A comprehensive dataset of annotated oral cavity images for diagnosis of oral cancer and oral potentially malignant disorders.

OBJECTIVES: This study aims to address the critical gap of unavailability of publicly accessible oral cavity image datasets for developing machine learning (ML) and artificial intelligence (AI) technologies for the diagnosis and prognosis of oral cancer (OCA) and oral potentially malignant disorders (OPMD), with a particular focus on the high prevalence and delayed diagnosis in Asia. MATERIALS AND METHODS: Following ethical approval and informed written consent, images of the oral cavity were obtained from mobile phone cameras and clinical data was extracted from hospital records from patients attending to the Dental Teaching Hospital, Peradeniya, Sri Lanka. After data management and hosting, image categorization and annotations were done by clinicians using a custom-made software tool developed by the research team. RESULTS: A dataset comprising 3000 high-quality, anonymized images obtained from 714 patients were classified into four distinct categories: healthy, benign, OPMD, and OCA. Images were annotated with polygonal shaped oral cavity and lesion boundaries. Each image is accompanied by patient metadata, including age, sex, diagnosis, and risk factor profiles such as smoking, alcohol, and betel chewing habits. CONCLUSION: Researchers can utilize the annotated images in the COCO format, along with the patients' metadata, to enhance ML and AI algorithm development.

Comment on, "Single nucleotide polymorphisms as markers of genetic susceptibility for oral potentially malignant disorders risk: Review of evidence to date".

This study by Shridhar et al. 2016 reviews the genetic susceptibility to oral potentially malignant disorders (OPMD) through the analysis of single nucleotide polymorphisms (SNPs). By examining data from 47 studies conducted between 2000 and 2016, the research highlights genetic markers involved in carcinogen metabolism, DNA repair, cell cycle control, and immune-inflammatory responses. Despite the insights provided, the over-reliance on small sample sizes limits the statistical power and generalizability of the findings. Future research should focus on larger, more diverse populations and advanced genotyping technologies to enhance detection of significant genetic variants. Integrating multi-omics data and conducting longitudinal studies will further elucidate the molecular mechanisms underlying OPMD and its progression to oral cancer. Collaborative efforts are essential to validate these findings and develop biomarkers for early detection and prevention.

Epidemiological Trends and Clinicopathological Characteristics of Oral Leukoplakia: A Retrospective Analysis From a Single Institution in Chennai, Tamil Nadu, India.

Background India has a high prevalence of oral potentially malignant disorders and malignant transformation. Cases of oral leukoplakia are not commonly encountered, and only a small cohort of patients undergo biopsies for the same. This study aims to assess the various etiological factors causing leukoplakia, the clinical features, histopathological findings, and treatment received by the patients who were histopathologically diagnosed with oral leukoplakia. Methodology Oral leukoplakia cases were included in this study from total biopsy samples received in the oral pathology department. Details were collected from the Dental Information Archival Software of our institution. The period analyzed was from January 1, 2021, to December 31, 2023. Relevant clinical and histopathological details were retrieved and tabulated. Statistical analysis (chi-square test) was used to assess the association between the clinicopathological parameters using SPSS software version 21.0 (IBM Corp., Armonk, NY, USA) with a significance level set at a p-value <0.05. Results A total of 76 oral leukoplakia cases were retrieved from 2,600 biopsy samples. The prevalence of oral leukoplakia was 3.1% to 3.4% for the three years. Leukoplakia was commonly observed in those aged 51 to 60 years (33%). Overall, 21% of the patients with leukoplakia showed severe epithelial dysplasia, 22% showed mild epithelial dysplasia, and 39% showed moderate epithelial dysplasia. Moreover, 30% of the patients presented with leukoplakia and oral submucous fibrosis and showed varying degrees of epithelial dysplasia. Finally, 45% of the patients were managed conservatively using pharmacotherapy. Conclusions Severe epithelial dysplasia was commonly associated with oral leukoplakia. Oral submucous fibrosis was also found to be associated with leukoplakia and showed epithelial dysplasia. None of our proliferative verrucous leukoplakia cases showed any association with oral submucous fibrosis. Surgical management was the preferred treatment.

Surgical treatment compared with "wait and see" in patients affected by oral leukoplakia to prevent oral cancer: Preliminary data from a multicenter randomized controlled trial.

OBJECTIVE: Oral leukoplakia (OL) is one of the most common and investigated oral potentially malignant disorders (OPMD). Preventing OSCC occurrence should be the primary outcome in the clinical management of OL. Surgical removal of OL is performed by most clinicians, although its effectiveness in reducing OSCC onset has still not been established by randomized controlled trials (RCT). Wait and see approach is characterized by frequent clinical examinations and periodical biopsies of OL, avoiding unnecessary surgical procedures. This is the first multicenter RCT in literature aiming at comparing the effectiveness of surgical removal and the "wait and see" approach in preventing OSCC onset in patients affected by dysplastic and non-dysplastic OL. METHODS: Two Italian referral care centres for oral diseases were involved in this multicenter two-arm RCT comparing the surgical removal of OL (group A) and the "wait and see" approach (group B), with the aim of reducing oral cancer onset. RESULTS: This report shows preliminary data on the first 161 patients, with a mean follow-up of 19.14 ± 11.25 months. Eight cases of OSCC occurred (6 out 8 involving the tongue): one case in group A and seven cases in group B. Moreover, OL recurred in 13 (20%) cases after surgical excision. CONCLUSIONS: Within the limitations of this preliminary report, these initial data underline the increased risk of OSCC onset in the case of OL of the tongue in the presence of epithelial dysplasia in group B ("wait and see") compared to group A (surgery). This RCT is currently ongoing at the same clinical departments, with the aim of enrolling 310 patients and collecting data at 5-year follow-up, in order to achieve conclusive results, in an evidence-based medicine approach.

Oral Pre-malignancy: An Update on Novel Therapeutic Approaches.

PURPOSE OF REVIEW: This review aims to provide a comprehensive overview of the current advances in managing and preventing progression of oral potentially malignant disorders (OPMDs), focusing on their histological and clinicopathological features, and management. RECENT FINDINGS: Recent studies, including a multicenter cross-sectional study, have identified oral leukoplakia as the most prevalent form of OPMD, comprising over half of the cases examined. Advances in histological grading, specifically the World Health Organization's three-tier system (mild, moderate, and severe dysplasia), have significantly enhanced the accuracy of risk assessment for malignant transformation. Additionally, treatments such as surgical interventions, photodynamic therapy, and chemopreventive and molecularly targeted agents are being evaluated for their safety and efficacy as well as, immune checkpoint inhibitors being evaluated as potential preventive strategies to halt the progression of OPMDs. The management of OPMDs remains challenging due to the lack of standardized screening protocols and varied clinical management approaches. Despite this, recent advancements in diagnostic grading and therapeutic interventions provide a framework for improved treatment outcomes. Continued research into the molecular and cellular mechanisms driving development and progression of OPMDs and innovative treatment trials are essential to optimize strategies that prevent malignant progression and thereby reduce the global health burden of oral cancer.

Feasibility, Reliability, and Effectiveness of Oral cancer screening in South Asia and Southeast Asian countries: A systematic review and Meta-analysis.

OBJECTIVES: The incidence of oral cancer is significantly high in South Asia and Southeast Asia. Organized screening is an effective approach to early detection. The aim of this systematic review and meta-analysis was to evaluate the reliability, diagnostic accuracy, and effectiveness of visual oral screening by community health workers (CHWs) in identifying oral cancer/oral potentially malignant disorders (OPMDs) in this region. MATERIALS AND METHODS: We conducted a bibliographic search in PubMed, Scopus, the gray literature of Google Scholar, ProQuest dissertations, and additional manual searches. Twelve articles were included for qualitative synthesis and six for meta-analysis. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), and forest plot analysis were performed. RESULTS: Meta-analysis showed CHWs identified 8% (n = 6365) as suspicious and 92% (n = 74,140) as normal. The diagnostic accuracy of visual oral screening by CHWs showed a sensitivity of 75% (CI: 74-76) and specificity of 97% (CI: 97-97) in the detection of OPMDs/oral cancer. Forest plots were obtained using a random effects model (DOR: 24.52 (CI: 22.65-26.55)) and SAUC: 0.96 (SE = 0.05). CONCLUSIONS: Oral visual examination by trained CHWs can be utilized for community screenings to detect oral cancer early. This approach can be used in primary healthcare to triage patients for further referral and management.

Knowledge About the Importance of Early Diagnosis and Treatment of Oral Potentially Malignant Disorders Among the South Indian Population: An Institutional Retrospective Study.

BACKGROUND: The significant malignant transformation rates of oral potentially malignant disorders (OPMDs) demand early diagnosis and proper management of OPMDs not only to reduce symptoms but also to prevent their aggressive outcomes. This retrospective study aimed to quantify the need for patient-related awareness in identifying OPMDs by quantitatively evaluating the association between the type of referral in OPMD cases. This study also aims to analyze the association between gender and types of referral in OPMDs. MATERIALS AND METHODS: The sample size of n=1577 (500-leukoplakia, 500-oral submucous fibrosis (OSMF), 500-lichen planus, 77-lichenoid reaction) was considered in the present retrospective study. Data regarding the sample cases were extracted from the common patient database of the Saveetha Dental College and Hospitals from June 2019 to February 2024. Random sampling method was used, and the OPMDs were categorized into two groups based on the chief complaint as self-referred and specialist-referred cases. The segregated data were tabulated in Microsoft Excel (Microsoft® Corp., Redmond, WA) and then exported to IBM SPSS Statistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, New York, United States) for statistical analysis. Pearson's chi-square test was conducted to analyze the association of referral type, OPMDs, and gender. RESULTS: Out of 1577 OPMD cases, 929 (58.9%) were specialist-referral cases and 648 (41.1%) were self-referral cases. Among OPMDs, lichen planus was the most self-referred 310 (62%) and leukoplakia was the most specialist-referred 470 (78.6%) category. This study found a statistically significant correlation between the type of referrals and the type of OPMDs (p=0.000). Self-referral was more commonly observed in females (23.3%) than males (17.8%) in general and among all categories of OPMDs except lichenoid reactions. This observation was also statistically significant (p=0.000).  Conclusion: Among OPMDs selected in the present study, lichen planus and OSMF were more self-referred and leukoplakia cases were mostly specialist-referred. This study highlights the need of detecting less symptomatic lesions, such as leukoplakia, which has a high risk of malignant transformation. The lack of awareness about the identification of OPMDs among patients can result in delayed diagnosis and treatment, which may further result in progression to aggressive outcomes.

Cancer Precursor Syndromes and Their Detection in the Head and Neck.

This article explores the multifaceted landscape of oral cancer precursor syndromes. Hereditary disorders like dyskeratosis congenita and Fanconi anemia increase the risk of malignancy. Oral potentially malignant disorders, notably leukoplakia, are discussed as precursors influenced by genetic and immunologic facets. Molecular insights delve into genetic mutations, allelic imbalances, and immune modulation as key players in precancerous progression, suggesting potential therapeutic targets. The article navigates the controversial terrain of management strategies of leukoplakia, encompassing surgical resection, chemoprevention, and immune modulation, while emphasizing the ongoing challenges in developing effective, evidence-based preventive approaches.

CLINICAL EFFICACY OF PHOTODYNAMIC THERAPY IN MANAGEMENT OF ORAL POTENTIALLY MALIGNANT DISORDERS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVES: Despite phototherapy (in the form of photodynamic therapy (PDT)-mediated oxidative stress) being utilized in the management of oral potentially malignant disorders (OPMDs), the evidence of certainty remains unclear. Hence, this systematic review and meta-analysis (PROSPERO # CRD42021218748) is aimed to evaluate the clinical efficacy of PDT-induced oxidative stress in OPMDs METHODS: PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases were searched without restriction of language or year of publication. In addition, gray literature was searched and a manual search was performed. Two independent reviewers screened all the studies, assessing data extraction, risk of bias and certainty of evidence. A narrative synthesis was carried out. For the meta-analysis, random effects were considered to determine the prevalence of a total and a partial remission (PR) of oral potentially malignant disorders (OPMDs). The certainty of evidence was explored using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Twenty-three studies were included in the qualitative and quantitative syntheses. A total of 880 patients were included (564 males; 218 females) with an age range between 24 and 89-years-old. The results showed the prevalence of the total and partial remissions respectively for the following OPMLs: actinic cheilitis (AC): 69.9% and 2.4%; oral leukoplakia (OL): 44% and 36.9%; oral verrucous hyperplasia (OVH): 98.5%; oral erythroleukoplakia (OEL): 92.1% and 7.9%. The prevalence of no remission of OL was 18.8%. CONCLUSIONS: PDT demonstrated significant results in clinical remission of OPMDs and most of the eligible studies have shown a total or a partial remission of the included lesions, but at a low or a very low certainty of evidence. Hence, further clinical studies with robust methodology are warranted to offer further validated data. Also, further evidence is required to understand further the mechanism of PDT-induced oxidative stress.

Oral Potentially Malignant Disorders and Oral Cancer in Saudi Arabia: An Epidemiological Review of the Literature.

Background: Oral potentially malignant disorders (OPMDs) are a group of chronic oral mucosal diseases associated with an increased risk of malignant transformation. Multiple studies have investigated the prevalence of these conditions in multiple regions; however, there are limited data about the prevalence of OPMDs in the Kingdom of Saudi Arabia (KSA). This paper aims to review the prevalence of OPMDs in the KSA, to ensure better understanding of the population risk and propose a more standardised approach to the diagnosis and management of this group across the KSA. In addition, this review will discuss the prevalence of oral cancer in the KSA, considering independent risk factors for oral cancer development. Methods: Electronic databases including PubMed, Medline, Medscape, ScienceDirect, StatPearls, BMC Oral Health and the Cochrane Library were searched with the keywords "Oral Potentially Malignant Disorders"; "Saudi Arabia"; and "Oral Cancer". Identified articles were reviewed independently by 2 reviewers against defined inclusion and exclusion criteria. Results: 16 studies were included in this review. The prevalence of OPMDs in KSA varies significantly depending on age, gender, social habits, background disease and dental status. Conclusions: This review highlights the need for up-to-date data on the prevalence, distribution, and characteristics of OPMDs in KSA. The diverse prevalence rates and distinct characteristics of various OPMDs emphasise the necessity for targeted preventive measures. As the data on OPMDs in KSA remains limited, future research efforts should prioritise the establishment of comprehensive epidemiological studies to inform effective public health interventions in this region.

Assessment of Potentially Malignant Disorders among Men and Women in South Bihar Population.

Oral cancer is detected in 270,000 people per annum or around 3% of all malignancies. It ranks sixth among males and twelve among females in terms of prevalence. Mostly, all oral squamous cell carcinomas (OSCC) are responsible for 92-95% of cases. Oral carcinoma starts five years before the average age of PMD patients, who range in age from 5th to 6th decade of life. Thus, the goal of this study is to identify any relevant risk factors and assess the incidence of oral possibly malignant disorders in both men and women living in rural Bhojpur District, Bihar. A cross-sectional study has been carried out at the Sadar Hospital in Bhojpur by surveying volunteers at various oral health screening and treatment camps held from January 2022 to July 2022. A pre-validated questionnaire adapted and modified from Kumar S et al. was utilized to collect data in a qualitative interview. It was discovered that (17%) of all people had an oral possibly malignant disease. OSMF was the lesion with the greatest prevalence (7%) and lichen planus having the smallest prevalence (1%). Malignancy frequently develops from oral potential malignant diseases. Diabetes and BMI were inversely related, which is expected provided the socioeconomic position.

Deep neural network uncertainty estimation for early oral cancer diagnosis.

BACKGROUND: Early diagnosis in oral cancer is essential to reduce both morbidity and mortality. This study explores the use of uncertainty estimation in deep learning for early oral cancer diagnosis. METHODS: We develop a Bayesian deep learning model termed 'Probabilistic HRNet', which utilizes the ensemble MC dropout method on HRNet. Additionally, two oral lesion datasets with distinct distributions are created. We conduct a retrospective study to assess the predictive performance and uncertainty of Probabilistic HRNet across these datasets. RESULTS: Probabilistic HRNet performs optimally on the In-domain test set, achieving an F1 score of 95.3% and an AUC of 96.9% by excluding the top 30% high-uncertainty samples. For evaluations on the Domain-shift test set, the results show an F1 score of 64.9% and an AUC of 80.3%. After excluding 30% of the high-uncertainty samples, these metrics improve to an F1 score of 74.4% and an AUC of 85.6%. CONCLUSION: Redirecting samples with high uncertainty to experts for subsequent diagnosis significantly decreases the rates of misdiagnosis, which highlights that uncertainty estimation is vital to ensure safe decision making for computer-aided early oral cancer diagnosis.

Applying Machine Learning for Enhanced MicroRNA Analysis: A Companion Risk Tool for Oral Squamous Cell Carcinoma in Standard Care Incisional Biopsy.

Machine learning analyses within the realm of oral cancer outcomes are relatively underexplored compared to other cancer types. This study aimed to assess the performance of machine learning algorithms in identifying oral cancer patients, utilizing microRNA expression data. In this study, we implemented this approach using a panel of oral cancer-associated microRNAs sourced from standard incisional biopsy specimens to identify cases of oral squamous cell carcinomas (OSCC). For the model development process, we used a dataset comprising 30 OSCC and 30 histologically normal epithelium (HNE) cases. We initially trained a logistic regression prediction model using 70 percent of the dataset, while reserving the remaining 30 percent for testing. Subsequently, the model underwent hyperparameter tuning resulting in enhanced performance metrics. The hyperparameter-tuned model exhibited high accuracy (0.894) and ROC AUC (0.898) in predicting OSCC. Testing the model on cases of potentially malignant disorders (OPMDs) revealed that leukoplakia with mild dysplasia was predicted as having a high risk of progressing to OSCC, emphasizing machine learning's advantage over histopathology in detecting early molecular changes. These findings underscore the necessity for further refinement, incorporating a broader set of variables to enhance the model's predictive capabilities in assessing the risk of oral potentially malignant disorders.

Evaluation of Serum and Salivary Lactate Dehydrogenase Levels in Patients with Oral Potentially Malignant Conditions/Lesions: A Clinical and Biochemical Study.

Background: Oral cancer encompasses all malignancies that originate in the oral tissues and remains a major public health problem throughout the world as an important case of poor health and illness. Head and neck cancer accounts for 9.8% of the estimated 6,44,600 incidental cancer cases in India. Oral Squamous Cell Carcinoma (SCC) is a serious and developing concern globally, accounting for more than 90% of malignant cancers of the oral cavity. Salivary diagnostics have been demonstrated to have potential in the detection and screening of oral pre-cancer and cancer in a variety of research settings. The continual and close contact between saliva and the mucosa, where cancer develops, is the foundation of this diagnostic capability. Materials and Methods: This research utilized spectrophotometry to quantify Lactate Dehydrogenase levels in serum and saliva of 30 healthy people which consisted the control group and 31 Oral Potentially Malignant people which constituted the study group. Results: On estimation and comparison, the mean Lactate Dehydrogenase levels in serum (397.4968+71.6392 IU/L) and saliva (675.4935+139.3352 IU/L) among patients with Oral Potentially malignant lesions/conditions were higher than the mean Lactate Dehydrogenase levels in serum (390.8667+71.0953 IU/L) and saliva (201.3700+89.1439 IU/L) among controls. Conclusion: Higher serum and salivary LDH levels in Oral Potentially malignant lesions/conditions than in control groups signifies the importance of assessing salivary LDH levels, in the prognosis of the same. Further prospective longitudinal studies are required to assess the salivary LDH levels among the patients with malignant transformation of Oral Potentially malignant lesions/conditions to oral cancers.

Update on Oral and Oropharyngeal Cancers: A guide for oral health care providers.

Oral squamous cell carcinomas (OSCC) signs and symptoms may be first identified by dental hygienists during routine extra and intra-oral examinations. A comprehensive extra-oral and intra-oral examination during regular dental hygiene assessment is paramount to identifying oral potentially malignant disorders (OPMD) and cancerous lesions for timely referral and treatment. Integrating a systematic list of questions during the medical and dental assessment along with careful visual and tactile examinations is critical to identifying OPMDs and cancerous lesions. Understanding the relationship between oropharyngeal squamous cell carcinomas (OPSCC) and Human Papilloma Virus (HPV) and how vaccination can prevent HPV-related OPSCC is critical to providing evidence-based recommendations and care. The purpose of this report is to provide an update on current epidemiological trends of OSCC and OPSCC rates in the United States (US) and provide the latest evidence on what dental hygienists must know to improve health outcomes and mitigate the consequences of undiagnosed cancer. This report considers enduring challenges with the annual rise in OPSCC rates and the public health burden of HPV-related cancers in the US. Emphasis on regular, quality continuing education about OSCC and OPSCC is emphasized along with recommendations for evidence-based training.

Eosinophils in Oral Disease: A Narrative Review.

The prevalence of diseases characterised by eosinophilia is on the rise, emphasising the importance of understanding the role of eosinophils in these conditions. Eosinophils are a subset of granulocytes that contribute to the body's defence against bacterial, viral, and parasitic infections, but they are also implicated in haemostatic processes, including immunoregulation and allergic reactions. They contain cytoplasmic granules which can be selectively mobilised and secrete specific proteins, including chemokines, cytokines, enzymes, extracellular matrix, and growth factors. There are multiple biological and emerging functions of these specialised immune cells, including cancer surveillance, tissue remodelling and development. Several oral diseases, including oral cancer, are associated with either tissue or blood eosinophilia; however, their exact mechanism of action in the pathogenesis of these diseases remains unclear. This review presents a comprehensive synopsis of the most recent literature for both clinicians and scientists in relation to eosinophils and oral diseases and reveals a significant knowledge gap in this area of research.

OralImmunoAnalyser: a software tool for immunohistochemical assessment of oral leukoplakia using image segmentation and classification models.

Oral cancer ranks sixteenth amongst types of cancer by number of deaths. Many oral cancers are developed from potentially malignant disorders such as oral leukoplakia, whose most frequent predictor is the presence of epithelial dysplasia. Immunohistochemical staining using cell proliferation biomarkers such as ki67 is a complementary technique to improve the diagnosis and prognosis of oral leukoplakia. The cell counting of these images was traditionally done manually, which is time-consuming and not very reproducible due to intra- and inter-observer variability. The software presently available is not suitable for this task. This article presents the OralImmunoAnalyser software (registered by the University of Santiago de Compostela-USC), which combines automatic image processing with a friendly graphical user interface that allows investigators to oversee and easily correct the automatically recognized cells before quantification. OralImmunoAnalyser is able to count the number of cells in three staining levels and each epithelial layer. Operating in the daily work of the Odontology Faculty, it registered a sensitivity of 64.4% and specificity of 93% for automatic cell detection, with an accuracy of 79.8% for cell classification. Although expert supervision is needed before quantification, OIA reduces the expert analysis time by 56.5% compared to manual counting, avoiding mistakes because the user can check the cells counted. Hence, the SUS questionnaire reported a mean score of 80.9, which means that the system was perceived from good to excellent. OralImmunoAnalyser is accurate, trustworthy, and easy to use in daily practice in biomedical labs. The software, for Windows and Linux, with the images used in this study, can be downloaded from https://citius.usc.es/transferencia/software/oralimmunoanalyser for research purposes upon acceptance.

State of the Art in the Diagnosis and Assessment of Oral Malignant and Potentially Malignant Disorders: Present Insights and Future Outlook-An Overview.

Oral Potentially Malignant Disorder (OPMD) is a significant concern for clinicians due to the risk of malignant transformation. Oral Squamous Cell Carcinoma (OSCC) is a common type of cancer with a low survival rate, causing over 200,000 new cases globally each year. Despite advancements in diagnosis and treatment, the five-year survival rate for OSCC patients remains under 50%. Early diagnosis can greatly improve the chances of survival. Therefore, understanding the development and transformation of OSCC and developing new diagnostic methods is crucial. The field of oral medicine has been advanced by technological and molecular innovations, leading to the integration of new medical technologies into dental practice. This study aims to outline the potential role of non-invasive imaging techniques and molecular signatures for the early detection of Oral Malignant and Potentially Malignant Disorders.

Oral carcinogenesis and non-invasive biomarkers for the diagnosis of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most prevalent cancer in Pakistani population because of consumption of different tobacco-containing products whether smoked or chewed. These patients commonly report at a late stage of the disease. The patient's survival only depends upon early-stage diagnosis. Literature has reported that there is an increased tendency of transformation of oral potentially malignant disorder (OPMD) into OSCC. Biopsy is the gold standard measure for diagnosis but for OPMD cases biopsy was not recommended and most of the times the patients were also not willing to have a biopsy done. So, along with the biopsy there is a need for non-invasive protein biomarker that might aid in the early detection of oral cancer as well as highlight the high-risk individuals. This short communication focuses on the role of early diagnostic biomarkers present in literature, such as synuclein-γ (SNCG), Squamous cell carcinoma antigen (SCCAg), p53, MMPs-12, and IL-6. Furthermore, application of these biomarkers in multi-centre longitudinal studies is needed to establish their role as a non-invasive diagnostic biomarker for OSCC.