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The present investigation aimed to assess the safety of photobiomodulation (PBM) on the oral carcinogenesis process induced by 4NQO, focusing on cell proliferation and apoptosis. Sixty-six Wistar rats received systemic 4NQO for 12 (n = 33) and 20 weeks (n = 33), divided into Control group, PBM 0.3 J, and PBM 1 J. Applications for PBM occurred three times a week. At weeks 12 and 20, the animals were euthanized. The immunoreactivity for anti-ROS1 and anti-p53 antibodies was also assessed. Statistical analysis was assessed by multiple t-tests, Kruskal-Wallis, and Spearman's correlation. At 12 weeks, PBM 1 J group had nodular lesions, distinct from control and PBM 0.3 J groups (p = 0.005). At 20 weeks, nodular lesions were common in control and PBM 0.3 J groups. Histopathological characteristics did not significantly differ between groups at 12 (p = 0.30) and 20 weeks (p = 0.58). Epithelial dysplasia (n = 21) was common at 12 weeks. After 20 weeks, most of the cases revealed squamous cell carcinoma (n = 24). No differences were observed in the immunostaining of p53 and ROS1 among the control and experimental groups and there was no correlation of these proteins with clinicopathological data. During the carcinogenesis process, the PBM did not modify the development of oral lesions and the expression of proliferative and apoptosis proteins. [ABSTRACT FROM AUTHOR]

To explore diagnostic and prognostic biomarkers in the progression of oral squamous cell carcinoma (OSCC) and to reveal their regulatory mechanisms in key pathways. A RayBiotech protein chip was used to screen differentially expressed serum proteins in OSCC, oral leukoplakia (OLK), and healthy participants. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to determine the pathways enriched by characteristic differential proteins. Immunohistochemical analysis and western blotting were used to verify the expression of characteristic differential proteins and key regulatory factors in human tissues and in a nude mouse model. Fibroblast growth factor 6 (FGF6) was identified as a key differential protein and was weakly expressed in OSCC tissues. The mitogen-activated protein kinases (MAPK) and PI3K-AKT pathways were identified as key signaling pathways. The results showed that pERK, Cyclin D1, pAKT, and BCL2 were highly expressed in OSCC, Caspase9 was lowly expressed in OSCC. With an increase in FGF6 expression in nude mice, the expression of FGFR4, pERK, Cyclin D1, pAKT, BCL2, GPX4, and ACSL4 increased, and the expression of Caspase9 decreased. FGF6 may change the expression of apoptosis-related proteins and proliferation factors by binding to FGFR4 in the PI3K-AKT/MAPK pathway and may inhibit the ferroptosis of OSCC, thereby possibly participating in the process of inhibiting OSCC. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Key points Plain language summary Proliferative verrucous leukoplakia (PVL) is a rare and refractory form of oral leukoplakia. The etiology of PVL remains unknown. The lesion is characterized by a high rate of malignant transformation. There is no definitive treatment for PVL.This case study presents a patient diagnosed in 2000 with a localized hyperkeratinized/verrucous lesion involving the facial gingivae of teeth #6–#8. Over the next 24 years, the lesion was biopsied five times. Further, two attempts to ablate the lesion with a CO2 laser (10.6 µm wavelength) were performed. Both ablation treatments were unsuccessful as the lesion recurred and progressed to involve more areas of gingival tissue. To date, biopsy has not revealed transformation into verrucous or squamous cell carcinoma (SCCA).This case study demonstrates that two attempts at ablation of PVL using a CO2 laser had no short‐ or long‐term benefit. The patient eventually lost all maxillary teeth due to root caries and inability to maintain adequate oral hygiene. The PVL lesion currently involves the entire maxillary edentulous ridge, extending from the 2nd molar site to the opposite corresponding site. During the 24 years encompassed by this report, the patient has not experienced a malignant transformation.The results of CO2 laser ablation of the PVL lesion in this case provided no short‐ or long‐term benefit. Given the potential for a sinister outcome, PVL patients require frequent clinical evaluation and biopsy for early detection of a malignant transformation into oral verrucous or SCCA. Proliferative verrucous leukoplakia (PVL) is a clinical diagnosis and represents a refractory form of multifocal oral mucosal leukoplakia of unknown origin. Currently, there is no reliable and successful treatment for PVL. PVL may undergo transformation to a verrucous or squamous cell carcinoma, thereby necessitating frequent oral examination and biopsy of sinister‐appearing mucosal sites. Proliferative verrucous leukoplakia (PVL) is a clinical diagnosis and represents a refractory form of multifocal oral mucosal leukoplakia of unknown origin.Currently, there is no reliable and successful treatment for PVL.PVL may undergo transformation to a verrucous or squamous cell carcinoma, thereby necessitating frequent oral examination and biopsy of sinister‐appearing mucosal sites.Proliferative verrucous leukoplakia (PVL) is a rare disorder that affects the gum tissue around the teeth. PVL is a pre‐cancerous disorder for which the cause is unknown and there is no treatment that yields a consistently successful result. This case study presents a patient diagnosed in 2000 with PVL involving the facial gum tissue of the upper right cuspid, lateral, and central incisor teeth. Over the next 24 years, the lesion was biopsied five times and two attempts to irradicate the lesion with a CO2 laser were performed. All attempts at treatment were unsuccessful and the lesion slowly progressed to involve more areas of gum tissue. The last biopsy taken in February 2024 did not reveal any areas of developing cancer. During the 24 years covered in this report, the patient did not develop oral cancer. However, treatment with the CO2 laser afforded no measurable benefit. Given the potential for developing cancer of the gum tissues, PVL patients should receive frequent oral exams and periodic biopsies for the detection of early cancer. [ABSTRACT FROM AUTHOR]

ABSTRACT Dyskeratosis congenita (DC) is a rare inherited bone marrow disease that classically presents with the triad of oral leukoplakia, nail dystrophy, and reticular hyperpigmentation. It is most commonly caused by a defect in the DKC1 gene involved in telomere stability. Malignant progression of oral leukoplakia to squamous cell carcinoma (SCC) is rare in DC, especially in younger patients, and cutaneous SCC is only reported in 1.5% of cases of DC. Here we report a case of a 12‐year‐old female with a familial heterozygous RTEL1 (regulator of telomere elongation helicase 1) gene mutation associated with a severe phenotype of DC characterized by multiple cutaneous SCCs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The role of microbes in diseases, especially cancer, has garnered significant attention. However, research on the oral microbiota in oral potentially malignant disorders (OPMDs) remains limited. Our study investigates microbial communities in OPMDs. Materials and methods: Oral biopsies from19 oral leukoplakia (OLK) patients, 19 proliferative verrucous leukoplakia (PVL) patients, 19 oral lichen planus (OLP) patients, and 19 oral lichenoid lesions (OLL) patients were obtained. 15 SCC specimens were also collected from PVL patients. Healthy individuals served as controls, and DNA was extracted from their paraffin-embedded tissues. 2bRAD-M sequencing generated taxonomic profiles. Alpha and beta diversity analyses, along with Linear Discriminant Analysis effect size analysis, were conducted. Results: Our results showed the microbial richness and diversity were significantly different among groups, with PVL-SCC resembling controls, while OLK exhibited the highest richness. Each disease group displayed unique microbial compositions, with distinct dominant bacterial species. Noteworthy alterations during PVL-SCC progression included a decline in Fusobacterium periodonticum and an elevation in Prevotella oris. Conclusions: Different disease groups exhibited distinct dominant bacterial species and microbial compositions. These findings offer promise in elucidating the underlying mechanisms of this disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to assess the effectiveness of the best performing interpretable machine learning models in the diagnoses of leukoplakia and oral squamous cell carcinoma (OSCC). Methods: A total of 237 patient cases were analysed that included information about patient demographics, lesion characteristics, and lifestyle factors, such as age, gender, tobacco use, and lesion size. The dataset was preprocessed and normalised, and then separated into training and testing sets. The following models were tested: K-Nearest Neighbours (KNN), Logistic Regression, Naive Bayes, Support Vector Machine (SVM), and Random Forest. The overall accuracy, Kappa score, class-specific precision, recall, and F1 score were used to assess performance. SHAP (SHapley Additive ExPlanations) was used to interpret the Random Forest model and determine the contribution of each feature to the predictions. Results: The Random Forest model had the best overall accuracy (93%) and Kappa score (0.90). For OSCC, it had a precision of 0.91, a recall of 1.00, and an F1 score of 0.95. The model had a precision of 1.00, recall of 0.78, and F1 score of 0.88 for leukoplakia without dysplasia. The precision for leukoplakia with dysplasia was 0.91, the recall was 1.00, and the F1 score was 0.95. The top three features influencing the prediction of leukoplakia with dysplasia are buccal mucosa localisation, ages greater than 60 years, and larger lesions. For leukoplakia without dysplasia, the key features are gingival localisation, larger lesions, and tongue localisation. In the case of OSCC, gingival localisation, floor-of-mouth localisation, and buccal mucosa localisation are the most influential features. Conclusions: The Random Forest model outperformed the other machine learning models in diagnosing oral cancer and potentially malignant oral lesions with higher accuracy and interpretability. The machine learning models struggled to identify dysplastic changes. Using SHAP improves the understanding of the importance of features, facilitating early diagnosis and possibly reducing mortality rates. The model notably indicated that lesions on the floor of the mouth were highly unlikely to be dysplastic, instead showing one of the highest probabilities for being OSCC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) comprises more than 90% of oral cavity cancer and remains the leading cause of death in oral disease. Limited studies have been conducted to evaluate cellular histomorphometry changes in OSCC compared to premalignant lesions such as Dysplastic leukoplakia (DL), Nondysplastic leukoplakia (NDL), and normal epithelial. This cross-sectional descriptive-analytical study was conducted on total 72 samples, including superficial areas of squamous cell carcinoma (SCCSF), Invasive Front of Squamous Cell Carcinoma (SCCIF), Apparently Normal Adjacent Oral Mucosa (SCCANM) or normal margin, Dysplastic leukoplakia (DL), Nondysplastic leukoplakia (NDL), and normal oral mucosa tissue (NOM) (N = 12 per group). ANOVA was used to compare the nucleus-to-cytoplasm ratio (N/C), nucleus area (NA), and cellular area (CA) of the stained hematoxylin and eosin (H&E) samples in the studied groups. A P value less than 0.05 was considered to be a significant level. There was a significant increase in the CA, NA, and N/C in the basal and parabasal layers from normal epithelium to dysplastic epithelium and OSCC. The highest NA, CA, and N/C were in the SCCIF and SCCSF groups, respectively, and the lowest was observed in NOM. In addition, SCCANM basal and parabasal layer cells had a significant difference in N/C compared to NOM, which indicates a high risk of SCCANM transformation into malignancy. Cell histomorphometry changes were observed from normal tissue to premalignant lesions and OSCC. These parameters can be used as indicators of the potential for transformation into malignancy in premalignant lesions. [ABSTRACT FROM AUTHOR]

Oral leukoplakia (OLK) is themost common oral precancerous lesion, and 3%-17% of OLK patients progress to oral squamous cell carcinoma. OLK is susceptible to recurrence and has no effective treatment. However, conventional drugs have significant side effects and limitations. Therefore, it is important to identify drugs that target OLK. In this study, scavenger receptor A (SR-A) was found to be abnormally highly expressed in the oral mucosal epithelial cells of OLK patients, whereas molecular biology studies revealed that low molecular weight fucoidan (LMWF) promoted apoptosis of dysplastic oral keratinocytes (DOK) and inhibited the growth and migration of DOK, and the inhibitory effect of LMWF on OLK was achieved by regulating the SR-A/Wnt signaling axis and related genes. Based on the above results and the special situation of the oral environment, we constructed LMWF/poly(caprolactone-co-lactide) nanofiber membranes with different structures for the in-situ treatment of OLK using electrospinning technology. The results showed that the nanofiber membranes with a shell-core structure had the best physicochemical properties, biocompatibility, and therapeutic effect, which optimized the LMWF drug delivery and ensured the effective concentration of the drug at the target point, thus achieving precise treatment of local lesions in the oral cavity. This has potential application value in inhibiting the development of OLK. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy (RT) has numerous effects on the oral mucosa, primarily genetic alterations and changes in the microenvironment. The characteristics of oral leukoplakia (OL) may differ between patients who have received previous head and neck cancer (HNC) treatment with radiation therapy and those who have not. Due to a lack of data on this scenario, we aimed to investigate the surgical outcomes of OL by comparing these two patient groups. Methods: This retrospective cohort study enrolled a total of 224 OL lesions in 124 patients who underwent carbon dioxide laser (CO2 laser) surgery from July 2002 to Aug 2021. All patients had received previous treatments for HNC, with 59 patients undergoing only surgical approach, 65 patients undergoing RT, and 46 patients undergoing concurrent chemotherapy during RT. The analysis was performed on a per-lesion basis, not a per-capita basis. We investigated the associations of clinicopathological characteristics and treatment outcomes of OL lesions that developed from irradiated or nonirradiated oral mucosa. Results: The median follow-up time was 5.87 years. Postoperative recurrence of OL occurred in 30 patients. Malignant transformation occurred in 17 patients with the incidence rate 4.19% annually and 13.7% cumulatively. The average time for OL transforming into squamous cell carcinoma was 3.27 ± 3.26 years (median 1.82, range 0.11 – 11.90). In univariate analysis, non-homogeneous morphology (P = 0.042), moderate to high-grade dysplasia (P = 0.041), and nonirradiated oral mucosa (P = 0.0047) were predictors for malignant transformation. However, in the Cox proportional hazard model, only nonirradiated oral mucosa remained an independent prognostic factor related to postoperative malignant transformation of OL (P = 0.031, HR 5.08, CI95 1.16 – 22.25). Conclusion: In the population whose OL is strongly aetiologically linked to environmental carcinogens such as betel nut and tobacco, OL lesions that develop on previously irradiated oral mucosa have a lower risk for postoperative malignant transformation compared to those that develop on nonirradiated mucosa. This finding highlights the potential impacts of radiation on OL. Further research is needed to confirm this observation and elucidate the underlying mechanism. [ABSTRACT FROM AUTHOR]

Objectives: Evaluate whether regular follow‐up of oral leukoplakia (OL) resulted in early detection of malignant transformation (MT). Method: Two hundred and twenty‐two consecutive patients with OL (147 females, 75 males); median follow‐up period of 64 months (range: 12–300). Three groups were distinguished: group A (n = 92) follow‐up at the hospital; group B (n = 84) follow‐up by their dentist; group C (n = 46) lost to follow‐up. Results: OLs in group B compared to group A, were smaller in size (<2 cm; p < 0.001), showed more hyperkeratosis (p < 0.001) and less moderate/severe dysplasia (p < 0.001). MT occurred in 45 (20%) patients: 32 (35%) in group A, five (6%) in group B and eight (17%) in group C. There was no significant difference in clinical tumour size between group A (median: 15 mm, range: 1–40) and group B (median: 10 mm, range: 3–25; p = 0.496). Tumour size was smaller for patients in groups A and B (median: 10 mm, range 1–40) compared to group C (median: 33 mm, range: 3–100; p = 0.003). There was a positive correlation between tumour size and interval between the last visit in all patients (p = 0.022). Conclusion: Regular follow‐up of OL resulted in early detection of MT. If properly selected, follow‐up of OL performed by the dentist seems feasible. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of oral squamous cell carcinoma (OSCC) associated or not with oral potentially malignant disorders (OPMD), and the epidemiological profile and traditional risk factors in Latin America. Methods: A retrospective observational study was conducted in 17 Latin American centres. There were included cases of OSCC, analysing age, gender, OSCC and their association with previous OPMD. Clinicopathological variables were retrieved. The condition of sequential‐OSCC versus OSCC‐de novo (OSCC‐dn) was analysed concerning the aforementioned variables. Quantitative variables were analysed using Student's t‐test, and qualitative variables with chi‐square. Results: In total, 2705 OSCC were included with a mean age of 62.8 years old. 55.8% were men. 53.75% of the patients were smokers and 38% were common drinkers. The lateral tongue border was the most affected site (24.65%). There were regional variations in OPMD, being leukoplakia the most frequent. Of the overall 2705 OSCC cases, 81.4% corresponded to OSCC‐dn, while s‐OSCC were 18.6%. Regarding lip vermillion SCC, 35.7% corresponded to de novo lip SCC and 64.3% were associated with previous OPMD. Conclusions: In Latin America, OSCC‐dn seems to be more frequent with regional variations of some clinical and histopathological features. Further prospective studies are needed to analyse this phenomenon. [ABSTRACT FROM AUTHOR]

Objective: DNA methylation data can be used to derive mitotic indices from complex tissues. Here, we assessed if the DNA methylation‐derived mitotic ageing indices are associated with oral squamous cell carcinoma (OSCC) development and recurrence‐free survival (RFS). Methods: DNA methylation‐based mitotic indices (MitoticAge, TNSC and hypoSC) were derived using algorithms "MitoticAge" and "epiTOC2" for the discovery [non‐malignant (n = 22), premalignant (n = 22) and OSCC (n = 68) tissues] and validation datasets (GSE87053, GSE136704 and TCGA‐HNSCC). Differences in mitotic indices between non‐malignant, premalignant and OSCC tissues were assessed. Finally, the association between estimated mitotic indices and RFS was evaluated in OSCCs. Results: In the discovery and validation datasets, increased mitotic ageing was observed in OSCC compared to non‐malignant and premalignant oral tissues. HPV‐positive HNSCCs had higher mitotic index TNSC. Mitotic age index hypoSC was associated with RFS in OSCC (p = 0.011, HR 2.61, 95% CI 1.24–5.48). Conclusions: DNA methylation‐derived mitotic indices are associated with OSCC development and RFS. Thus, DNA methylation‐derived mitotic indices may be a valuable research tool to reliably estimate the cumulative number of stem cell divisions in malignant and non‐malignant oral tissues. Future research utilizing mitotic indices for predicting clinical outcomes in OSCC is warranted. [ABSTRACT FROM AUTHOR]

Introduction and aim. Oral squamous cell carcinoma (OSCC) and premalignant disorders (PMDs) are becoming common in India as the use of tobacco in different forms is increasing from a young age, and the prevalence of this disease is becoming more common in middle age. Identifying disease at earlier stages is an important measure for limiting disease incidence and improving patient prognosis. The micronuclei count can be a valid biomarker for screening suspected patients and can be helpful in educating patients about the discontinuation of treatment, diagnosing the disease in its early stages and planning a treatment for a better prognosis. Different stains that are nuclear specific can be used to identify micronuclei. The aim was to establish diagnostic efficacy of various staining techniques in OSCC and potentially malignant disorders on oral brush cytology smears with observation of micronuclei as a valid biomarker for evaluation of the disease. Material and methods. Exfoliative cytology was done with oral brush and smears are obtained from 25 oral squamous cell carcinoma, 25 leukoplakia, 25 lichen planus, 25 oral sub mucous fibrosis patients and 15 samples with no disease. Each smear was stained with five different stains Papanicolaou (PAP), hematoxylin and eosin (H&E), toluidine blue, Leishman and Giemsa (LG) cocktail and Feulgen and observed for staining efficacy of micronuclei and cellular structures. Results. The best stain to observe DNA content as micronuclei is Feulgen which gives clear and crisp details of micronuclei without giving any false count as it is nuclear specific stain. PAP can be the second choice stain. Micronuclei count is definitely increased in OSCC and PMDs compared to samples without disease confirming its use as biomarker. Conclusion. Micronuclei count in oral brush cytology smears is a valid biomarker for evaluation of premalignant disorders and OSCC and can be used for detection of disease in individuals and for screening purposes of large populations at risk. Feulgen stain is best to study DNA content as micronuclei, on the other hand PAP can be used in large sampling investigations where there is lack of armamentarium. [ABSTRACT FROM AUTHOR]

Background: This study aims to compare the efficacy between conventional exfoliative cytology (EC) and centrifuged liquid-based cytology (CLBC) in control, leukoplakia, and oral squamous cell carcinoma (OSCC) patients. Oral leukoplakia and oral cancer require an early definitive diagnosis for better prognostic outcome. Oral EC, a minimally invasive technique that involves the examination of desquamated cells from the tissue surfaces used as a method of early diagnosis. CLBC is a modified technique that is used to achieve improved quality of the cytology findings. Materials and Methods: A comparative study was done in 30 subjects, of which, 10 cases from control group, 10 oral leukoplakia, and 10 OSCC cases. These subjects were selected according to the appropriate inclusion and exclusion criteria. The cases in each group underwent conventional as well as CLBC. The comparison was carried out between these groups with respect to the cellular and background stromal factors. Appropriate qualitative evaluation of the samples was collected and statistical analysis was done using the Chi-squared test. The significance level of value was P < 0.05. Results: Significant results were obtained for certain parameters such as cellular overlap clear background, uniform distribution in control, leukoplakia, and OSCC with a P = 0.004**, P = 0.001**, P = 0.006** using CLBC. Conclusion: CLBC is better and give clearer vision as compared to conventional cytology and can be used in the early diagnosis. [ABSTRACT FROM AUTHOR]

Background: To investigate the association between tooth loss and oral potentially malignant disorders and oral squamous cell carcinoma, focusing on epidemiological factors and genetic variants. Methods: Case–control study, including histologically confirmed oral potentially malignant disorders and oral squamous cell carcinoma cases and healthy controls. Unadjusted and adjusted odds ratios for this association were calculated. Single‐nucleotides polymorphisms were tested for individuals with and without missing teeth. Results: Case individuals were more edentulous while controls had fewer missing teeth (p = 0.006). There was an increased risk for the outcomes associated with edentulism (OR = 6.95, p = 0.000), even after adjustments for educational level (OR = 4.7, p = 0.034) and smoking habits (OR = 5.01, p = 0.022). Among individuals with tooth loss, rs1533767 (WNT11), rs3923087, and rs11867417 (AXIN2) were associated with the outcomes (OR = 1.67, p = 0.03, OR = 0.53, p = 0.05, and OR = 0.42, p = 0.00, respectively). Conclusions: Tooth loss could increase the risk for oral potentially malignant disorders and oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

Objective: Proliferative verrucous leukoplakia (PVL) has high rates of malignant transformation into oral squamous cell carcinoma (OSCC), but the clinical and evolutionary pattern of OSCC from PVL (PVL‐OSCC) is more favorable than that of OSCC not preceded by PVL (OSCC). Here, we aimed to explore the pathophysiologic differences between PVL‐OSCC and OSCC through transcriptomic and DNA methylation analyses. Materials and methods: In this case‐control study, oral biopsies from 8 PVL‐OSCC and 10 OSCC patients were obtained for global sequencing using RNAseq and a genome‐wide DNA methylation analysis via the Infinium EPIC Platform (graphical abstract). Results: One hundred and thirty‐three differentially expressed genes (DEGs) were detected, 94 of them upregulated in OSCC. Most of these genes were previously described in cancer and associated with prognosis. The integrative analysis revealed 26 DEGs, corresponding to 37 CpGs, whose promoters were regulated by DNA methylation. Twenty‐nine of the CpGs were found as hypermethylated in PVL‐OSCC. Only 5 of the genes that were aberrantly methylated and differentially expressed were upregulated in PVL‐OSCC patients, whereas 21 were underexpressed. Conclusions: PVL‐OSCC patients presented lower expression of cancer‐related genes. Hypermethylation of the promoter region of many genes was also noticed, indicating that DNA methylation could be a regulatory mechanism. [ABSTRACT FROM AUTHOR]

Oral leukoplakia (OLK) is a common type of potentially malignant disorder. Early identification of the malignancy potential leads to a better management of OLK and prediction of development of oral squamous cell carcinoma (OSCC). However, there has been no effective biomarker to assess the risk of malignancy in OLK. Genomic copy number alteration (CNA) is a complex chromosomal structural variation in the genome and has been identified as a potential biomarker in multiple cancers. This study aimed to develop a predictive model for the malignant transformation risk of OLK by copy number analysis. A total of 431 OLK samples with long-term follow-up (median follow-up of 67 mo) from multiple academic centers were analyzed for CNAs. CNA events increased with the severity of hyperplasia, mild dysplasia, moderate dysplasia, and severe dysplasia. More CNA events were present in patients with OLK who later developed OSCC than in those with OLK who did not. By multivariate Cox regression analysis, the OLK of the CNA scorehigh group showed an increased risk of malignant transformation than the CNA scorelow group (P < 0.001). A CNA score model was developed to accurately predict the prognosis (area under the receiver operating characteristic curve [AUC] = 0.879; 95% confidence interval [CI], 0.799–0.959) and was validated using data from 2 external centers (AUC = 0.836, 95% CI, 0.683–0.989; AUC = 0.876, 95% CI, 0.682–1.000), and all of them showed better prediction performances than histopathological grade in assessing the transformation risk of OLK. Furthermore, we performed CNA models among 4 subgroups of OLK with hyperplasia, mild dysplasia, moderate dysplasia, and severe dysplasia and found that CNA score can accurately predict malignant transformation of different subgroups. CNA score may be a useful biomarker to predict malignant transformation of OLK. Subtyping of OLK by the CNA score could contribute to better management of OLK and predicting development of OSCC. [ABSTRACT FROM AUTHOR]

Sirtuins (SIRTs) are a family of proteins involved in the metabolic process responsible for extending the lifespan. The role of SIRT1, 6, and 7 in oral squamous cell carcinoma (OSCC) and oral leukoplakia (OLP), one of its precursors, is still elusive. In this study, 82 OLP and 77 OSCC were immunohistochemically examined for SIRT1, 6, and 7. Stained sections were thoroughly scanned and evaluated using a digital image analysis program. The SIRT1, 6, and 7 expressions were detected in the nuclei of epithelial and carcinoma cells in various degrees. Afterward, any correlations among SIRTs, including associations with clinicopathological features and the Kaplan–Meier curves were analyzed. OSCC demonstrated significantly higher SIRT1 expression than OLP, while non-dysplastic lesions showed significantly higher SIRT6 expression than other lesions. A strong correlation was observed between SIRT6 and 7 in OLP, SIRT1 and 6 in in OSCC and in SIRT6 and 7 when all lesion types were considered. There were no significant differences between SIRTs reactivity and the clinical features in OLP. For OSCC, SIRT1 and 6 was found to be directly associated with site of the lesion, while SIRT7 showed a direct relationship between gender, stromal lymphocytic infiltration, and depth of the invasion. OSCC with high SIRT7 expression revealed a slightly lower survival probability, although not statistically significant (p = 0.1019). Our findings suggest that SIRT1, 6, and 7 may play correlated and diverse roles in the development and advancement of OSCC. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study is to evaluate the expression of S100A7 levels in saliva of oral sub-mucous fibrosis, oral leukoplakia patients, and healthy control. Materials and Methods: The study comprised of saliva samples from 15 patients each with clinically diagnosed oral sub-mucous fibrosis, oral leukoplakia, and healthy control. Salivary S100A7 levels were estimated using Enzyme-Linked Immunosorbent Assay. Statistical analysis was performed using SPSS. The significance level is fixed at 5% (α = 0.05). To compare the mean values of concentration between the disease group oral leukoplakia (OL) and oral submucous fibrosis (OSMF) and control, one-way analysis of variance was used followed by a post hoc test for multiple pairwise comparisons. Results: The results of the study indicated a statistically significant increase in the salivary S100A7 level among the OSMF and OL when compared with the control group. When a pairwise comparison was done between OSMF with a control group and leukoplakia with a control group, a statistically significant difference was observed, subsequently while comparing OSMF with leukoplakia, and no statistically significant difference was observed. Conclusion: Results from this study demonstrated increased S100A7 levels in OSMF and OL when compared with control group. This indicated that salivary S100A7 can be used as an adjunctive marker to identify patients at risk of progression into oral squamous cell carcinoma (OSCC). [ABSTRACT FROM AUTHOR]

Background: Oral leukoplakia (OLK) and oral lichen planus (OLP) are common precancerous lesions of the oral mucosa. The role of circular RNAs (circRNAs) in OLK and OLP is unclear. The aim of this study was to evaluate the circRNA expression profiles of OLK and OLP, and further explore the potential role of circRNAs in the pathogenesis of these two diseases. Methods: High throughput sequencing technology was performed to detect the differentially expressed circRNA in OLK (n = 6), OLP (n = 6), oral squamous cell carcinoma (n = 6), and normal oral mucosa tissues (n = 6). Expression of selected circRNAs was validated by qRT-PCR, enzyme tolerance assay, and Sanger sequencing. Expanded sample size validation was done in 20 tissue pairs. The biological processes and signal pathways involved in differential circRNA were analyzed by GO and KEGG enrichment. TargetScan and MiRanda were used to predict miRNAs downstream of circRNA and draw competitive endogenous RNA network diagram. Results: Forty-nine circRNAs were significantly altered in OLK and OLP, including 30 upregulated and 19 downregulated circRNAs. The five selected circRNAs were validated by qRT-PCR, Sanger sequencing, and RNase R assay. GO and KEGG analyses indicated that the upregulated circHLA-C may be involved in the biological process of immune function of OLK and OLP. Bioinformatics analysis indicated that circHLA-C may be involved in the progression of OLK and OLP as a ceRNA. In validation with expanded sample size, PCR results showed that circHLA-C expression was significantly upregulated in OLK and OLP. ROC analysis indicated that circHLA-C has potential diagnostic value with good accuracy and specificity. Conclusion: Our study revealed that circHLA-C is the most significantly upregulated circRNA co-existing in OLK and OLP, and we preliminarily discuss the role of circHLA-C in the etiopathogenesis and progression of OLK and OLP. [ABSTRACT FROM AUTHOR]

CD44 and SALL4 are markers of stemness and expressed in cancer stem cells (CSCs). Their deregulated expression was seen in various tumors and has been correlated with clinical severity. We evaluated immunohistochemical expression of CD44 and SALL4 in leukoplakia and oral squamous cell carcinoma (OSCC). CD44 was expressed in all the cases of leukoplakia and Its expression correlated with severity of the dysplasia in leukoplakia but varied with differentiation in OSCC. SALL4 did not express in leukoplakia. Its expression was varied in OSCC cases. We opine that CD44 expression is consistent with the progression of dysplasia in leukoplakia and differentiation in OSCC. [ABSTRACT FROM AUTHOR]

Background: Oral erythroplakia (OE) is a rare oral potentially malignant disorder, that has a high rate of malignant transformation. The definition of OE still lacks uniformity. In particular, lesions that look clinically like erythroplakias, but are histopathologically diagnosed as squamous cell carcinomas are still sometimes called erythroplakias. The purpose of this study is to present demographic and clinicopathologic features of a series of OEs and clinically oral erythroplakia -like squamous cell carcinomas (OELSCC), to study their differences and to discuss the definition of OE. Methods: A multicenter retrospective case series of OEs and OELSCCs. Descriptive statistics were used to analyze the data. Results: 11 cases of OEs and 9 cases of OELSCCs were identified. The mean age of the OE patients was 71 years and 72.7% were female, while the mean age of the OELSCC patients was 69 years, and all were female. 9% of the OE and 22% of the OELSCC patients had smoked or were current smokers. 72.7% of the OEs and 55.5% of OELSCCs were uniformly red lesions. 63.6% of the OE and 22% of the OELSCC patients had a previous diagnosis of oral lichenoid disease (OLD). The malignant transformation rate of OE was 9% in a mean of 73 months. Conclusions: OE and OELSCC may arise de novo or in association with OLD. Tobacco and alcohol use were not prevalent in the present cases. The clinical features of OEs and OELSCC are similar, but symptoms, uneven surface and ulceration may be more common in OELSCCs than in OEs. Clinical recognition of OE is important since it may mimic other, more innocuous red lesions of the oral mucosa. The diagnosis of OE requires biopsy and preferably an excision. Clarification of the definition of OE would aid in clinical diagnostics. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the relation between the expression of PD‐1, PD‐L1, CD3, CD8, Foxp3 and clinicopathological features in patients with oral leukoplakia (OLK) and oral squamous cell carcinomas (OSCC) as well as the malignant outcome in OLK patients, and to study the effect of PD‐1 and PD‐L1 on immune microenvironment in the progression of oral carcinogenesis. Methods: We evaluated the expression of PD‐1/PD‐L1 and composition of CD3+, CD8+and Foxp3+ T lymphocytes in OLK and OSCC samples by immunohistochemical (IHC) staining and analyzed their relation with clinical information and malignant transformation in OLK patients. Results: IHC staining demonstrated that the expression of PD‐1 was significantly increased in the high‐grade OLK group than in the low‐grade OLK group, while PD‐L1 was detected mainly in OSCC. The expression of CD3, CD8, and Foxp3 was found higher in the high‐grade OLK group than in the low‐grade OLK group, and the Foxp3+ cells were found more in the OSCC group than in the high‐grade OLK group. PD‐1 was significantly correlated with CD3 (p < 0.05, R = 0.52), CD8 (p < 0.05, R = 0.46), and Foxp3 (p < 0.05, R = 0.46), and the low PD‐1‐expression group showed a better malignant‐free survival than high PD‐1 expression group in the OLK (p < 0.05). Conclusion: The PD‐1/PD‐L1 may induce immune suppression in OLK and accelerate the progress of malignant transformation. [ABSTRACT FROM AUTHOR]

Objective: Oral leukoplakia is the most common oral potentially malignant disorder. Malignant transformation of oral leukoplakia occurs at an annual rate of 1%–7%. WHO‐defined classic epithelial dysplasia is an important predictor of malignant transformation of oral leukoplakia, but we have previously shown in a proof of concept study that prediction improves by incorporation of an architectural pattern of dysplasia, also coined as differentiated dysplasia. We aimed to analyze this finding in a larger cohort of patients. Method: For this retrospective study 176 oral leukoplakia patients were included. Biopsies for all patients were assessed for the presence of dysplasia and analyzed for cytokeratin 13 and 17 expression. Moreover, the inter‐observer agreement for the diagnosis of differentiated dysplasia was determined. Results: In total, 33 of 176 patients developed oral squamous cell carcinoma during follow‐up. Presence of classic epithelial dysplasia increased cancer risk two‐fold (HR = 2.18, p = 0.026). Lesions without classic epithelial dysplasia could be further risk‐stratified by the presence of differentiated dysplasia (HR = 7.36, p < 0.001). Combined classic epithelial and differentiated dysplasia imparted a seven‐fold increased risk of malignant transformation (7.34, p = 0.001). Inter‐observer agreement for the diagnosis of dysplasia, including differentiated dysplasia, was moderate (κ = 0.56, p < 0.001). Discussion: This study emphasizes the importance of the recognition of the architectural pattern of differentiated dysplasia as a separate entity for risk prediction of malignant transformation of oral leukoplakia. Presence of any pattern of dysplasia results in accurate prediction of malignant transformation risk of oral leukoplakia. [ABSTRACT FROM AUTHOR]

Background: Cancer of the lip and the oral cavity is collectively the sixth most common malignancy worldwide, out of which 90% are oral squamous cell carcinomas (OSCCs). Oral cancer survival rates depend mainly upon the stage in which it is diagnosed. Successful early detection would eventually increase the survival rate. OSCCs may be preceded by potentially malignant disorders (PMDs) that are characterised by visible clinical changes in the oral mucosa. Correct diagnosis and timely treatment of PMDs may help prevent malignant transformation in oral lesions. Oral leukoplakia (OL) is the best known potentially malignant disorder of the oral mucosa with a malignant transformation rate of about 3% to 33%. Tumour markers in saliva have emerged as a new diagnostic tool in the early detection of oral cancer. Matrix metalloproteinase 9 (MMP-9) is a gelatinase which plays an important role in tumourogenisis. The present study was done to evaluate the salivary levels of MMP-9 in OSCC and oral leukoplakia patients using enzyme-linked immunosorbent assay (ELISA). Materials and Methods: The study was conducted among 102 subjects, which included 34 OSCC patients (group I), 34 OL patients (group II), and 34 healthy subjects (group III). Unstimulated saliva was collected by the passive drooling method from all the study subjects during the study period, centrifuged, and stored at -80°C. The salivary MMP-9 was estimated in mg/ml using the sandwich ELISA technique. The data were analysed using a statistical software package, EZR. One-way analysis of variance was used for the comparison of salivary MMP-9 levels in OSCC, OL, and normal oral mucosa. Scheffe's multiple comparison was carried out to compare salivary MMP-9 levels among the different histological grades of OSCC and oral epithelial dysplasia. For all statistical interpretations, P ≤ 0.0 was considered the threshold for statistical significance. Results and Conclusion: The mean salivary MMP-9 level in OSCC, OL, and normal oral mucosa was 50.9 ± 5.7 ng/ml, 31.6 ± 6 ng/ml, and 16.2 ± 4.8 ng/ml, respectively. Patients with OSCC had significantly higher levels of salivary MMP-9 when compared to OL and normal mucosa. Higher levels of salivary MMP-9 were observed in poorly differentiated OSCC when compared to well and moderately differentiated OSCCs. The salivary MMP-9 was higher in severe oral epithelial dysplasia when compared to mild and moderate oral epithelial dysplasias. As malignant transformation rates are higher in patients with severe oral epithelial dysplasia when compared to mild and moderate oral epithelial dysplasia, salivary MMP-9 could be considered as a surrogate marker of malignant transformation. [ABSTRACT FROM AUTHOR]

OBJECTIVES: About 90% of oral cancers are oral squamous cell carcinomas (OSCC) whose appropriate treatment requires early diagnosis, based on knowledge about biomarkers which are expressed during the complex process of carcinogenesis. Growth differentiation factor-15 (GDF-15) has been considered an important serum and immunohistochemical marker in several cancers. Saliva has several advantages as a diagnostic biofluid. This research intends to evaluate the salivary GDF-15 levels in oral leukoplakia (OL) and in OSCC. MATERIALS AND METHODS: We estimated and compared levels of salivary GDF-15 in cases of OL, OSCC, and healthy controls. Study groups comprised 30 cases each of OL and OSCC. Control group comprised 30 healthy individuals. Saliva samples were assessed using the enzyme-Linked immunosorbent assay for GDF-15 levels. RESULTS: Salivary GDF-15 levels showed a gradual increase from healthy volunteers to cases of OL and highest GDF-15 levels were noted in OSCC group. Increase in concentration of GDF-15 was also noted with increasing grades of OSCC. CONCLUSION: Increased level of GDF-15 in premalignant cases reflects its antitumorigenic role, whereas its expression in later stages of OSCC demonstrates its protumorigenic role. The regulatory mechanism associated with GDF-15 may help in developing some novel therapeutic strategies based on its expression. [ABSTRACT FROM AUTHOR]

Approximately 1 in 60 men and 1 in 141 women will develop oral and oropharyngeal cancer in the US. This article presents the risk factors, pathogenesis, clinical presentation, and management of patients with oral and oropharyngeal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: This meta‐analysis aimed to assess the rate of malignant transformation (MT) of oral leukoplakia (OL) and to study potential risk factors for the MT of OL into oral squamous cell carcinoma (OSCC). Method: We performed a bibliographic search on nine electronic databases, including PubMed, MEDLINE, and Wanfang Data, for data on the MT rate of OL. Possible risk factors were calculated using Comprehensive Meta‐Analysis and Open Meta [Analyst] software. Results: The pooled proportion of OL MT for the total population described in the 26 selected studies was 7.20% (95% confidence interval: 5.40–9.10%). Nonhomogeneous type lesions, higher grades of dysplasia, the location of the lesion (tongue and multifocal), and female sex had significant effects on the MT of OL. Conclusion: OL tended to develop into OSCC (7.2%), and those with significant MT risk factors should be subjected to regular follow‐up and observation. However, we require large‐scale prospective studies to validate these results, together with unified clinicopathological diagnostic criteria, standardized risk factor recording/assessment methods, and long‐term follow‐up guidelines. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Chemerin is a multifunctional chemoattractant cytokine, encoded by RARRES2 gene. Its role in oral carcinogenesis is largely unexplored. Study was undertaken to evaluate the role of salivary chemerin as a potential biomarker in the early diagnosis of oral cancer and to elucidate the clinicopathologic and prognostic significance of chemerin in different grades of Oral Squamous Cell Carcinoma (OSCC) and oral leukoplakia. Materials and Methods: The study comprised 96 subjects, divided into 3 groups, each consisting of 32 subjects. These groups were clinically and histopathologically diagnosed with OSCC, oral leukoplakia, and healthy controls, respectively. The whole unstimulated saliva (1.5 mL) was collected from the subjects using passive drool technique and immediately centrifuged at 3000 rpm for 10 minutes. The salivary chemerin level was estimated using the competitive sandwich enzyme-linked immunosorbent assay method. The statistical analysis was performed using R software EZR version 1.32. Independent t-tests, analysis of variance tests, and Scheffe Multiple Comparisons were carried out to compare quantitative parameters. A receiver operating characteristic (ROC) curve was plotted to assess diagnostic accuracy of salivary chemerin. Results: Significantly higher levels of salivary chemerin were observed in OSCC and oral leukoplakia patients compared to healthy controls (P < 0.05). The study further established an increase in salivary chemerin concentration in different histological grades of OSCC and oral leukoplakia. ROC curve analysis suggested that salivary chemerin is a highly sensitive and specific indicator for early screening and detection of oral leukoplakia and OSCC. Conclusion: Salivary chemerin can be considered as a reliable and specific indicator for the early screening and detection of oral leukoplakia and OSCC and a highly sensitive biomarker which may aid in detection of malignant transformation of oral leukoplakia. [ABSTRACT FROM AUTHOR]

Oral and oropharyngeal cancers have been recognized as a major global health problem and are the sixth most common cancers in the world, with increasing rates of incidence and mortality. Dentists have an important role and responsibility in the early diagnosis of oral cancer. This study aimed to assess knowledge, awareness, and attitudes regarding oral cancer among dentists in North Cyprus. This study was conducted via a questionnaire that was distributed to the dentists in different provinces of Northern Cyprus. The questionnaire comprised 19 main items about the demographic information, dentist's oral cancer knowledge, attitude, opinions, and practices. The study consisted of 120 dentists and an overall response rate of 81.6% (98) was achieved. Nearly, all respondents were knowledgeable about tobacco use (98%) and previous oral cancer history (98%). The percentage of correct answers to questions concerning knowledge about risk factors of oral cancer ranged from 4.1% (family history of cancer) to 98%. Two-thirds of the participants pointed out correctly that the tongue and floor of the mouth are the most affected sites for oral cancers and leukoplakia and erythroplakia are two lesions most commonly correlated with oral cancer. However, 47% of participants were able to identify squamous cell carcinoma as the most frequent form of oral cancer. In conclusion, dental faculty curriculums and continuing education programs should aim at managing oral cancer need to address not only increase the knowledge and awareness about oral cancers but also include the clinical cases and practices. [ABSTRACT FROM AUTHOR]

Leukoplakia, a potentially malignant oral condition, manifests as a nonremovable white lesion that is often linked to risk factors such as smoking, alcohol, and HPV. Pegylated liposomal doxorubicin (PLD), which is used in cancer treatment, has been associated with secondary oral cancers, particularly in patients with leukoplakia. A case study revealed the development of squamous cell carcinoma (SCC) on the tongue following PLD treatment, suggesting a potential link between the drug and malignant transformation. Despite the benefits of PLD in reducing cardiac toxicity, long-term oral monitoring is essential due to the persistent risk of oral cancer posttreatment. [ABSTRACT FROM AUTHOR]

Background: In the case of oral potentially malignant disorders (OPMD), the possibility of malignant transformation of the lesion necessitates a decision on the need for an additional biopsy at each visit. Among many clinical characteristics, change on the lesion surface is one of the important factors that determine the need for additional biopsy at each visit. The purpose of the study was to provide information on the characteristics of lesions related to malignant transformation during the follow-up period of OPMD. Methods: Eight patients (four men and four women) with OPMD that transformed into malignancy during long-term follow-up were included and their mean age was 65.8 ± 12.4 years. Clinical information and histopathological diagnosis were investigated at the initial visit and during the long-term follow-up period. The focus was on information on changes on the lesion surface at the time the lesion was confirmed to be malignant. The period from initial diagnosis to dysplasia and from dysplasia to malignancy was also investigated. Results: The OPMD diagnoses were oral lichen planus or oral lichenoid lesions (n = 2), oral leukoplakia (n = 5), and hyperplastic candidiasis (n = 1). During the follow-up period of the lesions, when dysplasia was obtained by additional biopsy, changes in the lesions consisted of an increase in the size of the white or red area. The lesion surface of the OPMD showed verrucous, papillary, exophytic, corrugated, and ulcerative changes at the time of malignancy diagnosis. The period for the initial lesion to become dysplasia, from dysplasia to malignancy, and from the initial lesion to malignancy was very variable. Conclusions: Attention should be paid to verrucous, papillary, exophytic, corrugated, and ulcerative changes on the lesion surface of OPMD. Considering that the period for OPMD to become malignant is highly variable, a longer follow-up of the lesion is necessary. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate prognostic outcomes of PVL‐derived oral squamous cell carcinomas (P‐OSCC) based on recurrence, new primary tumour, metastasis and survival information. Study design: Five databases and grey literature were searched electronically with the following main keywords (proliferative verrucous leukoplakia, squamous cell carcinoma and malignant transformation) to answer the following review question: 'Are survival outcomes for P‐OSCC worse?' based on the PECOS principle. The Joanna Briggs Institute Critical Appraisal tool was used to identify possible biases and assess the quality of each of the primary studies. Results: A total of 21 articles met the inclusion criteria, and the results of this systematic review suggest that P‐OSCC can recur and generate new primary tumours; however, metastases are rare. Thus, most patients remain alive for an average period of 5 years. Conclusion: Apparently, P‐OSCC has better clinical prognostic characteristics than conventional OSCC. There is a lack of information on the main prognostic outcomes of P‐OSCC; therefore, specific studies must be performed to achieve a better comparison between P‐OSCC and conventional OSCC progression. [ABSTRACT FROM AUTHOR]

Pericytes are perivascular cells related to vessel structure and angiogenesis that can interact with neoplastic cells, interfering with cancer progression and outcomes. This study focused on the characterization of pericytes in oral squamous cell carcinoma (OSCC) using clinical samples and a transgenic mouse model of oral carcinogenesis. Nestin-/NG2+ (type-1) and nestin+/NG2+ (type-2) pericytes were analyzed by direct fluorescence after induction of oral carcinogenesis (4-nitroquinoline-1-oxide). Gene expression of neuron glial antigen-2 (NG2), platelet-derived growth factor receptor beta (PDGFR-β), and cluster of differentiation 31 (CD31) was examined in human OSCC tissues. The protein expression of von Willebrand factor and NG2 was assessed in oral leukoplakia (i.e., oral potentially malignant disorders) and OSCC samples. Additionally, clinicopathological aspects and survival data were correlated and validated by bioinformatics using The Cancer Genome Atlas (TCGA). Induction of carcinogenesis in mice produced an increase in both NG2+ pericyte subsets. In human OSCC, advanced-stage tumors showed a significant reduction in CD31 mRNA and von Willebrand factor-positive vessels. Low PDGFR-β expression was related to a shorter disease-free survival time, while NG2 mRNA overexpression was associated with a reduction in overall survival, consistent with the TCGA data. Herein, oral carcinogenesis resulted in an increase in NG2+ pericytes, which negatively affected survival outcomes. [ABSTRACT FROM AUTHOR]

Aims and objective: Apoptosis is essential physiological process of eliminating cells with damaged DNA. Any alterations in the apoptotic pathway may result increased malignant potential. Oral leukoplakia is an important health issue, especially in countries where the use of tobacco is almost a social habit. A significant proportion of cases of oral leukoplakia progress to the squamous cell carcinoma. Although the role of tobacco in causation and malignant transformation of oral leukoplakia is well established, but the cellular pathways affected by the tobacco use are not yet clear. The aim of the present paper was to study the effect of tobacco in alteration of apoptosis and proteins involved in apoptotic pathway and K-ras in oral leukoplakia. Material and Methods: Two hundred and thirty cases of oral leukoplakia were included in the study. These cases were divided into tobacco-consuming and non tobacco-consuming groups depending upon the history of tobacco intake (smoking or chewing). The presence and grade of dysplasia was noted from the histopathological reports. The apoptotic cells were identified by insitu terminal TdT-mediated dUTP-biotin nick-end labeling (TUNEL). The expression of caspase-3, caspase-8, caspase-9, bax and K-ras was studied in all the cases by immunohistochemistry. The apoptosis and caspase protein expression was then compared with control subjects using chisquare test. Result: The cases diagnosed with leukoplakia were grouped according to use of tobacco. In both the groups a statistical significant increase in apoptosis, caspase-3, caspase-8, caspase-9, bax and K-ras was observed as compared to controls. On comparison between the groups, the apoptosis and proteins involved in apoptotic pathway in tobacco group with dysplasia were significantly lower than the non tobacco-consuming group with dysplasia. An increase in Kras oncogene expression was found in leukoplakia-dysplasia of tobacco-consuming group. Conclusion: A significant decrease in the proteins mediating the extrinsic and intrinsic pathway of apoptosis was observed in the tobacco-consuming group, which indicates possible role of tobacco carcinogens in malignant transformation of oral leukoplakia. [ABSTRACT FROM AUTHOR]

Context: The increasing death rate because of oral cancer is mainly due to its late diagnosis. Tumour markers are often detected in abnormal amounts in blood, urine or saliva of patients with certain types of cancer. Diagnosing cancer through human saliva has advantages such as low invasiveness, minimum cost and easy sample collection. We have used serum immunoglobulin A (IgA) and salivary IgA for our present study. Aims: The aim of present study was to estimate serum and salivary IgA levels in oral leukoplakia and oral squamous cell carcinoma (OSCC) patients. Settings and Design: The study included 40 patients; 10 in the control group, 15 cases with oral leukoplakia and 15 cases with OSCC. Methods and Material: The blood samples and saliva were taken from clinically diagnosed oral leukoplakia and OSCC patients and were tested for IgA levels. Statistical analysis used: The data were analysed using SPSS 16.0. The mean values were compared between the groups by using analysis of variance (ANOVA) followed by post-hoc test for group-wise comparison. P value ≤ 0.05 was considered significant. Results: It was observed that the comparison of levels of serum IgA in control and leukoplakia group; control and OSCC group; leukoplakia and OSCC group were found to be statistically significant. Also, comparison between the levels of salivary IgA in control and OSCC group was found to be statistically significant. Conclusion: It is suggested that the serum and salivary IgA levels could be a better adjuvant diagnostic marker along with routine markers in patients with premalignant and malignant lesions. [ABSTRACT FROM AUTHOR]

Abstarct: The histopathological investigations of oral lesions are a basic approach for diagnosing ongoing cancer or pre-cancer associated pathological attributes in the dissected biopsy. The early detection and management of potentially malignant disorders of the lip and oral cavity that require intervention may reduce malignant transformations, or in case any malignancy is detected during surveillance, the appropriate treatment may improve survival rates. This would guide the clinicians to decide the appropriate treatment modality or lesion to achieve a more favorable prognosis. MCM2 protein is involved in DNA replication providing additional information about the prognosis of neoplasms. Some authors have pointed out that MCM proteins have been inversely correlated with salivary tumour differentiation and therefore could be an indicator of proliferation potential. Therefore, it is essential to find the expression of the MCM2 gene in oral leukoplakia and oral squamous cell carcinoma. Electronic databases like Ebscohost, Livivo, Google Scholar and PubMed were searched. Based on the inclusion and exclusion criteria, 2 reviewers (MS and SN) independently selected the relevant articles. Any disagreement was discussed until a consensus was reached. We used the QUADAS-2 tool to assess the quality of the included studies over four key domains: patient selection, index test, reference standard and flow and timing of participants through the study. 10 out of 57 titles were found to meet the eligibility criteria. Biopsied tissue with immunohistochemical staining or advanced diagnostic studies were included. A total of 901 samples were included in the study and different groups were normal oral mucosa (NOM), oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). MCM2 proteins are useful diagnostic markers for distinguishing malignant from benign epithelial dysplasia and for early detection and diagnosis of OSCC as an adjunct to clinicopathological parameters. [ABSTRACT FROM AUTHOR]

Objective: MUCIN4 (MUC4) glycosylation is linked to the oncogenesis and progression of a neoplastic process. It can suggest information pertaining to tumor progression, management and its natural properties. Thus, MUC4 can play a pivotal role in prognostic diagnosis. This study aimed to analyze the MUC4 expression in oral cell squamous carcinoma and oral dysplastic epithelium. Materials and Methods: The research included 45 samples of oral epithelial dysplasia (OED) and 45 cases of oral squamous cell carcinoma (OSCC). In order to carry out the investigation, tissue blocks of previously diagnosed cases of OED and OSCC were retrieved from the relevant archives. Forty-five OED cases were categorized into three group's mild, moderate and severe dysplasia, with 15 cases in each respective category. Forty-five OSCC cases were categorized into three groups: well differentiated, moderately differentiated, and poorly differentiated OSCC with 15 cases in each respective category. Ten tissue biopsies of normal oral mucosa were obtained from subjects in the control group. The chi-square test and one-way ANOVA were used for statistical analysis. Result: There was an absence of MUC4 expression in normal mucosa, whereas the OED and OSCC groups had a significant amount of observable variance. Within the OED category of cases, a consistent progression from mild to severe dysplasia was seen in terms of the staining pattern. Cases with severe dysplasia displayed a staining pattern that covered the complete thickness of the tissue in the epithelium. Expression of MUC4 was shown to be lower in moderate differentiated squamous cell carcinoma (MDSCC), and poorly differentiated squamous cell carcinoma (PDSCC) as compared to well differentiated squamous cell carcinoma (WDSCC). It showed decreasing pattern across all grades of OSCC. In WDSCC, an intense highest staining response was noticed, particularly among the cells that are highly differentiated and take the form of a honeycomb pattern. Conclusion: Analysis of the expression profile of MUC4 and the aberrant expression of this gene in OSCC suggests that it may serve as a useful diagnostic marker. Therefore, it is possible to draw the conclusion that MUC4 plays a very significant part in the pathogenesis of OSCC and also acts as a marker that may be taken into consideration for the accurate diagnosis of OED and OSCC. [ABSTRACT FROM AUTHOR]

The gold standard for the diagnosis of oral cancer is the microscopic analysis of specimens removed preferentially through incisional biopsies of oral mucosa with a clinically detected suspicious lesion. This dataset contains captured histopathological images of oral squamous cell carcinoma and leukoplakia. A total of 237 images were captured, 89 leukoplakia with dysplasia images, 57 leukoplakia without dysplasia images and 91 carcinoma images. The images were captured with an optical light microscope, using 10x and 40x objectives, attached to a microscope camera and visualized through a software. The images were saved in PNG format at 2048 × 1536 size pixels and they refer to hematoxylin-eosin stained histopathologic slides from biopsies performed between 2010 and 2021 in patients managed at the Oral Diagnosis project (NDB) of the Federal University of Espírito Santo (UFES). Oral leukoplakias were represented by samples with and without epithelial dysplasia. Since the diagnosis considers socio-demographic data (gender, age and skin color) as well as clinical data (tobacco use, alcohol consumption, sun exposure, fundamental lesion, type of biopsy, lesion color, lesion surface and lesion diagnosis), this information was also collected. So, our aim by releasing this dataset NDB-UFES is to provide a new dataset to be used by researchers in Artificial Intelligence (machine and deep learning) to develop tools to assist clinicians and pathologists in the automated diagnosis of oral potentially malignant disorders and oral squamous cell carcinoma.

The role of dysbiosis in the development and progression of oral potentially malignant disorders (OPMDs) remains largely unknown. Here, we aim to characterize and compare the oral microbiome of homogeneous leucoplakia (HL), proliferative verrucous leukoplakia (PVL), oral squamous cell carcinoma (OSCC), and OSCC preceded by PVL (PVL-OSCC). Fifty oral biopsies from HL (n = 9), PVL (n = 12), OSCC (n = 10), PVL-OSCC (n = 8), and healthy (n = 11) donors were obtained. The sequence of the V3–V4 region of the 16S rRNA gene was used to analyze the composition and diversity of bacterial populations. In the cancer patients, the number of observed amplicon sequence variants (ASVs) was lower and Fusobacteriota constituted more than 30% of the microbiome. PVL and PVL-OSCC patients had a higher abundance of Campilobacterota and lower Proteobacteria than any other group analyzed. A penalized regression was performed to determine which species were able to distinguish groups. HL is enriched in Streptococcus parasanguinis, Streptococcus salivarius, Fusobacterium periodonticum, Prevotella histicola, Porphyromonas pasteri, and Megasphaera micronuciformis; PVL is enriched in Prevotella salivae, Campylobacter concisus, Dialister pneumosintes, and Schaalia odontolytica; OSCC is enriched in Capnocytophaga leadbetteri, Capnocytophaga sputigena, Capnocytophaga gingivalis, Campylobacter showae, Metamycoplasma salivarium, and Prevotella nanceiensis; and PVL-OSCC is enriched in Lachnospiraceae bacterium, Selenomonas sputigena, and Prevotella shahii. There is differential dysbiosis in patients suffering from OPMDs and cancer. To the best of our knowledge, this is the first study comparing the oral microbiome alterations in these groups; thus, additional studies are needed. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is the most common cause of morbidity and mortality in India. Buccal mucosa is the most common site because of tobacco quid. Several parameters for the assessment of OSCC have been studied like lymph node metastasis, tumor stage, grade, and perineural invasion. Tumor-associated tissue eosinophilia is another parameter, on which several studies have been done because of its favorable and unfavorable prognosis. The aim of our study is to study quantitative and qualitative eosinophilia in premalignant and malignant lesions of squamous origin in oral cavity with respect to tumor-associated blood eosinophilia. A retrospective study was done at Tertiary care hospital between January 2016 and December 2016. A total of 150 cases of premalignant (oral leukoplakia and dysplasia) and malignant oral squamous cell carcinoma (of various grades) along with blood pictures were evaluated. [ABSTRACT FROM AUTHOR]