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• Utilizing deep learning for automated detection of oral lesions. • Detection of Oral Lichen Planus (OLP), Oral Leukoplakia (OLK), and OSCC. • Analysis of clinical photographs to enhance targeted accuracy for OSCC detection. • Accurately identify oral lesions and support healthcare professionals. [ABSTRACT FROM AUTHOR]

• Our model outperforms experienced experts in detecting oral cancer-related diseases. • Our model improved oral lesion diagnosis accuracy of general dentists and specialists. • It brought general dentists and specialists comparable to experienced experts. • Our app integrates our model for timely detection of oral cancer in smartphone photos. We aim to develop a YOLOX-based convolutional neural network model for the precise detection of multiple oral lesions, including OLP, OLK, and OSCC, in patient photos. We collected 1419 photos for model development and evaluation, conducting both a comparative analysis to gauge the model's capabilities and a multicenter evaluation to assess its diagnostic aid, where 24 participants from 14 centers across the nation were invited. We further integrated this model into a mobile application for rapid and accurate diagnostics. In the comparative analysis, our model overperformed the senior group (comprising three most experienced experts with more than 10 years of experience) in macro-average recall (85 % vs 77.5 %), precision (87.02 % vs 80.29 %), and specificity (95 % vs 92.5 %). In the multicenter model-assisted diagnosis evaluation, the dental, general, and community hospital groups showed significant improvement when aided by the model, reaching a level comparable to the senior group, with all macro-average metrics closely aligning or even surpassing with those of the latter (recall of 78.67 %, 74.72 %, 83.54 % vs 77.5 %, precision of 80.56 %, 76.42 %, 85.15 % vs 80.29 %, specificity of 92.89 %, 91.57 %, 94.51 % vs 92.5 %). Our model exhibited a high proficiency in detection of oral lesions, surpassing the performance of highly experienced specialists. The model can also help specialists and general dentists from dental and community hospitals in diagnosing oral lesions, reaching the level of highly experienced specialists. Moreover, our model's integration into a mobile application facilitated swift and precise diagnostic procedures. [ABSTRACT FROM AUTHOR]

• Significant gene expression differences between PVL and non-PVL oral lesions. • HOX and keratin-associated protein gene families upregulated in PVL. • Connective tissue pathways and fibroblast signatures lower in PVL. • Classifying biomarker models discriminated PVL from non-PVL lesions. Proliferative verrucous leukoplakia (PVL) is a rare and enigmatic oral potentially malignant disorder which almost invariably results in oral squamous cell carcinoma (OSCC). The aims of this project were to use transcriptome profiling to characterise PVL gene expression patterns for biomarker identification and gain insight into the molecular aetiopathogenesis of PVL. Forty-three oral cavity mucosal biopsies from 32 patients with oral lesions clinically compatible with either PVL or non-PVL conventional oral leukoplakia (OLK) underwent transcriptome profiling by RNA sequencing. Data was analysed by hierarchical clustering, differential gene expression, functional enrichment and network analysis, sparse partial least squares discriminant analysis sPLS-DA, and immune cell phenotypic estimation. We found 464 genes significantly differentially expressed at least 2-fold between PVL and non-PVL OLK (193 up and 271 down). HOX genes, including HOXA1 and HOXB7, keratin-associated proteins (KRTAPs) and olfactory receptor G proteins (OR) were significantly upregulated in PVL. Other upregulated genes in PVL included FOS , WNT16 and IFNA1. Pathway analysis showed that there was a significant downregulation of connective tissue signalling in PVL. Classifying multivariate models based upon 22 genes discriminated PVL from non-PVL OLK. Bioinformatic profiling showed that immune cell profiles in PVL and OLK were similar except that fibroblast markers were reduced in PVL. These results demonstrate that PVL and conventional OLK are molecularly distinct with upregulation of many cancer-associated genes. They provide insight into the pathogenesis of PVL and show that biomarker based molecular diagnostics is feasible to discriminate and inform diagnosis and management. [ABSTRACT FROM AUTHOR]

• The review summarizes the available published data on OSCC/OPMD in FA patients. • May provide useful information for clinicians. • Lesions occur more frequently in young adult women. • Most OSCC/OPMD are treated with surgical resection. • High death rates are observed within a short period time. The purpose of the present study was to perform a systematic review focusing on oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) in Fanconi anemia (FA) individuals. Electronic searches were undertaken in five databases supplemented by manual scrutiny and gray literature. Case reports and/or cases series were included. The searches yielded 55 studies describing 112 cases of OSCC (n = 107) and/or OPMD (n = 5) in FA individuals. The mean age at diagnosis of OSCC/OPMD was 27.1 (±9.6) years, and females (51.8 %) were slightly more affected. Ulcer (n = 37) or mass (n = 25) were described as clinical presentations for OSCC and OPMD. White lesions (n = 4) were the most common manifestation in OPMD. Tongue (47.2 %) was the most frequent location. Sixty-one (54.5 %) individuals underwent HSCT. Surgical resection (n = 75) was the main treatment adopted. The estimated rate of OPMD malignant transformation was 1.8 % and recurrences following OSCC excision occurred in 26.8 % of individuals. Overall, at 60 months of follow-up, the probability of survival fell to 25.5 % and at 64 months the probability of recurrence increased to 63.2 %. The present data support the need for strict surveillance of patients with FA, even in the absence of OPMD, for early OSCC detection and reduction of mortality. [ABSTRACT FROM AUTHOR]

Objectives: To map the genomic pathways of patients with oral leukoplakia (OLK) which transformed to cancer (progressive) and those which did not (non-progressive), and to compare their exomic profiles.Materials and Methods: Whole exome sequencing was performed on 42 sequential samples from five progressive and eight non-progressive patients. Association of genomic variant frequencies with progression or lesion severity were analysed by non-parametric tests (Kruskal-Wallis and Mann-Whitney-Wilcoxon) and multivariate sparse partial least squares discriminant analysis (sPLS-DA). Enrichment analysis was used to characterise the effect of mutations upon biological pathways. Confirmatory studies used qPCR and immunohistochemistry.Results: Using sPLS-DA, the variant frequency of a small number of genes could be used to classify the samples based on lesion severity or progressive status. Enrichment analysis showed that DNA damage repair gene related pathways were highly impacted in lesions which progressed to cancer. Multivariate analysis of a set of 148 DNA damage repair genes could be used to classify progressive lesions using mutation frequency. BRCA1, BRCA2 and other double strand break (DSB) repair Fanconi anaemia (FA)/BRCA pathway genes were prominent contributors to this classification.Conclusion: Patients with progressive and non-progressive OLK can be differentiated using the frequency of exomic variants, particularly in DNA damage repair pathway genes. To our knowledge, this is the first report of FA/BRCA (DSB) pathway involvement in malignant transformation of OLK to oral squamous cell carcinoma (OSCC). [ABSTRACT FROM AUTHOR]

Recent advances in DNA sequencing technology have facilitated rapid advances in the analysis of the human microbiome and its role in human disease. Several studies have now shown that OSCC and some oral premalignant conditions are associated with alterations in the oral microbiome. These studies raise questions regarding the role of the oral microbiome in the progression of oral malignancies and whether microbiome change is a significant risk factor in the development of oral cancer. This short review summarises current knowledge in the field and highlights questions that require further investigation. [ABSTRACT FROM AUTHOR]

Objectives: Tobacco usage is the strongest risk factor in the development of oral squamous cell carcinoma (OSCC), which mandates careful screening for oral cancers in smokers. However, there are indications that oral potentially malignant lesions, such as oral epithelial dysplasia (OED), in non-smokers (NS) have a higher cancer risk than those in smokers. Without tobacco as an etiology, the development of these lesions in NS may suggest genetic susceptibility. The increasing incidence of OSCC in NS calls for a better understanding of the natural history of OED in NS as compared to that of smokers.Materials and Methods: Patients from a population-based longitudinal study with more than 10 years of follow up were analyzed. Of the 455 patients with primary OED (233 mild and 212 moderate dysplasia), 139 were NS and 306 were smokers. Demographic and habit information, clinical information (lesion site, size and appearance; toluidine blue and fluorescent visualization), microsatellite analysis for loss of heterozygosity (LOH) and outcome (progression) were compared between the two groups.Results and Conclusions: The majority of patients with OED were smokers. Of these, more were males, non-Caucasians and heavy drinkers. A significantly higher number of OED in NS were in the tongue, whereas a significantly higher number of OED in smokers were in the floor of mouth (FOM). OED in NS showed a greater than 2-fold increase in cancer progression. Strikingly, OED located in the FOM in NS showed a 38-fold increase in cancer progression as compared to those in smokers. [ABSTRACT FROM AUTHOR]

Objectives: Oral leukoplakia (OL) has a well-documented potential risk of malignant transformation into oral squamous cell carcinoma (OSCC), although biomarker(s) predicting malignant potential are limited in capability. The aim of this cross-sectional and retrospective cohort study was to investigate the predictive role of canonical Wnt genes Axin2 and Snail (SNAI1) expression in the malignant transformation of OL lesions.Materials and Methods: The expression of epithelial-mesenchymal transition (EMT) genes Snail and Axin2, which are regulated by the canonical Wnt pathway, were determined using immunohistochemical staining in an OL cohort consisting of 154 samples of patients with long-term follow-up and then evaluated as risk factors for malignant transformation of OL.Results: Increased Axin2 and Snail abundance were found in 107 (69.5%) and 58 (37.7%) of OL patients, respectively. In a multivariate analysis using gender, age, lesion site, Axin2, and Snail as cofactors, both Axin2 and Snail were independent risk factors for malignant transformation with a hazard ratio of 7.47 (95% confidence interval, 2.23-25.02; P=0.001) and 4.41 (95% confidence interval, 1.78-10.93; P=0.001), respectively. A nomogram for predicting 5-, 10-, and 15-year cancer-free survival probability was developed in patients with OL by including gender, age, lesion site, Axin2, and Snail expression with ac-index of 0.760.Conclusion: The increased abundance of Snail and Axin2 is highly correlated to malignant transformation of OL, making them novel biomarker(s) predicting oral cancer development. [ABSTRACT FROM AUTHOR]

Objective: Squamous cell carcinomas (SCC) are the most common malignancies in the oral mucosa; these carcinomas have been preceded by potentially malignant oral disorders (PMODs), mostly oral leukoplakia (OL). No specific biomarker has been widely accepted for predicting the risk of malignant transformation of PMODs. The aim of this study was to develop an accurate prediction model for the malignant transformation of OL using clinical variables and candidate biomarkers.Materials and Methods: To achieve this goal, 10 candidate biomarkers that had previously been reported as useful molecules were investigated: P53, Ki-67, P16, β-catenin, c-jun, c-met, insulin like growth factor II mRNA-binding protein (IMP-3), cyclooxygenase (COX-2), podoplanin (PDPN) and carbonic anhydrase 9 (CA9). For this study, malignant transformed (n=22, median interval of malignant conversion: 3.3years) and untransformed (n=138) OL specimens with median follow-up period of 11.3years (range: 4.6-23.2years) were immunohistochemically stained.Results: Using univariate Cox regression analysis, all biomarkers were proven to be significant for predicting malignant transformation in OL. To reach the highest prediction accuracy, the repeated simulation was performed, revealing that the combination of P53 and CA9 with the clinical factors including age and degree of dysplasia achieved the highest prediction accuracy. We constructed a nomogram with the identified prognostic factors for predicting the 5-, 10-, and 15-year progression free survival of OL.Conclusions: The proposed nomogram may be useful for the accurate and individual prediction of the transformation to SCC in OL patients and may help clinicians offer appropriate treatments and follow up. [ABSTRACT FROM AUTHOR]

Objectives: Cancer immunoediting represents a relatively novel concept attempting to explain the process of tumor escape from the host immune system response. Here, we attempted to elucidate the role of programmed death ligand 1 (PD-L1), the tumor microenvironment, and tumor escape mechanisms that allow malignant transformation of oral precancerous lesions.Materials and Methods: Patients with oral precancerous lesions managed at the Nara Medical University Hospital, Japan, (n=120) were enrolled in this study. Epithelial dysplasias were graded by experienced pathologists, and subepithelial PD-L1-, CD163-, and CD8-positive cells were counted in the superficial lamina propria of oral mucosa. Epithelial PD-L1 expression was evaluated according to the staining intensity. The association of clinicopathological factors with epithelial dysplasia, malignant-free survival time, and significance of risk factors for malignant transformation were determined.Results: Multivariate analysis showed that the subepithelial CD163-positive cell count was the only significant risk factor for high-grade epithelial dysplasia (P<0.001), while subepithelial CD163- and PD-L1-positive cell counts, and epithelial PD-L1 positivity were significantly associated with malignant-free survival (P=0.004, 0.04, and <0.001, respectively). Subepithelial PD-L1-positive cell count and epithelial PD-L1 positivity were significantly associated with malignant transformation (P=0.01 and 0.04, respectively).Conclusion: Our results indicate that PD-L1-expressing dysplastic epithelial and recruited subepithelial cells in oral precancerous legions may evade the host immune system, and that the inhibition of PD-1/PD-L1 pathway may potentially prevent malignant transformation of oral precancerous legions as well as can treat advanced cancers. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: We review the use of topical chemoprevention agents in patients with oral potentially malignant disorders (PMD).Methods: A systematic review of studies on topical chemoprevention agents for oral PMD from 1946 to November 2016 was conducted using the MEDLINE database, Embase, and Cochrane Library. Data were extracted and analyzed from selected studies including study type, sample size, demographics, treatment length, response rate, follow-up time, adverse effects, and recurrence.Results: Of 108 studies, twenty-four, representing 679 cases met the inclusion criteria. The clinical lesions evaluated included oral leukoplakia, erythroplakia (OEL), verrucous hyperplasia (OVH), oral lichen planus, larynx squamous cell carcinoma, and oral squamous cell carcinoma (OSCC). The mean complete response rate for topical retinoid therapy was 32%. The mean complete response rate for 1% bleomycin therapy and 0.5% bleomycin was 40.2% and 25%, respectively. The complete response rate of OVH, OEL, and OSCC to photodynamic therapy ranged from 66.7% to 100%.Conclusion: There are a paucity of data examining topical treatment of oral PMDs. However, the use of topical agents among patients with oral lesions may be a viable complement or even alternative to traditional surgery, radiation, or systemic chemotherapy, with the advantage of reducing systemic side effects and sparing important anatomic structures. This study of 679 cases represents the largest pooled sample size to date, and the preliminary studies in this systematic review provide support for further inquiry. [ABSTRACT FROM AUTHOR]

• Oral leukoplakia is a challenging process to manage, with no official guidelines or recommendations. • This survey asseses practice patterns for oral leukoplakia otolaryngologists and oral and maxillofacial surgeons. • This is the largest survey for practice patterns for oral leukoplakia across multiple specialties, to our knowledge. • Practice patterns across oral surgery and otolaryngology can potentially lead to consensus guidelines. Oral leukoplakia is encountered frequently by otolaryngologists and oral and maxillofacial surgeons (OMFS). There are no consensus practice management guidelines for oral leukoplakia, resulting in heterogeneity in practice patterns. Characterization of practice patterns of providers who treat oral leukoplakia will be valuable to establish standards of care and future practice guidelines. A survey was designed by the American Head and Neck Society Cancer Prevention Service collecting demographic and practice management data for treating oral leukoplakia. The survey was approved and distributed to members of the American Academy of Otolaryngology-Head and Neck Surgery and American Association of Oral and Maxillofacial Surgeons. Data analysis was performed using chi square and t -test where appropriate. 396 responses were collected: 83 OMFS, 81 head and neck fellowship-trained providers, and 232 otolaryngologists (non-head and neck fellowship-trained). Providers saw a wide volume of oral leukoplakia (23.0% >30 cases/year, 35.1% 11–30 cases/year, 41.2% 10 or less cases/year), with OMFS seeing more cases of oral leukoplakia. Factors most associated with consideration of initial biopsy included physical exam findings (94.4%), erythroplakia (82.3%), and smoking status (81.6%). The majority of respondents saw patients in follow-up within 1 month (24.8%) or within 1–3 months (46.5%). This survey identifies a range of practice patterns in initial management of oral leukoplakia, including indications for biopsy, and time for follow-up. This data provide insight into practice patterns amongst different groups of providers and can potentially lead to consensus guidelines for initial management of oral leukoplakia. [ABSTRACT FROM AUTHOR]

Objectives: The aim of our study is to explore the role of the history of oral lesions and chronic diseases on the risk of head and neck cancer in a Chinese population.Materials and Methods: Our case-control study included 921 head and neck cancer cases and 806 controls. We obtained medical history information by administering questionnaires to both cases and controls. We used unconditional logistic regression to estimate odds ratios for oral lesions and chronic conditions.Results: Oral submucous fibrosis (OR=24.24, 95% CI=7.39-79.52), oral leukoplakia (OR=4.05, 95% CI=2.44-6.71) and repetitive dental ulcers (OR=5.12, 95% CI=3.17-8.28) increased the risk of HNC. Depression was associated with HNC risk when adjusted for several covariates (OR=2.10, 95% CI=1.06-4.15), but the association was not statistically significant after adjusting for smoking and alcohol drinking (OR=1.53, 95% CI=0.72-3.25). Also, the crude OR suggested an association between diabetes and HNC risk (OR=1.51, 95% CI=1.09-2.11), but it was not significant after adjusting for confounders.Conclusion: Our study reported on strong associations between HNC risk and oral leukoplakia, oral submucous fibrosis, which is consistent with prior research. We also observed repetitive dental ulcer to be associated with HNC risk. Future studies may focus on studying the association between depression and HNC, using medical records or psychological evaluation results to get more accurate information about depression, with careful assessment of tobacco and alcohol history. [ABSTRACT FROM AUTHOR]

Objectives: Oral lichen planus (OLP) was classified as an oral potentially malignant disorder due to the association with oral squamous cell carcinoma (OSCC). However, the malignant potential of OLP has been controversial. Whether epithelial dysplasia should be differentiated from OLP and lichenoid dysplasia could be identified as a pathological entity has been the subject of debate.Materials and Methods: We recruited a large retrospective cohort with 3568 patients, and 10 of them developed OSCC. These cases were reviewed retrospectively to investigate association between OLP and OSCC.Results: In 10 cases of OSCC, three of them were primary cancers distinct from the site with OLP, two were malignant transformation of proliferative verrucous leukoplakia, and five were malignant transformation of oral leukoplakia. All OSCC is not transformed from OLP. Therefore, previous insights into OLP might have overestimated its transformation risk. There may be the reasons: I. did not distinguish OLP from epithelial dysplasia, II. neglect of oral leukoplakia with dysplasia developed in the course after OLP, III. misdiagnosis in the early stage of proliferative verrucous leukoplakia.Conclusion: The pathological and molecular biological features of OLP differed from those of oral leukoplakia and OSCC. Strict control of the diagnostic criteria for OLP and close surveillance during the course could contribute to correctly identify the origin of OSCC and avoid overestimating the risk of OLP transformation. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the probability of malignancy of an oral leukoplakia lesion using Deep Learning, in terms of evolution to cancer and high-risk dysplasia.Materials and Methods: A total of 261 oral leukoplakia lesions with a mean of 5.5 years follow-up were analysed from standard digital photographs. A deep learning pipeline composed by a U-Net based segmentation of the lesion followed by a multi-task CNN classifier was used to predict the malignant transformation and the risk of dysplasia of the lesion. An explainability heatmap is constructed using LIME in order to interpret the decision of the model for each output.Results: A Dice coefficient of 0.561 was achieved on the segmentation task. For the prediction of a malignant transformation, the model provided a sensitivity of 1 with a specificity of 0.692. For the prediction of high-risk dysplasia, the model achieved a specificity of 0.740 and a sensitivity of 0.928.Conclusion: The proposed model using deep learning can be a helpful tool for predicting the possible malignant evolution of oral leukoplakias. The generated heatmap provides a high confidence on the output of the model and enables its interpretability. [ABSTRACT FROM AUTHOR]

Unlabelled: The standard treatments for oral leukoplakia range from careful observation to complete resection. No surgical intervention is chosen for several supposable reasons. Surgical treatment and no surgical treatment for oral leukoplakia have no defined basis for comparisons, and few studies have reported on the long-term outcomes of oral leukoplakia without surgery.Objectives: This study aimed to identify the important factors using a long-term wait-and-see policy in patients with oral leukoplakia.Materials and Methods: In total, 237 lesions from 218 patients selected for non-surgical therapy between 2001 and 2010 were analyzed. On the basis of long-term follow-up data, lesions were classified as unchanged, reduced, disappeared, expanded, and malignantly transformed.Results: In total, 135 (57.0%) lesions remained unchanged, 30 (12.7%) lesions were characterized by a reduction in size or clinical severity, and 44 (18.6%) lesions had disappeared. Another 17 (7.2%) lesions resulted in spread or clinical deterioration, and 11 (4.6%) lesions developed oral squamous cell carcinoma.Conclusions: We demonstrated a cumulative malignant transformation rate of 11.6% in 10years without resection. The lesions that were nonhomogeneous, and higher degree of epithelial dysplasia, located on the tongue were likely to progress into cancer. In addition, 32.5% of lesions without surgical treatment were reduced or disappeared. There is a possibility that removal of considerable irritation for a long time contributes to the treatment of this disease. The development of appropriate treatments for oral leukoplakia is required, which will enable successful differentiation between surgical and observation cases. [ABSTRACT FROM AUTHOR]

The early diagnosis of oral precancer and cancer is crucial and could have the highest impact on improving survival rates. A meta-analysis was conducted to compare the accuracy between the OralCDx brush biopsy and DNA-image cytometry in diagnosing both conditions. Bibliographic databases were systematically searched for original relevant studies on the early diagnosis of oral precancer and oral cancer. Study characteristics were evaluated to determine the accuracy of the two screening strategies. Thirteen studies (eight of OralCDx brush biopsy and five of DNA-image cytometry) were identified as having reported on 1981 oral mucosa lesions. The meta-analysis found that the area under the summary receiver operating characteristic curves of the OralCDx brush biopsy and DNA-image cytometry were 0.8879 and 0.9885, respectively. The pooled sensitivity, specificity, and diagnostic odds ratio of the OralCDx brush biopsy were 86% (95% CI 81-90), 81% (95% CI 78-85), and 20.36 (95% CI 2.72-152.67), respectively, while these modalities of DNA-image cytometry were 89% (95% CI 83-94), 99% (95% CI 97-100), and 446.08 (95% CI 73.36-2712.43), respectively. Results of a pairwise comparison between each modality demonstrated that specificity, area under the curve (AUC), and Q(∗) index of DNA-image cytometry was significantly higher than that of the OralCDx brush biopsy (Z=2.821, p<0.05; Z=1.711, p<0.05; Z=1.727, p<0.05), but no significant difference in sensitivity was found (Z=1.520, p>0.05). In conclusion, the meta-analysis of the published studies indicated that DNA-image cytometry is more accurate than the OralCDx brush biopsy in diagnosing oral precancer and oral cancer. [ABSTRACT FROM AUTHOR]

Summary Objectives Oral leukoplakia (OL) is the most common potentially malignant lesion of the oral cavity, and OL diagnosis is a risk factor for developing subsequent oral squamous cell carcinomas (OSCC). Notably, loss of heterozygosity (LOH) profiles have been validated as risk predictors of malignant transformation of OL. Similar to other solid malignant tumors, OSCC exhibit molecular heterogeneity. However, if and to what extent tumor heterogeneity is present in premalignant lesions of the oral cavity has not been addressed. As LOH analysis is currently being used to stratify OL patients at risk for OSCC development in chemoprevention studies, insight into the issue of molecular heterogeneity of OL is of clinical significance. Materials and methods To address this issue, 11 polymorphic microsatellite markers localizing to chromosomes 3, 9, 11 and 17 were used to detect LOH in 28 samples of 14 OL patients, by capillary electrophoresis analysis. These samples were either clinically recurrent lesions, or two anatomically distinct biopsies from the same lesion, or even two different OL lesions located at distinct intraoral sites. Results In all but one of the biopsies pairs, distinct LOH patterns were displayed regardless of histopathological grade. These data provide evidence for inter- and intra-lesional molecular heterogeneity in OL. Conclusions On the basis of these findings, molecular heterogeneity needs to be addressed in subsequent studies targeting specific carcinogenic pathways/genes in chemoprevention of malignant transformation of OL. [ABSTRACT FROM AUTHOR]

Summary Background Oral leukoplakia (OL) is the best-known potentially malignant disorder of oral cancer. The hypothesis was tested that DNA content abnormality may contribute to risk prediction of malignant potential of OL. Methods All OLs were staged according to a clinicopathologic classification and OL-staging system. DNA content status was investigated in a blinded prospective series of OL using brush biopsy with image cytometry, and examined the correlation of DNA content with the clinicopathologic features and OL-staging system in this preliminary study. Results Among 65 patients with OL, 27 (41.5%) was identified as DNA content abnormality. The frequency (77.8%) of DNA content abnormality in tongue was higher than that (22.2%) in other oral sites ( χ 2 test, P = 0.038), and moderate or severe dysplasia had a higher frequency (63.0%) of DNA content abnormality than that (37.0%) of no or mild dysplasia ( χ 2 test, P = 0.022). Moreover, the odds ratio of DNA content abnormality in high-risk patient group was 5.74-fold (95% confidence interval, 1.81–18.20; P = 0.003) increase compared with low-risk patient group. Importantly, the positive correlation between OL-staging system and DNA content status was significant ( P = 0.018, correlation coefficient = 0.292). Conclusion Our findings showed that DNA content status correlated with OL-staging system, suggesting that DNA content abnormality in OL as detected by image cytometry was an early event in oral carcinogenesis. The further large-scale prospective studies with clinical endpoints are warranted to validate the value of DNA image cytometry. [ABSTRACT FROM AUTHOR]

Background: There is few longitudinal study on oral potentially malignant disorder (OPMDs) focusing on oral leukoplakia (OLK) with clinical endpoints to investigate the role of autofluorescence imaging (AFI) for surveilling the malignant transformation.Methods: Based on our previous prospective diagnostic study enrolled 517 OPMD patients, 184 OLK patients were retrieved to further investigate the role of AFI using VELscope in predicting malignant transformation. During a median follow-up period of 44 months, 19 (10.33%) developed into oral cancer.Results: OLK patients were divided into loss of autofluorescence (LAF, n = 124) and retention of autofluorescence (RAF, n = 60) groups according to the results of AFI. Interestingly, difference between malignant transformation rate (MTR, 14.52%) of group LAF and overall MTR (10.33%) was not significant, but MTR (1.67%) of group RAF was significantly lower than overall MTR. Kaplan-Meier and Cox-regression analyses revealed that LAF could not directly distinguish the high-risk lesions, but RAF significantly discriminate the low-risk lesions. Importantly, time-dependent ROC curve analysis found that the sensitivity and negative predictive value (NPV) of AFI for the prediction of malignant transformation was 100% and 100% (2-year follow-up), 94.7% and 98.3% (5-year follow-up), respectively. Also, calibration curve and decision curve analyses showed high levels of predictive value and clinical relevance.Conclusion: This follow-up cohort study firstly evaluated AFI using VELscope for risk stratification of OLK malignant transformation. Whether conservative management is appropriate for OLK patients with RAF imaging due to minimal rate and risk of malignant transformation and great specificity and NPV is required to be further investigated. [ABSTRACT FROM AUTHOR]

Summary Background Oral leukoplakia is a precancerous disorder that is common among residents in Linxian. However, the associations between oral leukoplakia and upper gastrointestinal cancers have not been reported. We investigated the relationships between oral leukoplakia and upper gastrointestinal cancers in the Linxian General Population Trial cohort. Methods The Linxian General Population Trial cohort, with 29,584 healthy adults enrolled in 1985 and followed through the end of 2012. With collected baseline data, hazard ratios (HR) and 95% confidence intervals (95% CI) for developing upper gastrointestinal cancers were estimated using Cox proportional hazard models. Results During 28 years of follow-up, we confirmed a total of 2924 incident esophageal squamous cell carcinoma (ESCC) cases, 1644 gastric cardia cancers and 590 gastric non-cardia cancers. Overall, participants with oral leukoplakia had significantly higher risk of developing ESCC (HR = 1.18, 95% CI: 1.08, 1.29). Among individuals ⩽52 years old at baseline, oral leukoplakia was associated with elevated risk of ESCC (HR = 1.31, 95%CI: 1.15, 1.49). No significant associations were observed for gastric cardia or non-cardia cancers in either all subjects or subgroups. Conclusions Oral leukoplakia was associated with increased risk of ESCC, particularly in younger population. Future studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the current evidence in relation to the predictive value of p53 overexpression as a biomarker of the malignant transformation risk in oral potentially malignant disorders (OPMD).Material and Methods: We searched PubMed, Embase, Web of Science and Scopus for studies published before July-2021, not restricted by date or publication language, with longitudinal design and assessing p53 overexpression by immunohistochemistry. We evaluated the quality of primary-level studies using QUIPS tool. We carried out meta-analyses, examined inter-study heterogeneity through subgroup and meta-regression analyses, and performed sensitivity and small-study effects analyses to test the stability and reliability of results.Results: Twenty four studies (1,210 patients) met inclusion criteria. P53 overexpression was associated with a statistically significant about 2 fold risk (RR = 1.88, 95 %CI = 1.39-2.56, p < 0.001). Leukoplakia maintained this significant relationship after subgroup meta-analysis (p = 0.002). Regarding the immunohistochemical technique, better results were obtained by the subgroups using anti-p53 DO7 antibody (p = 0.001), at high concentration (dilution < 1: 100, p < 0.001), incubated for long periods (overnight, p = 0.02), and at low temperature (4 °C, p = 0.007). Furthermore, meta-regression analysis showed that the association between p53 overexpression and higher oral cancer risk was independent of the presence and/or severity of epithelial dysplasia (p > 0.05).Conclusion: Our systematic review and meta-analysis supports the assessment of p53 overexpression in the prediction of the malignant transformation risk of OPMD. [ABSTRACT FROM AUTHOR]

Summary: Background: Photodynamic therapy with aminolevulinic acid (ALA PDT) for oral leukoplakia has shown promising effects in regression of oral leukoplakia. Although ALA has been extensively studied and is an ideal photosensitizer, the optimal light dose for treatment of oral leukoplakia has not been determined. We conducted a phase I study to determine MTD and DLT of PDT in patients treated with ALA for leukoplakia. Methods: Patients with histologically confirmed oral leukoplakia received a single treatment of ALA PDT in cohorts with escalating doses of light (585nm). Clinical, histologic, and biologic markers were assessed. Results: Analysis of 11 participants is reported. No significant toxicity from ALA PDT was observed in patients who received ALA with a light dose of up to 4J/cm2. One participant experienced transient grade 3 transaminase elevation due to ALA. One participant had a partial clinical response 3months after treatment. Biologic mucosal risk markers showed no significant associations. Determination of MTD could not be accomplished within a feasible timeframe for completion of the study. Conclusions: ALA PDT could be safely administered with a light dose up to 4J/cm2 and demonstrated activity. Larger studies are needed to fully elucidate the MTD and efficacy of ALA-PDT. [ABSTRACT FROM AUTHOR]

Objectives: Recent studies have identified podoplanin, a mucin-type transmembrane glycoprotein, as a biomarker for oral cancer risk in patients with oral leukoplakia (OPL). The aim of this study was to inves-tigate the potential association between podoplanin and the risk of malignant transformation of OPL with epithelial dysplasia. Materials and methods: In this retrospective study, podoplanin immunoexpression was analyzed in 58 patients with oral leukoplakia that showed epithelial dysplasia. Lesions with podoplanin expression in the basal and suprabasal layers of oral epithelium at one area or showing suprabasal expression at two or more areas were considered as positive. Association between podoplanin expression and oral can-cer development was analyzed. Results: Twenty-two of the 58 lesions (38%) were classified as podoplanin-positive, and the remaining 36 (62%) lesions were considered podoplanin-negative. The expression of podoplanin was correlated with the grade of dysplasia (p < 0.0005), and with the risk of progression to oral cancer (p < 0.0005). In multivariate survival analysis, only premalignant oral lesions displaying positive podoplanin expression showed a sig-nificantly increased risk of developing an oral squamous cell carcinoma (hazard ratio = 8.738, p = 0.007). Conclusion: Podoplanin could be a valuable biomarker for risk assessment of malignant transformation in patients with OPL along with histological assessment. [ABSTRACT FROM AUTHOR]

Summary: Background: Oral cancer (OC) is the leading cause of death from cancer in men between the ages of 25 and 44 in Taiwan. The survival rate for the last stage of OC is <20% while that for the earliest stage is >75%, which suggests the importance of the diagnosis of oral precancerous lesions (OPLs) in reducing OC mortality. The aim of this study was to analyze the time to OC event after OPL diagnosis, and to suggest the surveillance period necessary according to OPL type. Materials and methods: This was a retrospective cohort study based on 1.0million people randomly selected from the Taiwan National Health Insurance Database, which provided data on 3058 adult male patients aged ⩾20years who were diagnosed with OPL for the first time between 1996 and 2009. The patient population was divided into two groups according to the type of lesion: oral submucous fibrosis (OSF) or oral leukoplakia (OLE). Age-standardized incidence rate (ASIR) and hazards rate (HR) were then estimated. Results: The ASIR for OPL showed an increasing trend over the study period, the main contributor to this being OSF. The OSF group demonstrated a higher OC incidence rate than the OLE group. Conclusion: Patients with both OLE and OSF carry a higher risk for OC than those with either OLE or OSF alone, and they may also experience malignant transformation at an earlier date (mostly within 5years). The 5- and 10-year OC rate for both OLE and OSF was found to be 5% and around 10%, respectively. However, 10years after the diagnosis of OPL, OSF carries a higher risk of developing into OC than OLE. [ABSTRACT FROM AUTHOR]

Summary: Background: Oral leukoplakia is an oral lesion suspected to be of premalignant character. Besides smoking and alcohol, the risk factors for the development of this oral lesion are still less identified. The purpose of this study was the search for a possible influence of periodontitis on the risk of leukoplakia. Methods: We used data from 4233 subjects (2116 women and 2117 men) who were recruited for the population-based Study of Health in Pomerania (SHIP) and finished a standard medical and dental examination. One hundred two-three cases with oral leukoplakia were 1:2 age and sex-matched with 246 healthy control subjects. Measures of bleeding on probing and clinical attachment loss were related to oral leukoplakia. Results: We found increased periodontal measures in subjects with leukoplakia. Adjusting for risk factors and possible confounders revealed a periodontitis-related dose-dependent increase in the probability of having oral leukoplakia. Odds ratios adjusted for socioeconomic factors and smoking computed for the second, third and fourth quartiles of clinical attachment loss were OR=1.7 (0.6–5.0), 3.3 (0.8–13.1) and 5.3 (1.2–22.7), respectively. For bleeding on probing the respective odds ratios were OR=2.0 (0.8–4.90), 2.9 (1.1–7.8) and 3.8 (1.5–9.8), respectively. Measures of systemic inflammation and of lipid metabolism were important cofactors attenuating these figures. While smoking is a risk factor of leukoplakia, oral hygiene is protective. In a follow-up survey, the leukoplakia subjects had lost more teeth than their counterparts (p =0.043). Conclusion: Periodontitis increases the risk of oral leukoplakia and, therefore, the risk of mucosal lesions predisposing to oral cancers. [ABSTRACT FROM AUTHOR]

Summary: Objectives: The early detection of oral cancer improves patient outcomes. However, despite our growing knowledge of oral cancers, patients often present with advanced disease. The development of simple screening methods is desirable to provide an alternative to screening examinations by specialists. Thus, we developed a method of oral cancer detection among exfoliated oral mucosal cells, and we evaluated the feasibility of implementing an oral cancer screening test that is examiner independent. Material and methods: The study population consisted of 185 subjects: 89 with oral cancer, 18 with oral leukoplakia, and 78 controls. We used real-time polymerase chain reaction (PCR) to detect the biomarkers serpin peptidase inhibitor B3 (SCCA1), interleukin 15 (IL-15), and thrombomodulin (THBD). Results: The sensitivities for the detection of oral cancer and oral leukoplakia were 72.0% (77/107) with SCCA1, 75.7% (81/107) with IL-15, and 56.1% (60/107) with THBD, and the specificities were 73.1% (57/78) with SCCA1, 64.1% (50/78) with IL-15, and 78.2% (61/78) with THBD. Analysis of the sensitivity according to tumor size revealed that sensitivity was lower for large tumors. When analyzing the sensitivity according to the clinical growth pattern, the sensitivity was observed to be low for endophytic tumors. Conclusion: We developed an oral cancer screening test based on real-time PCR analysis of SCCA1 that is examiner independent, and the sensitivity and specificity were approximately 70%; therefore, we concluded that the performance of this method using a single biomarker was suboptimal. [ABSTRACT FROM AUTHOR]

Summary: The estimated prevalence of oral leukoplakia is worldwide approximately 2%, with an annual malignant transformation rate of approximately 1%. The aim of the present study was to evaluate the possible contribution of ploidy measurement to the prediction of the clinical course, in a well defined cohort of patients with oral leukoplakia. Ploidy was measured by both flow cytometry (FCM-DNA) and image cytometry (ICM-DNA) and we focussed on the comparison of the two different techniques to determine ploidy. A total of 41 patients have been included, with a mean age of 59years (range 36–78years). With FCM-DNA, three lesions were aneuploid, with ICM-DNA, 19 lesions were aneuploid. DNA ploidy was compared with clinicopathological and patients parameters. There were no statistically significant differences between DNA ploidy and any patient factor with both FCM-DNA and ICM-DNA. Using FCM-DNA, DNA aneuploid lesions showed statistically significant more dysplasia (p =0.04) than diploid lesions. Furthermore, DNA aneuploid lesions were more frequently encountered at high-risk locations (p =0.03) as being determined with FCM-DNA. These relations were not found when DNA ploidy was determined with ICM-DNA. [Copyright &y& Elsevier]

Summary: Differential Path-length Spectroscopy (DPS) was used to non-invasively determine the optical properties of oral leukoplakias in vivo. DPS yields information on microvascular parameters such as the mucosal blood content, the microvascular blood oxygenation and the average micro-vessel diameter as well as on tissue morphological parameters such as the scattering slope and scattering amplitude. DPS measurements were made on non-dysplastic and dysplastic oral leukoplakias using a novel fiber-optic probe, and were correlated to the histological outcome of biopsies taken from the same location. Our data show borderline significant increases in mucosal blood content in dysplastic lesions compared to non-dysplastic lesions, with no changes in microvascular oxygen saturation and light scattering signatures. These results suggest that dysplastic and non-dysplastic leukoplakias may be discriminated non-invasively in vivo through differences in their microvascular properties, if they can be reproducibly quantified in the presence of a variable thickness keratin layer that optically shields the mucosal layer. [Copyright &y& Elsevier]

Summary: Oral leukoplakia is a potentially malignant disorder that will develop into oral cancer at an estimated rate of 1–2% per year. Aim of the present study is to assess the possible predictive value of DNA ploidy for malignant progression of oral leukoplakia. A cohort of 62 leukoplakia patients was studied and their biopsy was examined with standard histopathology and DNA image cytometry. Cox regression analysis was performed to establish the relationship between progression-free survival and the DNA ploidy status. During the follow-up time (median of 69months) 13 patients developed an oral squamous cell carcinoma (OSCC). DNA aneuploidy was observed in 27 (44%) patients and was significantly associated with a shorter progression-free survival [Hazard ratio of 3.7, 95% confidence intervals (CI) of 1.1 and 13.0 and a p-value of 0.04]. Sensitivity and specificity scores were 54% and 60%, respectively. Aneuploidy was not correlated with dysplasia grading (chi-square analysis). DNA aneuploidy in oral leukoplakia is associated with an increased risk of progression to OSCC. However, for the individual leukoplakia patient, DNA ploidy status as single biomarker has limited value to predict progression to cancer. [ABSTRACT FROM AUTHOR]

Summary: The objective of this study was to clarify the expression and epigenetic regulation of DLEC1, a candidate tumor suppressor gene (TSG) located at 3p21.3-p22, in oral squamous cell carcinoma (OSCC) and the clinical relevance of its down-expression. Quantitative RT-PCR was performed to exam the expression level of DLEC1 in matched OSCC and normal oral samples from 57 prospectively enrolled patients (with additional matched leukoplakia samples from 9 patients). We defined DLEC1 down-expression as a 2-fold decrease in expression of DLEC1 between normal tissues and tumors, and determined its correlation with clinical characteristics. Methylation-specific PCR (MSP) and bisulfite sequencing were used to evaluate the promoter methylation status of DLEC1 in 19 OSCC, 19 oral leukoplakia (OL), and 17 normal oral tissues. A statistically significant association between DLEC1 down-expression and invasive depth of OSCC was observed (P =0.026). Besides, expression of DLEC1 decreased sequentially from normal tissues to OL and then to OSCC (P <0.05), which was inversely correlated with methylation status of the DLEC1 promoter. Promoter methylation of DLEC1 increased progressively among normal tissues, OL, and OSCC, as revealed by MSP, and confirmed by sequencing. Treatment of OSCC cell lines with 5-aza-2′-deoxycytidine (5-Aza-dC) reversed the methylation and restored DLEC1 expression. Our results demonstrating that down-expression and promoter methylation of DLEC1 increased from normal tissues to premalignancies and then to malignancies. Furthermore, its transcriptional repression is associated with the depth of tumor invasion. [ABSTRACT FROM AUTHOR]

Summary: Micronuclei (MN) are extensively used as an indicator of chromosomal damage and early biomarker of cancer risk. The genetic host factors are known to influence the level of chromosomal alterations consequently affecting MN frequencies. Hence, in the present study, we investigated the extent of chromosomal damage by analyzing micronucleated cell (MNC) frequency in exfoliated buccal epithelial cells (BEC) and its possible relationship with genetic polymorphisms in patients with oral leukoplakia (OL). The study group comprised of habit-free (NHC, n =39), habit controls (HC, n =62) and OL patients (n =66). Micronucleus assay was carried out to determine the MNC frequency and the genotyping was performed by PCR–RFLP for metabolizing (CYP1A1, GSTM1, GSTT1, GSTP1) and DNA repair (hOGG1, XRCC1, XPD) genes. The correlation between MNC frequency and genetic polymorphisms was analyzed. We found significant increase in overall MNC frequency in OL patients as compared to habit-matched controls (p =0.01). The higher proportion of multiple micronucleated cells (>5 MN per cell) indicate increased DNA damage in the buccal mucosa of OL patients than the controls (p =0.004). The polymorphic alleles of XPD751 and hOGG1 showed significant association with total MNC frequency in OLs (p =0.034 and p =0.03 respectively). In conclusion, the extent of chromosomal damage in target tissues is higher in patients with OL. MNC frequency in combination with genetic polymorphisms in DNA repair genes may serve as better predicator of risk. [ABSTRACT FROM AUTHOR]

Summary: We investigated the prevalence of, and risk factors for, oral potentially malignant disorders (OPMDs) in rural Sri Lanka. A cross-sectional community-based study was conducted by interview and oral examination of 1029 subjects aged over 30years. A community-based nested case-control study then took those with OPMDs as ‘cases’, “controls” being those with no oral abnormalities at time of initial screening. The prevalence of OPMD was 11.3% (95% CI: 9.4–13.2), after weighting for place of residence and gender. Risk factors were betel-quid (BQ) chewing daily [OR=10.6 (95% CI: 3.6–31.0)] and alcohol drinking daily or weekly [OR=3.55 (1.6–8.0)]. A significant dose–response relationship existed for BQ chewing. Smoking did not emerge when adjusted for covariates. A synergistic effect of chewing and alcohol consumption existed. The attributable risk (AR) of daily BQ chewing was 90.6%, the population AR 84%. This study demonstrates high prevalence of OPMD, betel-quid chewing with or without tobacco being the major risk factor. [Copyright &y& Elsevier]

Summary: Oral leukoplakia is defined as a white patch in the oral cavity that cannot be diagnosed as any other known disorder. These lesions carry an increased risk of malignant progression, and approximately 2–3% per year do progress to cancer. At present biopsies are histopathologically graded for dysplasia to assess the risk of progression, but this grading is somewhat subjective and of limited use for the individual patient. In a previous study we discovered by a comprehensive proteomics approach that compared to normal mucosa, protein expression of cornulin, keratin 4 and keratin 13 is decreased in tumors and severe dysplasia, preneoplastic tissue with a high risk of malignant progression. Here, we studied whether loss of expression of these proteins can predict malignant transformation of oral leukoplakia. Biopsies of 12 progressing and 36 non-progressing leukoplakia lesions were analyzed for cornulin, keratin 4 and keratin 13 expression by immunohistochemistry, and graded for dysplasia. Kaplan–Meier analysis showed that loss of expression of neither cornulin (p =0.075), keratin 4 (p =0.789) nor keratin 13 (p =0.732) was significantly associated with malignant transformation of leukoplakia lesions. However, decreased expression of these proteins was significantly associated with the presence of hyperkeratosis. Only dysplasia grading correlated significantly with malignant progression of leukoplakia (p =0.024). Despite the promising outlook that decreased cornulin, keratin 4 and keratin 13 expression in the oral mucosa is associated with a premalignant state, these markers do not predict malignant transformation of leukoplakia lesions. The most likely explanation is that the aberrant differentiation state of hyperkeratotic leukoplakia lesions already causes a decreased expression, obscuring the putative association with malignant transformation. Our results support the significance of dysplasia grading for the prediction of malignant transformation. [Copyright &y& Elsevier]

Summary: ZengShengPing (ZSP), a mixture of six medicinal herbs, has been reported to prevent esophageal squamous cell carcinoma (SCC) in human patients with dysplasia. This study was designed to investigate the chemopreventive effects of ZSP on oral cancer in animal models and human patients. In the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster cheek pouch model, ZSP (6g/kgBW/day by gavage for 10 weeks) significantly reduced the number of visible tumor, the tumor volume, and the incidence of SCC (P <0.01). Two biomarkers associated with cell proliferation, silver stained nucleolar organizer region (AgNOR) and proliferating cell nuclear antigen (PCNA)-labeling index, were also significantly suppressed by ZSP treatment (P <0.01). In the 4-nitroquinoline 1-oxide (4NQO)-induced oro-esophageal cancer model in mice, ZSP (10% in diet) also significantly reduced the incidence of tongue SCC from 55.2% (16/29) to 22.2% (6/27) (P <0.05), and slightly reduced the incidence of esophageal SCC from 34.5% (10/29) to 22.2% (6/27). Furthermore, in a randomized clinical trial on patients with oral leukoplakia, ZSP (4 tablets, 3 times per day for 8–12months) reduced the size of oral lesion in 67.8% (40/59) patients, whereas the placebo was effective in 17% (9/53) patients (P <0.01). Such an effect was associated with significant decrease of AgNOR and PCNA-labeling index. In summary, our studies have demonstrated the chemopreventive effects of ZSP on two animal models of oral cancer, and human patients with oral leukoplakia. [Copyright &y& Elsevier]

Summary: In a recently held WHO workshop it has been recommended to abandon the distinction between potentially malignant lesions and potentially malignant conditions and to use the term potentially malignant disorders instead. Of these disorders, leukoplakia and erythroplakia are the most common ones. These diagnoses are still defined by exclusion of other known white or red lesions. In spite of tremendous progress in the field of molecular biology there is yet no single marker that reliably enables to predict malignant transformation in an individual patient. The general advice is to excise or laser any oral of oropharyngeal leukoplakia/erythroplakia, if feasible, irrespective of the presence or absence of dysplasia. Nevertheless, it is actually unknown whether such removal truly prevents the possible development of a squamous cell carcinoma. At present, oral lichen planus seems to be accepted in the literature as being a potentially malignant disorder, although the risk of malignant transformation is lower than in leukoplakia. There are no means to prevent such event. The efficacy of follow-up of oral lichen planus is questionable. Finally, brief attention has been paid to oral submucous fibrosis, actinic cheilitis, some inherited cancer syndromes and immunodeficiency in relation to cancer predisposition. [Copyright &y& Elsevier]

Objective: Oral potentially malignant disorders have increased the risk of oral squamous cell carcinoma. This study developed a nomogram model to assess the risks of malignant transformation of oral potentially malignant disorders.Materials and Methods: A retrospective analysis of patients diagnosed with oral potentially malignant disorders confirmed by pre-treatment biopsy was performed between 2010 and 2017 at the Peking University Hospital of Stomatology. The candidate risk factors for malignant transformation were screened from clinicopathological variables using Cox and stepwise regression analyses. The nomogram model was constructed based on the regression results and was validated through receiver operating characteristic curves and calibration curves. Decision curve analysis was used to estimate clinical usefulness.Results: A total of 6964 cases of oral potentially malignant disorders were assessed. The malignant transformation rate of oral potentially malignant disorders was 2.00%. Risk factors (age, site, kind of oral potentially malignant disorder, existence of dysplasia and its grade, and other cancers) derived from the regression analyses were entered into the nomogram model. Time-dependent receiver operating characteristic curve, calibration curve, and decision curve analyses showed high levels of predictive value and clinical relevance, although not for all oral potentially malignant disorders.Conclusion: A specific dynamic nomogram could be adopted to predict the malignant transformation of oral potentially malignant disorders and implement interventions. [ABSTRACT FROM AUTHOR]

Summary: Oral leukoplakia is the most prevalent and potentially malignant disorder of the oral mucosa. Previous studies have demonstrated that molecular changes of the WWOX gene (WW-domain containing oxidoreductase), a candidate tumor suppressor gene located at 16q23.3–24.1 that spans FRA16D, the second most common fragile site, are present in several malignant neoplasias, including oral squamous cell carcinoma. In this report, the role of the WWOX gene was investigated in 23 cases of oral leukoplakias. Using nested RT-PCR and immunohistochemistry, altered mRNA transcription and/or reduced Wwox protein expression was observed in 35% of the lesions when compared with normal mucosa. The majority of lesions (4/6) with altered transcripts had a reduction in the expression of Wwox protein. Although normal WWOX expression was found in some lesions with dysplasia, all lesions with WWOX mRNA and/or protein expression showed histological evidence of dysplasia and none of the cases without dysplasia presented this alteration. These results show that the WWOX gene alteration is an early genetic alteration and may contribute to oral carcinogenesis. [Copyright &y& Elsevier]

Summary: c-Jun, one of the components of the transcription factor activating protein-1 (AP-1), is suggested as a factor in malignant progression of oral lesions. c-Jun and other AP-1 components relationships with human papillomavirus (HPV) infection have been investigated, but not yet focusing on oral carcinogenesis. The aim of this study was to verify whether c-Jun immunohistochemical expression is related to HPV DNA detection in oral premalignant and malignant lesions. Fifty cases diagnosed as oral leukoplakias, with different degrees of epithelial dysplasia, and as oral squamous cell carcinomas (OSCC) were submitted to immunohistochemistry to detect c-Jun and to in situ hybridization with signal amplification to assess HPV DNA. It was verified that c-Jun nuclear expression increased according to the degree of dysplasia within the lesion, with the greatest expression in OSCC. The same did not happen concerning HPV infection – a discrete proportional relation was observed in indexes found in leukoplakia with no dysplasia, leukoplakia with dysplasia and OSCC, but statistically insignificant. When separating the group of leukoplakia by degrees of dysplasia, this relation of proportion was not observed. Nevertheless, the overall prevalence of HPV infection was 24% and the high-risk HPV types were the most frequently identified, which does not allow excluding HPV as a risk factor in oral carcinogenesis. When relating c-Jun expression and HPV infection, no statistically significant relationship is observed. Results suggest then that malignant progression mediated by c-Jun is independent of the presence of HPV in oral carcinogenesis. [Copyright &y& Elsevier]

Summary: Early diagnosis of oral squamous cell carcinoma (OSCC) and precursor lesions is an attractive strategy to decrease patient morbidity and mortality, but presently there are no satisfied diagnostic approaches. This study proposed a metabonomics-based diagnostic approach for OSCC and its precancerous lesions, including oral lichen planus (OLP) and oral leukoplakia (OLK). Saliva samples were collected from patients and healthy donors, and HPLC/MS analysis was performed to acquire metabolic profiles. Diagnostic model was then constructed with hierarchical principal component analysis (HPCA) and discriminate analysis algorithms. The results indicate that metabolic profiling can properly describe the pathologic characteristics of OSCC, OLP and OLK. HPCA combined with kernel fisher discriminant analysis achieved 100% accuracy in diagnosis of test samples, which is superior to direct principal component analysis and other modeling algorithms. The metabonomic approach based on the integral investigation of oral metabolites enables the detection of OSCC and precancerous lesions on noninvasive saliva samples. The proposed approach is noninvasive, efficient and low-cost, and it can be developed as a promising method for population-based screening of cancers and precancers in the oral cavity. [Copyright &y& Elsevier]

Summary: On the Chinese mainland, betel quid (BQ) chewing is common in the Hunan and Hainan provinces. The BQ chewing habit in Hunan consists of dried husks and betel nuts, which are sold as industrially packaged, areca nut-based products. In Hainan, the fresh nut is chewed. Tobacco is not added. Reported prevalence of BQ chewing in Hunan province is high (64.5–82.7%). Oral diseases associated with BQ chewing are oral submucous fibrosis (OSF), oral leukoplakia (OL) and oral cancer. Reported prevalence of OSF among BQ chewers ranges from 0.9% to 4.7%. People most commonly affected are between the ages of 30 and 39 years, and 40 and 49 years. The reported prevalence of OL in Hainan ranges from 2.1% to 2.5%. In BQ chewers who also smoke, the reported prevalence is 20.3%. The prevalence of OL in Hunan province ranges from 0.1% to 0.5%. The prevalence of oral cancer among BQ chewers is low, ranging from 0.02% to 0.05%. In cases of OSF, reported prevalence is 2.6% and 1.2%. Presently, data on prevalence of BQ chewing in southern provinces of Mainland China is limited. BQ chewing habits, however, seem to differ between geographic areas. Future case–control studies are necessary to evaluate the risk for oral cancer and other associated oral mucosal diseases resulting from variations in BQ chewing habits. [Copyright &y& Elsevier]