Displaying publications 1 - 20 of 36 in total

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  1. Chan SW, Kallarakkal TG, Abraham MT
    Asian Pac J Cancer Prev, 2014;15(5):2145-52.
    PMID: 24716948
    BACKGROUND: The survival rate for oral squamous cell carcinoma (OSCC) has remained generally unchanged in the past three decades, underlining the need for more biomarkers to be developed to aid prognostication and effective management. The prognostic potential of E-cadherin expression in OSCCs has been variable in previous studies while galectin-9 expression has been correlated with improved prognosis in other cancers. The aim of the present study was to investigate the expression of galectin-9 and E-cadherin in OSCC and their potential as prognostic biomarkers.

    MATERIALS AND METHODS: E-cadherin and Galectin-9 expression was examined by immunohistochemistry in 32 cases of OSCC of the buccal mucosa (13 with and 19 without lymph node metastasis), as well as 6 samples of reactive lesions and 5 of normal buccal mucosa.

    RESULTS: The expression of E-cadherin in OSCC was significantly lower than the control tissues but galectin-9 expression was conversely higher. Median E-cadherin HSCOREs between OSCCs positive and negative for nodal metastasis were not significantly different. Mean HSCOREs for galectin-9 in OSCC without lymph node metastasis (127.7 ± 81.8) was higher than OSCC with lymph node metastasis (97.9 ± 62.9) but this difference was not statistically significant.

    CONCLUSIONS: E-cadherin expression is reduced whilst galectin-9 expression is increased in OSCC. However, the present results suggest that E-cadherin and galectin-9 expression may not be useful as prognostic markers for OSCC.

  2. Tegginamani AS, Shivakumar VH, Kallarakkal TG, Ismail SM, Abraham MT, Bin Zamzuri AT
    J Oral Maxillofac Pathol, 2020 09 09;24(2):400.
    PMID: 33456258 DOI: 10.4103/jomfp.JOMFP_272_19
    Background: Oral potentially malignant disorders have a risk for malignant transformation but are difficult to reliably identify and predict which patients are at the risk for malignant transformation. OCT4 has been hypothesized to play a key oncogenic driver in a variety of solid tumors. A deeper understanding of the aberrant molecular pathways which lead to carcinogenesis needs to be identified by the potential markers.

    Aims: To assess the OCT4 stemness factor in oral leukoplakia for its potential risk to malignant transformation.

    Settings and Design: 20 cases of oral leukoplakia were obtained from archives at Oral Cancer Research & Coordinating center (OCRCC) Malaysia Subjects and Methods: 20 cases of oral leukoplakia were assessed by OCT4 immunohistochemically. Oral squamous cell carcinoma was used as a control.

    Result: no expression of OCT 4 was observed in any cases of oral leukoplakia.

    Conclusion: The molecular mechanisms of Oct4 regulation and in particular of its switch on and off in tissues depends upon its microenvironment, which makes it challenging in fundamental and applied research fields of regenerative medicine and cancer therapy. It's better that patients should undergo multiple biopsies for the early detection of malignant transformation with close follow-up during the first two to three years, a large amount of work remains to be done with multi-marker panel investigation, as cure rates have remained constant over three decades.

  3. Fadlullah MZ, Chiang IK, Dionne KR, Yee PS, Gan CP, Sam KK, et al.
    Oncotarget, 2016 May 10;7(19):27802-18.
    PMID: 27050151 DOI: 10.18632/oncotarget.8533
    Emerging biological and translational insights from large sequencing efforts underscore the need for genetically-relevant cell lines to study the relationships between genomic alterations of tumors, and therapeutic dependencies. Here, we report a detailed characterization of a novel panel of clinically annotated oral squamous cell carcinoma (OSCC) cell lines, derived from patients with diverse ethnicity and risk habits. Molecular analysis by RNAseq and copy number alterations (CNA) identified that the cell lines harbour CNA that have been previously reported in OSCC, for example focal amplications in 3q, 7p, 8q, 11q, 20q and deletions in 3p, 5q, 8p, 18q. Similarly, our analysis identified the same cohort of frequently mutated genes previously reported in OSCC including TP53, CDKN2A, EPHA2, FAT1, NOTCH1, CASP8 and PIK3CA. Notably, we identified mutations (MLL4, USP9X, ARID2) in cell lines derived from betel quid users that may be associated with this specific risk factor. Gene expression profiles of the ORL lines also aligned with those reported for OSCC. By focusing on those gene expression signatures that are predictive of chemotherapeutic response, we observed that the ORL lines broadly clustered into three groups (cell cycle, xenobiotic metabolism, others). The ORL lines noted to be enriched in cell cycle genes responded preferentially to the CDK1 inhibitor RO3306, by MTT cell viability assay. Overall, our in-depth characterization of clinically annotated ORL lines provides new insight into the molecular alterations synonymous with OSCC, which can facilitate in the identification of biomarkers that can be used to guide diagnosis, prognosis, and treatment of OSCC.
  4. Kong YH, Syed Zanaruddin SN, Lau SH, Ramanathan A, Kallarakkal TG, Vincent-Chong VK, et al.
    PLoS One, 2015;10(7):e0134045.
    PMID: 26214683 DOI: 10.1371/journal.pone.0134045
    Oral squamous cell carcinoma (OSCC) is an aggressive disease accounting for more than 260,000 cancer cases diagnosed and 128,000 deaths worldwide. A large majority of cancer deaths result from cancers that have metastasized beyond the primary tumor. The relationship between genetic changes and clinical outcome can reflect the biological events that promote cancer's aggressive behavior, and these can serve as molecular markers for improved patient management and survival. To this end, epithelial-mesenchymal transition (EMT) is a major process that promotes tumor invasion and metastasis, making EMT-related proteins attractive diagnostic biomarkers and therapeutic targets. In this study, we used immunohistochemistry to study the expression of a panel of transcription factors (TWIST1, SNAI1/2, ZEB1 and ZEB2) and other genes intimately related to EMT (CDH1 and LAMC2) at the invasive tumor front of OSCC tissues. The association between the expression of these proteins and clinico-pathological parameters were examined with Pearson Chi-square and correlation with survival was analyzed using Kaplan Meier analysis. Our results demonstrate that there was a significant differential expression of CDH1, LAMC2, SNAI1/2 and TWIST1 between OSCC and normal oral mucosa (NOM). Specifically, CDH1 loss was significantly associated with Broder's grading, while diffused LAMC2 was similarly associated with non-cohesive pattern of invasion. Notably, co-expression of TWIST1 and ZEB2 in OSCC was significantly associated with poorer overall survival, particularly in patients without detectable lymph node metastasis. This study demonstrates that EMT-related proteins are differentially expressed in OSCC and that the co-expression of TWIST1 and ZEB2 could be of clinical value in identifying patients with poor survival for appropriate patient management.
  5. Haron N, Zain RB, Nabillah WM, Saleh A, Kallarakkal TG, Ramanathan A, et al.
    Telemed J E Health, 2017 03;23(3):192-199.
    PMID: 27541205 DOI: 10.1089/tmj.2016.0128
    INTRODUCTION: This study examined the concordance in clinical diagnosis of high-risk lesions in the oral cavity and referral decisions between clinical oral examination (COE) and teledentistry.

    MATERIALS AND METHODS: Sixteen individuals with a range of oral potentially malignant disorders (OPMD) and normal oral mucosa were included. Five areas of the oral cavity were photographed by three dentists using mobile phone cameras with 5 MP-13 MP resolutions. On the same day, the patients were given COE by two oral medicine specialists (OMS) and 3 weeks later, they reviewed the images taken using the phone, and concordance was examined between the two by Kappa statistics. The sensitivity and specificity of clinical diagnosis using the phone images were also measured. Pre- and post-program questionnaires were answered by both the dentists and the OMS to determine the feasibility of integrating teledentistry in their clinical practice.

    RESULTS: The Kappa values in determining the presence of lesion, category of lesion (OPMD or not), and making referral decision were moderate to strong (0.64-1.00). The overall sensitivity was more than 70% and specificity was 100%. The false negative rate decreased as the camera resolution increased. All dentists agreed that the process could facilitate early detection of oral mucosal lesion, and was easy to use in the clinic.

    CONCLUSIONS: This study provides evidence that teledentistry can be used for communication between primary care and OMS and could be readily integrated into clinical setting for patient management.

  6. Ng SW, Syamim Syed Mohd Sobri SN, Zain RB, Kallarakkal TG, Amtha R, Wiranata Wong FA, et al.
    PMID: 35068209 DOI: 10.1177/13558196211053110
    OBJECTIVE: Oral cancer is amenable to early detection but remains a prominent cause of mortality in the Asia Pacific region. This study aimed to identify barriers to early detection and management of oral cancer in the Asia Pacific region.

    METHODS: A mixed-methods approach was employed triangulating findings from a survey and focus groups. The survey was conducted among seven representative members of the Asia Pacific Oral Cancer Network (APOCNET) across six countries. Focus groups were conducted to gain deeper insights into the findings of the survey.

    RESULTS: The identified barriers were a lack of national cancer control strategies and cancer registries and the limited availability of trained health care professionals. Overcoming these challenges in the Asia Pacific region where resources are scarce will require collaborative partnerships in data collection and novel approaches for continuous professional training including eLearning. Further, to overcome the lack of trained health care professionals, innovative approaches to the management of oral potentially malignant lesions and oral cancer including telemedicine were suggested.

    CONCLUSION: The findings of this study should be taken into account when charting national cancer control plans for oral cancer and will form the basis for future collaborative studies in evaluating effective measures to improve oral cancer detection and management in low- and middle-income countries.

  7. Haron N, Rajendran S, Kallarakkal TG, Zain RB, Ramanathan A, Abraham MT, et al.
    Oral Dis, 2023 Mar;29(2):380-389.
    PMID: 33914993 DOI: 10.1111/odi.13892
    OBJECTIVE: To evaluate the accuracy of MeMoSA®, a mobile phone application to review images of oral lesions in identifying oral cancers and oral potentially malignant disorders requiring referral.

    SUBJECTS AND METHODS: A prospective study of 355 participants, including 280 with oral lesions/variants was conducted. Adults aged ≥18 treated at tertiary referral centres were included. Images of the oral cavity were taken using MeMoSA®. The identification of the presence of lesion/variant and referral decision made using MeMoSA® were compared to clinical oral examination, using kappa statistics for intra-rater agreement. Sensitivity, specificity, concordance and F1 score were computed. Images were reviewed by an off-site specialist and inter-rater agreement was evaluated. Images from sequential clinical visits were compared to evaluate observable changes in the lesions.

    RESULTS: Kappa values comparing MeMoSA® with clinical oral examination in detecting a lesion and referral decision was 0.604 and 0.892, respectively. Sensitivity and specificity for referral decision were 94.0% and 95.5%. Concordance and F1 score were 94.9% and 93.3%, respectively. Inter-rater agreement for a referral decision was 0.825. Progression or regression of lesions were systematically documented using MeMoSA®.

    CONCLUSION: Referral decisions made through MeMoSA® is highly comparable to clinical examination demonstrating it is a reliable telemedicine tool to facilitate the identification of high-risk lesions for early management.

  8. Rajendran S, Lim JH, Yogalingam K, Kallarakkal TG, Zain RB, Jayasinghe RD, et al.
    Oral Dis, 2023 Jul;29(5):2230-2238.
    PMID: 35398971 DOI: 10.1111/odi.14206
    OBJECTIVE: To describe the development of a platform for image collection and annotation that resulted in a multi-sourced international image dataset of oral lesions to facilitate the development of automated lesion classification algorithms.

    MATERIALS AND METHODS: We developed a web-interface, hosted on a web server to collect oral lesions images from international partners. Further, we developed a customised annotation tool, also a web-interface for systematic annotation of images to build a rich clinically labelled dataset. We evaluated the sensitivities comparing referral decisions through the annotation process with the clinical diagnosis of the lesions.

    RESULTS: The image repository hosts 2474 images of oral lesions consisting of oral cancer, oral potentially malignant disorders and other oral lesions that were collected through MeMoSA® UPLOAD. Eight-hundred images were annotated by seven oral medicine specialists on MeMoSA® ANNOTATE, to mark the lesion and to collect clinical labels. The sensitivity in referral decision for all lesions that required a referral for cancer management/surveillance was moderate to high depending on the type of lesion (64.3%-100%).

    CONCLUSION: This is the first description of a database with clinically labelled oral lesions. This database could accelerate the improvement of AI algorithms that can promote the early detection of high-risk oral lesions.

  9. Zain RB, Pateel DGS, Ramanathan A, Kallarakkal TG, Wong GR, Yang YH, et al.
    J Cancer Educ, 2020 Aug 21.
    PMID: 32821988 DOI: 10.1007/s13187-020-01814-1
    Early diagnosis of oral cancer results in less aggressive treatment and improves the quality of life and overall 5-year survival rate. Well-trained dental professionals can play a crucial role in the early detection of oral cancers. The present study aims to determine the effectiveness of the training program "OralDETECT", a spaced repetitive, test-enhanced learning tool with a corrective feedback mechanism for early detection of oral cancer. Thirty-two dentists and 259 dental students from three Malaysian dental schools were involved in this study. All participants were trained and calibrated to recognize oral potentially malignant disorders (OPMD) and oral cancer using "OralDETECT", which is comprised of a series of pre-test, lecture, post-tests and review sessions. The percentage of correct answers (scores) for each test given by the participants was calculated and analysed using a paired t test. It was found that the overall percentage of diagnostic accuracy for both dental professionals and student groups increased to above 80% from the pre-tests to the final post-tests. There was a significant improvement in overall scores between the pre-tests and all three post-tests for the dental professional groups and the student groups. The diagnostic accuracy for individual OPMD and lesions suspicious of oral cancer also increased to above 80% for both groups. The results of our study demonstrate that the "OralDETECT" is an efficient and effective competency tool which can be used to train dental professionals and students for the early detection of OPMD and oral cancer.
  10. Zain RB, Kallarakkal TG, Ramanathan A, Kim J, Tilakaratne WM, Takata T, et al.
    Asian Pac J Cancer Prev, 2016 01 09;17(9):4491.
    PMID: 27865210 DOI: 10.7314/APJCP.2016.17.(9).4491
    Verruco-papillary lesions (VPLs) of the oral cavity described in the literature involve a spectrum of conditions
    including squamous papilloma, verruca vulgaris, focal epithelial hyperplasia, condyloma, proliferative verrucous
    leukoplakia and verrucous carcinoma. A majority of the VPLs are slow growing, benign in nature and have a
    viral aetiology. Virus associated benign mucosal outgrowths are not too difficult to diagnose either clinically or
    by microscopy. Apart from virus-associated lesions, VPLs harboring malignant potential or behaviour such as
    verrucous carcinoma, proliferative verrucous leukoplakia, oral verrucous hyperplasia (OVH), oral papillary
    squamous cell carcinoma (PSCC) and oral conventional squamous cell carcinoma with papillary features (CSCC)
    need to be further clarified for better understanding of their predictable biologic behavior and appropriate
    treatment. Current understanding of potentially malignant VPLs is perplexing and is primarily attributed to
    the use of confusing and unsatisfactory terminology. In particular, the condition referred to as oral verrucous
    hyperplasia (OVH) poses a major diagnostic challenge. OVH represents a histopathological entity whose clinical
    features are not well recognised and is usually clinically indistinguishable from a verrucous carcinoma and a
    PSCC or a CSCC. A consensus report published by an expert working group from South Asia as an outcome of
    the ‘First Asian Regional Meeting on the Terminology and Criteria for Verruco-papillary Lesions of the Oral
    Cavity’ held in Kuala Lumpur, Malaysia, recognised the clinical description of these OVH as a new entity named
    ‘Exophytic Verrucous Hyperplasia’. Previously described clinical features of OVH such as the ‘blunt’ or ‘sharp’
    variants; and the ‘mass’ or ‘plaque’ variants can now collectively fall under this newly described entity. This paper
    discusses in detail the application of the standardized criteria guidelines of ‘Exophytic Verrucous Hyperplasia’
    as published by the expert group which will enable clinicians and pathologists to uniformly interpret their pool
    of OVH cases and facilitate a better understanding of OVH malignant potential.
  11. Kazakydasan S, Rahman ZA, Ismail SM, Abraham MT, Kallarakkal TG
    J Oral Pathol Med, 2016 Jul 15.
    PMID: 27417330 DOI: 10.1111/jop.12476
    Lymph node metastasis in oral squamous cell carcinoma (OSCC) is a well-known independent prognostic factor. However, the identification of occult tumour cells within the lymph nodes has remained a challenge for the pathologist as well as the clinician.
  12. Abdelrahim LM, Peh SC, Kallarakkal TG
    Malays J Pathol, 2018 Apr;40(1):49-56.
    PMID: 29704384
    INTRODUCTION: Epstein-Barr virus (EBV) might be an aetiological agent involved in the pathogenesis of certain Non-Hodgkin's Lymphomas (NHLs). EBV infection has been diagnosed by serologic testing within the tumour biopsies of patients with NHL. However, the association between EBV and NHL is inconsistent with a preference for certain anatomic sites, histologic subtypes and immunosuppressed patients. The objective of this study was to characterise the B-cell NHLs of the oral cavity and maxillofacial region using histological and immunophenotypical techniques and to determine its association with EBV infection.

    MATERIALS AND METHODS: This was a descriptive cross-sectional study that included 14 cases of B-cell NHLs of the oral cavity and maxillofacial region. The haematopoietic and lymphoid tissue tumours classification of WHO was used to categorize the cases. In-situ hybridisation for EBV-encoded RNA was performed to confirm the EBV infection.

    RESULTS: The average age of the patients included in the study was found to be 48.8 ± 23 years with a higher female to male ratio (1.3:1). Our study suggested that diffuse large B-cell lymphomas (DLBCLs) and Burkitt's lymphomas (BLs) constitute the predominant subtypes of lymphomas affecting the oral cavity and maxillofacial regions.

    CONCLUSION: The findings from our study support the view that at least a relatively smaller proportion of B-cell NHLs that occur in the oral cavity and maxillofacial region do not have a pathogenic association with EBV.

  13. Burhanudin NA, Zaini ZM, Rahman ZAA, Ismail SM, Gopinath D, Abraham MT, et al.
    PMID: 36229363 DOI: 10.1016/j.oooo.2022.07.014
    OBJECTIVE: Extranodal extension (ENE) is an important prognostic factor in oral squamous cell carcinoma (OSCC). However, ENE is only confirmed postoperatively by histologic assessment of the lymph nodes after neck dissection. Accurate identification of ENE preoperatively would help in management of OSCC.

    STUDY DESIGN: We determined the expression of molecular markers gamma glutamyl hydrolase (GGH), cyclin-dependent kinase inhibitor-3 (CDKN3), and chromobox homolog-7 (CBX7) using immunohistochemistry in OSCC clinical samples (n = 35). The intensity of staining was scored using a semiquantitative index (HSCORE). The association between clinicopathologic parameters and expression of molecular markers with ENE status was analyzed using chi-square test.

    RESULTS: The number of positive nodes and the highest anatomic level of nodal involvement significantly correlated with ENE (P < .05). High GGH expression was significantly associated with ENE (P < .05), with an increased risk for ENE (odds ratio [OR] 9.9, 95% CI 1.08-91.47, P = .04), whereas no significant association was seen for CDKN3 and CBX7 expression with ENE. However, a trend toward significance was observed with a high level of CDKN3 and a low level of CBX7 expression with ENE.

    CONCLUSIONS: Gamma glutamyl hydrolase offers potential as a predictor for ENE in OSCC, whereas the role of CDKN3 and CBX7 need to be validated in a larger sample.

  14. Govindaraj PK, Kallarakkal TG, Mohd Zain R, Tilakaratne WM, Lew HL
    PLoS One, 2021;16(12):e0261575.
    PMID: 34941961 DOI: 10.1371/journal.pone.0261575
    BACKGROUND: Local relapse of oral squamous cell carcinoma in non-involved mucosal surgical margins indicated possibility of field alteration in the margins, which could be predicted with certain biomarkers. The objectives were to evaluate the expression of Ki-67, Cornulin and ISG15 in non-involved mucosal surgical margins and the association of clinicopathological prognosticators with local relapse in oral squamous cell carcinoma.

    METHODS: Surgical margins from the study (relapse) group (n = 23), control (non-relapse) group (n = 32) and normal oral mucosa (n = 5) were immunohistochemically stained using Ki-67, Cornulin and ISG15 antibodies. Association between expression of markers and clinicopathological prognosticators with local relapse in oral squamous cell carcinoma was analyzed statistically.

    RESULTS: The study group surgical margins demonstrated significantly decreased Cornulin expression (p = 0.032). Low Cornulin expression was significantly associated with local relapse (p = 0.004) and non-tongue primary tumor (p = 0.013). Although not significantly associated with local relapse, expression of Ki-67 was significantly reduced in female patients (p = 0.041). Age above 57.5 years, Chinese & Indian ethnicity, alcohol consumption, epithelial dysplasia in surgical margins, and type III and IV patterns of invasion of tumor were also significantly related to local relapse. Regression analysis showed low expression of Cornulin (p = 0.018), and increased patient's age (p = 0.008) were predictors of local relapse in oral squamous cell carcinoma, with 34-fold risk and 18-fold risk, respectively. Expression of Ki-67 and ISG15 did not show significant association with local relapse in oral squamous cell carcinoma.

    CONCLUSION: Low expression of Cornulin is an independent predictor of relapse in oral squamous cell carcinoma.

  15. Wang C, Zainal NS, Chai SJ, Dickie J, Gan CP, Zulaziz N, et al.
    Front Immunol, 2021;12:763086.
    PMID: 34733290 DOI: 10.3389/fimmu.2021.763086
    HPV-independent head and neck squamous cell carcinoma (HNSCC) is a common cancer globally. The overall response rate to anti-PD1 checkpoint inhibitors (CPIs) in HNSCC is ~16%. One major factor influencing the effectiveness of CPI is the level of tumor infiltrating T cells (TILs). Converting TILlow tumors to TILhigh tumors is thus critical to improve clinical outcome. Here we describe a novel DNA vaccines to facilitate the T-cell infiltration and control tumor growth. We evaluated the expression of target antigens and their respective immunogenicity in HNSCC patients. The efficacy of DNA vaccines targeting two novel antigens were evaluated with or without CPI using a syngeneic model. Most HNSCC patients (43/44) co-expressed MAGED4B and FJX1 and their respective tetramer-specific T cells were in the range of 0.06-0.12%. In a preclinical model, antigen-specific T cells were induced by DNA vaccines and increased T cell infiltration into the tumor, but not MDSC or regulatory T cells. The vaccines inhibited tumor growth and improved the outcome alone and upon combination with anti-PD1 and resulted in tumor clearance in approximately 75% of mice. Pre-existence of MAGED4B and FJX1-reactive T cells in HNSCC patients suggests that these widely expressed antigens are highly immunogenic and could be further expanded by vaccination. The DNA vaccines targeting these antigens induced robust T cell responses and with the anti-PD1 antibody conferring excellent tumor control. This opens up an opportunity for combination immunotherapy that might benefit a wider population of HNSCC patients in an antigen-specific manner.
  16. Tegginamani AS, Kallarakkal TG, Vanishree HS, Muttalib KBA
    J Coll Physicians Surg Pak, 2019 Jul;29(7):688.
    PMID: 31253228 DOI: 10.29271/jcpsp.2019.07.688
  17. Kallarakkal TG, Zaini ZM, Ghani WMN, Karen-Ng LP, Siriwardena BSMS, Cheong SC, et al.
    J Oral Pathol Med, 2024 Jan;53(1):53-60.
    PMID: 38081145 DOI: 10.1111/jop.13501
    INTRODUCTION: A major pitfall of many of the established oral epithelial dysplasia (OED) grading criteria is their lack of reproducibility and accuracy to predict malignant transformation. The main objective of this study was to determine whether calibration of practicing oral pathologists on OED grading could improve the reproducibility of the WHO 2017 and the binary OED grading systems.

    METHODS: A nationwide online exercise was carried out to determine the influence of calibration on the reproducibility of the WHO 2017 and the binary OED grading systems.

    RESULTS: A significant improvement was observed in the inter-observer agreement for the WHO 2017 OED grading system (K 0.196 vs. 0.448; Kw 0.357 vs. 0.562) after the calibration exercise. The significant difference (p = 0.027) in the level of agreement between those with five or more years and less than 5 years of experience was no more observed (p = 0.426) after the calibration exercise. The percent agreement for binary grading was significantly higher (91.8%) for buccal mucosal lesions as compared to lesions on the tongue after the calibration exercise.

    CONCLUSION: This study validates the significance of calibration in improving the reproducibility of OED grading. The nationwide exercise resulted in a statistically significant improvement in the inter-observer agreement for the WHO 2017 OED grading system among a large number of oral pathologists. It is highly recommended that similar exercises should be organized periodically by professional bodies responsible for continuing education among oral pathologists to improve the reliability of OED grading for optimal treatment of oral potentially malignant disorders.

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