Advances in Raman spectroscopy for characterising oral cancer and oral potentially malignant disorders.

Oral cancer survival rates have seen little improvement over the past few decades. This is mainly due to late detection and a lack of reliable markers to predict disease progression in oral potentially malignant disorders (OPMDs). There is a need for highly specific and sensitive screening tools to enable early detection of malignant transformation. Biochemical alterations to tissues occur as an early response to pathological processes; manifesting as modifications to molecular structure, concentration or conformation. Raman spectroscopy is a powerful analytical technique that can probe these biochemical changes and can be exploited for the generation of novel disease-specific biomarkers. Therefore, Raman spectroscopy has the potential as an adjunct tool that can assist in the early diagnosis of oral cancer and the detection of disease progression in OPMDs. This review describes the use of Raman spectroscopy for the diagnosis of oral cancer and OPMDs based on ex vivo and liquid biopsies as well as in vivo applications that show the potential of this powerful tool to progress from benchtop to chairside.

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.

Calibration improves the agreement in grading oral epithelial dysplasia-Findings from a National Workshop in Malaysia.

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.

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.

Epigenetics in the diagnosis and prognosis of head and neck cancer: A systematic review.

BACKGROUND: Aberrant epigenetic modifications significantly develop and progress human malignancies including head and neck squamous cell carcinoma (HNSCC). Taking into account issues of late diagnosis and poor prognosis associated with HNSCC, this systematic review is designed to provide an up-to-date insight of epigenetic changes in the management of HNSCC. METHODS: All studies that assessed the diagnostic and prognostic utilities of epigenetic changes (DNA methylation and histone modifications) among patients diagnosed with HNSCC or oral potentially malignant disorders (OPMDs) were considered for inclusion till June 2023. Pre-defined Medical Subject Headings terms were used to search Web of Science, Pubmed, Scopus and Embase Ovid databases. RESULTS: Twenty-five studies were deemed eligible for inclusion with a total number of 3790 samples (2123 HNSCCs, 334 OPMDs and 1333 as controls). DNA methylation was investigated in 18 studies while the role of histone modifications was assessed in seven studies. The most investigated biomarkers among the studies were H3, DAPK and TIMP3. The diagnostic accuracy of the epigenetic biomarkers in detecting HNSCC was assessed in eight studies where the following biomarkers showed the highest area under the curve values: TIPM3, DCC, DAPK, SEPT9, SHOX9, HOXA9 and TRH. None of the studies assessed the predictability of the epigenetic biomarkers in HNSCC and OPMDs. CONCLUSION: Although initial promising results were seen using the epigenetic biomarkers in the early detection of HNSCC, the limited number of patients and the absence of well-designed longitudinal studies limit the clinical applicability of the outcomes.

Barriers to early diagnosis and management of oral cancer in Latin America and the Caribbean.

OBJECTIVE: This study aimed to explore perceived barriers to early diagnosis and management of oral cancer, as well as potential pathways for improvement in Latin America and the Caribbean (LAC). METHODS: This cross-sectional study used a self-administered online questionnaire created via the Research Electronic Data Capture platform. The survey was distributed to health professionals trained in Oral Medicine, Oral Pathology, Oral and Maxillofacial Surgery, and Dentists with clinical and academic expertise in oral potentially malignant disorder (OPMD) and oral cancer. Data obtained were systematically organized and analyzed descriptively using Microsoft Excel. RESULTS: Twenty-three professionals from 21 LAC countries participated. Major barriers included the limited implementation of OPMD and oral cancer control plans (17.4%), low compulsory reporting for OPMD (8.7%) and oral cancer (34.8%), unclear referral pathways for OPMD (34.8%) and oral cancer (43.5%), and a shortage of trained professionals (8.7%). Participants endorsed the utility of online education (100%) and telemedicine (91.3%). CONCLUSION: The survey highlights major perceived barriers to early diagnosis and management of OPMD and oral cancer in LAC, as well as potential avenues for improvement.

Betel-quid addictive use disorders and Oral potentially malignant disorders and Oral cancer in south, southeast, and East Asia: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide a comprehensive assessment of the measurement and prevalence of betel-quid (BQ) abuse, dependence, and BQ use disorder (BUD), as well as to evaluate the impact of BQ addiction on oral malignant diseases. METHODS: We used the PRISMA guidelines to perform a systematic review and meta-analysis. We searched for relevant publications up to April 2024 in PubMed, Web of Science, and Embase. The articles were evaluated for BQ addiction and its relationship with oral potentially malignant disorders (OPMD) and oral cancer. RESULTS: The prevalence of BQ abuse, dependence, and BUD in South, Southeast, and East Asia varied between 0.8%-46.3%, 0.4%-43.5%, and 4.7%-39.2%, respectively. Among BQ chewers, the corresponding proportions of these disorders ranged from 40.5%-99.6%, 20.9%-99.6%, and 55.2%-99.3%. The pooled risks of OPMD associated with BQ abuse, dependence, and BUD were 16.3, 18.7, and 9.6-35.5, respectively. The risk of oral cancer for mild, moderate, and severe BUD was 8.5, 8.2, and 42.3, respectively. CONCLUSIONS: BUD mediates the link between BQ use and an increased risk of oral malignant disorders. Addressing and treating BQ addiction is an important component of comprehensive OPMD and oral cancer preventive and intervention programs that go beyond simple cessation efforts.

Comparative analysis of two arecoline-induced oral submucous fibrosis models.

OBJECTIVE: The limited understanding of the molecular mechanism for oral submucosal fibrosis (OSF) poses challenges to the development of effective prevention and treatment strategies. The lack of suitable animal models is a major hindrance. Therefore, this study aimed to address this issue by comparing commonly used arecoline-induced water drinking and injection mouse models. MATERIALS AND METHODS: The mice were subjected to two protocols: receiving 2 mg/mL arecoline in drinking water and 4 mg/mL arecoline saline solution injections every other day. Tissues were collected at regular 4-week intervals, with a final time point of 20 weeks. Stereo microscopy and histomorphological analysis were performed on live and harvested tissues, respectively. RESULTS: During arecoline treatment, collagen deposition and myofibroblast proliferation progressively increased in both models. Changes in the collagen I/III ratio indicated that both models exhibited characteristics of the early and intermediate stages of OSF after 20 weeks of arecoline induction. The water-drinking model also demonstrated multi-organ fibrosis involving the tongue, lungs, and small intestine. CONCLUSION: Both the water drinking and injection mouse models effectively induced OSF, but the water-drinking model better mirrored the observed pathogenesis in patients with OSF. These models provide valuable tools for investigating the mechanisms underlying OSF.

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.

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.

Optical coherence tomography: Promising imaging technique for the diagnosis of oral mucosal diseases.

OBJECTIVE: This review aims to summarize the latest application of optical coherence tomography (OCT) in oral mucosal diseases, promoting an accurate and earlier diagnosis of such disorders, which are difficult to be differentiated. SUBJECTIVE AND METHODS: References on the application of OCT in oral mucosal diseases were mainly obtained from PubMed, Embase, Web of Science and Scopus databases, using the keywords: "optical coherence tomography and 'oral mucosa/oral cancers/oral potentially malignant diseases/oral lichen planus/oral leukoplakia/oral erythroplakia/discoid lupus erythematosus/oral autoimmune bullous diseases/oral ulcers/erythema multiforme/oral mucositis'". RESULTS: It is found that OCT is showing a promising application potential in the early detection, diagnosis, differential diagnosis, monitoring of oral cancer and oral dysplastic lesions, as well as the delineation of tumor margins. OCT is also playing an increasingly important role in the diagnosis of oral potentially malignant disorders, oral mucosal bullous diseases, oral ulcerative diseases, erythema multiforme, and the early detection of oral mucositis. CONCLUSION: Optical coherence tomography, as a novel optical technique featured by real-time, noninvasive, dynamic and high-resolution imaging, is of great use to serve as an adjunct tool for the diagnosis, differential diagnosis, monitoring and therapy evaluation of oral mucosal diseases.

Diagnosis of differentiated dysplasia as a variant of oral epithelial dysplasia.

OBJECTIVES: The World Health Organization's definition of oral epithelial dysplasia includes differentiated dysplasia, which is defined by purely architectural abnormalities of oral mucosa without cytological changes. We analysed differentiated dysplasia's frequency, progression risk and correlation with oral brush cytology. MATERIALS AND METHODS: Cytoarchitectural criteria and expression patterns of keratin 13/17 and ki67 were studied in oral biopsies clinically diagnosed with leukoplakia. Biopsies were assessed for dysplasia and its grade. Available brush cytology findings were obtained from clinical records. RESULTS: We included 159 biopsies from 112 patients (33% differentiated dysplasia; 27% keratosis without dysplasia; oral epithelial dysplasia with atypia of mild, moderate and severe degree including invasive cancers in 9%, 8% and 7%, respectively). Keratin 13 loss and keratin 17 gain were higher in differentiated-dysplasia cases (p < 0.0001), which had the highest hypergranulosis frequency. Keratin 17 expression was associated with higher malignant-transformation rates (p = 0.0028). The transformation rate and time were comparable between dysplasia with atypia and differentiated-dysplasia cases, which had higher progression rates and shorter time periods than keratosis cases without dysplasia (p = 0.08). Cytology prior to differentiated dysplasia all indicated normal oral mucosa. CONCLUSIONS: Keratin 17 but not oral brush cytology can help identify patients with differentiated dysplasia with higher risk for malignant transformation.

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.

A study of risk factors associated with the presence of oral potentially malignant disorders: a community-based study from Northeastern Thailand.

BACKGROUND: The principal objective of this study is to ascertain the connections between well-known risk factors of oral cancer, including smoking (cigarette and tobacco), alcohol consumption, betel quid chewing, irritations in the oral cavity, history of head and neck cancer, and history of working outdoor more than 4 days/week, and the presence of OPMDs within the Thai population. METHOD: 349,318 subjects were recruited for initial screening, then 1,483 subjects who had at least 1 risk factor and a suspicious lesion underwent comprehensive oral examinations followed by a clinical diagnosis and then received initial treatment from either oral surgeons or oral medicine specialists. Among these subjects, individuals with at least 1 risk factor and with a clinical diagnosis of OPMDs were classified as cases, while those with at least 1 risk factor but without OPMDs were categorized as controls. The case group comprised a total of 487 subjects, whereas the control group consisted of 996 subjects. Exclusion criteria were known cases of currently having oral cancer or OPMDs. RESULTS: The outcomes of the multivariate analysis revealed that among the variables assessed, betel quid (adjusted OR 5.12 [3.93-6.68], p < 0.001) and smoking (adjusted OR 1.46 [1.08-1.97], p = 0.013), there were an association with the presence of OPMDs. Conversely, alcohol drinking, having irritations in the oral cavity, a history of head and neck cancer, and a history of working outdoors more than 4 days/week were not associated with the presence of OPMDs. Furthermore, we also study the synergistic effect of alcohol drinking, irritations in the oral cavity, history of head and neck cancer, and history of working outdoors more than 4 days/week using subgroup analysis. The analysis showed that alcohol consumption combined with smoking or betel quid chewing expressed a significantly increased risk of OPMDs, from 1.46 to 2.03 (OR 2.03 [1.16-3.56], p = 0.014) and from 5.12 to 7.20 (OR 7.20 [3.96-13.09], p < 0.001). CONCLUSION: Smoking and exposure to betel quid were a significant risk factors for the presence of OPMDs. The combination of alcohol with smoking or betel quid chewing was also found to increase the risk of OPMDs in this Thai northeastern population.

Serum mRNA levels of cytokeratin-19 and vascular endothelial growth factor in oral squamous cell carcinoma and oral potentially malignant disorders using RT-PCR.

BACKGROUND: Oral cancers, which include tumors of the oral cavity, salivary glands, and pharynx, are becoming increasingly prevalent worldwide. Squamous cell carcinoma accounts for over 90% of malignant oral lesions, with oral squamous cell carcinoma (OSCC) being notably common in the Indian subcontinent and other regions of Asia. This is especially true in South-Central Asia, including Sri Lanka, where it is particularly prevalent among men. This study aims to evaluate the levels of Vascular Endothelial Growth Factor-A (VEGF-A) and Cytokeratin-19 (CK-19) mRNAs in whole blood as a potential method for the early detection of OSCC. METHODS: The study included 40 patients (each from OSCC, Oral Submucous Fibrosis (OSF), Oral Leukoplakia (OLK), Oral Lichen Planus (OLP), and 10 healthy controls. The expression levels of VEGF-A and CK-19 mRNAs were measured from extracellular RNA extracted from whole blood samples using real-time reverse transcription polymerase chain reaction (RT-PCR) with sequence-specific primers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of these biomarkers in detecting OSCC. RESULTS: The results demonstrated a significant increase in blood transcripts of the candidate mRNAs CK-19 and VEGF-A in patients with OSCC, OSF, OLK, and OLP. The Wilcoxon signed-rank test revealed a p-value of 0.002 for each specific comparison between diseased patients and healthy controls (i.e., OSCC vs. HC, OSF vs. HC, OLP vs. HC, OLK vs. HC) for both CK-19 and VEGF-A. When these two biomarkers were used together, they provided a 60% predictive probability for patients with OSCC (p = 0.023). CONCLUSION: This study highlights the efficacy of blood mRNA transcriptome diagnostics in detecting OSCC. This innovative clinical approach has the potential to be a robust, efficient, and reliable tool for early cancer detection. Blood-based transcriptomes could be further explored for their effectiveness in various health contexts and for routine health monitoring.

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.

Artificial intelligence-integrated optical coherence tomography for screening and early detection of oral cancer.

Early detection of oral cancer is essential for improving patient survival rates and leads to higher chances of successful treatment, reduced cost of complex treatments, and improved quality of life of patients. Oral cancer often arises from oral potentially malignant disorders (OPMDs), among which leukoplakia is the most common. Numerous chairside diagnostic aids and imaging modalities have been reviewed for screening detection of OPMDs and oral cancer, but these techniques have limitations. Novel optical diagnostic modalities work on the assumption that neoplastic and dysplastic tissues have different absorbance and reflectance properties when exposed to specific wavelengths of light. Optical coherence tomography (OCT) imaging is a promising new technology in the field of oral oncology. The ability of OCT to provide real-time, nondestructive, high-resolution, radiation-free images makes it an ideal modality for screening and detection of neoplastic changes in the oral mucosa, but interpretation of OCT images requires training and expertise. To overcome this limitation, artificial intelligence-based diagnostic algorithms are being combined with OCT imaging to assist professionals in achieving high-accuracy interpretation of OCT images. This review highlights the applications and scope of artificial intelligence in OCT imaging for the screening and detection of early-stage oral cancer.

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.

Biological biomarkers of oral cancer.

The oral squamous cell carcinoma (OSCC) 5 year survival rate of 41% has marginally improved in the last few years, with less than a 1% improvement per year from 2005 to 2017, with higher survival rates when detected at early stages. Based on histopathological grading of oral dysplasia, it is estimated that severe dysplasia has a malignant transformation rate of 7%-50%. Despite these numbers, oral dysplasia grading does not reliably predict its clinical behavior. Thus, more accurate markers predicting oral dysplasia progression to cancer would enable better targeting of these lesions for closer follow-up, especially in the early stages of the disease. In this context, molecular biomarkers derived from genetics, proteins, and metabolites play key roles in clinical oncology. These molecular signatures can help predict the likelihood of OSCC development and/or progression and have the potential to detect the disease at an early stage and, support treatment decision-making and predict treatment responsiveness. Also, identifying reliable biomarkers for OSCC detection that can be obtained non-invasively would enhance management of OSCC. This review will discuss biomarkers for OSCC that have emerged from different biological areas, including genomics, transcriptomics, proteomics, metabolomics, immunomics, and microbiomics.

Diagnostic Accuracy of Liquid Biopsy for Oral Potentially Malignant Disorders and Head and Neck Cancer: an Overview of Systematic Reviews.

PURPOSE OF REVIEW: The aim of this overview is to appraise the evidence on salivary biomarkers for H&N cancer diagnosis. The acronym PICOS was used to develop the eligibility criteria and the focused review question: are liquid biopsies (saliva biomarkers) reliable for cancer detection in H&N cancer patients? Electronic database search encompassed PubMed, EMBASE, Scopus, Cochrane Library, Web of Science, and LILACS. Risk of Bias (RoB) was assessed through AMSTAR 2. RECENT FINDINGS: A total of 20 SRs were included. Only seven SRs were able to reach more solid conclusions around the retrieved findings by calculating the pooled sensitivity, specificity, and the overall area under the curve (AUC). Despite the limitations, significant RoB, and lack of test metrics in primary studies, all SRs recognize and encourage the potential role of saliva in the early diagnosis of oral cancer.