Detection Of Oral Premalignant Lesions Research Articles

Past, Present, and Future Diagnostic Methods for the Early Noninvasive Detection of Oral Premalignant Lesions: A State of the Art and Systematic Review.

Objectives: To provide an in-depth analysis of noninvasive methods for the early diagnosis of oral premalignant lesions, focusing on novel biomarkers and optical technologies, and to discuss their potential in improving the prognosis of patients with oral oncological diseases. Methods: This state-of-the-art review examines various noninvasive diagnostic techniques, including the utilization of salivary microRNAs and optical technologies such as Raman spectroscopy, elastic scattering spectroscopy, diffuse reflectance spectroscopy, narrow-band imaging, autofluorescence imaging, toluidine blue staining, and microendoscopy. Results: Several noninvasive techniques have shown varying degrees of effectiveness in detecting oral cancer. Autofluorescence imaging exhibited sensitivities up to 100% but had variable specificity. toluidine blue staining reported sensitivity between 77% and 100% for high-risk lesions or cancer, with specificity around 45% to 67%. Spectroscopy techniques achieved 72% to 100% sensitivities and specificities of 75% to 98%. Microendoscopy presented a sensitivity of 84% to 95% and a specificity of 91% to 95%. Conclusion: The review highlights the strengths and limitations of each noninvasive diagnostic method and their recent advancements. Although promising results have been demonstrated, there is a need for further development of reliable strategies for early detection and intervention in oral oncology.

The role of MicroRNAs in the diagnosis and treatment of oral premalignant disorders.

Oral premalignant disorders (OPMDs) are a group of potentially malignant conditions that pose a significant health burden globally. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as crucial regulators of gene expression and have been implicated in various biological processes, including carcinogenesis. This review synthesizes existing knowledge to provide a comprehensive understanding of the molecular mechanisms underlying OPMDs and to highlight the potential of miRNAs as promising biomarkers and therapeutic targets. Additionally, this review seeks to explore the potential of miRNA-based diagnostic biomarkers for early detection of OPMDs in the current literature on miRNAs in OPMDs, examining their involvement in disease pathogenesis, diagnostic potential, and therapeutic implications. Dysregulated miRNAs can target genes involved in critical cellular processes, such as cell cycle regulation, apoptosis, and DNA repair, leading to disease progression. Notably, miR-21, miR-31, miR-135b, and miR-486-5p have shown promise as potential biomarkers for early detection of oral premalignant lesions. Furthermore, the paper discusses the therapeutic implications of miRNAs in OPMDs. Preclinical studies have demonstrated the efficacy of miRNA-targeted therapies, such as miRNA mimics and inhibitors, in suppressing the growth of oral premalignant lesions. Early-phase clinical trials have shown promising results, indicating the potential for personalized treatment approaches. The findings underscore the importance of understanding the molecular mechanisms underlying these disorders and provide insights for the development of improved diagnostic and therapeutic strategies. However, they pose certain limitations given their intrinsic variability in expression profiles, the need for optimized isolation and detection methods, and potential hurdles in transitioning from preclinical success to clinical applications. Thus, future clinical studies are warranted to fully exploit the potential of miRNAs in the management of OPMDs.

370 Point-of-Service Salivary Microbiome Analysis in the Prevention and Detection of Oral Premalignant Lesions

OBJECTIVES/GOALS: Our aim is to establish soluble salivary biomarkers indicative of increased risk of oral premalignancy to be used in a point-of-service technology. Our goal is to non-invasively assess risk level for premalignancy by characterizing a molecular signature pattern that can be applied to such a diagnostic tool at routine dental or medical visits. METHODS/STUDY POPULATION: Adult patients 18 years of age and older who are non-smokers and patients of the University of Maryland School of Dentistry Oral Medicine Clinic and have been diagnosed with oral premalignancy (proliferative verrucous leukoplakia) are eligible. Exclusion criteria include history of immunosuppression or immune compromise; use of antifungal, antibiotic, and/or antiviral medications within the past three months; and gross dental disease. Serial unstimulated saliva samples will be collected at baseline or diagnosis of oral premalignancy, 6 months and 12 months. Solubility testing will be completed to determine whether malignant markers such as EGFR/mTOR/PI3K/p53 are soluble in saliva, and patient samples will be analyzed by ELISA and compared to appropriate controls. RESULTS/ANTICIPATED RESULTS: We anticipate demonstrating increased activity of molecular pathways known to be involved in malignant transformation, such as EGFR/mTOR/PI3K/p53, or increased burden of select microbial pathogens to be associated with increased risk of oral premalignancy in the form of proliferative verrucous leukoplakia. Preliminary sensitivity and specificity testing of the identified markers will provide additional insight to the utility of a diagnostic tool with salivary specimen. Therefore, the microbiome and/or molecular profile proposed from these results will serve as a translational application to development of future point-of-service test devices to be used in the prevention and detection of oral premalignant lesions. DISCUSSION/SIGNIFICANCE: Oral cancer is the sixth most common cancer worldwide, and presents challenges in its diagnosis and clinical management. Later diagnosis is associated with poorer patient outcomes—therefore, a molecular and microbiome profile that may be used in a noninvasive diagnostic test technology would prove beneficial to providers and patients.

Advancement in Diagnostic Aids for Oral Premalignant Lesions

Introduction: Precancerous lesions, conditions, and early-stage oral cancer cannot be sufficiently identified solely through visual inspection and may be prone to be inadvertently disregarded. Distinguishing between early-stage cancer, precancerous lesions, and benign tumors can pose a challenge due to the striking resemblance in their visual characteristics. Using surgical biopsy as a diagnostic modality is widely regarded as the gold standard in the medical community. However, it is essential to acknowledge that acquiring professional services for this procedure can prove impractical in certain circumstances. Hence this paper presents a concise review of a wide range of advanced diagnostic aids employed in detection of Oral Premalignant Lesions (OPL).
 Methods: The literature search utilized appropriate keywords to search online databases like PubMed, Medline, Google Scholar, EBSCO, Wiley science library, and Saudi digital library.
 Results: Alternative screening methods that are noninvasive, readily executed, and exhibit a high degree of accuracy are the established criteria for considering a test as a viable substitute for histopathology. Early diagnosis is a paramount factor in the effective management of oral cancer. Vital staining, immunocytochemistry, fluorescence imaging, laser confocal microscopy, Raman spectroscopy, and Fourier transform infrared spectroscopy diagnostic modalities are employed for the timely identification of oral premalignant lesions.
 Conclusion: Recent advances have improved the diagnostic aids in easy and accurate detection of oral premalignant lesions thereby facilitating effective management and mitigation strategies at an early stage of the lesion.

Evaluation of Role of Visual Inspection Using Acetic Acid (VIA) and Exfoliative Cytology in Screening and Early Detection of Oral Premalignant Lesions and Oral Cancer.

Objective:Oral cancer accounts for 50–70% of total cancer mortality. VIA screening has drastically changed the morbidity and mortality related to cervical cancer. In present study, we assessed the role of 5% Acetic Acid as a vital stain in oral mucosa of chronic tobacco chewers, to know if it can help in early diagnosis and improved prognosis of oral malignancies and to assess the sensitivity and specificity of VIA and exfoliative cytology for screening of Oral premalignant and malignant lesions in high risk population with limited health care infrastructure.Methods:This was an outpatient department based prospective study done in a tertiary hospital over a period of two years. 150 cases with a history of chronic tobacco use were evaluated. Visual inspection (VI) followed by VIA using 5% Acetic acid was done. Oral scrapes were taken for cytological examination followed by biopsy for histopathological evaluation, wherever possible. Results:Sensitivity, specificity, PPV, NPV and accuracy of VIA and Exfoliative cytology was 71%, 65%, 83%, 48%, 69% and 98%, 65%, 89%, 92%, 88% respectively keeping histology as gold standard. Conclusion:Acetic acid along with exfoliative cytology can be used as simple, cost effective and convenient methods for mass screening of OPMDs and OSCC in high risk population where biopsy is not possible.

EFFECT OF QUARANTINE ON THE RATE OF DIAGNOSTICS OF ORAL SQUAMOUS CELL CARCINOMA

Oral squamous cell carcinoma is the most prevalent manifestations of malignant tumors in the cranial and cervical regions and they cannot be frequently established until symptoms appear. So there is an urgent need to device methods for the detection of oral premalignant lesions and oral cancer at an early stage in order to improve further patients’ conditions.
 The whole world was suddenly affected the uncontrolled spread of the coronavirus. All spheres of life were affected, especially medicine. The strict quarantine for 2 months created problems for the patients. Patients who needed dental care they also suffered from it. Dental medical institutions provided only emergency medical care during the period of quarantine restrictions. The planned treatment was postponed until the quarantine restrictions stopped.
 In fact, the entire population of the country was in a state of significant psycho-emotional stress. This was combined with the state of chronic stress, and influenced the number of cancers. This trend can be traced worldwide.
 According to the literature, in the United States, squamous cell carcinoma of the oral cavity takes 3% of all cancers in men and 2% in women. The tendency of this disease in people 50 years older observed all over the world, however, the disease occurs in people aged 32-49 years. About 40% of intraoral squamous cell carcinomas begin on the floor of the mouth or on the lateral and ventral surfaces of the tongue. About 38% of all oral squamous cell carcinomas occur on the lower lip; these are usually solar-related cancers on the external surface.
 The symptoms of this disease in the initial stages are absolutely nonspecific. Many patients do not attach importance to them. Quarantine restrictions on the provision of advisory assistance make this problem of particular relevance.
 The authors of the article have determined that their goal to attract the attention of dentists and family doctors to the problem of early diagnosis of oncological diseases and oral cancer is enough important nowadays. Early, curable lesions are rarely symptomatic; thus, preventing fatal disease requires early detection by screening.
 The main goal for such investigations is to attract the attention of dentists and family doctors to the problem of early diagnosis of cancer, including oral cavity.
 The article presents the clinical characteristics of squamous cell carcinoma of the oral cavity. Particularly, doctors should pay attention to the variety of symptoms characteristic of the initial period of the disease. Patients may complain of thickening of the tissues of the oral cavity, the presence of white spots, ulcerative lesions, which may be covered with plaque. Slight painful sensations are distinguished as manifestations of other diseases. Sometimes the symptoms are relieved by taking analgesics. Patients self-medicate and postpone visiting a specialized specialist for an indefinite time. This does not trouble both patients and some health workers. It should be noted that a typical symptom in the developed period is fetid odor from the mouth due to decay and infection of the tumor.
 Oral lesions are asymptomatic initially, highlighting the need for oral screening. Most dental professionals carefully examine the oral cavity and oropharynx during routine care and may do a brush biopsy of abnormal areas. The lesions may appear as areas of erythroplakia or leukoplakia and may be exophytic or ulcerated. Cancers are often indurated and firm with a rolled border. As the lesions increase in size, pain, dysarthria, and dysphagia may result.
 During the period of neglect, cancer of the oral cavity organs quickly spreads and destroys the surrounding tissues, infiltrates the floor of the oral cavity, palatine arches, pharynx, etc.
 To illustrate the problems outlined in the article, the authors took a clinical case that combines the problems of early diagnosis of oral cancers. It should be noted that in addition to the “inactivity” of the patient in solving problems that occurred in the oral cavity, the resolution of the situation was inhibited by the introduced quarantine measures.

Comparison of the efficacy of cytodiagnostic instruments in exfoliative cytology

Aims and Objectives: The aims and objectives of the study were to determine the efficacy of wooden spatula, cytobrush, and toothbrush in obtaining cytology smears for early detection of oral premalignant lesions and also to compare the analysis of cytology smears with the histopathological diagnosis. The smears were observed and analyzed under a compound light microscope. Materials and Method: Fifty patients of clinically diagnosed oral leukoplakia patients attending the outpatient department of oral pathology and microbiology were considered for the study. The smear samples were obtained using wooden spatula, cytobrush, and toothbrush. The samples were manually analyzed in a double-blinded fashion. Histopathological diagnosis was confirmed using scalpel biopsy and a comparison was made between cytological and histopathological diagnosis. Statistical analysis was performed using Chi-square test. Results: In our study, toothbrush cytology was comparatively better (P

Efficacy of Fluorescence Technology vs Conventional Oral Examination for the Early Detection of Oral Pre-Malignant Lesions. A Clinical Comparative Study.

Oral cancer is one of the most common malignancies that affect human beings across the world and early detection of oral cancer is believed to reduce the morbidity significantly. Fluorescence diagnosis is emerging as a promising method in the differentiation of cancerous lesions and thus helping in the determination of resolution for the surgical resection of affected area of malignancy very accurately. The aim of this study was to evaluate the usefulness of an autofluorescence hand held device (OralID) to detect oral premalignant lesions. 98 potentially high-risk oral cancer patients were divided into two groups (n=49/group). Both the groups were first examined by conventional oral examination under white light and oral findings were noted. Subjects under group B were further examined under fluorescence light through hand held device, i.e. OralID. After the examinations, a surgical biopsy sample was taken from the suspected lesions under local anaesthesia from both the groups to confirm the diagnosis through histopathological analysis. The positive potential malignant lesions (PMLs) observed in Group A when compared with biopsy reporting was 89.47% true positive while in Group B was 95.24%. The sensitivity reported of Group A was 89.47% and Group B was 97.56%. We observed 8.09% more sensitivity and 11.36% more specificity when we incorporate adjunctive the fluorescence examination using OralID. Results from this study suggests that OralID is a true adjunct to conventional oral examination in detecting early potential malignant changes in subjects visiting for regular dental check-up.

Global Scenario of Research in Oral Cancer.

With 300,000 new cases diagnosed worldwide, oral cancer continues to be a major global public threat. In Indian subcontinent, oral cancer accounts for 30-40% of all cancer types. Early detection of oral cancer is still considered as the most effective way to improve survival. In this regard, early detection of oral premalignant lesions and conditions is quite important as it may help in prevention of oral cancer. Scientific evidence is available which clearly indicates that transition from normal epithelium to premalignancy to oral carcinoma is the result of accumulation of genetic and epigenetic alterations in a multi-step process. Proper oral screening and understanding of the genetic and environmental factors involved in oral carcinogenesis will allow the emphasis of cancer medicine to shift from the therapy of established oral cancer to the prevention of oral carcinogenesis.

Diagnostic modalities for squamous cell carcinoma: an extensive review of literature-considering toluidine blue as a useful adjunct.

Oral Squamous Cell Carcinomas have been considered as the most prevalent malignancies in the head and neck region and are frequently undiagnosed until symptomatic with an advanced stage of disease. So there is an urgent need to device methods for the detection of oral premalignant lesions and oral cancer at an early stage in order to improve the survival rate for patients. A number of tests have been done for the detection of oral cancer which include oral brush biopsy, the Vizilite, oral autofluorescence including chemiluscence, photodynamic detection, toluidine blue staining, methylene blue staining, incisional biopsy and many more. The article reviews various diagnostic modalities available at present for detection of squamous cell carcinomas and oral epithelial dysplasias based on advanced PUBMED search of the English language literature from the year 1972 to present in order to help us select the most suitable among them fulfilling the desired criteria of being non-invasive, highly specific and sensitive, economically viable, having a scope to be used for mass screening, easy to process, having low inter examiner variability and possibly not requiring high expertise to conduct and interpret the results. After reviewing various diagnostic modalities, we conclude that toluidine blue staining emerges as a clear winner among all these and it can act as a valuable adjunct to incisional biopsy in detection of oral cancer and may not substitute it except in certain circumstances when its results are carefully correlated with the patient history and clinical characteristics of the mucosal disorder, considering the fact that incisional biopsy has been reported to cause dissemination of cancer cells in the circulation there by increasing the possibility of metastasis. We must emphasize that toludine blue is a screening modality and not a diagnostic procedure like biopsy and hence cannot replace a confirmatory biopsy as a whole.

The identification of significant chromosomal regions correlated with oral tongue cancer progression

Oral squamous cell carcinoma (OSCC) is associated with substantial mortality and morbidity, and oral tongue squamous cell carcinoma (SCC) is representative in OSCC. Early detection of oral premalignant lesions (OPLs) that will develop into invasive tumors is necessary to improve the poor prognosis of this cancer. To identify potential biomarkers that could be used for early detection, we compared the gene expression of incident primary oral tongue SCC, severe dysplasia, mild and moderate dysplasia. For this, we used three expression datasets obtained from a public database and selected chromosomal locations related with the progress of oral tongue cancer from a dataset. We then evaluated the gene set, which is included in the selected chromosomal locations, using out of bag (OOB) error and plots in two validation datasets. Sixty-two chromosomal locations were detected, and most genomic aberrations were shown in chromosome 3. We identified 62 genes included in those locations, and three precancerous and SCC groups were well classified with low OOB error rates. These were also discriminative in the two validation datasets. The selected probes with genomic alteration in low-grade dysplasia can be used as an effective predictor for disease progression.

A Community-based RCT for Oral Cancer Screening with Toluidine Blue

Early detection of oral premalignant lesions (OPMLs) by visual inspection with toluidine blue has not been addressed. We conducted a community-based randomized controlled trial to assess whether using toluidine blue as an adjunctive tool for visual screening had a higher detection rate of OPMLs and could further reduce the incidence of oral cancer. In 2000, in Keelung, we randomly assigned a total of 7975 individuals, aged 15 years or older and with high-risk oral habits, to either the toluidine-blue-screened (TBS) group or the visual screening group. Results showed 5% more oral premalignant lesions and 79% more oral submucous fibrosis detected in the TBS group than in the control group. After a five-year follow-up ascertaining oral cancer development through linkage to the National Cancer Registry, the incidence rate in the TBS group (28.0 x 10−5) was non-significantly 21% lower than that in the control group (35.4 x 10−5).

Autofluorescence-Guided Surveillance for Oral Cancer

Early detection of oral premalignant lesions (OPL) and oral cancers (OC) is critical for improved survival. We evaluated if the addition of autofluorescence visualization (AFV) to conventional white-light examination (WLE) improved the ability to detect OPLs/OCs. Sixty high-risk patients, with suspicious oral lesions or recently diagnosed untreated OPLs/OCs, underwent sequential surveillance with WLE and AFV. Biopsies were obtained from all suspicious areas identified on both examinations (n = 189) and one normal-looking control area per person (n = 60). Sensitivity, specificity, and predictive values were calculated for WLE, AFV, and WLE + AFV. Estimates were calculated separately for lesions classified by histopathologic grades as low-grade lesions, high-grade lesions (HGL), and OCs. Sequential surveillance with WLE + AFV provided a greater sensitivity than WLE in detecting low-grade lesions (75% versus 44%), HGLs (100% versus 71%), and OCs (100% versus 80%). The specificity in detecting OPLs/OCs decreased from 70% with WLE to 38% with WLE + AFV. Thirteen of the 76 additional biopsies (17%) obtained based on AFV findings were HGLs/OCs. Five patients (8%) were diagnosed with a HGL/OC only because of the addition of AFV to WLE. In seven patients, additional HGL/OC foci or wider OC margins were detected on AFV. Additionally, AFV aided in the detection of metachronous HGL/OC in 6 of 26 patients (23%) with a history of previously treated head and neck cancer. Overall, the addition of AFV to WLE improved the ability to detect HGLs/OCs. In spite of the lower specificity, AFV + WLE can be a highly sensitive first-line surveillance tool for detecting OPLs/OCs in high-risk patients.

Oral Lesions in Patients Participating in an Oral Examination Screening Week at an Urban Dental School

Dental education must emphasize early diagnosis and management of oral mucosal disease, including early detection of oral premalignant lesions and cancer. The authors evaluated clinical findings of oral screening examinations of dental patients during a one-week period in an urban dental school clinic. Third- and fourth-year dental students conducted clinical screening examinations for all dental patients of record seen during the Yul Brynner Foundation's Oral, Head and Neck Cancer Awareness Week in April 2006. Of 262 patients, 100 (38.2 percent) reported that they had used tobacco for a mean of 8.1 years. Most patients reported having denture or tooth and gingival problems. The dental students reported abnormal findings in 55 patients (21 percent). Two patients had suspected premalignant lesions that were diagnosed as lichen planus and traumatic keratosis. The one-week screening provided an educational opportunity for the dental students, and the results demonstrate the value of having a focused week to reinforce the importance of head and neck and oral soft-tissue examination. The finding of mucosal lesions in 21 percent of patients of record reflects the fact that lesions were present but undetected. In addition, there are important implications for teaching and patient care. The screening week provided an opportunity for students to be active in a national campaign for cancer detection, and it represents an opportunity for visible community participation in the recognition of oral mucosal diseases in dental training programs and broadly for the profession.

Toluidine Blue Staining Identifies High-Risk Primary Oral Premalignant Lesions with Poor Outcome

There is a pressing need for the development of visual aids that will facilitate the detection of oral premalignant lesions (OPLs) with a high-risk of progression. Preliminary data suggest that toluidine blue stain may be preferentially retained by OPLs with high-risk molecular clones. In this study, we monitored OPLs from 100 patients without any history of oral cancer for an average of 44 months in order to evaluate the association of toluidine blue status with clinicopathologic risk factors, molecular patterns (microsatellite analysis on seven chromosome arms: 3p, 9p, 4q, 8p, 11q, 13q, and 17p) and outcome. Toluidine blue-positive staining correlated with clinicopathologic risk factors and high-risk molecular risk patterns. Significantly, a >6-fold elevation in cancer risk was observed for toluidine blue-positive lesions, with positive retention of the dye present in 12 of the 15 lesions that later progressed to cancer (P = 0.0008). This association of toluidine blue status with risk factors and outcome was evident even when the analysis was restricted to OPLs with low-grade or no dysplasia. Our results suggest the potential use of toluidine blue in identifying high-risk OPLs.

Toluidine blue staining for detection of oral premalignant lesions and carcinomas.

The discriminative value of toluidine blue vital staining for detecting oral premalignant lesions and carcinomas was tested in the hamster DMBA buccal pouch model. The stain technique was further tested for specificity using the turpentine liquid petrolatum (TLP) hamster cheek pouch model for hyperplasia. Although carcinomas frequently exhibited toluidine blue staining, a 27.8% false negative result was noted. Premalignant lesions (dysplasia and carcinoma in situ) seldom retained toluidine blue stain and yielded a histologically confirmed (95.2%) false negative result. DMBA induced papillomas yielded a 5% false positive result. The TLP model failed to produce either clinically or histologically evident hyperplastic/hyperkeratotic lesions.