Oral Epithelial Dysplasia Research Articles

Quantitative proteogenomic characterization in MUC1 and MUC4 in oral squamous cell carcinoma, oral potentially malignant disorders, and normal oral mucosa in carcinogenesis.

Mucins are glycoproteins with a significant molecular weight that have a diverse range of biological functions. MUC1 & MUC4 are transmembrane mucin family members that are expressed in airway epithelial cells and body fluids. It is expressed excessively in numerous carcinomas in addition to their alteredexpression. A thorough review of the literature reveals very limited research about MUC1 & 4 expressionsin oral malignancies and oralpremalignant disorders. The aim of the research is to assess the pattern and quantity of gene expression in MUC1 & MUC4 individually in various grades of oral squamous cell carcinoma (OSCC), oral premalignant disorders (OPMDs)- oral epithelial dysplasia (OED), oral submucous fibrosis (OSF), oral lichen planus (OLP), and compared with normal oral mucosa (NOM). Immunohistochemistry and qRTPCR evaluation of MUC1 & 4 on sixty-three cases of OSCC, OPMD, and NOM was accomplished. The one-way ANOVA test and Chi-square test were done for statistical analysis. The overall immunoexpression of MUC1 & 4 increased significantly from NOM to OPMDs to OSCC. In the subgrades of OSCC and OPMDs, the staining intensity varied. For MUC4, the intensity was strongest in well-differentiated grades and MUC1, exhibiting a higher expression in poorly differentiated grades of OSCC and OPMDs. The study's results indicate that MUC1 & 4 individually are crucial formonitoringOSCC and OPMD pathogenesis as the former gives an idea of highly undifferentiated grades while the latter indicated more differentiated tumors and perhaps a better prognosis. Therefore, the two can be useful tumor markers for determining the severity and eliminating it in its early phases.

Oral epithelial dysplasia with lichenoid features shares proteomic overlap with oral epithelial dysplasia without lymphocytic immune response

Oral epithelial dysplasia with lichenoid features shares proteomic overlap with oral epithelial dysplasia without lymphocytic immune response

Evaluation of BUBR1, MCM2, and GMNN as oral cancer biomarkers.

Oral cancer is a public health problem worldwide. Late diagnosis results in a low survival rate. However, this tumor can arise from oral precancerous lesions and identification of biomarkers in precursor lesions has the potential for early diagnosis, improving patient survival. In this context, proteins involved in the cell cycle control are potentially promising. This study aimed to evaluate the importance of immunohistochemical expression of BUBR1, MCM2, and GMNN as biomarkers of oral carcinogenesis considering different oral sites. Sixty-six samples of oral epithelial dysplasia (from 33 males and 33 females) and 63 samples of oral squamous cell carcinoma (from 44 males and 19 females) were subjected to immunohistochemistry to detect some human proteins. Ki67 expression was included as a marker of cell proliferation. Marker expression was quantified by manually counting at least 1000 cells, and the labeling index was used in all statistical analyses. GMNN, MCM2, BUBR1 (nuclear and cytoplasmic labeling), and Ki67 expression levels were higher in carcinomas than in dysplasia (P < 0.05). Cytoplasmic BUBR1 was a good marker of malignancy (AUC = 0.8525, P < 0.05), but Ki67 was not (AUC = 0.5943, P = 0.0713). GMNN, MCM2, BUBR1, and Ki67 had higher expression in carcinoma than in dysplasia, regardless of the site of the lesion. Cytoplasmic BUBR1 has the potential to be used as a marker of tumor progression.

Anti-VEGFR2 neutralising antibody slows the progression of multistep oral carcinogenesis.

Angiogenesis plays an important role in cancer growth and metastasis, and it is considered a therapeutic target to control tumour growth following anti-angiogenic therapy. However, it is still unclear when tissues initiate angiogenesis during malignant transformation from premalignant condition and whether this premalignant condition could be a therapeutic target of anti-angiogenic therapy. In this study, we aimed to analyse the onset of angiogenesis by evaluating morphological and functional alterations of microvessels during oral multistep carcinogenesis using a 4-nitroquinoline 1-oxide (4NQO)-induced oral carcinogenesis mouse model. In the study, we initially confirmed that with the use of 4NQO, oral lesions develop in a stepwise manner from normal mucosa through oral epithelial dysplasia (OED) to oral squamous cell carcinoma (OSCC). Evaluation of CD31-immunostained specimens revealed that microvessel density (MVD) increases in a stepwise manner from OEDs. Histological and functional analyses revealed the structural abnormalities and leakage of blood vessels had already taken place in OED. Then we evaluated the expression profiles of Hif1a and Vegfa along with hypoxic status and found that OED exhibited increased Vegfa expression under hypoxic conditions. Finally, we tested the possibility of OEDs as a target of anti-angiogenic therapy and found that anti-VEGFR2 neutralising antibody in OED slowed the disease progression from OED to OSCC. These data indicate that an angiogenic switch occurs at the premalignant stage and morphological, and functional alterations of microvessels already exist in OED. These findings also elucidate the tumour microenvironment, which gradually develops along with carcinogenic processes, and highlight usefulness of the 4NQO-induced carcinogenesis model in the study of epithelial and stromal components, which will support epithelial carcinogenesis. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Human Papilloma Virus-Related Oral Mucosal Lesions in Turkey: A Retrospective Cohort Study

Introduction: The human papillomavirus (HPV) is the etiological agent of a variety of oral mucosal benign and pre/malignant lesions, which demonstrate a wide range of prevalence according to geographic regions. Material and Methods: This study specifically examined the typing of HPV-associated oral mucosal lesions in Turkish patients. The DNA from FFPE blocks of 228 lesions was utilized for this purpose. A total of 87 oral mucosal lesions were classified as benign, 68 as premalignant, and 73 as malignant. DNA from these lesions was amplified using polymerase chain reaction, and genotypes were identified using restriction fragment length polymorphisms (RFLP). Results: HPV-DNA was identified in 17 out of 228 patients, indicating a prevalence incidence of 7.4%. In benign oral lesions, the prevalence of HPV-DNA was 9.2% (8/87 cases), whereas in premalignant, oral epithelial dysplasia, and oral squamous cell carcinoma lesions, it was 6.9% (9/141 cases). A significant statistical difference was found between patients who tested positive for HPV and those who tested negative in terms of the location of the lesion and the age of the patients (p = 0.0097, p = 0.02, respectively). Conclusions: This study underscores the considerable prevalence of HPV infection in oral mucosal lesions among individuals in Central Anatolia, Turkey.

Artificial Intelligence Applications in Oral Cancer and Oral Dysplasia.

Oral squamous cell carcinoma (OSCC) is a highly unpredictable disease with devastating mortality rates that have not changed over the past decades, in the face of advancements in treatments and biomarkers, which have improved survival for other cancers. Delays in diagnosis are frequent, leading to more disfiguring treatments and poor outcomes for patients. The clinical challenge lies in identifying those patients at the highest risk of developing OSCC. Oral epithelial dysplasia (OED) is a precursor of OSCC with highly variable behavior across patients. There is no reliable clinical, pathological, histological, or molecular biomarker to determine individual risk in OED patients. Similarly, there are no robust biomarkers to predict treatment outcomes or mortality in OSCC patients. This review aims to highlight advancements in artificial intelligence (AI)-based methods to develop predictive biomarkers of OED transformation to OSCC or predictive biomarkers of OSCC mortality and treatment response. Biomarkers such as S100A7 demonstrate promising appraisal for the risk of malignant transformation of OED. Machine learning-enhanced multiplex immunohistochemistry workflows examine immune cell patterns and organization within the tumor immune microenvironment to generate outcome predictions in immunotherapy. Deep learning (DL) is an AI-based method using an extended neural network or related architecture with multiple "hidden" layers of simulated neurons to combine simple visual features into complex patterns. DL-based digital pathology is currently being developed to assess OED and OSCC outcomes. The integration of machine learning in epigenomics aims to examine the epigenetic modification of diseases and improve our ability to detect, classify, and predict outcomes associated with epigenetic marks. Collectively, these tools showcase promising advancements in discovery and technology, which may provide a potential solution to addressing the current limitations in predicting OED transformation and OSCC behavior, both of which are clinical challenges that must be addressed in order to improve OSCC survival.

The expression of immune checkpoint proteins PD-L1 and TIM3 in mouse and human head and neck squamous cell carcinoma.

The aim of this study was to examine the expression of programmed death-ligand 1 (PD-L1) and of T cell immunoglobulin and mucin domain-containing protein (TIM3) in oral epithelial dysplasia and head and neck squamous cell carcinoma (HNSCC). Mouse HNSCC was induced with 4-nitroquinoline-1 oxide (4NQO). Oral epithelial dysplastic lesions, carcinoma in situ and HNSCC lesions were stained with anti-PD-L1 and TIM3 antibodies. The expression of PD-L1 and TIM3 in tumor cells and immune cells was semiquantitatively measured and compared. In parallel, human dysplasia and HNSCC were stained with anti-PD-L1 and anti-TIM3. The expression pattern of PD-L1+ and TIM3+ cells was further compared. In human and mouse samples both PD-L1 and TIM3 were found to be expressed in neoplastic and immune cells in HNSCC, but not in dysplasia. There was no significant difference in PD-L1 and TIM3 expression between metastatic and nonmetastatic HNSCC. We conclude that the 4NQO-induced mouse HNSCC model may be an excellent preclinical model for immune checkpoint therapy.

Molecular profiling of oral epithelial dysplasia and oral squamous cell carcinoma using next generation sequencing

BackgroundNext generation sequencing (NGS) is a massive, high-throughput sequencing technology used to analyze various mutations and genetic changes in cancer. Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck region. OSCC usually arises from oral potentially malignant disorders, like oral leukoplakia, oral submucous fibrosis and erythroplakia, and shows mutation of tumor suppressor genes, and several other critical genes involved in apoptotic pathways, cell migration, and cell growth. AimTo analyze the molecular profiles of oral epithelial dysplasia and different grades of oral squamous cell carcinoma using NGS in the Indian subpopulation. Methodology21 patients (5 patients each of well differentiated, moderately differentiated, poorly differentiated squamous cell carcinoma, severe epithelial dysplasia, and 1 normal appearing mucosal tissue from apparently healthy individuals) were included in the study. Next generation sequencing was carried out using 50 hotspot gene panel. Protein-protein analysis was carried out using STRING Consortium 2023 and the methylation profile of the expressed genes was evaluated using the UALCAN portal. ResultsSevere epithelial dysplasia showed TP53 (c.743G>A, p.R248Q) pathogenic mutations (SNV) in suboptimal QC parameters. Well differentiated squamous cell carcinoma showed TP53 (c.328delC, p.Arg110fs*13), APC (c.4135G>T, p.Glu1379*), and FBXW7 (c.832C>T, p.Arg278*) mutations. CTNNB1 (c.134C>T, p.Ser45PheS45F), TP53 (c.637C>T, Arg213TerR213*), NRAS (c.183A>C, p.Gln61HisQ61H) and PDGFRA (c.1672C>T, p.Arg558Cys) mutations were seen in moderately differentiated squamous cell carcinoma. No pathogenic mutations were evident in poorly differentiated squamous cell carcinoma. STRING analysis showed that all the expressed proteins in each group were interrelated to each other. No significant difference was evident in the methylation profile of all the expressed genes when compared to the normal controls. ConclusionThe results obtained in this study explain the diverse genetic mutations in various grades of oral squamous cell carcinoma. Identification of these mutations would help in providing better treatment, designing a proper treatment plan for the patients with OSCC and support minimal intervention medicine.

P53 Abnormal Oral Epithelial Dysplasias are Associated With High Risks of Progression and Local Recurrence—A Retrospective Study in a Longitudinal Cohort

Grading of oral epithelial dysplasia (OED) can be challenging with considerable intraobserver and interobserver variability. Abnormal immunohistochemical staining patterns of the tumor suppressor protein, p53, have been recently shown to be potentially associated with progression in OED. We retrospectively identified 214 oral biopsies from 203 patients recruited in a longitudinal study between 2001 and 2008 with a diagnosis of reactive, nondysplastic lesions, low-grade lesions (mild OED and moderate OED) and high-grade lesions (HGLs; severe OED/carcinoma in situ). Tissue microarrays were constructed from the most representative area of the pathology. Three consecutive sections were sectioned and stained for hematoxylin and eosin, p53 immunohistochemistry, and p16 immunohistochemistry. The staining results were reviewed by 2 pathologists (Y.C.K.K., C.F.P.) blinded to clinical outcome. Samples were categorized into p53 abnormal OED (n = 46), p53 conventional OED (n = 118), and p53 human papillomavirus (HPV) OED (HPV associated) (n = 12) using a previously published pattern-based approach. All cases of p53 HPV OED (HPV associated) were identified in HGLs. In contrast, cases of p53 abnormal OED were observed in mild OED (9.5%), moderate OED (23%), and severe OED/carcinoma in situ (51%). None of the 27 reactive or nondysplastic lesions showed abnormal p53 staining patterns. Among the 135 low-grade lesions, 23 cases (17.0%; 2 mild OEDs and 21 moderate OEDs) progressed to HGL or squamous cell carcinoma, with 11 cases showing progression within the first 3 years. Remarkably, 82% (9/11) of these faster progressors showed abnormal p53 patterns. Survival analysis revealed that p53 abnormal OED had significantly poorer progression-free probability (P < .0001) with hazard ratio of 11.24 (95% CI, 4.26-29.66) compared with p53 conventional OED. Furthermore, p53 abnormal OED had poorer local recurrence–free survival compared with p53 wild-type OED (P = .03). The study supports that OED with p53 abnormal pattern is at high risk for progression and recurrence independent of the dysplasia grade.

Dental pulp stem cells promote malignant transformation of oral epithelial cells through mitochondrial transfer.

Oral epithelial dysplasia includes a range of clinical oral mucosal diseases with potentially malignant traits. Dental pulp stem cells (DPSCs) are potential candidates for cell-based therapies targeting various diseases. However, the effect of DPSCs on the progression of oral mucosal precancerous lesions remains unclear. Animal experiments were conducted to assess the effect of human DPSCs (hDPSCs). We measured the proliferation, motility and mitochondrial respiratory function of the human dysplastic oral keratinocyte (DOK) cells cocultured with hDPSCs. Mitochondrial transfer experiments were performed to determine the role mitochondria from hDPSCs in the malignant transformation of DOK cells. hDPSCs injection accelerated carcinogenesis in 4NQO-induced oral epithelial dysplasia in mice. Coculture with hDPSCs increased the proliferation, migration, invasion and mitochondrial respiratory function of DOK cells. Mitochondria from hDPSCs could be transferred to DOK cells, and activated mTOR signaling pathway in DOK cells. Our study demonstrates that hDPSCs activate the mTOR signaling pathway through mitochondrial transfer, promoting the malignant transformation of oral precancerous epithelial lesions.

Prognostic nomogram for proliferative verrucous leukoplakia

BackgroundProliferative verrucous leukoplakia (PVL) is a special type of leukoplakia characterized by high rate of malignant transformation into oral squamous cell carcinoma (OSCC). This study aimed to analyze the canceration risk and prognostic factors of PVL and establish effective diagnostic and prognostic predictive models. Materials and methodsA total of 467 patients were enrolled, including 170 cases of PVL. The independent risk and prognostic factors of PVL were analyzed by univariable and multivariable logistic regression. Nomogram models were constructed to predict the canceration risk and prognosis of PVL. The predictive power was evaluated by Hosmer–Lemeshow test, receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis. ResultsMultivariable logistic regression analyses identified that canceration risk factors of PVL included sex, lesion sites, clinical presentation, non-smoker and oral epithelial dysplasia (OED). The independent prognostic factors of PVL were sex, clinical presentation, local irritants and OED. Diagnosis and prognostic nomogram models were constructed. The areas under the ROC curve were 0.945 and 0.893, respectively. The calibration plots showed strong agreement between the prediction and observation. Decision curve analysis indicated that the models provided significant clinical benefits for patients. ConclusionOur study established and validated the diagnosis and prognostic predictive nomogram models, which were accurate to predict the canceration risk and prognostic factors of PVL, providing individualized clinical decisions for clinical work.

A Deep-Learning Model to Predict Risk of Malignant Transformation in Oral Epithelial Dysplasia

A Deep-Learning Model to Predict Risk of Malignant Transformation in Oral Epithelial Dysplasia

Utility of p53 Immunohistochemistry in Diagnosis of Human Papillomavirus Associated Oral Epithelial Dysplasia: A Retrospective Study of 105 Patients

Utility of p53 Immunohistochemistry in Diagnosis of Human Papillomavirus Associated Oral Epithelial Dysplasia: A Retrospective Study of 105 Patients

The Correlation of p53, CK13, CK17, and Ki67 Immunostaining Patterns in Assisting the Histopathologic Grading of Oral Epithelial Dysplasia

The Correlation of p53, CK13, CK17, and Ki67 Immunostaining Patterns in Assisting the Histopathologic Grading of Oral Epithelial Dysplasia

Consensus in Diagnosis and Classification of Oral Epithelial Dysplasia: A Comparative Analysis of H&E-Stained Sections with and without p53/p16 Immunohistochemistry

Consensus in Diagnosis and Classification of Oral Epithelial Dysplasia: A Comparative Analysis of H&E-Stained Sections with and without p53/p16 Immunohistochemistry

Fluorescence Visualization-Guided Surgery Improves Local Control for Mandibular Squamous Cell Carcinoma

BackgroundLocal recurrence is common in mandibular squamous cell carcinoma. Fluorescence visualization is a non-invasive technology that can detect oral epithelial dysplasia around mandibular squamous cell carcinoma, and it can potentially reduce local recurrence. PurposeThe purpose of this study was to measure and compare local control between fluorescence visualization-guided surgery and conventional surgery for patients with Stages I or II mandibular SCC. Study design, setting, sampleThis retrospective cohort study was conducted at Tokyo Dental College, Chiba Hospital, or Chiba Dental Center. The medical records of mandibular squamous cell carcinoma patients from 2000 to 2021 were analyzed. Patients from any sex and 18 years of age or older with complete records who received surgery for mandibular squamous cell carcinoma in the early stages were included in this study. Predictor variableThe predictor variable was operative treatment and was divided into two groups, conventional or fluorescence visualization-guided surgery. Outcome variablesThe outcome variable is 5-year local control defined as no recurrence at or within 20 mm of the surgical site. CovariatesCovariates included demographic variables of age, sex, clinical and pathological characteristics, forms of resection, lifestyle, and quality of life. AnalysisData analysis was performed by carrying out chi-square tests. Survival outcome was performed by the Kaplan-Meier method, which was used to calculate and stratify the log-rank test.; P-values <0.05 indicated statistical significance. ResultsThis study sample was composed of 56 subjects with a mean age of 68.5 years old (SD 13.7), and 33 (58.9%) were female. There were 36 (64.3%) and 20 (35.7%) subjects in the conventional and fluorescence visualization-guided surgery groups. The characteristics and quality of life did not differ significantly between the two groups. Five-year local control with fluorescence visualization-guided surgery was statistically significantly higher than conventional surgery (P=0.04, 94.4% vs. 77.2%). Multivariate analysis for local control rate only identified fluorescence visualization-guided surgery (P=0.004; hazard ratio=0.11, 95% confidence interval=0.46, 0.88). Conclusions and RelevanceOn mandibular squamous cell carcinoma, local control was 94.4% in fluorescence visualization-guided surgery vs. 77.2% in conventional surgery. For mandibular squamous cell carcinoma at stages I and II, fluorescence visualization-guided surgery was associated with improved local control.

Evaluation of Immunohistochemical Marker Bcl-2 in Epithelial Dysplasia and Squamous Cell Carcinoma of the Oral Cavity.

Squamous cell carcinoma of the oral cavity is the most common malignancy noted globally.Pathogenesis of premalignant and malignant oral lesions is mainly attributed to the alteration in the molecular mechanisms that regulate apoptosis and cell proliferation. B-cell lymphoma gene 2 (Bcl-2) is the anti-apoptotic gene that prolongs cell survival by inhibiting apoptosis and is associated with the aggressive behaviour of malignant tumours. The aim of the study was to evaluate Bcl-2 expression in oral squamous cell carcinoma and dysplastic lesions of the oral cavity and to compare its expression with various grades of dysplasia and carcinoma. A hospital-based cross-sectional study was done on 80 clinically suspected cases of dysplastic and malignant oral cavity lesions received in the histopathology section of the Department of Pathology of Shri BM Patil Medical College Hospital and Research Center, Vijaypura, Karnataka. Out of 80 cases, 40 were squamous cell carcinoma, and 40 were dysplastic lesions of the oral cavity. For each case, two sections measuring 4 μm thickness were prepared. Hematoxylin and eosin staining was performed on one section, and Bcl-2 IHC staining was performed on another. Bcl-2 expression evaluation was done for each case of oral epithelial dysplasia and squamous cell carcinoma. Out of 40 cases of squamous cell carcinoma, 15 were well-differentiated, 22 were moderately differentiated, and three were poorly differentiated. In well-differentiated oral squamous cell carcinoma, Bcl-2 positivity was grade 0 in 66.7% of cases and grade 1 in 33.3% of cases. In moderately differentiated oral squamous cell carcinoma, Bcl-2 positivity was grade 1 in 63.6% of cases and grade 2 in 36.4% of cases. In poorly differentiated oral squamous cell carcinoma, Bcl-2 positivity was grade 1 in 33.3% and grade 2 in 66.7% of cases. Out of 40 cases of dysplastic lesions, 11 cases showed severe dysplasia, 11 cases showed moderate dysplasia and 18 cases showed mild dysplasia. grade 2 positivity was seen in 72.7% of cases of severe dysplasia and 63.6 % of cases of moderate dysplasia. In mild dysplasia, all of the cases showed grade 0 Bcl-2 expression. In poorly differentiated oral squamous cell carcinoma Bcl-2 positivity was high and low in well-differentiated oral squamous cell carcinoma. Bcl-2 expression was higher in severe dysplasia compared to moderate dysplasia, which may indicate aggressive behaviour of tumour in poorly differentiated oral squamous cell carcinoma and severe dysplasia.

Understanding interobserver variability of pathologists to improve oral epithelial dysplasia grading.

This study aimed to understand reasons for interobserver variability in the grading of oral epithelial dysplasia (OED) through a survey of pathologists to provide insight for improvements in the reliability and reproducibility of OED diagnoses. The study design included quantitative and qualitative methodology. A pre-validated 31-item questionnaire was distributed to general, head and neck, and oral and maxillofacial histopathology specialists worldwide. A total of 132 pathologists participated and completed the questionnaire. Over two-thirds used the three-tier grading system for OED, while about a third used both binary and three-tier systems. Regular reporters of OED preferred the three-tier system and grading architectural features. Continuing education significantly aided recognition of architectural and cytological changes. Irregular epithelial stratification and drop-shaped rete ridges had the lowest prognostic value and recognition scores, while loss of epithelial cell cohesion had the highest. Most participants used clinical information and often sought a second opinion when grading OED. Our study has found that frequency of OED reporting and attendance of CME/CPD can play an important role in grading OED. Variations in the prognostic value of individual histological features and the use of clinical information may further contribute to interobserver variability.

QuPath for automated analysis of digital images of oral epithelial dysplasia

Abstract Objectives: Grading of oral epithelial dysplasia (OED) has been plagued with intra-observer and inter-observer variations. To overcome this subjectivity, a more objective digital image analysis is obligatory using computer-aided software. The use of open-source software like QuPath, which is a new bio-image evaluation software program, may fulfil this growing need in virtual pathology. This study used the QuPath software for automatic analysis of morphometric parameters in hematoxylin and eosin (H and E)-stained digital images of oral epithelial dysplasia. Methodology: 150 H and E digital images of varying grades of OED captured under 40x magnification were processed using QuPath software for automatic analysis of cellular and nuclear parameters. Results: The parameters that showed statistical significance included nuclear hematoxylin OD, nuclear eosin OD, cellular hematoxylin OD, cellular eosin OD, cytoplasm hematoxylin OD, and cytoplasmic eosin OD (P &lt; 0.05), while none of the other parameters showed statistically significant differences. A prediction accuracy of 76%, 74%, and 70% for mild, moderate, and severe dysplasia was obtained, respectively. Conclusion: The quantitative results outlined in this paper are encouraging to indicate that the use of this technique may improve the diagnostic reliability of OED. Morphometric analysis of OED using Qupath software can be fast and reproducible and can be quantitated automatically.

Correlation between clinicopathological indices and expression of cluster of differentiation 24 and cluster of differentiation 44 biomarkers in oral epithelial dysplasia and oral squamous cell carcinoma patients: A follow-up study

Correlation between clinicopathological indices and expression of cluster of differentiation 24 and cluster of differentiation 44 biomarkers in oral epithelial dysplasia and oral squamous cell carcinoma patients: A follow-up study