Evaluating the efficacy of OralDETECT training: Face-to-face versus online delivery in dental education.

OBJECTIVE: This study evaluated the effectiveness of face-to-face (F2F) and online OralDETECT training programme in enhancing early detection skills for oral cancer. METHODS: A total of 328 final-year dental students were trained across six cohorts. Three cohorts (175 students) received F2F training from the academic years 2016/2017 to 2018/2019, and the remaining three (153 students) underwent online training during the Covid-19 pandemic from 2019/2020 to 2021/2022. Participant scores were analysed using the Wilcoxon signed rank test, the Mann-Whitney test, Cohen's d effect size, and multiple linear regression. RESULTS: Both F2F and online training showed increases in mean scores from pre-test to post-test 3: from 67.66 ± 11.81 to 92.06 ± 5.27 and 75.89 ± 11.03 to 90.95 ± 5.22, respectively. Comparison between F2F and online methods revealed significant differences in mean scores with large effect sizes at the pre-test stage (p < 0.001), while significant differences with small effect sizes were noted for post-test 1 (p = 0.002) and post-test 3 (p = 0.041). Regression analysis indicated that the delivery method is associated with the participants' final scores. CONCLUSION: F2F and online versions of the OralDETECT training programme significantly enhance participants' knowledge and skills in oral cancer detection. Although F2F appeared to be more effective, the difference was not substantial enough to be considered educationally meaningful.

Salivary metabolomics in oral potentially malignant disorders and oral cancer patients-a systematic review with meta-analysis.

OBJECTIVES: The aim of this systematic review and meta-analysis is to assess the diagnostic potential of salivary metabolomics in the detection of oral potentially malignant disorders (OPMDs) and oral cancer (OC). MATERIALS AND METHODS: A systematic review was performed in accordance with the 3rd edition of the Centre for Reviews and Dissemination (CRD) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Electronic searches for articles were carried out in the PubMed, Web of Science, and Scopus databases. The quality assessment of the included studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS) and the new version of the QUADOMICS tool. Meta-analysis was conducted whenever possible. The effect size was presented using the Forest plot, whereas the presence of publication bias was examined through Begg's funnel plot. RESULTS: A total of nine studies were included in the systematic review. The metabolite profiling was heterogeneous across all the studies. The expression of several salivary metabolites was found to be significantly altered in OPMDs and OCs as compared to healthy controls. Meta-analysis was able to be conducted only for N-acetylglucosamine. There was no significant difference (SMD = 0.15; 95% CI - 0.25-0.56) in the level of N-acetylglucosamine between OPMDs, OC, and the control group. CONCLUSION: Evidence for N-acetylglucosamine as a salivary biomarker for oral cancer is lacking. Although several salivary metabolites show changes between healthy, OPMDs, and OC, their diagnostic potential cannot be assessed in this review due to a lack of data. Therefore, further high-quality studies with detailed analysis and reporting are required to establish the diagnostic potential of the salivary metabolites in OPMDs and OC. CLINICAL RELEVANCE: While some salivary metabolites exhibit significant changes in oral potentially malignant disorders (OPMDs) and oral cancer (OC) compared to healthy controls, the current evidence, especially for N-acetylglucosamine, is inadequate to confirm their reliability as diagnostic biomarkers. Additional high-quality studies are needed for a more conclusive assessment of salivary metabolites in oral disease diagnosis.

High referral accuracy for oral cancers and oral potentially malignant disorders using telemedicine.

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.

Preparedness of recent dental graduates and final-year undergraduate dental students for practice amidst the COVID-19 pandemic.

INTRODUCTION: Dental education involves performing clinical procedures on patients under expert supervision. The COVID-19 pandemic has disrupted routine face-to-face teaching-learning-assessment dynamics world over. This study assessed the self-perceived preparedness of dental undergraduate students for practice, whose clinical training was interrupted by the COVID-19 pandemic from dental schools across Malaysia. MATERIALS AND METHODS: This cross-sectional web-based questionnaire survey was done among new dental graduates of the academic year 2019-2020 and the final year undergraduate students (academic year 2020-2021) from dental schools in Malaysia, using the Dental Undergraduates Preparedness Assessment Scale (DU-PAS), from 6th to 26th April 2021. The questionnaire addressed clinical skill competence, and cognitive and behavioral attributes. The number of respondents needed to achieve a confidence level of 95% with margin of error of 5% was 306. RESULTS: A total of 453 (243 final year students and 210 new graduates) responded from dental schools nationwide, with a response rate of 30.6%. The overall mean score for preparedness for dental practice was 76.3±14.7, for clinical skills 39.7±7.3, and behavioral and cognitive attributes 36.5±9.1. New graduates had significantly higher mean preparedness score (78.6±14.4) as compared to students in their final year (74.2±14.7). Performing endodontic treatment on multi-rooted teeth had the lowest perceived competency (29.8%), followed by assessing treatment needs of patients requiring orthodontics (37.1%), prescribing drugs (46.6%) and providing crowns using principles of tooth preservation (48.1%). CONCLUSIONS: Satisfactory scores were obtained for most attributes. The final-year cohort was significantly less prepared for dental practice compared to the newly graduated cohort.

Homeobox Genes in Odontogenic Lesions: A Scoping Review.

BACKGROUND: Homeobox genes play crucial roles in tooth morphogenesis and development and thus mutations in homeobox genes cause developmental disorders such as odontogenic lesions. The aim of this scoping review is to identify and compile available data from the literatures on the topic of homeobox gene expression in odontogenic lesions. METHOD: An electronic search to collate all the information on studies on homeobox gene expression in odontogenic lesions was carried out in four databases (PubMed, EBSCO host, Web of Science and Cochrane Library) with selected keywords. All papers which reported expression of homeobox genes in odontogenic lesions were considered. RESULTS: A total of eleven (11) papers describing expression of homeobox genes in odontogenic lesions were identified. Methods of studies included next generation sequencing, microarray analysis, RT-PCR, Western blotting, in situ hybridization, and immunohistochemistry. The homeobox reported in odontogenic lesions includes LHX8 and DLX3 in odontoma; PITX2, MSX1, MSX2, DLX, DLX2, DLX3, DLX4, DLX5, DLX6, ISL1, OCT4 and HOX C in ameloblastoma; OCT4 in adenomatoid odontogenic tumour; PITX2 and MSX2 in primordial odontogenic tumour; PAX9 and BARX1 in odontogenic keratocyst; PITX2, ZEB1 and MEIS2 in ameloblastic carcinoma while there is absence of DLX2, DLX3 and MSX2 in clear cell odontogenic carcinoma. CONCLUSIONS: This paper summarized and reviews the possible link between homeobox gene expression in odontogenic lesions. Based on the current available data, there are insufficient evidence to support any definite role of homeobox gene in odontogenic lesions.

Prognostic Abilities of Pre- and Post-Treatment Inflammatory Markers in Oral Squamous Cell Carcinoma: Stepwise Modelling.

Background and Objectives: Studies examining the importance of inflammatory markers before treatment as prognosticators of OSCC are available, but information on post-therapy inflammatory markers and their prognostic significance is limited. This study aimed to evaluate the prognostic abilities of pre- and post-treatment inflammatory markers in patients with OSCC. Materials and Methods: In this retrospective analysis, information on 151 OSCC patients' socio-demographic, clinico-pathological, recurrence, metastasis, and survival data were gathered from clinical records. A multivariable Cox proportional hazards regression (stepwise model) was conducted to identify the prognostic predictors of OS and DFS. The multivariable models' performances were evaluated using Harrell's concordance statistics. Results: For OS, high pre-treatment LMR (HR 3.06, 95%CI 1.56, 5.99), and high post-treatment PLC (HR 3.35, 95%CI 1.71, 6.54) and PLR (HR 5.26, 95%CI 2.62, 10.58) were indicative of a poor prognosis. For DFS, high pre-treatment SII (HR 2.59, 95%CI 1.50, 4.48) and high post-treatment PLC (HR 1.92, 95%CI 1.11, 3.32) and PLR (HR 3.44, 95%CI 1.98, 5.07) were associated with increased mortality. The fitness of the OS and DFS stepwise Cox regression models were proven with a time-dependent AUC of 0.8787 and 0.8502, respectively. Conclusions: High pre-treatment levels of LMR and SII and high post-treatment levels of PLC and PLR are independent predictors of a poor prognosis for patients with OSCC.

Lactate Dehydrogenase: The Beacon of Hope?

Lactate dehydrogenase enzyme (LDH) helps in the conversion of glucose into pyruvic acid during aerobic glycolysis and is found in the cytoplasm of most cells in the human body. When oxidative stress occurs in the body, LDH may be released extracellularly and its level is usually indicative of the severity of tissue damage. LDH has proved to be an inestimably resourceful marker in early prediction of serious diseases involving extensive tissue or cellular damage. This short communication explores the potential of LDH as a salivary biomarker of cell injury and death.

Combination Treatment of TRPV4 Agonist with Cisplatin Promotes Vessel Normalization in an Animal Model of Oral Squamous Cell Carcinoma.

Background and Objectives: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy in the world. Transient receptor potential vanilloid 4 (TRPV4) channel has been shown to be involved in angiogenesis in multiple types of tumors. However, not much is known about TRPV4's involvement in OSCC. Thus, in this study, we investigate the effect of administering a TRPV4 agonist on angiogenesis in OSCC. Materials and Methods: Thirty-six Sprague Dawley (SD) rats were used in this study. 4-nitroquinoline 1-oxide (4NQO) was used to induce OSCC. Cisplatin (an anticancer drug), and GSK1016790A (an agonist for TRPV4) was used in this study. Immunohistochemistry was employed to examine the TRPV4 expression. An RT2 Profiler PCR Array was performed for gene expression analysis of TRPV4, vascular growth factors that correspond directly with angiogenesis, such as angiopoietin (Ang-1 and Ang-2), and tyrosine kinase (Tie-1 and Tie-2) receptors. Tumor vessel maturity was assessed by microvessel density and microvessel-pericyte-coverage index. Results: RT2 profiler PCR array showed significant elevated levels of Ang-1 (2.1-fold change; p < 0.05) and Tie-2 (4.5-fold change; p < 0.05) in OSCC following the administration of a combination of GSK1016790A and cisplatin. Additionally, the combination treatment significantly reduced the microvessel density (p < 0.01) and significantly increased the percentage of microvessels covered with pericytes (p < 0.01) in OSCC. Furthermore, tumor size was significantly reduced (p < 0.05) in rats that received cisplatin alone. The combination treatment also greatly reduced the tumor size; however, the data were not statistically significant. Conclusions: The findings suggest that combining a TRPV4 agonist with cisplatin for treatment of OSCC promote vessels normalization via modulation of Ang-1/Tie-2 pathway.

Do Clear Cell Changes in Oral Squamous Cell Carcinoma Warrant It Being Recognised as a Variant?

Histological variants of oral squamous cell carcinoma (OSCC) include verrucous, basaloid, spindle cell, adenosquamous, papillary, and acantholytic types. Clear-cell changes in OSCC are rare. We report a case of a 65-year-old male Chinese patient who presented with a swelling in the lower-left mandible for three weeks, causing ill-fitting of his lower denture and an ulcer on the floor of the mouth. Histologically, the lesion showed a dense proliferation of malignant tumor cells arranged in islands and sheets consisting of squamoid cells intermixed with signet ring-shaped clear cells. The clear cells were negative for mucicarmine, periodic acid Schiff (PAS), periodic acid Schiff-diastase (PAS-D), and alcian blue (AB). Immunohistochemistry showed the tumor cells were immuno-positive for cytokeratin (CK) and p63, but CK7, CK20, and S100 were immuno-negative. Therefore, a metastatic tumor in the oral cavity was suggested. However, the CT scan did not show any primary tumors in other sites. Histopathologically, the surgical specimen showed signet-ring-shaped clear cells in the stroma with squamoid cells invading the underlying connective tissue from the surface epithelium, suggesting a diagnosis of clear cell changes in OSCC. Follow-up showed recurrent OSCC at the base of the tongue with lymph node metastasis and distant metastasis in the lung. Only a few cases of clear-cell changes have been reported, with most having a poor prognosis. This case report adds one more case of clear cell changes in the OSCC with a poor prognosis. We reviewed the literature to understand their clinical behavior. Due to the rarity of its (clear cell changes) occurrence, further research is required in order to obtain a better understanding of the clinical behavior and prognosis of these clear cell changes seen in OSCC.

Aberrant Expression of p63 in an Adenocarcinoma of the Prostate That Has Metastasized to the Oral Cavity.

Metastasis specifically to the oral cavity is uncommon in cases of prostate adenocarcinoma. Only 4% of prostate cancer patients present with metastases to the oral cavity originating from the prostate. In the oral cavity, the mandible is the primary site of metastases. p63 is said to be a reliable marker to distinguish benign from malignant lesions of prostate origin, with benign lesions staining positive and malignant lesions staining negative. However, in rare instances, malignant prostate lesions have shown aberrant expression of p63. This case report highlights such a rare incidence of metastasis of prostate adenocarcinoma to the oral cavity involving the right buccal mucosa and the right side of the mandible and having an aberrant expression of p63 in a 76-year-old Chinese male. A computed tomography (CT) scan and bone scan revealed multiple bone metastases, and in three months, the patient succumbed to the disease. Thus, p63 is not exclusively expressed in benign lesions of the prostate, as the aberrant expression may also be evident in malignant lesions such as prostate adenocarcinoma. Therefore, the determination of benign or malignant lesions of the prostate using p63 must be interpreted with caution.

Bone Formation in Pleomorphic Adenoma: A Case Report.

Pleomorphic adenoma is a benign tumour with variable cytomorphological and architectural elements. It is the most common salivary gland tumour in children and adults. We report a case of a 32-year-old Malay woman who presented with a slow-growing, painless, firm, and mobile nodule of 1 cm x 1 cm in size at the angle of her mandible on the right side which could be palpated bimanually. Intraorally, this nodule could be palpated at the retromolar area. On excisional biopsy, this nodule was reported as a pleomorphic adenoma with predominant chondroid stromal elements and a large area of bone formation in the stroma. We discuss the possible pathogenesis, differential diagnosis, and clinical significance of this exceptionally rare phenomenon of bone formation in pleomorphic adenoma in minor salivary glands with the literature review. The clinical significance and relevance on treatment outcome for pleomorphic adenoma with bone formation is currently uncertain as there are only a few cases reported in the literature. A good follow-up study is recommended to assess the clinical significance of pleomorphic adenoma with extensive bone formation.

Oral Squamous Cell Carcinoma and Warthin Tumour Occurring As Synchronous Tumours: A Report of Two Cases.

Oral cancer is a common site of cancer worldwide with oral squamous cell carcinoma (OSCC) comprising the major segment. The risk factors include tobacco and alcohol abuse, betel quid, and areca nut consumption. Warthin tumour (WT), also known as papillary cystadenoma lymphomatosum is a benign tumour of the salivary gland. It is one of the most common benign parotid neoplasms with cigarette smoking and radiation exposure as possible cited etiologic factors. Rarely, two or more histologically distinct neoplasms may occur synchronously. The synchronous occurrence of OSCC and WT is infrequent. The aim of this case series is to report the incidence rate of synchronous OSCC and WT in our centre between 2010 and 2019 and their socio-demographic, clinical, histopathological features, management, and prognosis and discuss the relevant literature. Out of 143 OSCC cases reported in our centre from the year 2010 to 2019, two had synchronous OSCC and WT with an incidence rate of 1.4%. These two cases occurred in a 63-year-old female and a 68-year-old male both with smoking habits. One OSCC was present in the left buccal mucosa and the other in the right ventral surface of the tongue, whereas the WT in both cases occurred in the tail of the parotid. One patient had a recurrence and died while the other is under follow-up without any recurrence. These unusual findings of synchronous occurrence of WT at a distant site from the primary tumour may mimic a malignant disease, more likely a metastasis from the primary OSCC, which could further complicate the management of these patients. Therefore, radiologists, head and neck surgeons, and pathologists should be aware of the occurrence of these unusual presentations to avoid overtreatment in such cases.

Effectiveness of "OralDETECT": a Repetitive Test-enhanced, Corrective Feedback Method Competency Assessment Tool for Early Detection of Oral Cancer.

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.

Lactate Dehydrogenase Levels in the Saliva of Cigarette and E-Cigarette Smokers (Vapers): A Comparative Analysis.

BACKGROUND: We examined the lactate dehydrogenase (LDH) enzyme levels in the saliva of vapers (e-cigarette users) and compared the data with cigarette smokers and a control group of non-smokers and non-vapers. METHODS: Subjects were recruited among those responding to a social media announcement or patients attending the SEGi Oral Health Care Centre between May and December 2019, and among some staff at the centre. Five ml of unstimulated   whole saliva was collected and salivary LDH enzyme activity levels were measured with a LDH colorimetric assay kit. Salivary LDH activity level was determined for each group and compared statistically. RESULTS: Eighty-eight subjects were categorized into three groups (control n=30, smokers n=29, and vapers n=29). The mean ± standard deviation (SD) values for salivary LDH activity levels for vapers, smokers, and control groups were 35.15 ± 24.34 mU/ml, 30.82 ± 20.73 mU/ml, and 21.45 ± 15.30 mU/ml, respectively. The salivary LDH activity levels of smoker and vaper groups were significantly higher than in the control group (p = 0.031; 0.017). There was no significant difference of salivary LDH activity level in vapers when compared with smokers (p= 0.234). CONCLUSION: Our findings showed higher LDH levels in the saliva of vapers when compared with controls, confirming cytotoxic and harmful effects of e-cigarettes on the oral mucosa.

Oral Lichen Planus in a Patient With a Thymoma: A Rare Finding.

We present a rare case of ulcerative oral lichen planus that was associated with a thymoma discovered during the management phase, seven months after the initial diagnosis of oral lichen planus. Thymectomy was performed and investigations revealed pure red cell aplasia. Although rare, the association of a thymoma should be considered in recording the medical history of patients presenting with oral lichen planus.

Comparative sera proteomics analysis of differentially expressed proteins in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) has increased in incidence from 1990 to 2017, especially in South and Southeast Asia. It is often diagnosed at an advanced stage with a poor prognosis. Therefore, early detection of OSCC is essential to improve the prognosis of OSCC. This study aims to identify the differentially expressed serum proteins as potential biomarkers for oral squamous cell carcinoma (OSCC). METHODS: Comparative proteomics profiling of serum samples from OSCC patients, oral potentially malignant disorder (OPMD) patients, and healthy individuals were performed using two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry (MS) (n = 60) and bioinformatics analysis. The enzyme-linked immunosorbent assay (ELISA) (n = 120) and immunohistochemistry (IHC) (n = 70) were used to confirm our findings. RESULTS: The 2-DE analysis revealed that 20 differentially expressed proteins were detected in OPMD and OSCC (p < 0.05). Bioinformatics analysis indicated that the activation of classical complement, liver X receptor/retinoid X receptor (LXR/RXR) activation, and acute phase response signaling pathway are associated with the development and progression of OSCC. Most of the detected proteins are acute-phase proteins and were related to inflammation and immune responses, including apolipoprotein A-I (APOA1), complement C3 (C3), clusterin (CLU), and haptoglobin (HP). The expression levels of CLU and HP in ELISA are consistent with the findings from the 2-DE analysis, except for the mean serum level of HP in OPMD, whereby it was slightly higher than that in control. IHC results demonstrated that CLU and HP are significantly decreased in OSCC tissues. CONCLUSION: Decreased expression of CLU and HP could serve as complementary biomarkers of OSCC. These proteins may assist in predicting the outcomes of OSCC patients. However, a larger cohort is needed for further investigation.

Application of optical coherence tomography to study the structural features of oral mucosa in biopsy tissues of oral dysplasia and carcinomas.

OBJECTIVE: This study aims to examine the ability of optical coherence tomography (OCT) to differentiate ex vivo epithelial structure of benign disorders, dysplastic, and oral squamous cell carcinoma (OSCC) in comparison with the structure of normal marginal mucosa of oral biopsies. As a secondary objective, we examined the inter- and intra-observer variations of OCT measurements of two calibrated assessors. MATERIALS AND METHODS: Oral biopsies (n = 44) were scanned using the swept source OCT (SSOCT) and grouped by pathology diagnosis to benign, dysplasia or carcinoma. Two trained and calibrated assessors scored on the five OCT variables: thickness of keratin layer (KL), epithelial layer (EL), homogeneity of lamina propria (LP), basement membrane integrity (BMI), and the degree of reflection of the epithelial layer (Ep Re). Chi-square tests and Fischer's exact method were used to compare the data. RESULTS: The OCT images showed breached BM status in all the OSCC samples (100%). Epithelial reflection was noted to be hyper-reflective in all the OSCC and oral dysplasia samples (100%). An increase in KL in 66.67% of the OSCC and 100% of the oral dysplasia samples was found. EL was increased in all the OSCC samples (100%) and 85.72% of the oral dysplasias. Kappa values showed that there was very good agreement (over 0.7) when scoring individual parameters between the two assessors. CONCLUSION: The study showed that the BM status was a key parameter in the detection of SCC and for differentiating SCC from oral dysplasia or benign disorders. CLINICAL RELEVANCE: OCT is a non-invasive and non-radioactive adjunct diagnostic tool that can provide immediate results on the structure of oral mucosa. The BM status measured ex vivo was a key parameter in the detection of SCC and for differentiating SCC from oral dysplasia or benign disorders.

Autophagy: The "Pac-Man" within Us-Ally or Adversary?

Autophagy, first described by the Belgian biochemist Christian De Duve in 1963, is derived from the Greek word "autóphagos," which means "self-devouring." It is a cellular homeostatic process in which the body rids itself of flawed or damaged cells and other defective cellular organelles.1 The implication of defective autophagy in various human diseases has been well documented. The vital importance of autophagy is underscored by the fact that robust cellular health and function are intricately linked with it.

Healthcare Professional in the Loop (HPIL): Classification of Standard and Oral Cancer-Causing Anomalous Regions of Oral Cavity Using Textural Analysis Technique in Autofluorescence Imaging.

Oral mucosal lesions (OML) and oral potentially malignant disorders (OPMDs) have been identified as having the potential to transform into oral squamous cell carcinoma (OSCC). This research focuses on the human-in-the-loop-system named Healthcare Professionals in the Loop (HPIL) to support diagnosis through an advanced machine learning procedure. HPIL is a novel system approach based on the textural pattern of OML and OPMDs (anomalous regions) to differentiate them from standard regions of the oral cavity by using autofluorescence imaging. An innovative method based on pre-processing, e.g., the Deriche-Canny edge detector and circular Hough transform (CHT); a post-processing textural analysis approach using the gray-level co-occurrence matrix (GLCM); and a feature selection algorithm (linear discriminant analysis (LDA)), followed by k-nearest neighbor (KNN) to classify OPMDs and the standard region, is proposed in this paper. The accuracy, sensitivity, and specificity in differentiating between standard and anomalous regions of the oral cavity are 83%, 85%, and 84%, respectively. The performance evaluation was plotted through the receiver operating characteristics of periodontist diagnosis with the HPIL system and without the system. This method of classifying OML and OPMD areas may help the dental specialist to identify anomalous regions for performing their biopsies more efficiently to predict the histological diagnosis of epithelial dysplasia.