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Background: The purpose of this study was to investigate the expression of nuclear EGFR (nEGFR) and the stem cell marker ABCG2 in oral leukoplakia (OL) and oral erythroplakia (OE) and to assess their significance as prognostic biomarkers for malignant transformation. Methods: In this study we included 50 patients with oral potentially malignant disorders (OPMD), 31 with OL and 19 with OE, in whom we examined the expression of nEGFR and ABCG2 by immunohistochemical methods. Results: Twenty-one (42%) of 50 patients with OL and OE developed oral squamous cell carcinoma (OSCC). The malignant transformation was increased 12, 84-fold (95% CI, 2.15-76.44, p = 0.005) in OPMD expressing both ABCG2 and nEGFR. Expression of nEGFR is a strong indicator of malignant transformation, unlike ABCG2 expression, respectively. Conclusions: Determining the co-expression of the biomarkers nEGFR and ABCG2 in OPMD may serve us to determine the risk of malignant transformation in OSCC.

This study evaluated and compared the expression of secreted protein acidic and rich in cysteine (SPARC) in epithelial cells and fibroblasts of oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) using normal oral mucosa as a control.The expression of SPARC was determined in samples of normal oral mucosa (n = 12), OL without dysplasia (n = 31), OL with dysplasia (n = 54), and OSCC (n = 69) using immunohistochemistry. The percentage of positive cells in epithelial cells and fibroblasts was independently evaluated.Epithelial SPARC was found in 33.3%, 35.5%, 25.9%, and 66.7% of normal oral mucosa, OL without dysplasia, OL with dysplasia, and OSCC, respectively. Fibroblast SPARC was found in 50.0%, 29.0%, 46.3%, and 84.1% of normal oral mucosa, OL without dysplasia, OL with dysplasia, and OSCC, respectively. OSCC had higher epithelial and fibroblast SPARC expression than normal oral mucosa, OL without dysplasia, and OL with dysplasia (P.05). No significant differences were observed in epithelial and fibroblast SPARC among normal oral mucosa or OL with and without dysplasia.Overexpression of epithelial and fibroblast SPARC was observed in OSCC but not in OL, suggesting that SPARC is involved in the late stage of oral carcinogenesis.

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

Background MiRNAs are small non-coding RNAs that regulate gene expression at the post-transcriptional level and have been associated with malignant transformation of oral epithelial precursor lesions such as oral leukoplakia. The aim was to perform a scoping review of the contemporary literature about the different roles of miRNAs during the malignant transformation of oral leukoplakia. Material and Methods We conducted a systematic search with the following MeSH terms: ‘oral leukoplakia’, ‘carcinoma in situ’, ‘microRNAs’, ‘mouth neoplasms’ and ‘epithelial–mesenchymal transition’ in PubMed/MEDLINE, EMBASE and SpringerLink. Results Fifteen articles were included for analysis, among which in vivo and in vitro articles were included. A total of 21 different miRNAs were found to be involved in the malignant transformation process of oral leukoplakia. Regarding their possible effects, 6 miRNAs were classified as oncogenic, 5 as tumour suppressors and 10 were related to epithelial–mesenchymal transition, invasion and migration. Conclusions Based on the current review, we concluded that miRNAs-21, 345, 181-b and 31* seem to be potential markers of malignant transformation of oral leukoplakia. However, further clinical prospective studies are needed in order to validate their utility as prognostic biomarkers. Key words:miRNAs, oral leukoplakia, oral squamous cell carcinoma, biomarkers, malignant transformation.

Human papillomavirus (HPV) infection is mainly a problem of the female reproductive tract. It can occur in the oral cavity as well. Commonly HPV infections are subclinical, without any visible symptoms, and last no longer than 2 years. Usually the clinical manifestation of HPV infection is benign, but in some cases it can also promote malignant transformation. In the paper we have tried to estimate the prevalence of HPV detected in samples of oral leukoplakia (OLK), the most common premalignant lesions of the oral mucosa.To review the current literature to estimate the prevalence of HPV (HPV DNA) detected in samples of oral leukoplakia.We searched PubMed/Medline, Scopus, and Cochrane Library databases for studies that examined the prevalence of HPV in leukoplakia with HPV DNA detection by polymerase chain reaction.HPV positive cases in OLK ranged from 0% to 100% in studies. The overall HPV prevalence in leukoplakia was 6.66%. The prevalence of HPV 16 positive cases was 2.95%. The high-risk HPV prevalence was 5.16%, when the low-risk HPV prevalence was 3.32%. When dysplasia is mentioned, HPV was detected in 19.56% of lesions with dysplasia, compared to 38.16% among non-dysplastic lesions.Further studies should be extended also to include low-risk HPV and compare its prevalence with presence of dysplasia in leukoplakia. Besides, leukoplakia and other premalignant lesions can no longer be treated as one lesion.

By using a meta-analytical approach, this study aimed to analyse the diagnostic capacity of protein-based biomarkers in saliva for the differential diagnosis of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) from healthy individuals as control group (HCG). Articles on protein-based biomarkers in saliva, which provided quantitative expression in individuals with clinical and histopathological diagnosis of OPMD or oral leukoplakia (OL) were considered eligible. Searches were conducted in eight electronic databases. The methodological quality was assessed using the Quality Assessment of Diagnostic Studies tool (QUADAS-2). Functional analysis was also performed. Meta-analyses were performed using the OpenMeta tool (Analyst). Meta-analysis was possible for 4 of the 11 biomarkers studied. Only the carcinoembryonic antigen (CEA) and the soluble fragment of cytokeratin 19 (CYFRA21) were significant for the OSCC/OPMD subgroup, both with a very low heterogeneity. CEA had an OE = 25.854 (CI95%: 13.215–38.492, p< 0.001, I2 = 0) and CYFRA21 had an OE = 9.317 (CI95%: 9.014–9.619, p< 0.001, I2 = 0). For the OPMD/HCG subgroup, only CYFRA21 was significant, with an OE = 3.679 (CI95%: 0.663–6.696, p= 0.017) although with high heterogeneity (I2 = 91.24). The CEA and CYFRA21 markers proved very useful when differentiating OSCC from OPMD. The CYFRA21 was the only protein that was capable of distinguishing between OPMD and healthy controls.

Oral leukoplakia is common and may, in some cases, progress to carcinoma. Proliferative leukoplakia is a progressive, often multifocal subtype with a high rate of malignant transformation compared with the more common localized leukoplakia. We hypothesized that the immune microenvironment and gene expression patterns would be distinct for proliferative leukoplakia compared with localized leukoplakia. We summarize key clinicopathologic features among proliferative leukoplakia and localized leukoplakia and compare cancer-free survival (CFS) between subgroups. We analyze immunologic gene expression profiling in proliferative leukoplakia and localized leukoplakia tissue samples (NanoString PanCancer Immune Oncology Profiling). We integrate immune cell activation and spatial distribution patterns in tissue samples using multiplexed immunofluorescence and digital image capture to further define proliferative leukoplakia and localized leukoplakia. Among N = 58 patients (proliferative leukoplakia, n = 29; localized leukoplakia, n = 29), only the clinical diagnosis of proliferative leukoplakia was associated with significantly decreased CFS (HR, 11.25; P < 0.01; 5-year CFS 46.8% and 83.6% among patients with proliferative leukoplakia and localized leukoplakia, respectively). CD8+ T cells and T regulatory (Treg) were more abundant among proliferative leukoplakia samples (P < 0.01) regardless of degree of epithelial dysplasia, and often colocalized to the dysplasia–stromal interface. Gene set analysis identified granzyme M as the most differentially expressed gene favoring the proliferative leukoplakia subgroup (log2 fold change, 1.93; Padj < 0.001). Programmed death ligand 1 (PD-L1) was comparatively overexpressed among proliferative leukoplakia samples, with higher (>5) PD-L1 scores predicting worse CFS (Padj < 0.01). Proliferative leukoplakia predicts a high rate of malignant transformation within 5 years of diagnosis. A prominent CD8+ T-cell and Treg signature along with relative PD-L1 overexpression compared with localized leukoplakia provides strong rationale for PD-1/PD-L1 axis blockade using preventative immunotherapy. Significance: This is the first in-depth profiling effort to immunologically characterize high-risk proliferative leukoplakia as compared with the more common localized leukoplakia. We observed a notable cytotoxic T-cell and Treg signature with relative overexpression of PD-L1 in high-risk proliferative leukoplakia providing a strong preclinical rationale for investigating PD-1/PD-L1 axis blockade in this disease as preventative immunotherapy.

Early detection of Oral Cancer (OC) with non-invasive tools and screening of high-risk populations remains to be an unmet need. Metabolic reprogramming is an important hallmark of cancer. This review discusses the role of Salivary metabolomics (SM) in the diagnosis of OC and precancer. An electronic search was carried out in various databases with keywords "Salivary Metabolomics" “Oral Cancer” “Oral leukoplakia” and “Oral Lichen planus” from 2005 to July 2020. A total number of 48 studies were included out of which 38 were excluded. Several characteristic salivary metabolites were significantly altered in OC and precancer patients. SM techniques can be used to explore the metabolic signatures in OC and precancer, unravel its pathogenesis and develop targeted therapies.

The aim of the study is to identify key genes during the progression from oral leukoplakia (OL) to oral squamous cell carcinoma (OSCC) and predict effective diagnoses. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were performed to identify seven genes associated with the progression from OL to OSCC. Twelve machine learning algorithms including k-nearest neighbor (KNN), neural network (NNet), and extreme gradient boosting (XGBoost) were used to construct multi-gene models, which revealed that each model had good diagnostic efficacy. The functional mechanism or the pathways associated with these genes were evaluated using enrichment analysis, subtype clustering, and immune infiltration analysis. The enrichment analysis revealed that the genes enriched were associated with the cell cycle, cell division, and intracellular energy metabolism. The immunoassay results revealed that the genes primarily affected the infiltration of proliferating T cells and macrophage polarization. Finally, a nomogram and Kaplan–Meier survival analysis were used to predict the prognostic efficacy of key genes in OSCC patients. The results showed that genes could predict the prognosis of the patients, and patients in the high-risk group had a poor prognosis. Our study identified that the seven key genes, including DHX9, BCL2L12, RAD51, MELK, CDC6, ANLN, and KIF4A, were associated with the progression from OL to OSCC. These genes had good diagnostic efficacy and could be used as potential biomarkers for the prognosis of OSCC patients.

Objective The objective of this study was to develop the first edition of a Chinese evidence-based position paper on the management of oral leukoplakia (OLK). Study Design The consultant group for drafting the position paper consisted of 31 oral medicine specialists and 2 evidence-based medicine specialists. English studies (searched in PubMed, EMBASE, and the Cochrane Library) and Chinese studies (searched in China National Knowledge Infrastructure and WanFang) published before January 2018 were used. The quality of the study was assessed using the Grading of Recommendations Assessment, Development, and Evaluation grid, and the strength of the recommendations was determined based on the results of 3 rounds of voting among the consultant group members using the Delphi method. Results Twenty-two evidence-based guidelines for clinical management and monitoring of OLK were established in this position paper. A clinical path diagram for oral health practitioners was constructed based on the recommendations. Conclusion Current evidence suggests that management and monitoring of patients with OLK should be performed by experienced clinicians to control the lesion and for early detection of malignant transformation. However, all recommendations are based on evidence of low or extremely low quality and may require further modification as new evidence is produced.

Objective: The objective of this study was to investigate the levels of salivary SIRT-1 and CD44 in patients suffering from oral squamous cell carcinoma (OSCC), dysplastic and non-dysplastic oral leukoplakia to assess their potential role as early diagnostic biomarkers for patients with oral leukoplakia and OSCC. Subjects and Methods: sixty patients were recruited from the outpatient clinic of the Department of Oral Medicine and Periodontology, Faculty of Dentistry, Cairo University. Participants were divided into four groups:15 healthy individuals, 15 patients with non-dysplastic leukoplakia, 15 patients with dysplastic leukoplakia, and 15 patients with oral squamous cell carcinoma. Whole unstimulated saliva (WUS) was collected from all participants. Soluble CD44 (solCD44) and SIRT1 were measured using ELISA. Results: CD44 was expressed in all the four study groups with different levels. OSCC showed a statistically significant highest CD44 level. While the control group showed the lowest CD44 level. There was no statistically significant difference between dysplastic leukoplakia and non-dysplastic leukoplakia groups. Similarly, there was no statistically significant difference between non-dysplastic leukoplakia and control groups. OSCC showed the statistically significantly highest SIRT-1 level. There was no statistically significant difference between dysplastic leukoplakia, non-dysplastic leukoplakia, and control groups; all showed statistically significantly lower SIRT-1 levels than the OSCC group. Conclusion: salivary SIRT-1 and CD44 could be used as a screening tool to improve early detection and diagnostic precision of oral leukoplakia and OSCC.

Oral leukoplakia (OL) has the potential for malignant transformation; unfortunately, there are no strategies to prevent this possible outcome. Surgical intervention has been reported to be effective in reducing but not eliminating the risk of malignant transformation. Meta-analyses have reported that patients who underwent excision of OL lesions had a significantly lower chance of malignant transformation than those whose lesions were not excised. The present study aimed to report a case of successful management of extensive OL using a high-power laser. The patient has been under periodic monitoring, and we aim to continue the follow-up as long as possible. Recurrence or signs of malignancy were not observed at the 2-year follow-up.

Background/Purpose: Several previous studies have reported higher serum tumor marker levels in patients with oral or head and neck squamous cell carcinomas. This study evaluated whether 232 patients with oral precancerous lesions (oral precancer patients) had significantly higher serum carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and ferritin levels than healthy control subjects. Methods: The serum CEA, SCC-Ag, and ferritin levels in 232 oral precancer patients and 187 healthy control subjects were measured and compared. Patients with serum CEA level ≥3 ng/mL, SCC-Ag level ≥2 ng/mL, and ferritin level ≥250 ng/mL were scored as serum positive for CEA, SCC-Ag, and ferritin, respectively. Results: We found significantly higher mean serum CEA, SCC-Ag, and ferritin levels in 232 oral precancer patients than in 187 healthy control subjects (all P-values

Oral leukoplakia, which presents as white lesions in the oral cavity, including on the tongue, is precancerous in nature. Conservative treatment is preferable, since surgical removal can markedly reduce the patient’s quality of life. In the present study, we focused on the flavonoid apigenin as a potential compound for preventing carcinogenesis, and an apigenin-loaded mucoadhesive oral film was prepared using a three-dimensional (3D) bioprinter (semi-solid extrusion-type 3D printer). Apigenin-loaded printer inks are composed of pharmaceutical excipients (HPMC, CARBOPOL, and Poloxamer), water, and ethanol to dissolve apigenin, and the appropriate viscosity of printer ink after adjusting the ratios allowed for the successful 3D printing of the film. After drying the 3D-printed object, the resulting film was characterized. The chemopreventive effect of the apigenin-loaded film was evaluated using an experimental rat model that had been exposed to 4-nitroquinoline 1-oxide (4NQO) to induce oral carcinogenesis. Treatment with the apigenin-loaded film showed a remarkable chemopreventive effect based on an analysis of the specimen by immunohistostaining. These results suggest that the apigenin-loaded mucoadhesive film may help prevent carcinogenesis. This successful preparation of apigenin-loaded films by a 3D printer provides useful information for automatically fabricating other tailored films (with individual doses and shapes) for patients with oral leukoplakia in a future clinical setting.

Objective. To assess the clinical-pathological factors related to the malignant transformation of oral leukoplakia. Materials and Methods. A search for articles on malignant transformation factors related to oral leukoplakia was conducted in the following electronic databases: PubMed (MEDLINE, Cochrane Library), Web of Science (WoS) and Google Scholar. Thirty-seven articles with a low-moderate risk of bias according to the Newcastle-Ottawa methodological quality scale were included in this meta-analysis. The data were analyzed using the statistical programs RevMan 5.4 (The Cochrane Collaboration, Oxford, UK) and MedCalc Statistical Software version 16.4.3 (MedCalc Software Ltd. Ostend, Belgium) programs. The estimated prevalence was calculated according to DerSimonian and Laird random method. For dichotomous outcomes, the estimates of effects of an intervention were expressed as odds ratios (OR) using the Mantel-Haenszel (M-H) method with 95% confidence intervals. Results. The estimated global prevalence of malignant transformation of oral leukoplakia was 9.15%. The factors with the highest malignant transformation risk of oral leukoplakia were: non-homogeneous clinical types (OR: 5.41; p0.05).Conclusions. Non-homogenous oral leukoplakias and with moderate-severe dysplasia are those with the highest probability of malignant transformation.

A 42-year-old man with a history of surgery for tongue cancer was referred to our hospital due to an abnormal chest shadow. High-resolution computed tomography showed lower lobe reticulation. A physical examination revealed nail dystrophy, oral leukoplakia, and reticulated hypopigmentation. Lung biopsy revealed subpleural and perilobular fibrosis, suggestive of usual interstitial pneumonia. However, multiple pathological findings, including homogenous fibrosis and cell infiltration in the centrilobular region, which were compatible with nonspecific interstitial pneumonia, and bronchiolitis were also seen. Genetic testing showed a hemizygous missense mutation in the DKC1 gene, and the patient was diagnosed with dyskeratosis congenita. Although anti-fibrotic therapy was initiated, the patient's respiratory function has continued to decrease.

To study the association of Candida and antifungal therapy with pro-inflammatory cytokines (PIC) in oral leukoplakia (OL). A prospective observational study where immunocompetent adult subjects with OL (30 homogenous (HL), 30 non-homogenous (NHL)) and 30 age and sex-matched healthy controls (C) with no predisposing factors for oral Candida infection were recruited. Sterile cotton swabs and ophthalmic sponges were used to sample the lesion surface in OL and buccal mucosa in C, for direct microscopy and culture for Candida and to determine levels of PIC (IL-6, IL-8. IL-17, TNF-α) by ELISA, respectively. Sampling for PIC was repeated at same sites in OL, 2 weeks after antifungal therapy. Candida was associated with 55.3% of NHL, 23.3% of HL and 13.3% of C. The oral secretary levels of PIC were raised in NHL as compared to HL and C. The levels of IL-6, IL-8, TNF-α (p

OBJECTIVE Oral leukoplakia (OL) is the most frequently encountered oral potentially malignant disorder. The aims of this systematic review are to estimate the overall malignant transformation of OL and to assess the risk factors associated with malignant transformation of OL published in the last 5 years (2015-2020). MATERIALS AND METHODS We performed a bibliographic search in PubMed, Scopus, Web of Science, Embase, and Cochrane databases with keywords "oral leukoplakia", "oral cancer", "oral carcinoma" and "oral squamous cell carcinoma". Meta-analysis was conducted using a random-effects model. RESULTS Twenty-four studies were selected, that reported a total of 16,604 patients. Malignant transformation proportion varied between 1.1% and 40.8%. Female gender, non-homogeneous clinical type, and presence of epithelial dysplasia were significantly related to MT. Other risk factors previously suggested did not show significant results. CONCLUSIONS The pooled proportion of malignant transformation MT was 9.8% (95% CI: 7.9-11.7). It is necessary to continue to conduct well-designed prospective clinicopathological studies on OL, using a uniform definition for OL to reduce the risk of bias for evaluating various factors associated with the MT.

To evaluate the application of medical magnifying loupes in diagnosis of oral mucosal diseases. Twenty-four patients with plaque-type oral lichen planus or homogeneous oral leukoplakia were inspected by naked eyes or assistance with magnifying loupes. Histopathological results were used as the gold standard to evaluate the sensitivity, specificity and accuracy of the two methods in clinical diagnosis. Questionnaires were used to evaluate the subjective effect of magnifying loupes on the diagnosis efficiency of oral mucosal diseases and to explore the most suitable parameters for application. The sensitivity, specificity and accuracy of medical magnifying loupes for the identification of plaque-type oral lichen planus and homogeneous oral leukoplakia were 94.74%, 100.00% and 95.83%, respectively, which were significantly higher than those of naked eye inspection (89.47%, 80.00% and 87.50%). The effective rate of magnifying loupes assisted diagnosis was 91.76% according to physicians' subjective evaluation. The most suitable parameters were 3.5 times magnification and working distance. The medical magnifying loupes can effectively improve the efficiency of the inspection and diagnosis of oral mucosal diseases, and have the characteristics of convenience and real-time. The recommended clinical parameters are 3.5 times magnification and working distance.

Made available in DSpace on 2022-05-01T09:30:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-01 Background: DNA damage is accumulated in the cells over time as the result of both exogenous and endogenous factors. The objective of this study was to analyze the immunohistochemical expression of the repair proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). Materials and Methods: Paraffin blocks were selected from the archives of the Laboratory of Hospital Clinico Universitario de Santiago de Compostela, Spain. The sample was composed of 16 cases of OL without dysplasia, 14 cases of OL with dysplasia, and 15 cases of OSCC. The patients' clinical data were collected and immunohistochemical analysis was performed for MLH1, MSH2, MRE11, and XRCC1. The data were submitted to the χ2and the Kruskal-Wallis (P≤0.05) tests. Results: MSH2 was overexpressed in OSCC (P=0.020) and was positive in 100% of patients with OL with dysplasia or OSCC (P=0.019). Positivity for MLH1 was significantly associated with comorbidity (P=0.040), especially in patients who presented with 2 or more pathologies (P=0.028). XRCC1 positivity was also associated with comorbidity (P=0.039). No significant associations were found for the MRE11A expression. Although the simultaneous positivity for the 4 markers was observed in presence of comorbidities (P=0.006). Conclusions: This study supports the effect of the overexpression of MSH2 protein in samples of OL with dysplasia and OSCC, most notably in patients who present with comorbidities and negativity for OL without dysplasia. Oral Medicine Unit Technology Research Center (NPT) Mogi das Cruzes University Mogi das Cruzes, 200 Dr. C ndido Xavier de Almeida Souza Avenue Department of Pathology Clinical Hospital Santiago de Compostela Department of Forensic Sciences and Pathology University of Santiago de Compostela Translational Oncology Laboratory Idichus Foundation Santiago de Compostela School of Medicine Anhembi Morumbi University Department of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (UNESP) Department of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (UNESP)

Background The best treatment approach for wide oral leukoplakia (OL) remains to be determined. Aims To evaluate the outcomes of using an allograft dermal matrix (ADM) for reconstructing large oral epithelial defects following resection of OLs. Patients and methods A total of 27 OLs in 26 patients were excised, and residual large lingual and buccal epithelial defects were reconstructed using an ADM, which ranged in size from 3.0 × 5.0 to 6.0 × 6.0 cm. The patients were classified into mild (n = 1), moderate (n = 13), and severe dysplasia (n = 12) groups; 57.7% of the patients were tobacco smokers, 46.2% were alcoholics, 47.2% were both smokers and alcoholics, and 11.5% were both smoking and betel quid chewers. Patients who underwent surgery were advised to quit smoking, drink alcohol in moderation, or quit betel quid chewing. Results Two patients developed slight hematomas that resolved spontaneously within 2 weeks. A total of 76.9% of the smokers followed the advice to quit smoking, 83.3% of the alcoholics followed the advice to drink in moderation, and all three betel quid chewers followed the advice to quit chewing betel quid. The mean follow-up was 26.7 months. No MT occurred and recurrence was seen in two patients. Conclusions Large epithelial defect reconstruction using an ADM following resection of wide lingual and buccal OLs was safe and reliable for preventing MT of OL. The recurrence of OL may be related to patient habits such as tobacco smoking or/and drinking alcohol.

Aim: To compare the clinical and histopathological presentation of oral leukoplakia among different forms of tobacco users. Material and Methods: This study was carried out among 300 patients with oral leukoplakia, analyzing the corresponding clinical factors and histopathological findings, different forms of tobacco usage and assessing associations between the different clinical presentations and epithelial dysplasia. Results: Out of a total of 300 subjects, most (87.33%) of the subjects were males, among 138 tobacco chewers, maximum (60.87%) were having homogenous leukoplakia, among 85 tobacco smokers, maximum (61.18%) were seen with homogenous leukoplakia and among 77 subjects having mixed habit, maximum of 51.95% were diagnosed as having homogenous leukoplakia. The association between clinical type of leukoplakia and habit type was statistically not significant (Chi-square= 5.0806, p=0.5336). Majority of the cases which were diagnosed clinically diagnosed as leukoplakias presented a histological diagnosis of hyperkeratosis (45%) and mild epithelial dysplasia (33.33%). The association between histopathological type of leukoplakia and habit type was found to be statistically significant (Chi-square= 23.2166, p=0.0007). Conclusion: Most of the patients were having homogenous leukoplakia and majority of the cases which were diagnosed clinically diagnosed as leukoplakias presented a histological diagnosis of hyperkeratosis, mild epithelial dysplasia.

Background Two-dimensional (2D) radiographic techniques are commonly used for assessing lesion prognosis after endodontic surgery. The present retrospective cohort study analyzes the sensitivity and ability of different radiographic techniques in obtaining area and volume measurements of periapical lesions. Material and Methods Preoperative and follow-up (6-48 months) periapical and panoramic radiographs (index test) and cone-beam computed tomography (CBCT) images (reference standard) were selected from an endodontic microsurgery database. Sensitivity was analyzed independently by two examiners. The areas of the 2D radiographic images and CBCT volumes were studied using Itk-Snap software and Romexis viewer. Results The sample comprised 105 patients and 105 teeth, with a mean follow-up of 21 months (range 6-48). Preoperatively, CBCT detected all the periapical areas, periapical radiography detected 67, and panoramic radiography detected 60. Postoperatively, of the 52 cases in which CBCT detected remains of the periapical area, periapical radiography detected 22, and panoramic radiography detected 17. The measurements of the areas obtained by the 2D methods, and the volumes obtained by CBCT, had to be transformed into linear measures for comparison purposes. The measurements were found to be significantly different in both the preoperative and the follow-up images. Conclusions Periapical radiography showed greater sensitivity than panoramic radiography, both preoperatively and at follow-up. The lesions measured with CBCT were larger, with significant differences than as evidenced by the periapical and panoramic radiographs. Key words:Periapical radiography, panoramic radiography, CBCT, sensitivity, treatment outcome, size of periapical radiolucency, area, volume.

Background: Oral leukoplakia (OL) is considered one of the most common potentially malignant oral disorders (OPMD), with a verified increased risk of developing oral cancer. The identification of the dysplasia grade (low–high) is the only consolidated factor used to evaluate this risk. The objective of this study was to verify the role of the fractal dimension (FD) in assessing this dysplasia. Methods: To begin, 29 OL and 10 normal oral mucosa (NOM) biopsies were retrieved for FD analysis of the epithelial (dime) and the connective (dimc) tissue. Results: In the OL group, the median value of dime is higher (1.67, IQR = 0.12) than for the NOM group (1.56, IQR = 0.08), with statistically significant differences (Wilcoxon test, p = 0.0031). There were no differences in relation to dimc. Significant differences were observed between the non-dysplasia vs. high-grade (p = 0.0156) and low-grade vs. high-grade (p = 0.0049) groups. No significant differences were identified in relation to dimc for the different degrees of dysplasia. For a cut-off point of 1.44 of dime, a specificity of 96.6% was obtained, a sensitivity of 100%, and an AUC = 0.819 (p = 0.003). Conclusions: FD at the level of the epithelium may be used as a diagnostic tool in OL This research was funded by Santiago de Compostela University SI

Tobacco is a common name for the plants belonging to the genus Nicotiana and nightshade family. It contains a highly addictive stimulant which is used in cigarettes and other smokeless forms of tobacco. The product has a lot of carcinogens and other harmful mixtures which lead to the causation of oral submucous fibrosis, leukoplakia and erythroplakia. In this study, we would be seeing how common it is to have a history of tobacco usage in the patients diagnosed with Leukoplakia between march 2019 and march 2020 in Saveetha dental college. Materials and methods: This study was done in Saveetha dental college, Chennai, Tamilnadu, India. The study data were taken between March 2019 to March 2020. We took patients reporting with oral leukoplakia and checked their history for Smoking or smokeless tobacco usage. These data are recorded by the dental students in saveetha dental college. A total of 100 patient's record was taken and among the patients with smoking, history was identified. The number of patients with and without smoking/smokeless tobacco usage record was deduced. Results: There were a total of 100 participants, in which 95 were males and 5 were females who reported to the clinic with oral leukoplakia. In this sample, a total of 76 patients had a homogenous variant of leukoplakia while 24 patients had a non-homogenous variant. Eighty-four patients had the habit of smoking, while 16 patients had the habit of smokeless tobacco usage. Conclusion: There were 100 participants and with the result deduced from the data obtained from the participants, it is clear that smoking is one of the major etiology of Oral leukoplakia.

The authors consider the possibilities of pain management during photodynamic therapy (PDT) of visible tumors based on the observation of 102 patients. Of the total number of patients, 62 had verified basal cell skin cancer, 10 people - squamous cell skin cancer, another 10 - oral and oropharynx mucosa cancer, 8 - oral leukoplakia and dysplasia, in 6 - lower lip cancer, in 4 - breast cancer, in 2 - other localizations of neoplasms. In 15 patients, nonsteroidal anti-inflammatory drugs (NSAID) were used as pain management, in 69 - a combination of NSAID with tramadol, in 14 - nerve block anesthesia, in 4 - PDT was performed under general anesthesia. The intensity of pain syndrome during laser irradiation of the tumor was assessed on the verbal rating scale (VRS). The absence of pain was recorded in 9% of cases. Mild pain was noted by 58% of patients, moderate pain - 20%, severe pain - 10%, very severe pain was noted by 3% of patients.The degree of expression of pain syndrome during PDT depends on the incidence of a lesion, histological form of tumor, and method of anesthesia. NSAID alone, or in combination with an opioid analgesic, allows effective control of pain syndrome in PDT of basal cell skin cancer in 89%, in PDT of squamous cell skin cancer in 66% of observations. Nerve block anesthesia allows stoping pain syndrome during PDT of oropharyngeal tumors.

Aim The COVID‐19 pandemic has resulted in society experiencing unprecedented challenges for health care practitioners and facilities serving at the frontlines of this pandemic. With regard to oral cancer, there is a complete absence of literature regarding the long‐term impact of pandemics on patients with oral potentially malignant disorders (OPMDs). The objective of this article is to put forth an institutional multidisciplinary approach for the evaluation and management of OPMDs. Methods A multidisciplinary approach was put formalized within our institution to risk stratify patients based on need for in‐person assessment vs telehealth assessment during the COVID‐19 pandemic. Results With judicious risk stratification of patients based on clinical features of their OPMD and with consideration of ongoing mitigation efforts and regional pandemic impact, providers are able to safely care for their patients. Conclusions The COVID‐19 pandemic has required health care practitioners to make novel decisions that are new to us with development of creative pathways of care that focused on patient safety, mitigation efforts, and clinical management of disease processes. The care of patients with OPMDs requires special considerations especially as patients at high risk for severe COVID‐19 illness are also higher risk for the development of OPMDs.

Objectives: The aim of the article was to evaluate Ki-67 expression in oral leukoplakia in snuff users and non-users. Study Design: Descriptive Cross sectional study. Setting: At different hospitals of Khyber Pakhtunkhwa province. Period: From August 2016 –March 2017. Material & Methods: Clinically diagnosed and histopathologically confirmed cases of oral leukoplakia in snuff users and non-users 30 cases each were immunohistochemically examined and percentage expression of nuclear Ki-67 was evaluated by a semi quantitative method in basal, parabasal and suprabasal layers of the lining epithelium. Results: The relationship of expression of Ki-67 in parabasal and suprabasal layers of affected epithelium in snuff users was found to be statistically significant with a p value of 0.007 and 0.002 respectively. Conclusion: The present study concludes that the proliferative index is high in snuff users as compared to non-users which can be a factor for malignant transformation.

Background Oral leukoplakia is the most common potentially malignant lesion, the etiology of this change is still uncertain which makes it difficult to predict when this will undergo malignant transformation. Recent studies have examined the involvement of mast cells in this process, it is believed that these cells through the release of pro-angiogenic factors influence the processing mechanism of such lesions through promoting angiogenesis. It was the objective of this study to evaluate the inflammatory process in oral leukoplakia comparing it to a non-cancerous lesion correlating the intensity of mast cells with inflammatory infiltrate and vascularization in these lesions. Methods A total of 20 selected cases divided into two groups, oral leukoplakia and inflammatory fibrous hyperplasia (IFH). Histochemical Technique of Toluidine Blue was applied to enhance mast cells and histomorphometry for quantifying mast cells, blood vessels and inflammatory cell infiltration by capturing digital images of the samples and analysis software Image Java version 1.48v. Mast cells and blood vessels were counted in 10 different areas and the intensity of the inflammatory infiltrate was measured in three areas. The analysis of variance (ANOVA) was used for between-group variation, a P value of 0.05 for statistical significance. Results It was observed a reduction in the concentration of mast cells in oral leukoplakia compared fibrous inflammatory hyperplasia. In contrast to the concentration of blood vessels were present in higher concentrations in the Oral leukoplakia lesions. The inflammatory infiltrate in most cases was considered scarce, except in a case where that IFH was intense and a case of moderate inflammatory infiltrate in oral leukoplakia. Conclusions The results showed reduction in the number of mast cells in the oral leukoplakia and greater intensity in the inflammatory process in the IFH, suggesting a possible carcinogenic influence in the microenvironment oral leukoplakia.

Objective: Oral cancer usually has an early precancerous stage before its actual malignant transformation. Although there are various approaches to diagnose early stages of cancer, yet there is one less explored, cost effective and simple technique known as crystallization test. The aim of the study was to reaffirm the effectiveness of Pfeiffer’s crystallization test in screening oral leukoplakia and squamous cell carcinoma. Methods: Fifty oral leukoplakia, sixty five oral squamous cell carcinoma and sixty healthy individuals participated in crystallization test. Single blood drop was used to perform the test and obtained crystal patterns were analysed. Cross tabulation and Chi-Square test was performed to find the frequency and association between the groups. Kruskal-Wallis H test and Mann Whitney U test was applied comparing mean transverse form. Results: Sensitivity of crystallization test was 80% and 93.84% in oral leukoplakia and squamous cell carcinoma. Chi-Square analysis revealed highly significant transverse form between the study groups (p < 0.000). Conclusion: Crystallization test proves to be simple, reliable and minimal invasive diagnostic approach under strictly maintained physical conditions.

Objectives: A systematic review was conducted to evaluate effectiveness and safety of beta carotenes for the treatment of oral leukoplakia regarding clinical resolution and prevention of malignant transformation. Material and Methods: The systematic search was conducted in three electronic databases and the study’s selection was performed according to pre-set eligibility criteria. Four studies evaluating the efficacy of beta carotenes in oral leukoplakia compared to placebo were included in the review; three of which were assigned for quantitative analysis. Data were extracted, tabulated, quality assessed and statistically analyzed. Results: The meta-analysis revealed that when comparing clinical resolution the beta carotene group favored was favored compared to placebo, with statistically significant difference. However, a meta-analysis comparing beta carotene and placebo groups regarding malignant transformation as a primary outcome failed to show any significant benefit. Furthermore, results showed evidence of beta carotene safety. Conclusion: the overall quality of evidence about efficacy of beta carotene in oral leukoplakia treatment was not high. However, given the obvious safety of this agent, data suggests it could have a promising effect in clinical improvement of oral leukoplakia lesions. However, no evidence supporting its benefits in reducing risk of malignant transformation in these lesions was found. Therefore, further long term, well designed randomized clinical trials are highly recommended.

The article presents the clinical and diagnostic aspects of oral leukoplakia and treatment approaches, depending on the clinical form of the disease. The aim of the study was to study the effectiveness of the treatment of verrucous form of oral leukoplakia using laser ablation and collagen-based drug. The study conducted a clinical examination and treatment of 28 patients (17 women and 11 men) aged 45 to 64 years with a verrucous form of oral leukoplakia, which were divided into two groups — the main (15 people) and a comparison group (13 people). In the main group, the lesion site was excised by laser ablation; after surgery collagen-based drug was applied to the wound surface. In the comparison group (12 people), the lesion site was excised with scalpel, and after surgery solcoseryl-based drug was applied to the wound surface. The results of observation in the postoperative period indicate reduction in the time of wound surface epithelization after the use of laser ablation and a collagen-based drug. This opens new possibilities in the treatment of verrucous form of oral leukoplakia.

Clinical evaluation of oral leukoplakia (OL), confirmed by the histological evaluation of the suspected area, provides the gold standard for diagnostics of this pathology. The aim of present study was to encrypt the significance of the histopathological results (oral intraepithelial neoplasia – OIN, WHO 2005, Ljubljana classification systems) of OL. The usefulness of osteonectin as a biomarker of changes in the oral cavity epithelium was evaluated. IRS Score to evaluate osteonectin (SPARC – secreted protein acidic and rich in cysteine) production in oral mucous tissues was modified, with the aim of adapting the diagnostic measurements to the OL cell environment. In total, 37 formalin-fixed, paraffin-embedded (FFPE) blocks from patients with clinically diagnosed OL, and 29 FFPE blocks from patients with OSCC were evaluated. The OIN and system from Ljubljana were compared, to adjudicate which was most compatible with WHO 2005 histopathological assessment. Increased production of SPARC was observed, with the progression in severity of pathological changes in the oral mucosa, from simple hyperplasia, through dysplasia, to OSCC. The WHO 2005 and the OIN classification systems can be applied interchangeably.

Background A retrospective clinical-histopathological study was made of the evolution of oral leukoplakia over time, staging the disease according to the classification of van der Waal. Material and Methods A study was made of 412 patients with oral leukoplakia, analyzing the corresponding clinical factors and histopathological findings; assessing associations between the different clinical presentations and epithelial dysplasia; and evaluating the factors influencing malignant transformation of the lesions. Results Clinically, homogeneous presentations were seen to predominate (n = 336, 81.6%), while histologically most of the lesions exhibited no dysplastic changes (n = 271; 65.7%). Stage 1 of the van der Waal classification was the most common presentation (n = 214; 51.9%). The lesion malignization rate was 8.3%, and the factors associated to a significantly increased malignization risk were non-homogeneous OL lesions (p=0.00), lesion location in the tongue (p=0.00), and the presence of epithelial dysplasia (p=0.00). Conclusions In our series of patients with oral leukoplakia, malignization was associated to the less common clinical presentations of the disease, i.e., non-homogeneous lesions, and the latter tended to exhibit high grade epithelial dysplasia. Sin financiación No data JCR 2020 0.481 SJR (2020) Q2, 63/141 Dentistry (miscellaneous) No data IDR 2019 UEV

Oral squamous cell carcinoma often arises from an oral potentially malignant disorder called oral leukoplakia (OL). With this work we aimed to develop a novel data-driven predictive model based on gene expression profiles to distinguish OL patients who underwent malignant transformation from those who did not. We used the Tree Augmented Naïve (TAN) Bayes classifier to predict the posterior probability of having oral cancer given the data. 86 patients were included with a median follow-up of 7.11 years. Fifty-one patients (51/86; 59%) underwent malignant transformation. We found that 16 genes were predictors of oral cancer in patients with OL and these included SLC7A11, SPINK6, SERPINA12, VIT, ATP1B3, CST6, FLRT2, ELMOD1, AZGP1, RNASE13, DIO2, ECM1, CYP4F11, SYTL4, AKR1C1, and AKR1C3. In conclusion, we showed that Bayesian gene networks are a data-driven approach which could be used also in other predictor models in oncology.

© 2021 The Authors. Oral Diseases published by Wiley Periodicals LLC.Objectives: To identify possible associations between patients’ demographics and habits and the clinical aspects and histopathological characteristics of oral leukoplakia (OL) at patients’ first visit. Method: A total of 140 consecutive patients with OL at a single institute between 1997 and 2019. All biopsies were microscopically examined for classic dysplasia (CD) (WHO definition oral epithelial dysplasia) and differentiated dysplasia (DD) known from differentiated vulvar intraepithelial neoplasia. Clinical characteristics were correlated to histopathological diagnosis and odds ratios (OR) were calculated. Results: A total of 96 females and 44 males, mean age 58 years, were presented. OLs were found mainly on the tongue (41%) and floor of mouth (FOM) (18%). Homogeneous OLs (58%) were associated with smoking, FOM and size