT) is a minimally invasive method for treating oral leukoplakia. In this paper, we propose a portable PDT device consisting of a flexible circuit board with a liquid flow cooling module on the back. The light source size was 17 mm × 1 1 mm × 4 mm, and the irradiation area of the light source was up to 100 mm2. The irradiance range of this device was from 10 mW/cm2 to 100 mW/cm2. Simulation and experimental results showed that the irradiance coefficient variation for a treatment area of 81 mm2 was less than 7%. At an irradiance of 100 mW/cm2, a device surface temperature of lower than 42∘C can be achieved to satisfy the safety requirements under the conditions that the temperature of cooling liquid is 10∘C and the liquid flow speed is above 12 mL/min. [ABSTRACT FROM AUTHOR]

Simple Summary: The treatment of oral potentially malignant disorders (OPMDs), including oral leukoplakia (OL), is controversial. Medical interventions currently used to prevent malignant transformation in OL include surgical treatment, photodynamic therapy, and chemotherapy. The main advantages of laser surgery are the selective removal of the lesion, minimal damage to surrounding healthy tissue, and excellent postoperative wound healing. However, no treatment has been shown to prevent recurrence or significantly reduce malignant development in long-term follow-up studies, so further research is needed to identify possible risk factors. Aim: The aim of this study is to assess the efficacy of CO2 laser treatment in oral leukoplakia and to analyse the recurrence rate of oral leukoplakia lesions at 18-month follow-up. Materials and methods: A prospective clinical study regarding CO2 laser treatment for oral leukoplakia was conducted, in which 39 patients with a total of 53 oral leukoplakias were included. Follow-up was performed at 18 months post-surgery and the following variables were studied: sex, age, associated risk factors, clinical classification, size, location and presence of epithelial dysplasia, recurrence, and rate of malignant transformation after resection. Results: In the analysis of the final results 18 months after baseline, a treatment success rate of 43.75% was observed. Oral leukoplakia recurred in 54.17% of cases, and 2.08% of leukoplakias progressed to cancer. Among all the studied variables (age, tobacco use, size, location, clinical type or histology), no significant differences were found with regard to recurrence. Conclusion: The use of CO2 laser therapy to treat leukoplakia lesions is sufficient to remove such lesions. However, parameters that can assess recurrence need to be sought. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify the risk factors associated with developing oral squamous cell carcinoma (OSCC) from surgically excised oral leukoplakia (OL) in patients with previous oral cavity cancer. Clinicopathological data of 84 patients who were treated for OL between July 2002 and July 2020 and who had previously received treatment for OSCC were reviewed retrospectively. The follow-up time ranged from 0.69 to 17.99 years (mean 6.78 ± 4.25 years). The overall cumulative malignant transformation rate was 25% and the annual transformation rate was 5.73%. Kaplan–Meier survival analysis and the log-rank test showed that Candida infection (P = 0.010) was a risk factor associated with malignant transformation. In the multivariate Cox regression analysis, tongue and floor of the mouth as the location of the leukoplakia (P = 0.039), multifocal lesions of OL (P = 0.047), and Candida infection (P = 0.018) were the three independent prognostic factors related to the development of OSCC from the treated OL. A cautious approach to OL of the tongue with Candida infection or multifocal disease in this group of patients would be appropriate. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the role of serum sialic acid as a non-invasive biomarker of Leukoplakia and oral cancer. METHODOLOGY: This comparative cross-sectional study was conducted from December 2017 to November 2019 at the Institute of Biochemistry and Tertiary care hospital, Larkana. The 34 diagnosed cases of oral Leukoplakia and Erythroplakia were 20 to 72 years age. The controls with history of using tobacco, areca nut, alcohol, corticosteroid drugs and systemic diseases were excluded from this study. The dysplasia was graded histopathologically as mild, moderate and severe. The Blood samples were collected and centrifuged at 3000 rpm for 15 minutes; then, serum was separated and Sialic Acid was analyzed spectrophotometrically. Finally, Statistical analysis was done by SPSS version 20 and results were expressed with mean and standard deviation. RESULTS: Out of 34 cases and controls15 (44.1%) were male, and 19(55.9%) were female. Their ages were from 20 to 72 years, and the mean age was 47.47±17.97. The typical sites of lesion were buccal mucosa 35.3%, tongue 26.5%, right cheek 14.70%, left cheek 8.8%, Juxta mandibular area 8.8% and lip 2.9%, respectively. Clinically Oral Leukoplakia was 58.8% and Erythroplakia 29.4%. The Sialic Acid levels were 78.7±16.6 mg/dl in Leukoplakia, 105.4±22mg/dl in Erythroplakia and was 60.2±4 mg/dl in controls. The serum sialic acid levels were increased in case group as compared to control group in both genders, with significant p-value 0.001. CONCLUSION: The Sialic Acid levels were significantly increased in cases of Oral Leukoplakia and Erythroplakia as compared to healthy controls. [ABSTRACT FROM AUTHOR]

Background & Objective: Emerging evidence suggests that KRAS could play an important role in squamous cell carcinoma; however, its role in oral squamous cell carcinoma (OSCC) is largely unknown. The aim of the current study was to investigate the expression of KRAS, Ki-67, Cyclin D1, and Bcl2 in OSCC and their association with clinicopathological features. Methods: Forty paraffin blocks of retrospective histologically diagnosed cases of OSCC and 20 blocks of oral leukoplakia with epithelial dysplasia were obtained from two hospitals between 2018 and 2021. The paraffin-embedded tissue was analyzed for the expression of KRAS for oral epithelial dysplasia and OSCC, and ki-67, Cyclin D1, and bcl2 were analyzed only for OSCC. The results were correlated with each other and with different clinicopathological features and were statistically analyzed. Results: KRAS expression was significantly associated with histological tumor grade, tumor extent, presence of nodal and distant metastasis, pathological stage, and the presence of lymphovascular invasion (P=<0.001, 0.001, 0.001, 0.009, <0.001, and <0.001, respectively). The KRAS expression was positively correlated with the histological grade, tumor extent, nodal status, and the pathological stage (r=0.712, 0.649, 0.646, and 0.865, respectively). A positive correlation was also found with the expression of Bcl2, Cyclin D1, and Ki-67 (r=0.81, 0.723, and 0.698, respectively). The KRAS expression in oral epithelial dysplasia was significantly lower than that in OSCC (P=0.003). Conclusion: KRAS may be a potential prognostic marker for OSCC and may play a role in its progression. [ABSTRACT FROM AUTHOR]

Background: Leukoplakia is an asymptomatic, potentially malignant lesion in the oral mucosa which often develops into oral cancer. Various follow-up studies done show that between <1 and 18% of oral pre-malignant lesions will develop into oral cancer. Periodontitis is related to different pathological states in the oral cavity including pre-malignant and malignant lesions. Frequently, periodontal sites are involved in proliferative types of leukoplakia. Therefore, Periodontitis increases the risk of oral leukoplakia and, therefore, the risk of mucosal lesions predisposing to oral cancers. Methods: A 39 year old male patient reported to the Department Of Periodontology with chief complaint of bleeding of gums and whitish patch on his right and left buccal mucosa since 6 months. A Complete clinical examination and detailed case history was recorded for the same. Proper treatment plan was planned and implemented. This cased showed a strong corelation between periodontitis and oral leukoplakia. Conclusion: Poor oral hygiene and the ensuing of plaque accumulation results in a chronic inflammatory process, creating an environment that promotes the development premalignant lesions and oral carcinoma. Our study supports the hypothesis that periodontitis is an individual risk factor for Oral premalignant lesions. Periodontal disease is a chronic inflammatory condition that may be prevented with regular dental visits and with the maintenance of the Oral hygiene. Dentists play an important role in preventing oral cancer by evaluating the socioeconomic status of each patient and appraising their lifestyle and habits. Therefore this case report mainly focuses on interrelationship between maintenance of good periodontal health and development of oral premalignant lesions. [ABSTRACT FROM AUTHOR]

Introduction: The role of E-cadherin and CD44 has been proven in the development and progression of cancerous and precancerous lesions. It seems that these two markers have a high ability to evaluate the premalignancy of lichen planus lesions and oral leukoplakia. This study aimed to investigate and compare the expression of CD44 and E-cadherin markers in oral leukoplakia, lichen planus, and oral squamous cell carcinoma (SCC). Material & Methods: This analytical-descriptive study was conducted on 60 blocks of lichen planus, leukoplakia, and squamous cell carcinoma. The blocks were stained by CD44 and E-cadherin antibodies. The obtained data were analyzed in SPSS software (version 22), and a P-value of 0.05 was considered statistically significant. Findings: Only 30% of the SCC samples expressed the CD44 marker, while 40% and 50% of leukoplakia and lichen planus samples expressed the CD44 marker, respectively. The expression of the E-cadherin marker in SCC samples was 40% in the range of staining, while it was 50% and 60% in leukoplakia and lichen planus, respectively. There was not a significant difference between the staining intensity of CD44 and E-cadherin (P<0.16). However, in SCC, 70% of the cases showed mild to moderate expression intensity that was statistically significant, compared to lichen planus and leukoplakia (P<0.004). Discussion & Conclusion: It seems that the severity of CD44 and E-cadherin incidence can indicate the changes in dysplasia and premalignancy of oral lichen planus and leukoplakia, compared to oral carcinomas. [ABSTRACT FROM AUTHOR]

Purpose: Dyskeratosis congenita (DC) is an inherited telomere biology disorder characterized clinically by mucocutaneous triad of reticulate hyperpigmentation, nail changes and oral leukoplakia. Bone marrow failure, pulmonary fibrosis and malignancies are the mainly life-threatening causes. There are X-linked recessive, autosomal dominant and autosomal recessive patterns of DC. DKC1 is the most common pathogenic mutation gene responsible for X-linked DC, and it encodes a protein, dyskerin, which is a component of telomerase holoenzyme complex essential for telomere maintenance. Patients with DC have very short telomeres, but the precise pathogenic mechanism remains unclear. This study aimed to identify the causative mutations in the DKC1 gene in three Chinese families with the X-linked form of DC. Patients and Methods: Three Chinese families with DC were included in this study. Whole exome sequencing and Sanger sequencing were performed to clarify the mutation of DKC1 gene. Measurement of relative telomere length through qPCR. Predictions of protein structure and function were performed using bioinformatics tools, including I-TASSER, Polyphen-2 and SIFT. Results: There were four males with DC and a female carrier in three Chinese pedigrees. The novel mutation c.92A>C (p. Q31P) and the missense mutation c.1058C>T (p. A353V) in DKC1 were identified. Both mutations locally changed the structure of dyskerin. Variant Q31P and A353V were predicted to have "deleterious" and "natural" effects on the function of dyskerin, respectively. Conclusion: The novel variant and missense variant detected in the DKC1 gene improve our understanding of DC and broaden the mutation spectrum of the DKC1 gene. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess the correlation between the expression of HSP70-2 and the development of oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC). Furthermore, the study evaluates the potential function of HSP70-2 in the pathogenesis of malignant diseases of the oral cavity., Methods: Using immunohistochemistry, RT-qPCR, Western blot, indirect immunofluorescence, and flow cytometry, the expression of HSP70-2 mRNA and protein in OPMD and OSCC tissues and cells was investigated. Using liposomal vector transient transfection to specifically knock down HSP70-2 gene expression in pertinent cell lines in vitro, the role of HSP70-2 in the development of oral malignant disorders was further investigated., Results: Studies on OPMD and OSCC tissues and cell lines revealed that HSP70-2 mRNA and protein were substantially expressed. Furthermore, it was discovered that the expression levels corresponded with the degree of disease development. Downregulating the HSP70-2 gene specifically reduces the proliferation, viability, colony-forming ability, migration, and invasion of OPMD and OSCC cells. Furthermore, it will cause apoptosis and control cell cycle arrest., Conclusion: HSP70-2 exhibited a significantly differential expression in both NM, OPMD, and OSCC tissues and cells. Furthermore, HSP70-2 plays a function in the development of oral malignant illnesses., Clinical Relevance: HSP70-2 is a promising biomarker for predicting the malignant transformation of Oral leukoplakia (OLK) and early diagnosis of OSCC. It is highly anticipated that HSP70-2 will be a potential target for the early intervention and blockage of OLK malignant transformation, given its established role in the development of oral malignant disorders. With regard to the treatment of OSCC, the same provides a referable target for siRNA-based therapeutic modalities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: 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., Methods: 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 CO 2 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)., Results: This case study demonstrates that two attempts at ablation of PVL using a CO 2 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., Conclusion: The results of CO 2 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., Key Points: 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., Plain Language Summary: 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 CO 2 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 CO 2 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., (© 2024 American Academy of Periodontology.)

Oral leukoplakia (OLK) is the most emblematic oral potentially malignant disorder that may precede the diagnosis of oral squamous cell carcinoma (OSCC) and has an overall malignant transformation rate of 9.8 %. Early intervention is crucial to reduce the malignant transformation rate from OLK to OSCC but the lack of effective local pharmaceutical preparations poses a challenge to clinical management. Rapamycin is speculated to prevent OLK from carcinogenesis and its inherent lipophilicity facilitates its penetration into stratum corneum. Nevertheless, hydrophilic hydrogels frequently encounter challenges when attempting to deliver lipophilic drugs. Furthermore, the oral cavity presents a complex environment defined by oral motor functions, saliva secretion cycles, dynamic fluctuations, and protective barriers comprising mucus and lipid layers. Consequently, addressing issues of muco-penetration and muco-adhesion is imperative for developing an effective drug delivery system aiming at delivering rapamycin to target oral potentially malignant disorders. Here, a dual-function hydrogel drug delivery system integrating adhesion and lipophilicity was successfully developed based on polyvinyl alcohol (PVA) and dioleoyl phosphatidylglycerol (DOPG) via dynamic boronic ester bonds. Rheological experiments based on orthogonal design revealed that PVA-DOPG hydrogels exhibited ideal adhesive strength (around 6 kPa) and could adhere to various surfaces in both dry and wet conditions. PVA-DOPG hydrogels also significantly promoted lipophilic molecules' penetration into stratum corneum (integrated fluorescence density of 6.95 ± 0.52 × 10 6 and mean fluorescence depth of 0.96 ± 0.07 mm) of ex-vivo porcine buccal mucosa ( p  < 0.001). Furthermore, PVA-DOPG hydrogels incorporating rapamycin inhibited malignant transformation of OLK mouse model induced by 4-Nitroquinoline N-oxide (4-NQO), distinct improvements in survival (the neoplasm incidence density at the 40th day is 0.0091) ( p  < 0.05), decrease in neoplasm incidence density of 36.36 % and inhibition rate in neoplasm volume of 75.04 ± 33.67 % have been demonstrated, suggesting the hydrogels were valuable candidates for potential applications in the management of OLK., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Introduction Oral lichen planus (OLP) comprises a chronic inflammatory autoimmune disease observed in the oral cavity. It most commonly manifests as white papules arranged confluently, drawing a picture of white lines in the form of a network (reticular form). It may emerge in other forms as well. In our study, the erosive form presents the most clinical interest. Among the biomarkers that participate in the tumorigenesis process, DAPK-1 seems promising, rendering its study necessary. This study focuses on the investigation of the presence of the DAPK-1 using immunohistochemistry in OLP compared to oral squamous cell carcinoma (OSCC), oral leukoplakia (OL), a well-established oral potentially malignant disorder, and normal oral epithelium to evaluate its possible role as an early predictor of the possibility of malignant transformation risk of OLP lesions. Methods To monitor the expression profile of the tumor suppressor protein DAPK-1, an immunohistochemical detection took place in 18 samples of OLP (reticular and erosive type), in 22 OSCC samples of all degrees of differentiation, in 30 OL samples of all degrees of dysplasia, and five normal tissue samples used as the control group. To complete the above procedure, immunohistochemistry was used in a semiquantative manner. The paraffin-embedded tissue samples were selected from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece, from biopsies performed in this department as well as from St. Lukas Hospital of Thessaloniki, Greece, between 2014 and 2019. The study was conducted per the Research and Ethics Committee guidelines of Aristotle University, School of Dentistry, and the Helsinki II declaration (protocol number 29/21.11.2018).  Results The statistical analysis showed that there was no statistically significant difference in DAPK-1 staining between normal tissues and OLP (p=0.588, independent-samples Kruskal-Wallis test). On the other hand, there was a statistically significant difference between OSCCs and OLPs (p<0,001, independent-samples Kruskal-Wallis test), with the extent of expression of DAPK-1 being greater in OLP than in OSCC. In addition, there was a statistical difference in DAPK-1 expression between OLPs and OLs (p=0,001, independent-samples Kruskal-Wallis test), with DAPK-1 being expressed more in OLP than in OL. Conclusion The DAPK-1, as a pro-inflammatory with its role as a tumor suppressor factor, was highly expressed in OLP, both reticular and erosive. The relatively milder expression of DAPK-1 in OL means that, between the two disorders, OLP is less likely to progress to oral cancer. On the other hand, OLP could also offer the background for further investigation of a possible correlation between methylation (immunohistochemical expression of proteins, deriving from potentially DNA-methylated genes) and the development of inflammation. It appears that DNA methylation is important in the regulation of inflammatory genes. Conversely, inflammation may regulate the DNA methylation of many genes involved in carcinogenesis and thus should be taken into account when studying the methylation behavior of genes such as DAPK-1 in pathologies characterized by a sparse inflammatory infiltrate., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of the School of Dentistry, Aristotle University of Thessaloniki issued approval 29/21.11.2018. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Papadopoulos et al.)

Objective: 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., Materials and Methods: 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., Results: 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., Conclusion: 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., (© 2024 The Author(s). Oral Diseases published by John Wiley & Sons Ltd.)