Search

Rationale: Predictive biomarkers can be effective in the identification of the oral leukoplakia with an increased probability of malignant transformation., Patients Concerns: A 63-year-old patient presents with persistent burning sensations throughout the oral cavity, accompanied by a white lesion on the tongue. Additionally, a 57-year-old patient with multiple white lesions in the oral cavity., Diagnosis: Histopathological analysis of the excised tissue., Interventions: Changes in the expression miRNAs (miR17, miR206, and miR23), the activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase), and concentration of reduced glutathione were detected, followed by meta-analysis of previous studies., Outcomes: In both patients (verrucous leukoplakia, oral squamous cell carcinoma) upregulated expression of miR-23a, miR-17, and downregulated expression of miR206 were detected when compared to healthy individuals. In the plasma of a patient diagnosed with carcinoma, higher activity of antioxidant enzymes connected to glutathione was measured in comparison to healthy individuals., Lessons: The connection between miRNA expression changes, the increase in glutathione-S-transferase and especially the decrease in superoxide dismutase activities in patients with white lesion potential malignant transformation using the provided statistical analysis was confirmed., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Oral leukoplakia is classified among oral potentially malignant disorders (OPMDs) by the World Health Organization (WHO). The visual oral examination (VOE) is the most used method for identifying lesions in their early stages. Given that the diagnosis of oral cancer is often late, there is an urgent need for early detection and examination of oral lesions. Surgical biopsy represents the gold standard as a diagnostic method, but because it is invasive, it cannot be repeated for periodic checks. We report the case of a lesion on the buccal mucosa of a 65-year-old male patient with a malignant appearance. The patient underwent a novel non-invasive cyto-salivary sampling and ELISA immunoassay for tumor biomarker detection and biopsy with histopathological analysis. The rapid ELISA test results excluded signs of malignancy, providing valuable insights into the lesion's immunophenotypic profile, which were consistent with the histopathological examination findings. This case report highlights the clinical and histopathological characteristics of a lesion with the aspect of Proliferative Verrucous Leukoplakia (PVL), emphasizing its challenging diagnosis and management. The integration of non-invasive cytobrush sampling with biomarker analysis proved valuable in detecting specific tumor biomarkers, potentially indicating ongoing tumor transformation. Monitoring these markers over time could enhance early detection and management strategies, thereby improving patient outcomes. This approach underscores the utility of non-invasive techniques in phenotyping oral lesions and supporting clinical decision-making in oral medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Rebaudi, Rebaudi, De Rosa, Rebaudi, Pesce, Greppi, Roghi, Boggio, Candiani and Marcenaro.)

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., (© 2024 Wiley Periodicals LLC.)

Background: We aimed to construct an artificial intelligence-based model for detecting oral cancer and dysplastic leukoplakia using oral cavity images captured with a single-lens reflex camera., Subjects and Methods: We used 1043 images of lesions from 424 patients with oral squamous cell carcinoma (OSCC), leukoplakia, and other oral mucosal diseases. An object detection model was constructed using a Single Shot Multibox Detector to detect oral diseases and their locations using images. The model was trained using 523 images of oral cancer, and its performance was evaluated using images of oral cancer (n = 66), leukoplakia (n = 49), and other oral diseases (n = 405)., Results: For the detection of only OSCC versus OSCC and leukoplakia, the model demonstrated a sensitivity of 93.9% versus 83.7%, a negative predictive value of 98.8% versus 94.5%, and a specificity of 81.2% versus 81.2%., Conclusions: Our proposed model is a potential diagnostic tool for oral diseases., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Objective: To identify potential salivary biomarkers for the diagnosis and monitoring of disease progression in oral squamous cell carcinoma and oral leukoplakia., Materials and Methods: An advance search from PubMed and Hindawi was performed with keywords; oral leukoplakia/oral squamous cell carcinoma, salivary biomarker and diagnosis/prognosis. An additional search of articles was done through a manual search from the Google Scholar database., Results: Twenty studies involving salivary biomarkers as diagnostic tools for oral squamous cell carcinoma and/or oral leukoplakia were identified. A narrative review was carried out., Conclusion: Single or multiple salivary biomarkers reported by most studies have shown great potential as diagnostic tools for oral squamous cell carcinoma and oral leukoplakia. However, the validation of sensitivity and specificity should be carried out to ensure the accuracy of the biomarkers. Furthermore, a standardised method for saliva collection should be established to prevent variability in the expression of biomarkers., (© 2023 Wiley Periodicals LLC.)

Proliferative verrucous leukoplakia (PVL) is a non-homogenous type of oral leukoplakia, characterized by multifocal white plaques, propensity to recur after treatment, with strong tendency towards malignant transformation. Interestingly, some studies show that, at initial stages, PVL may resemble oral lichen planus (OLP), potentially leading to misdiagnosis. A 52-year-old woman, with a previous OLP diagnosis, was referred to our service for implant installation and follow-up of OLP lesions. After clinicopathological re-evaluation, a diagnosis of PVL (early stage) was made, and a maxillary full-arch implant-supported prosthesis supported by implants was installed. After 6 years of follow-up, the patient developed squamous cell carcinoma around the implants. The current case emphasizes that PVL patients with oral lesions suggesting peri-implantitis or peri-implant mucositis deserve a more meticulous investigation.

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., Competing Interests: Disclosure Dr G.J. Hanna receives research funding to his institution from Bristol-Myers Squibb, United States (BMS) and has served in an advisory role for BMS. The other authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Context: Oral cancer is highly prevalent in India. Lack of awareness and delay in diagnosis and treatment of patients with oral cancer leads to high mortality and poor survival of patients. Salivary endothelin-1 is proposed as a prospective biomarker for oral squamous cell carcinoma., Aims: Aim of the study was to evaluate salivary level of endothelin-1 in oral cancer and precancer as a biomarker., Settings and Design: We planned a case control study to evaluate salivary level of Endothelin-1 in oral cancer and precancer as a biomarker., Materials and Methods: A total of 72 subjects were taken in study out of which 24 cases were of histopathologically confirmed premalignat oral lesion (oral leukoplakia and oral submucous fibrosis), 24 cases were of histopathologically confirmed oral squamous cell carcinoma, and 24 cases of healthy age and gender matched controls without any addiction to tobacco in any form from a tertiary care hospital were taken. Saliva was collected from all following standard guidelines and estimation of salivary endothelin-1 was done by ELISA., Statistical Analysis Used: SPSS software version 15., Results: Salivary endothelin-1 values of controls ranged between 0.09 and 1.88 pg/ml while that of premalignant cases ranged between 1.16 and 16.135 pg/ml and of SCC cases ranged between 2.567 and 22.98 pg/ml., Conclusions: Salivary endothelin-1 is raised in oral squamous cell carcinoma compared to premalignant and controls therefore, shows capability to differentiate between premalignant lesion and oral cancer. So, it could be used as a biomarker for early diagnosis., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Objectives: Diagnosing oral potentially malignant disorders (OPMD) is critical to prevent oral cancer. This study aims to automatically detect and classify the most common pre-malignant oral lesions, such as leukoplakia and oral lichen planus (OLP), and distinguish them from oral squamous cell carcinomas (OSCC) and healthy oral mucosa on clinical photographs using vision transformers., Methods: 4,161 photographs of healthy mucosa, leukoplakia, OLP, and OSCC were included. Findings were annotated pixel-wise and reviewed by three clinicians. The photographs were divided into 3,337 for training and validation and 824 for testing. The training and validation images were further divided into five folds with stratification. A Mask R-CNN with a Swin Transformer was trained five times with cross-validation, and the held-out test split was used to evaluate the model performance. The precision, F1-score, sensitivity, specificity, and accuracy were calculated. The area under the receiver operating characteristics curve (AUC) and the confusion matrix of the most effective model were presented., Results: The detection of OSCC with the employed model yielded an F1 of 0.852 and AUC of 0.974. The detection of OLP had an F1 of 0.825 and AUC of 0.948. For leukoplakia the F1 was 0.796 and the AUC was 0.938., Conclusions: OSCC were effectively detected with the employed model, whereas the detection of OLP and leukoplakia was moderately effective., Clinical Relevance: Oral cancer is often detected in advanced stages. The demonstrated technology may support the detection and observation of OPMD to lower the disease burden and identify malignant oral cavity lesions earlier., (© 2024. The Author(s).)

Oral cancer represents a significant global public health challenge, contributing substantially to the incidence and mortality of cancer. Despite established risk factors such as tobacco use and alcohol consumption, early detection remains crucial for effective treatment. This study introduces a novel approach using a transistor-based biosensor system for detecting the P90 (CIP2A) protein. We tested the presence of CIP2A in human leukoplakia samples, which can undergo malignant conversion into aggressive oral squamous cell carcinoma. The method used commercially available glucose test strips functionalized with P90 antibodies, providing high sensitivity and a low limit of detection which was five orders lower than that of commercial ELISA kits. A specially designed printed circuit board (PCB) facilitated accurate measurements, and the device's performance was optimized through characteristic tests. Human sample testing validated the biosensor's effectiveness in distinguishing samples after cell lysis. This study contributes to advancing accurate and cost-effective diagnostic approaches for oral pre-cancer and cancer tissues.

We have observed a distinct phenomenon of transient oral lingual leukoplakia in infancy and report 22 healthy infants with gray-white plaques on the dorsal tongue with sparing of the tip from four medical centers in three countries. The onset of the eruption ranged from 1 week to 7 months of life and resolved in 19 patients (86%, with 3 patients lost to follow-up). None of the eight patients examined at 1 year of age had residual findings. We believe this is a common entity that can be distinguished from oral candidiasis on clinical and/or laboratory examination and name this entity "transient infantile lingual leukoplakia.", (© 2024 The Authors. Pediatric Dermatology published by Wiley Periodicals LLC.)

Background: The grading of oral epithelial dysplasia is often time-consuming for oral pathologists and the results are poorly reproducible between observers. In this study, we aimed to establish an objective, accurate and useful detection and grading system for oral epithelial dysplasia in the whole-slides of oral leukoplakia., Methods: Four convolutional neural networks were compared using the image patches from 56 whole-slide of oral leukoplakia labeled by pathologists as the gold standard. Sequentially, feature detection models were trained, validated and tested with 1,000 image patches using the optimal network. Lastly, a comprehensive system named E-MOD-plus was established by combining feature detection models and a multiclass logistic model., Results: EfficientNet-B0 was selected as the optimal network to build feature detection models. In the internal dataset of whole-slide images, the prediction accuracy of E-MOD-plus was 81.3% (95% confidence interval: 71.4-90.5%) and the area under the receiver operating characteristic curve was 0.793 (95% confidence interval: 0.650 to 0.925); in the external dataset of 229 tissue microarray images, the prediction accuracy was 86.5% (95% confidence interval: 82.4-90.0%) and the area under the receiver operating characteristic curve was 0.669 (95% confidence interval: 0.496 to 0.843)., Conclusions: E-MOD-plus was objective and accurate in the detection of pathological features as well as the grading of oral epithelial dysplasia, and had potential to assist pathologists in clinical practice., (© 2024. The Author(s).)

Background and Aim: Precancer biomarkers help in early detection and management of oral potentially malignant disorders (OPMDs). Interleukin-1β (IL-1β), a biomarker, is known to be altered in oral submucous fibrosis (OSMF) and oral leukoplakia (OL). Therefore, we evaluated and compared the serum and salivary IL-1β levels in patients with OSMF/oral leukoplakia and in gender- and age-matched healthy individuals., Materials and Methods: An in vivo, prospective, observational study was conducted on 40 subjects. Subjects were divided into two groups with 20 individuals in each group, that is, Group I: OSMF/oral leukoplakia and Group II: control group. Salivary and serum IL-1β levels were quantitatively estimated using enzyme-linked immunosorbent assay (ELISA). The statistical tests used were unpaired t-test and Chi-square test., Results: The serum IL-1β levels were significantly (P 0.001) lesser in Group I in comparison to Group II. The salivary IL-1β levels remained insignificant between both the groups. However, in both the groups, the salivary IL-1β levels were significantly higher compared to the serum IL-1β levels., Conclusion: We found that the serum IL-1β level can be considered as a prospective biomarker for dysplasia, whereas salivary IL-1β alone needs more elaborated studies to account for its application as a potential biomarker in OPMD., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Background: Proliferative verrucous leukoplakia (PVL) is a rare and enigmatic oral potentially malignant disorder which almost invariably results in oral squamous cell carcinoma (OSCC). The aims of this project were to use transcriptome profiling to characterise PVL gene expression patterns for biomarker identification and gain insight into the molecular aetiopathogenesis of PVL., Methods: Forty-three oral cavity mucosal biopsies from 32 patients with oral lesions clinically compatible with either PVL or non-PVL conventional oral leukoplakia (OLK) underwent transcriptome profiling by RNA sequencing. Data was analysed by hierarchical clustering, differential gene expression, functional enrichment and network analysis, sparse partial least squares discriminant analysis sPLS-DA, and immune cell phenotypic estimation., Results: We found 464 genes significantly differentially expressed at least 2-fold between PVL and non-PVL OLK (193 up and 271 down). HOX genes, including HOXA1 and HOXB7, keratin-associated proteins (KRTAPs) and olfactory receptor G proteins (OR) were significantly upregulated in PVL. Other upregulated genes in PVL included FOS, WNT16 and IFNA1. Pathway analysis showed that there was a significant downregulation of connective tissue signalling in PVL. Classifying multivariate models based upon 22 genes discriminated PVL from non-PVL OLK. Bioinformatic profiling showed that immune cell profiles in PVL and OLK were similar except that fibroblast markers were reduced in PVL., Conclusion: These results demonstrate that PVL and conventional OLK are molecularly distinct with upregulation of many cancer-associated genes. They provide insight into the pathogenesis of PVL and show that biomarker based molecular diagnostics is feasible to discriminate and inform diagnosis and management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Proliferative verrucous leukoplakia (PVL) is a distinct type of oral leukoplakia which has the potential to enlarge or develop into new areas of leukoplakia coupled with areas of a warty surface texture. PVL is usually diagnosed from the fifth decade onwards and is more common in female patients. The most frequent sites involved tend to be gingivae, followed by buccal mucosa and lateral border of tongue. It is one of the oral potentially malignant conditions with a high risk of malignant transformation. It is important for general dental practitioners (GDPs) to identify such lesions to facilitate referral for further investigation and diagnosis. Management is challenging with long-term monitoring and surgical excision when appropriate; however, PVL tends to recur following surgical excision. This article provides an up-to-date review tailored for GDPs on the present knowledge of PVL and illustrates the management challenges with clinical cases., (© 2024. The Author(s).)

Objective: The aim of the study. Improving the efficiency of diagnosis and detailing the features of the clinic of «potentially malignant» diseases of the oral mucosa., Materials and Methods: Clinical and laboratory examination of 124 patients of the department of oral mucosa diseases aged 35 to 80 years, among whom there were 75 women and 49 men, with diseases such as erythroplakia - 12 patients, verrucous leukoplakia - 52 patients, erosive form of leukoplakia - 35 patients, cheilitis Manganotti - 25 patients. Histological and immunohistochemical methods of investigation were used as diagnostics. To assess the proliferative activity of epithelial cells, the determination of the Ki-67 index was used. The synthesis of keratin 15 (K15) in epithelial layers was determined as a diagnostic criterion for the severity of neoplasia. The expression of human papillomavirus type 16 (HPV 16) antigens and p16INK4a protein in epithelial cells was studied, as well as the expression of p53 protein., Results: A high prevalence of p53 mutations was observed in patients with erythroplakia. In leukoplakia, the expression of the Ki-67 protein was detected in the cell nuclei in both the basal and parabasal layers of the multilayer squamous epithelium, in 77% of cases, the expression of the p16INK4a protein in the epithelial nuclei with varying degrees of dysplastic changes was noted, and a positive reaction to HPV16 was also observed in the cell nuclei and cytoplasm of epithelial cells in the basal, parabasal and spiny epithelial layers. The appearance of K15 in the cytoplasm of cells above the basal layer with abrasive precancerous cheilitis was found in 48% of cases., Conclusion: To diagnose early manifestations of neoplastic processes in «potentially malignant» diseases of the oral mucosa, it is necessary to use both classical histological and immunohistochemical methods of investigation with various markers.

Oral epithelial dysplasia refers to a premalignant lesion of the oral cavity. The diagnosis of dysplasia is rendered via pathologic assessment of diseased tissue. There are many different premalignant conditions identified in the oral cavity. These include leukoplakias, erythroplakias, proliferative verrucous leukoplakia, oral submucosal fibrosis, actinic cheilitis, and lichen planus. This article will discuss these different conditions and how they are diagnosed. It will also review the treatment for these entities., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Oral submucous fibrosis (OSF) and proliferative verrucous leukoplakia (PVL) are established as oral potentially malignant disorders. Dual pathology of the two conditions is not commonly encountered in clinical practice. This study aims to present a case series of multifocal leukoplakia in patients with and without OSF to outline the clinical behavior and challenges in the management of this high-risk group in clinical practice., Material and Methods: We retrospectively analyzed cases of six Indian patients (four with OSF) managed over a period of 5.5 to 13 years at the Government Dental College, Nagpur. Patient data consisting of age, gender, medical history, habits, clinical findings, and biopsy reports were recorded at the initial visit. During follow-up visits, the clinicopathological data were reassessed. When surgical intervention failed to arrest the disease or when surgery was contraindicated metronomic therapy with Folitrax 15 mg once a week and Celecoxib 100mg twice daily was initiated., Results: All patients developed PVL after the initial pathology diagnosis of OSF or oral leukoplakia. Initial lesions were either homogenous or non-homogenous leukoplakia. All patients developed multiple recurrences, regional or systemic metastasis. Despite thorough interventions, the patients died of, or with the disease., Conclusions: The occurrence of two or more oral potentially malignant disorders poses challenges in patient management and possibly presents a higher risk of malignant transformation. More clinical trials are necessary to assess the benefits of metronomic therapy for patients diagnosed with aggressive PVL concurrently found with OSF.

Purpose: Oral leukoplakia (OL) is a common potentially malignant oral disorder. Therefore, there is a need for simple screening methods for OL before its transformation into oral cancer. Furthermore, because invasive open biopsy is the sole method to determine if an OL lesion is dysplastic, there is also a clinical need for non-invasive methods to differentiate dysplastic OL from non-dysplastic OL. This study aimed to identify salivary metabolites that can help differentiate patients with OL from healthy controls (HC) and also dysplastic OL from non-dysplastic OL., Material & Methods: Whole unstimulated saliva samples were collected from patients with OL (n = 30) and HCs (n = 29). The OL group included nine patients with dysplastic OL and 20 with non-dysplastic OL. Hydrophilic metabolites in the saliva samples were comprehensively analyzed through capillary electrophoresis mass spectrometry. To evaluate the discrimination ability of a combination of multiple markers, a multiple logistic regression (MLR) model was developed to differentiate patients with OL from HCs and dysplastic OL from non-dysplastic OL., Results: Twenty-eight metabolites were evidently different between patients with OL and HCs. Finally, three metabolites (guanine, carnitine, and N-acetylputrescine) were selected to develop the MLR model, which resulted in a high area under curve (AUC) of the receiver operating characteristic (ROC) to differentiate patients with OL from HCs (AUC = 0.946, p < 0.001, 95% confidential interval [CI] = 0.889- 1.000). Similarly, two metabolites were evidently different between patients with dysplastic and non-dysplastic OL. Finally, only one metabolite (7-methylguanine) was selected in the MLR model, which revealed a moderate discrimination ability for dysplastic and non-dysplastic OL (AUC = 0761, p = 0.027, 95% CI = 0.551-0.972)., Conclusion: Our candidate salivary metabolites showed potential not only to discriminate OL from HC, but also to discriminate dysplastic OL from non-dysplastic OL., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The management of oral potentially malignant disorders (OPMD) including oral leukoplakia (OL) is not currently structured according to agreed guidelines. The current report presents survey data gathered from Oral Medicine Practitioners (OMPs) in Europe and Australia and is aimed to investigate attitudes and practice in the diagnosis, risk stratification and treatment of OL. In the presence of a clinical provisional diagnosis of OL, respondents reported always undertaking biopsy in 83% of cases, with most OMPs also relying on diagnostic adjuncts. The potential for malignant transformation is almost invariably assessed through epithelial dysplasia status, with other biomarkers described in the literature used less often. Active treatment of OL was considered mandatory by 20% of OMPs, while others reserve treatment for selected cases only. OMPs are mostly driven to active treatment by lesion-related features which are frequently jointly considered including lesion site, clinical appearance and dysplasia status. Inconsistent assessment was observed regarding mild dysplasia, lesion size, presence of unavoidable trauma, exposure to tobacco and patient age. Frequently observed geographical variations were seldom statistically significant. In agreement with previous surveys, a lack of consensus around the management of OL was observed, supporting claims from learned academies and societies for treatment guidelines aiming to reduce inter-practitioner variability., (© 2022 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Proliferative verrucous leukoplakia (PVL) is one of the oral potentially malignant disorders (OPMD) with the highest malignant potential. PVL tends to be easily misdiagnosed owing to the resemblance in clinical manifestations between PVL and other diseases such as oral leukoplakia or oral lichen planus. PVL is considered as a special type of oral leukoplakia by some scholars, which is characterized by its tendency of recurrence and metastasis, along with its high risk of malignant transformation. So far, the accurate clinic diagnosis and management of PVL are still intractable due to the lack of definite histopathological definition, unified diagnostic criteria and effective treatment modalities. This review aims to provide the clinical practitioners with a series of advices on the clinical diagnosis and management of PVL by systematically reviewing the diagnostic logistics, therapeutic strategies, malignant transformation detection based on tremendous relevant data and evidence-based medicine.

Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder associated with high risk of malignant transformation. Currently, there is no treatment available, and restrictive follow-up of patients is crucial for a better prognosis. Oral leukoplakia (OL) shares some clinical and microscopic features with PVL but exhibits different clinical manifestations and a lower rate of malignant transformation. This study aimed to investigate the proteomic profile of PVL in tissue and saliva samples to identify potential diagnostic biomarkers with therapeutic implications. Tissue and saliva samples obtained from patients with PVL were compared with those from patients with oral OL and controls. Label-free liquid chromatography with tandem mass spectrometry was employed, followed by qualitative and quantitative analyses, to identify differentially expressed proteins. Potential biomarkers were identified and further validated using immunohistochemistry. Staining intensity scan analyses were performed on tissue samples from patients with PVL, patients with OL, and controls from Brazil, Spain, and Finland. The study revealed differences in the immune system, cell cycle, DNA regulation, apoptosis pathways, and the whole proteome of PVL samples. In addition, liquid chromatography with tandem mass spectrometry analyses showed that calreticulin (CALR), receptor of activated protein C kinase 1 (RACK1), and 14-3-3 Tau-protein (YWHAQ) were highly expressed in PVL samples. Immunohistochemistry validation confirmed increased CARL expression in PVL compared with OL. Conversely, RACK1 and YWHA were highly expressed in oral potentially malignant disorder compared to the control group. Furthermore, significant differences in CALR and RACK1 expression were observed in the OL group when comparing samples with and without oral epithelial dysplasia, unlike the PVL. This research provides insights into the molecular mechanisms underlying these conditions and highlights potential targets for future diagnostic and therapeutic approaches., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Oral squamous cell carcinoma (OSCC) is a widespread disease with only 50%-60% 5-year survival. Individuals with potentially malignant precursor lesions are at high risk., Methods: Survival could be increased by effective, affordable, and simple screening methods, along with a shift from incisional tissue biopsies to non-invasive brush biopsies for cytology diagnosis, which are easy to perform in primary care. Along with the explainable, fast, and objective artificial intelligence characterisation of cells through deep learning, an easy-to-use, rapid, and cost-effective methodology for finding high-risk lesions is achievable. The collection of cytology samples offers the further opportunity of explorative genomic analysis., Results: Our prospective multicentre study of patients with leukoplakia yields a vast number of oral keratinocytes. In addition to cytopathological analysis, whole-slide imaging and the training of deep neural networks, samples are analysed according to a single-cell RNA sequencing protocol, enabling mapping of the entire keratinocyte transcriptome. Mapping the changes in the genetic profile, based on mRNA expression, facilitates the identification of biomarkers that predict cancer transformation., Conclusion: This position paper highlights non-invasive methods for identifying patients with oral mucosal lesions at risk of malignant transformation. Reliable non-invasive methods for screening at-risk individuals bring the early diagnosis of OSCC within reach. The use of biomarkers to decide on a targeted therapy is most likely to improve the outcome. With the large-scale collection of samples following patients over time, combined with genomic analysis and modern machine-learning-based approaches for finding patterns in data, this path holds great promise., (© 2023 The Authors. Journal of Oral Pathology & Medicine published by John Wiley & Sons Ltd.)

Background: Dysregulation of the hypoxia-aerobic system has been postulated in various malignancies. Nonetheless, the contribution of hypoxia to oral carcinogenesis is yet to be elucidated. Understanding this mechanism is important for improving diagnostic tools and targeted therapies. This study aimed to assess the dysregulation of hypoxia-related factors during different stages of oral squamous cell carcinoma (OSCC) development., Methods: Ninety-two patients diagnosed clinically with oral leukoplakia or OSCC were included and classified according to their histopathological diagnoses. A panel of seven hypoxia-related antibodies were used for immunohistochemical staining of each case. Automated quantification of immunostaining was used for objective reporting. Microvessel density was also assessed., Results: Significant associations were reported for non-dysplastic epithelial changes and malignancy for Glut1, HIF-1α, vascular endothelial growth factor, and signal transducer and activator of transcription 3(p < 0.005). Similarly, microvessel density significantly increased with the severity of epithelial disorders. A multiple regression model including the H-score of HIF-1α and microvessel density could statistically significantly predict the grade of epithelial disorder (p < 0.005). The associated diagnostic accuracy of this approach was 88%., Conclusions: Hypoxia-associated events are observed during early epithelial dysplastic changes and have a potential role in oral carcinogenesis. The level of hypoxia may assist in stratifying the severity of epithelial changes among patients with oral leukoplakia., (© 2023 The Authors. Journal of Oral Pathology & Medicine published by John Wiley & Sons Ltd.)

Rationale: Proliferative verrucous leukoplakia (PVL) is a multifocal, slowly evolving lesion that resists all types of treatment and has a high propensity for malignant transformation into oral squamous cell carcinoma. Lack of awareness and acquaintance with white lesions of the oral cavity makes it difficult to diagnose. Besides being rare, PVL significantly aggressive, so clinicians need to be aware of it carefully. Therefore, it is recommended to have the earliest possible diagnosis and total excision of this lesion. We report this case to present typical clinical and histologic features of PVL so a For the purpose of sensitizing clinician., Patient Concern: A 61-year-old female came to the clinic concerning of recurring painless, white patch on the tongue 2 months ago, associated with oropharyngeal dryness., Diagnoses: This case satisfies these major and minor criteria to diagnosed PVL., Intervention: An excisional biopsy of the lesion was done to check for the presence of dysplasia, as lesions were persisting. Hemostasis was achieved with single interrupted sutures., Outcome: no recurrence has been observed since excisional 1 year follow-up., Lesson: The key feature is early detection, precisely in cases of PVL it is critical for better treatment outcomes, lifesaving, quality-of-life enhancement. To detect and treat any potential pathologies, clinicians should meticulously examine the oral cavity and patients have to be aware and informed of the importance of regular screenings. This lesion is resistant to the presently available treatment modalities; therefore, total excision with free surgical margins is critical combined with a lifelong follow-up., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

White lesions in the oral cavity may be diverse in etiology and may present with significant clinical and sometimes histologic overlap between categories, making accurate diagnosis difficult at times. Although white lesions of immune and infectious etiology are covered in another article, this article discusses the differential diagnosis between developmental, reactive, idiopathic, premalignant, and malignant white lesions focusing on clinical features of each category., (Copyright © 2022 Elsevier Inc. All rights reserved.)

White lesions of the oral mucosa may be caused by various disorders. In most instances of white lesions, diagnoses can be made solely on clinical grounds. When the clinical diagnosis is not compatible with a known disease, the term leukoplakia is used. This is of importance since the yearly malignant transformation rate of oral leukoplakia into a squamous cell carcinoma is 2-4%. The presence and degree of epithelial dysplasia is the most important predictor for malignant transformation.

Background: Establishing the risk of malignant transformation (MT) in oral leukoplakia is usually based on grading oral epithelial dysplasia (OED) on biopsy tissue, for which two systems are proposed: a 3-tier and a binary system. Only very few actuarial studies have tested the accuracy of such methods in predicting MT, especially for the binary system. This study aimed to assess the accuracy of the two grading systems in predicting MT in a cohort of oral leukoplakia (OL) from Brazil, with follow-up data., Methods: The sample comprised 878 individuals diagnosed with OL from 2005 to 2018. Follow-up data were obtained both locally and from the regional cancer registry. All lesions were graded using both the 3-tier and the binary systems. Kaplan-Meier curves (Log-rank Mantel-Cox) were used to assess risk and kappa to assess interobserver agreement., Results: Thirty-five individuals underwent MT (4%). Both systems demonstrated prognostic value, though the 3-tier system proved superior, with OR 9.23 (3.42-23.69), PPV 0.152, NPV 0.98, compared to binary OR 3.49 (1.79-6.79), PPV 0.079, NPV 0.976. Interobserver agreement was also superior in the 3-tier system (0.47, p < 0.05) compared to the binary system (0.139, p = 0.39). Combining the two systems enhanced prognostic values (OR 14.28, PPV 0.217, NPV 0.981)., Conclusion: The 3-tier system presented superior prognostic value to the binary system. Combining both systems to double-grade intermediate lesions might enhance risk assessment., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The oral brush cytology is an alternative method developed to improve the efficacy of conventional cytology in oral potentially malignant disorder (OPMD), and salivary lactate dehydrogenase (LDH) which is a cytoplasmic enzyme has been widely used as a marker for diagnosing various diseases. The purpose of the study is to evaluate the brush biopsy findings and salivary LDH levels for the early diagnosis of premalignant and malignant lesions of the oral cavity., Materials and Methods: Patients with deleterious habits including tobacco-related lesions such as leukoplakia, tobacco pouch keratosis, and oral cancer were included in the study. For each patient, saliva sample was collected, brush biopsy was done and smears were prepared. Collected saliva samples were analysed for salivary LDH levels and prepared smears were analysed for dysplastic changes and statistical analysis was performed., Results: Out of 80 samples, 30 were leukoplakia, 45 were tobacco pouch keratosis and 5 were oral cancer, and 13 samples showed positive dysplastic changes, 26 samples showed atypical dysplastic changes and 41 samples showed no signs of dysplastic changes and concluded as negative. On comparing the results of brush biopsy findings and salivary LDH levels, the mean salivary LDH value for positive dysplasia was elevated and the P value was statistically significant (P value: 0.00)., Conclusion: Brush biopsy showed good potential in detecting premalignant lesions and salivary LDH levels showed a marked increase which can be used as a diagnostic biomarker and serve as a potent diagnostic aid for early detection of malignancy., Competing Interests: None

Background: Oral proliferative verrucous leukoplakia (OPVL) is a chronic form of oral leukoplakia that progresses to a multifocal disease with confluent, exophytic and proliferative features. The clinical differential diagnosis for OPVL includes frictional keratosis, leukoplakia, chronic hyperplastic candidiasis, squamous papilloma, verrucous hyperplasia, verrucous carcinoma and squamous cell carcinoma. In this study, we aimed to delineate the dynamic changes in molecular signature during OPVL progression. We compare to a cohort of oral cavity keratinizing squamous cell carcinoma (OSCC) patients covering the spectrum of verrucous carcinoma to invasive squamous cell carcinoma including cytologically bland cuniculatum variant., Methods: Samples from a large OPVL lesion that exhibited a histopathologic continuum of OPVL progression., Results: Canonical hotspot TERT promoter mutations were identified in all patients. TERT C228T was dominant and mutually exclusive with TERT C250T. In patients with TERT C250T, there was concurrent PI3 point mutation. TP53 mutations were also consistently found (8/10). At the protein level, p53 was abnormal, with loss of function and gain of function., Conclusions: OPVL is a pathology that shows proximity to the gene expression profile of OSCC, highlighting signatures in common that can be important targets for drug treatment, as well as in the development of diagnostic and prognostic strategies for this disease., Competing Interests: Declaration of competing interest We have no financial interest or conflict of interest in association with this work., (Published by Elsevier Inc.)

Oral squamous cell carcinomas are mostly preceded by precancerous lesions such as leukoplakia and erythroplakia. Our study is aimed at identifying potential biomarker proteins in precancerous lesions of leukoplakia and erythroplakia that can flag their transformation to oral cancer. Four biological replicate samples from clinical phenotypes of healthy control, leukoplakia, erythroplakia, and oral carcinoma were annotated based on clinical screening and histopathological evaluation of buccal mucosa tissue. Differentially expressed proteins were delineated using a label-free quantitative proteomic experiment done on an Orbitrap Fusion Tribrid mass spectrometer in three technical replicate sets of samples. Raw files were processed using MaxQuant version 2.0.1.0, and downstream analysis was done via Perseus version 1.6.15.0. Validation included functional annotation based on biological processes and pathways using the ClueGO plug-in of Cytoscape. Hierarchical clustering and principal component analysis were performed using the ClustVis tool. Across control, leukoplakia, and cancer, L-lactate dehydrogenase A chain, plectin, and WD repeat-containing protein 1 were upregulated, whereas thioredoxin 1 and spectrin alpha chain, nonerythrocytic 1 were downregulated. Across control, erythroplakia, and cancer, L-lactate dehydrogenase A chain was upregulated whereas aldehyde dehydrogenase 2, peroxiredoxin 1, heat shock 70 kDa protein 1B, and spectrin alpha chain, nonerythrocytic 1 were downregulated. We found that proteins involved in leukoplakia were associated with alteration in cytoskeletal disruption and glycolysis, while in erythroplakia, they were associated with alteration in response to oxidative stress and glycolysis across phenotypes. Hierarchical clustering subgrouped half of precancerous samples under the main branch of the control and the remaining half under carcinoma. Similarly, principal component analysis identified segregated clusters of control, precancerous lesions, and cancer, but erythroplakia phenotypes, in particular, overlapped more with the cancer cluster. Qualitative and quantitative protein signatures across control, precancer, and cancer phenotypes explain possible functional outcomes that dictate malignant transformation to oral carcinoma., Competing Interests: There is no conflict of interest., (Copyright © 2023 Vipra Sharma et al.)

Introduction: Keratinized lesions have been a conceivable false-negative (FN) factor in oral exfoliative cytology (OEC); however, other factors are poorly analyzed. In this study, we aimed to identify the factors influencing the accuracy of OEC and FNs focusing on the lesion characteristics, patient background, and surgeon factors in oral potentially malignant disorders (OPMD)., Material and Methods: We retrospectively studied 44 patients who underwent both OEC and histopathological diagnosis. Sensitivity, specificity, FN rate, false-positive (FP) rate, and prevalence of both methods were compared. Similarly, accuracy indices were compared among clinical diagnosis groups (leukoplakia vs. other diagnosis). The association between patient and surgeon-related factors influencing FN OEC results were investigated using Fisher's exact test and a multiple logistic regression analysis., Results: Overall, the sensitivity; specificity; and FN, FP, and prevalence rates of OEC were 31.8%, 82.1%, and 68.8%, 17.9%, and 36.4%, respectively. Leukoplakia was significantly more common in clinical diagnosis (P = 0.007) with sensitivity, specificity, and FN rates of 20.0%, 95.2%, and 80.0%, respectively. Contrarily, non-keratinized lesions had sensitivity, specificity, and FN of 83.3%, 85.7%, and 16.7%, respectively. In the prevalent group, leukoplakia and anucleate squamous cells were significantly associated with FN cases (P = 0.013, P = 0.050). On multivariate analysis in OEC negative patients, age ≤64 (P = 0.050) and location on the tongue (P = 0.047) was independently associated with FNs., Conclusion: FN of OEC was conceivable to be due to poor deep-seated cell sampling, which was associated with leukoplakia, age, and location. Therefore, these factors may be considered in the evaluation of OEC results., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

PVL (proliferative verrucous leukoplakia) has distinct clinical characteristics. They have a proclivity for multifocality, a high recurrence rate after treatment, and malignant transformation, and they can progress to verrucous or squamous cell carcinoma. AI can aid in the diagnosis and prognosis of cancers and other diseases. Computational algorithms can spot tissue changes that a pathologist might overlook. This method is only used in a few studies to diagnose LB and PVL. To see if their cellular nuclei differed and if this cellular compartment could classify them, researchers used a computational system and a polynomial classifier to compare OLs and PVLs. 161 OL and 3 PVL specimens in the lab were grown, photographed, and used for training and computation. Exam orders revealed patients' sociodemographics and clinical pathologies. The nucleus was segmented using Mask R-CNN, and LB and PVL were classified using a polynomial classifier based on nucleus area, perimeter, eccentricity, orientation, solidity, entropies, and Moran Index (a measure of disorderliness). The majority of OL patients were male smokers; most PVL patients were female, with a third having malignant transformation. The neural network correctly identified cell nuclei 92.95% of the time. Except for solidity, 11 of the 13 nuclear characteristics compared between the PVL and the LB showed significant differences. The 97.6% under the curve of the polynomial classifier was used to classify the two lesions. These results demonstrate that computational methods can aid in diagnosing these two lesions., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Samar Zuhair Alshawwa et al.)

Objectives: Dentists play a major role in the diagnosis of oral potentially malignant disorders (OPMDs) that may lead to malignancy. Their knowledge on OPMDs and the risk factors associated with malignant disease needs to be sufficient. The aim of this study was to assess the level of knowledge, attitudes, and awareness of OPMDs amongst general dentists and dental specialists working in Saudi Arabia., Material and Methods: Questionnaires were distributed to dentists working in Saudi Arabia. A total of 303 dentists participated in the study. The questionnaire included 20 questions on knowledge, attitudes, and awareness of OPMDs., Results: The response rate was 55%. There was no significant difference between general dental practitioners and dental specialists regarding leukoplakia, which is the most common OPMD (P > .05) and in identifying tobacco and alcohol as the main risk factors for malignant transformation of OPMDs into cancer (P > .05). However, there was a significant difference (P < .05) between specialists (75.3%) and general practitioners (52.3%) in the diagnosis of OPMDs. There was a significant difference (P < .05) between specialists (63.5%) and general practitioners (28.0%) in recognising the likelihood of malignant transformation of proliferative verrucous leukoplakia. There was a significant difference between specialists (61.2%) and general practitioners (25.2%, P < .05) in recognising the erosive form or atrophic type of oral lichen planus, considering that it is more likely to undergo malignant transformation., Conclusions: Dental specialists have better knowledge and awareness than general dentists regarding OPMDs. Improved continuous education programmes on the risk factors and diagnosis of OPMDs should be organised to train dentists., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of the study improving the diagnosis of precancerous diseases and cancer of the oral mucosa using fluorescent immunocytochemical studies by direct immunofluorescence. A clinical laboratory examination of 111 patients was carried out: 46 patients with squamous cell carcinoma of the oral mucosa, 35 people with precancerous lesions (17 leukoplakia, 18 - oral lichen planus) and 30 healthy people. All patients underwent a traditional cytological examination and an additional immunocytochemical examination by direct immunofluorescence, the expression levels of tumor markers P53, P16 and Ki67 were determined. The data were compared with the results of histological analysis. As a result of the study, it was revealed that in patients with cancer, the expression of oncomarker P53 was four times higher than in patients with precancerous pathology. In 6.52% of cases, co-expression of markers Ki67 and P16 was found. Thus, the advantages of fluorescent immunocytochemical diagnostics were the absence of invasive traumatic intake of the biomaterial in the patient, reduction in the timing of obtaining the result, high sensitivity, and the possibility of remote evaluation of the results. Therefore, that increases the accessibility of the method, and the possibility of using this method for a screening study of population., Competing Interests: The authors declare no conflict of interest.

Oral squamous cell carcinoma (OSCC) is often preceded by a white patch on a surface of the mouth, called oral leukoplakia (OL). As accelerated telomere length (TL) shortening in dividing epithelial cells may lead to oncogenic transformation, telomere length measurement could serve as a predictive biomarker in OL. However, due to high variability and lack of a universal reference, there has been a limited translational application. Here, we describe an approach of evaluating TL using paired peripheral blood mononuclear cells (PBMC) as an internal reference and demonstrate its translational relevance. Oral brush biopsy and paired venous blood were collected from 50 male OL patients and 44 male healthy controls (HC). Relative TL was measured by quantitative PCR. TL of each OL or healthy sample was normalized to the paired PBMC sample (TL ratio). In OL patients, the mean TL ratio was significantly smaller not only in the patch but also in distal normal oral tissue, relative to healthy controls without a high-risk oral habit. Dysplasia was frequently associated with a subgroup that showed a normal TL ratio at the patch but significantly smaller TL ratio at a paired normal distal site. Our data suggest that evaluation of TL attrition using a paired PBMC sample eliminates the requirement of external reference DNA, makes data universally comparable and provides a useful marker to define high-risk OL groups for follow-up programs. Larger studies will further validate the approach and its broader application in other premalignant conditions., (© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

The objective of this study was to review the diagnostic accuracy of clinicians identifying leukoplakia and the diagnostic terminology used to indicate leukoplakic lesions at the University of Nebraska Medical Center (UNMC) oral biopsy service. Biopsy archives from the years 1983, 1995, 2005, and 2015 in the UNMC College of Dentistry were reviewed. Cases with a clinical diagnosis of leukoplakia (or white plaque), hyperkeratosis, dysplasia, and/or carcinoma were included in the study. Demographic and clinical information was recorded and descriptive statistics were utilized. Of 6113 cases, 517 lesions (8.46%) from 508 patients met the inclusion criteria. The mean age of the patients was 56.87 years, and the sample included 286 men and 222 women. Of these 517 lesions, 195 (37.72%) were clinically diagnosed as leukoplakia or white plaque. The records revealed that 133 (68.21%) of 195 clinical diagnoses were correct, with lesions histologically exhibiting hyperkeratosis (75 cases), dysplasia (52 cases), or carcinoma (6 cases). The remaining 62 lesions (31.79%) were found to have other histologic diagnoses. Hyperkeratosis made up the largest portion of the correct diagnoses. In general, the ability of clinicians to successfully identify leukoplakia improved over the years (46.15%, 73.68%, 64.29%, and 76.00% in 1983, 1995, 2005, and 2015, respectively). However, clinicians continue to misclassify identifiable pathoses such as lichen planus, lichenoid mucositis, and fibroma as leukoplakia. Hyperkeratosis and dysplasia, both of which represent histologic diagnoses, appear to be popularly misused clinical terms.

Objective: The aim: The purpose of research was to evaluate the efficiency of micronucleus test in buccal cells for the diagnosis of oral leukoplakia., Patients and Methods: Materials and methods: We have conducted a comprehensive clinical and laboratory examination of 155 patients with oral leukoplakia. It was conducted histological examination leukoplakia mucosal sites, to assess the buccal epithelium cell micronucleus test was carried out., Results: Results: Histological evaluation of the material was made according to the classification of leukoplakia WHO (2005). They are established 10 (14%) sites unmodified mucosa, 10 (14%) of the samples hyperkeratosis without atypia, 14 (19%) biopsies hyperkeratosis SIN1, 15 (21%) of hyperkeratosis SIN2, 10 (14%) -- SIN3 and 13 (18 %) of the cases of squamous cell carcinoma. Micronuclei, whose appearance is caused by violation of differentiation of epithelial cells, were found in patients with leukoplakia, the detection of micronuclei almost equally high as in patients with leukoplakia SIN2, and with SIN3 (a difference of 1.3 times (p <0,05, rxy = + 0.271)), and consequently the probability of occurrence of tumoral diseases of the oral mucosa or malignancy existing large., Conclusion: Conclusions: Thus, on the background of the general increase in proliferative activity of epithelial cells with increasing SIN, for each treatment group revealed the appearance of micronuclei in buccal cells. And the frequency of micronuclei and the fourth type of increases with hyperplasia, indicating an increase in the likelihood of malignancy and cancer of the oral mucosa in patients with leukoplakia SIN3.

Background: Proliferative verrucous/multifocal leukoplakia (PVML) is an oral potentially malignant disorder (OPMD) that exhibits high rates of malignant development (MD). This study aimed to analyse the risk of MD of PVML, as well as to investigate the possible risk factors associated with its malignization., Methods: A bibliographical search of the PubMed, Embase, Web of Science, and Scopus databases was conducted. PVML MD rates were calculated as a pooled proportion, and the risk factors were calculated as risk ratios, using fixed and random models based on the presence of heterogeneity., Results: From a total of 417 records, 16 articles were retrieved for inclusion. The subgroup analysis revealed a higher MD rate in the studies that were conducted in America, and, likewise, said studies involved a longer follow-up time (>6 years). There was a non-significant lower risk of malignization among males. A negative correlation was observed between MD and the year in which the studies were published., Conclusions: The pooled MD of PVML was 65.8% (95% CI: 55.3-76.2, p < 0.001). Prospective studies of PVML must be designed using simple and universal clinical diagnostic criteria to be able to make an early diagnosis of this important OPMD and acknowledge the frequency of MD., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The aim: To conduct a prospective clinical study to assess the prevalence, structure, risk factors and features of clinical manifestations of precancerous diseases of oral mucosa and red lip in Kyiv residents and to analyze opportunities to improve the quality of their primary diagnosis., Patients and Methods: Materials and methods: The examination of 423 patients with precancerous diseases of oral mucosa and red lip included clarification of the main complaints and anamnesis of the disease, objective assessment of the state of oral mucosa and red border of the lips according to visual, stomatoscopic, luminescent analysis, cyto-, histological studies., Results: Results: Attention is drawn to the prevalence among precancerous diseases of patients with leukoplakia - 41.37% and lichen planus - 44.21%. The levels of detection of precancerous diseases of the oral mucosa due to the current and preliminary history for individual nosological forms are almost identical, which indicates the reliability of the above indicators., Conclusion: Conclusions: Promotion between the people about timely dental treatment for precancerous diseases of the oral mocosa and the use of radical technologies in their treatment will not only increase the effectiveness of treatment, but significantly limit the malignancy of these diseases.

MUC1 and MUC4 are two transmembranous proteins, which have been seen to express aberrantly in various human neoplasms and advocated as independent prognostic markers. Till now no extensive studies have been carried out on combined expression of MUC1 and MUC4 in oral leukoplakia and Oral squamous cell carcinoma. This study is an endeavour to evaluate Immunohistochemical coexpression of MUC1 and MUC4 in Oral Leukoplakia and Oral squamous cell carcinoma and furthr establish them as prognostic markers. Immunohistochemical analysis of MUC1 and MUC4 was done on 24 cases of Oral squamous cell carcinoma, 24 cases of leukoplakia and 12 normal oral mucosal tissues. Chi square test and one way ANOVA test were employed for statistical analysis. Normal oral mucosa and leukoplakia group showed higher frequency of negative immunoexpression compared to oral squamous cell carcinoma group. Furthur in Oral squamous cell carcinoma group, higher frequency of double positive coexpression in well and moderately differentiated oral squamous cell carcinoma and single positive coexpression in poorly differentiated oral squamous cell carcinoma was obtained. A definite rise of immunoexpression of MUC1 and MUC4 was observed from normal oral mucosa to leukoplakia to oral squamous cell carcinoma indicative of their contribution as diagnostic and prognostic markers., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Objectives: Early detection of dysplasia in oral potentially malignant disorders (PMD) might facilitate screening for possible subsequent malignant transformation. Vital staining is a non-invasive clinical adjunct used for determining the biopsy site, which facilitates early detection of dysplastic changes in PMD. Some authors suggested that double staining method has superior results over staining with a single dye., Aim: The aim of the study was to evaluate the accuracy of in vivo staining with methylene blue (MB) and Lugol's iodine (LI) double staining method in comparison with MB staining alone., Materials and Methods: Fifty patients of oral leukoplakia were recruited for the study. After obtaining written informed consent from the patients, the lesions were stained consecutively with 5% MB and 3% LI. The pattern of dye retention of MB alone, followed by MB and LI was noted. Incisional biopsy from the lesion was taken based on the retention of MB and the absence of staining of LI or by clinical judgement in case both stains were not retained. The clinical uptake of the stains was correlated with the degree of dysplasia on histopathological examination., Results: Out of 50 subjects, MB was retained in 47 cases (94%), while 3 cases (6%) failed to retain the dye. However, out of 47 cases, 20 cases had dark blue stain and were considered as MB positive, while the rest 27 cases had pale blue stain and were considered to be negative for MB staining. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA) of MB staining were 57.82%, 100%, 100%, 26.53% and 46%, respectively. After applying both stains, i.e., double staining method, the outline of the lesion was better defined. Out of 50 PMD cases, 3 patients retained only LI and showed no dysplasia. Out of 47 cases which showed dysplasia, 27 cases showed pale blue retention of MB (-) and also were negative for LI. The rest 20 cases were positive for MB but negative for LI. The sensitivity, specificity, PPV and NPV with double staining technique were 100%., Conclusion: The accuracy and reliability of double staining method was superior to MB staining., Clinical Relevance: Increased accuracy of double staining method aids in better detection of dysplasia and is of great help to the clinician in deciding the nature of PMD in question., Competing Interests: None