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Simple Summary: In Sri Lanka, the authors are encouraging a cost-effective way to reduce the number of people developing oral cancer, which is a common cancer among men. The authors wanted to find out how well dentists can find signs of oral cancer and potential problems in their patients, and they did this by asking dentists questions in an online survey. Surprisingly, most of the dentists thought it would be better to only check people who are at a higher risk for oral cancer instead of checking everyone. Only about two thirds of the dentists regularly look for signs of oral cancer when people come for dental check-ups. The authors found that these dentists, on average, had noticed about 34 patients with concerning signs in the past year. Almost all the dentists believed that they needed more training to spot these problems. So, while opportunistic screening at the dentist's office is good, dental professionals also need to focus on other ways to prevent oral cancer, like checking high-risk groups and giving dentists more confidence to spot potential issues. In Sri Lanka, opportunistic screening is encouraged as a cost-effective tool to bring down the prevalence of oral cancer, which is the most common cancer among males. The objectives of the study were to determine the practices, attitudes, and level of competency of dental surgeons regarding the early detection of oral cancer and oral potentially malignant disorders (OPMDs) through opportunistic screening. A prospective study was conducted online via a Google form using a pretested, self-administered questionnaire of 22 close-ended questions and 3 open-ended questions. Out of the 137 dental surgeons who responded, 88% (121/137) of the participants believed that screening high-risk target groups would be more effective in the early detection of oral cancer rather than opportunistic screening. Only 64% (88/137) of the participants frequently check for oral cancer and OPMDs when patients visit for dental treatment. Participants recalled an average of 34 patients (4628/137) with clinically suspicious lesions being diagnosed during examination at general dental practice during the past year, and 98% (134/137) of the participants believed that they should receive additional training in order to identify and diagnose clinically suspicious OPMDs and oral cancer. Opportunistic screening in general dental practice as an oral-cancer prevention strategy is appreciable, but due emphasis should be given to other prevention strategies such as population screening and screening high-risk target groups. The level of confidence of general dental practitioners in the early detection of oral cancer has to be raised in order to achieve higher standards in oral cancer prevention through opportunistic screening. [ABSTRACT FROM AUTHOR]

Simple Summary: Early diagnosis of potentially malignant oral disorders (OPMD) is crucial in reducing oral cancer mortality. It is necessary to investigate and identify predictive biomarkers capable of estimating the risk of malignant transformation in potentially malignant oral lesions. In this study, we analyzed a panel of salivary markers, including adenosine deaminase (ADA), ferritin (FRR) and total protein (TP). We found no significant differences in salivary ADA between the OPMD group and controls. However, we did observe statistically significant differences in ferritin and total proteins when compared to the control group. Therefore, ferritin and total proteins may serve as potential salivary biomarkers for diagnosis. Furthermore, saliva tests are a reliable and non-invasive diagnostic tool, offering an intriguing alternative for screening large populations. Nevertheless, validation through extensive clinical studies is required. Introduction: Oral potentially malignant disorders (OPMD) are lesions associated with an increased risk of transformation (MT) into cancer. Objective: A study was made of the salivary levels of adenosine deaminase (ADA), ferritin (FRR) and total proteins (TP) in healthy individuals and in patients with oral potentially malignant disorders (OPMD), assessing the potential role of saliva as a diagnostic tool. Methods: A total of 91 subjects participated in the study, divided into two groups—59 patients with OPMD (oral leukoplakia or oral lichen planus) and 32 healthy controls—with measurements being made of salivary ADA, ferritin (FRR) and total proteins (TP). Results: There were no significant differences in salivary mean ADA between the OPMD group 0.85 ± 2.18 UI/I and the controls 0.71 ± 1.72 UI/I (p = 0.934), though the levels of both FRR mean OPMD, 12.66 ± 10.50 (µg/L), versus control, 7.19 ± 4.44 (p = 0.001), and TP, 23.41 ± 17, versus control, 14.15 ± 15.19, were significantly higher in the OPMD group (p = 0.001). Patients with oral lichen planus showed significant differences in terms of FRR (p = 0.009) and TP (p = 0.003). The ferritin in LPO with a cut-off point of 8.5C showed a sensitivity and specificity of 54.3% and 82.3, respectively. The area under the curve (AUC) was 0.69 (95% confidence interval (95% CI): 0.58–0.82; p = 0.003). Conclusions: Ferritin and total proteins may constitute potential salivary biomarkers for oral lichen planus, though further studies are still needed in this field. In addition, saliva testing is a reliable and noninvasive diagnostic tool and appears to be a reliable strategy offering an interesting alternative for the screening of large populations. [ABSTRACT FROM AUTHOR]

Simple Summary: The study was the first to screen seven genes and identify the set of genes using twelve machine learning algorithms that predict the progression from oral leukoplakia to oral squamous cell carcinoma. We verified these genes by RT-qPCR experiments and speculated on the possible molecular mechanisms through the results. These genes could be used as biomarkers for early diagnosis and predicting patients with a high risk of malignant transformation. This will aid in early intervention, improve the patient prognosis, and reduce the incidences of oral squamous cell carcinoma. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: The treatment of oral potentially malignant disorders (OPMDs), including oral leukoplakia (OL), is controversial. Medical interventions currently used to prevent malignant transformation in OL include surgical treatment, photodynamic therapy, and chemotherapy. The main advantages of laser surgery are the selective removal of the lesion, minimal damage to surrounding healthy tissue, and excellent postoperative wound healing. However, no treatment has been shown to prevent recurrence or significantly reduce malignant development in long-term follow-up studies, so further research is needed to identify possible risk factors. Aim: The aim of this study is to assess the efficacy of CO2 laser treatment in oral leukoplakia and to analyse the recurrence rate of oral leukoplakia lesions at 18-month follow-up. Materials and methods: A prospective clinical study regarding CO2 laser treatment for oral leukoplakia was conducted, in which 39 patients with a total of 53 oral leukoplakias were included. Follow-up was performed at 18 months post-surgery and the following variables were studied: sex, age, associated risk factors, clinical classification, size, location and presence of epithelial dysplasia, recurrence, and rate of malignant transformation after resection. Results: In the analysis of the final results 18 months after baseline, a treatment success rate of 43.75% was observed. Oral leukoplakia recurred in 54.17% of cases, and 2.08% of leukoplakias progressed to cancer. Among all the studied variables (age, tobacco use, size, location, clinical type or histology), no significant differences were found with regard to recurrence. Conclusion: The use of CO2 laser therapy to treat leukoplakia lesions is sufficient to remove such lesions. However, parameters that can assess recurrence need to be sought. [ABSTRACT FROM AUTHOR]

Simple Summary: Dysplasia grade identification is the only consolidated factor by which to evaluate the risk of developing oral cancer from oral leukoplakia lesions. An objective manner to determine dysplasia grade is still lacking and this has prompted our research. Our findings can help dentists and pathologists to predict oral leukoplakia prognosis with a non-invasive, easy-to-use tool, using the fractal dimension as invariant. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cavity is the most common site of head and neck cancer which is ranked as the eighth most common cancer worldwide. Oral cancer treatment is often associated with significant morbidity and is sometimes ineffective. These cancers, mainly due to tobacco and alcohol consumption, can develop from oral potentially malignant disorders, the most common of which is oral leukoplakia. Some of these oral potentially malignant disorders disappear, while others will transform to oral cancer. Patients may also develop cancer in the field of cancerization. Unfortunately, except for the surgical excision of lesions with dysplasia, there is no effective intervention to effectively prevent transformation or cancer development in the field of cancerization. Moreover, no standardized biomarker has been clearly identified as sufficient to predict malignant transformation. In this article, several experts discuss the main challenges in oral cancer prevention, in particular the need (i) to define new a new classification system integrating cellular and molecular features aiming (ii) at better identifying patients at high risk of malignant transformation, and (iii) at developing treatment strategies to prevent their malignant transformation of oral potentially malignant disorders. Oral potentially malignant disorders (OPMD) may precede oral squamous cell carcinoma (OSCC). Reported rates of malignant transformation of OPMD range from 3 to 50%. While some clinical, histological, and molecular factors have been associated with a high-risk OPMD, they are, to date, insufficiently accurate for treatment decision-making. Moreover, this range highlights differences in the clinical definition of OPMD, variation in follow-up periods, and molecular and biological heterogeneity of OPMD. Finally, while treatment of OPMD may improve outcome, standard therapy has been shown to be ineffective to prevent OSCC development in patients with OPMD. In this perspective paper, several experts discuss the main challenges in oral cancer prevention, in particular the need to (i) to define an OPMD classification system by integrating new pathological and molecular characteristics, aiming (ii) to better identify OPMD at high risk of malignant transformation, and (iii) to develop treatment strategies to eradicate OPMD or prevent malignant transformation. [ABSTRACT FROM AUTHOR]

Cancers of the head and neck region are among the leading causes of cancer-related mortalities worldwide. Oral leukoplakia and erythroplakia are identified as precursor lesions to malignancy. Patients cured of an initial primary head and neck cancer are also susceptible to developing second primary tumors due to cancerization of their mucosal field. Multi-step acquisition of genetic mutations leading to tumorigenesis and development of invasive cancer has been previously described. Recently, whole exome sequencing of tumor specimens has helped to identify driver mutations in this disease. For these reasons, chemoprevention or the use of systemic or biologic agents to prevent carcinogenesis is an attractive concept in head and neck cancers. Nonetheless, despite extensive clinical research in this field over the past couple decades, no standard of care option has emerged. This review article reports on targeted interventions that have been attempted in clinical trials to date, and focuses on novel molecular pathways and drugs in development that are worthy of being tested for this indication as part of future endeavors. [ABSTRACT FROM AUTHOR]

Simple Summary: Mouth cancer is the most common malignancy in the head-and-neck region. Usually, these tumors develop from white lesions in the mouth that appear long before cancer diagnosis. However, platforms that can estimate the time-factored risk of cancer occurring from these diseases and guide treatment and monitoring approaches are elusive. To this end, our study presents time-to-event models that are based on machine learning for prediction of the risk of malignancy from oral white lesions following pathological diagnosis as a function of time. These models displayed very satisfactory discrimination and calibration after multiple tests. To facilitate their preliminary use in clinical practice and further validation, we created a website supporting the use of these models to aid decision making. Machine-intelligence platforms for the prediction of the probability of malignant transformation of oral potentially malignant disorders are required as adjunctive decision-making platforms in contemporary clinical practice. This study utilized time-to-event learning models to predict malignant transformation in oral leukoplakia and oral lichenoid lesions. A total of 1098 patients with oral white lesions from two institutions were included in this study. In all, 26 features available from electronic health records were used to train four learning algorithms—Cox-Time, DeepHit, DeepSurv, random survival forest (RSF)—and one standard statistical method—Cox proportional hazards model. Discriminatory performance, calibration of survival estimates, and model stability were assessed using a concordance index (c-index), integrated Brier score (IBS), and standard deviation of the averaged c-index and IBS following training cross-validation. This study found that DeepSurv (c-index: 0.95, IBS: 0.04) and RSF (c-index: 0.91, IBS: 0.03) were the two outperforming models based on discrimination and calibration following internal validation. However, DeepSurv was more stable than RSF upon cross-validation. External validation confirmed the utility of DeepSurv for discrimination (c-index—0.82 vs. 0.73) and RSF for individual survival estimates (0.18 vs. 0.03). We deployed the DeepSurv model to encourage incipient application in clinical practice. Overall, time-to-event models are successful in predicting the malignant transformation of oral leukoplakia and oral lichenoid lesions. [ABSTRACT FROM AUTHOR]

Simple Summary: One way to facilitate the detection of early malignant transformation processes in oral potentially malignant disorders, including oral leukoplakia, involves the parallel evaluation of tissue and saliva biomarkers, as such indicators may elucidate both protein CD44 expression in leukoplakia tissue and its soluble form and total protein detection in saliva. We concluded that the OncAlert® Oral Cancer Rapid test is a non-invasive and simple but only screening method which can complement clinical diagnostics methods in daily clinical practice when considering oral leukoplakia, most importantly, in order to obtain information about the potential for early malignancy. The aim of this study was to determine whether and how pan-CD44 protein expression in leukoplakia tissues correlates with positive SolCD44 test presence and their role in oral leukoplakia. SolCD44 and total protein expression in saliva were determined using an OncAlert® Oral Cancer Rapid test. Comparison of paired associations of total protein, SolCD44, mean number of CD44 expressed epithelial layers in leukoplakia tissue, and macrophages below the basement membrane between control group and patients with leukoplakia showed statistically significant results (p < 0.0001). It is shown that the total protein indicates low or elevated risk of possible malignant transformation processes in leukoplakia. Statistically significant differences between higher total protein level and clinical forms of oral leukoplakia (p < 0.0001), as well as CD44-labeled epithelial cell layer decrease (p < 0.0001), were found. This possibly points to the onset of the stemness loss in leukoplakia tissue. CD9 antigen expression in the exosomes of the oral epithelium explained the intercellular flow of SolCD44 and other fluids in the leukoplakia area. We conclude that the OncAlert® Oral Cancer Rapid test is a valuable screening method in daily clinical practice, in terms of complementing clinical diagnostics methods and to assess the potential for early malignancy. [ABSTRACT FROM AUTHOR]

Simple Summary: Proliferative verrucous leukoplakia is considered by the WHO as an oral potentially malignant disorder that presents the highest tendency to recurrence and malignant transformation rate. However, to date limited evidence-based prognostic data for oral carcinomas developed in patients with proliferative verrucous leukoplakia (PVL-OC) have been published, and these carcinomas probably perform better than conventional oral carcinomas. In this study we present a systematic review and meta-analysis to evaluate the current evidence in relation to the prognosis of oral carcinomas developed in patients PVL-OC. Proliferative verrucous leukoplakia (PVL) is contemplated by the World Health Organization (WHO) as an oral potentially malignant disorder (OPMD) with a high the highest malignant transformation ratio among all OPMD (approximately 50%). Our aim was to evaluate the current evidence in relation to the prognosis of oral carcinoma developed in patients with proliferative verrucous leukoplakia (PVL-OC). We searched PubMed, Embase, Web of Science and Scopus for published studies (upper date limit = June 2021). We evaluated the quality of studies (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. 23 studies met inclusion criteria (505 patients with PVL, of which 288 developed a total of 504 carcinomas). The meta-analyzed overall mortality rate was 21.29% (pooled proportions [PP] = 95% confidence intervals [CI] = 8.77–36.36) for PVL-OC, clearly lower than the 34.7–50% mortality rate for conventional oral cancer reported in previous studies. In comparison with a single study reporting on conventional oral cancers, mortality was significantly lower for PVL-OC (hazard ratio = 0.29 [95%CI = 0.10–0.89], p = 0.03). Univariable meta-regression verified that case series that presented higher proportions of verrucous carcinomas showed a better survival of PVL-OC (p = 0.05), but not with higher proportion of oral squamous cell carcinomas (p = 0.74). Significant differences were not found for other relevant variables such as follow up period (p = 0.44) or multiple tumor development (p = 0.74). In conclusion, PVL-OC show favorable prognostic parameters, especially with regard to the mortality rate. [ABSTRACT FROM AUTHOR]

Simple Summary: Interactions of metallothioneins with the multiligand receptor megalin have been found to promote cell survival and proliferation after noxious stimuli in non-malignant tissues. However, the relationship between these proteins and their interaction remains to be addressed in malignancies and premalignant lesions. In this retrospective study, we compared the expression profiles of metallothioneins and megalin in different histological grades of oral squamous cell carcinoma, oral leukoplakia, and oral lichen planus. The data obtained show a gradual increase of both proteins concomitantly with the gaining of more malignant features, as well as their co-expression and direct interaction in carcinomatous tissue. The results point to the pro-oncogenic role of the metallothionein-megalin functional axis, which may impact tumor phenotype and behavior. This study aimed to assess the relationship and possible interactions between metallothioneins (MTs) and megalin (LRP-2) in different grades of oral squamous cell carcinoma (OSCC) and premalignant lesions of the oral mucosa (oral leukoplakia and oral lichen planus). The study included archived samples of 114 patients and control subjects. Protein expression was examined by immunohistochemistry and immunofluorescence, and staining quantification was performed by ImageJ software. Protein interaction in cancer tissue was tested and visualized by proximity ligation assay. Mann-Whitney and Kruskal-Wallis tests were used to determine the significance of differences between each group, whereas Pearson correlation coefficient was performed to test correlation. Expression of both proteins differed significantly between each group showing the same pattern of gradual increasing from oral lichen planus to poorly differentiated OSCC. Moreover, MTs and megalin were found to co-express and interact in cancer tissue, and their expression positively correlated within the overall study group. Findings of prominent nuclear and chromosomal megalin expression suggest that it undergoes regulated intramembrane proteolysis upon MTs binding, indicating its ability to directly affect gene expression and cellular division in cancer tissue. The data obtained point to the onco-driving potential of MTs-megalin interaction. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this narrative review is to better understand the role of the oral microbiota in oral cavity leukoplakia. We provide a comprehensive review, exhaustively summarizing the steps taken in this field. We reviewed the current published literature on the impact of oral microbiota on oral cavity leukoplakia (OLK), aiming at clarifying its role in disease transformation. The analysis unveiled that bacterial richness and diversity in the oral cavity tend to be decreased in OLK compared to healthy controls, with a reduction in the prevalent commensals, such as Streptococci, and elevation of anaerobes. Moreover, Fusobacterium nucleatum, Porphyromonas gingivalis and Prevotella intermedia are recurrent findings, and they already have been linked to periodontal disease. These microbial community changes may also represent a marker for the transition from OLK to oral squamous cell carcinoma. Unfortunately, the reviewed studies present several limitations, making an objective comparison difficult. To overcome these biases, longitudinal studies are necessary. [ABSTRACT FROM AUTHOR]

Background: Our goal was to identify a gene-expression-based surrogate of genomic instability (GI) associated with the transformation of oral potentially malignant disorder (OPMD) into oral squamous cell carcinoma (OSCC)., Methods: GI was defined as the fraction of genome altered (FGA). Training sets included the CCLE and TCGA databases. The relevance of the enrichment score of the top correlated genes, referred to as the GIN score, was evaluated in eight independent public datasets from the GEO repository, including a cohort of patients with OPMD with available outcome., Results: A set of 20 genes correlated with FGA in head and neck SCC were identified. A significant correlation was found between the 20-gene based GIN score and FGA in 95 esophagus SCC (r = 0.59) and 501 lung SCC (r = 0.63), and in 33 OPMD/OSCC (r = 0.38). A significantly increased GIN score was observed at different stages of oral carcinogenesis (normal-dysplasia -OSCC) in five independent datasets. The GIN score was higher in 10 OPMD that transformed into oral cancer compared to 10 nontransforming OPMD ( p = 0.0288), and was associated with oral-cancer-free survival in 86 patients with OPMD ( p = 0.0081)., Conclusions: The GIN score is a gene-expression surrogate of GI, and is associated with oral carcinogenesis and OPMD malignant transformation.

Simple Summary: Proliferative verrucous leukoplakia (PVL) was recognized in 2005 by the World Health Organization as a rare subtype of true oral leukoplakia, with unknown etiology. Since its first description in 1985, several diagnostic criteria have been proposed over the years. The aim of this systematic review is to investigate the percentage of patients diagnosed with proliferative verrucous leukoplakia who progressed to oral verrucous carcinoma (OVC) or conventional oral squamous cell carcinoma (OSCC). Aim: The aim of the present systematic review was to investigate the risk of malignant transformation of proliferative verrucous leukoplakia (PVL). Materials and Methods: the search was carried out using a combination of terms (leukoplakia OR leucoplakia) AND (multifocal OR proliferative) on the following databases: PubMed, Scopus, Web of Science (WOS Core Collection), Cochrane Library, selecting only articles published since 1985 and in the English language. Demographic, disease-related, and follow-up data extracted from the studies included in the qualitative synthesis were combined. Weighted means ± standard deviations were calculated for continuous variables, while categorical variables were reported as frequencies and percentages. Dichotomous outcomes were expressed as odd ratios (ORs) with 95% confidence intervals (CIs). Odd ratios for individual studies were combined using a random-effects meta-analysis, conducted using Review Manager 5.4 Software (Cochrane Community, Oxford, England). Results: twenty-two articles were included, with a total of 699 PVL patients, undergoing a mean follow-up of 7.2 years. Sixty-six percent of patients were females, with a mean age of 70.2 years, and 33.3% were males, with a mean age of 59.6 years. Most patients were non-smokers and non-alcohol users, and the gingiva/alveolar ridge mucosa was the most involved anatomical site by both PVL appearance and malignant transformation. A total of 320 PVL patients developed oral verrucous carcinoma (OVC) or conventional oral squamous cell carcinoma (OSCC) because of malignant transformation of PVL lesions (45.8%). A statistically significant 3.8-fold higher risk of progression to conventional OSCC was found compared to OVC in PVL patients, with women being 1.7 times more likely to develop oral cancer than men, as a consequence of PVL progression. Moreover, a statistically significant higher likelihood of developing conventional OSCC in female PVL patients than in males was found. In 46.5% of patients with PVL malignant transformation, multiple carcinomas, in different oral sites, occurred during follow-up. Conclusions: PVL is an aggressive lesion, which, in a high percentage of cases (almost 50%), undergoes malignant transformation, mainly toward OSCC. The female gender is most affected, especially in the elderly, with a negative history for alcohol and tobacco consumption. [ABSTRACT FROM AUTHOR]

Simple Summary: Proliferative verrucous leukoplakia is considered as an oral potentially malignant disorder that presents the highest tendency to recurrence and malignant transformation, alt-hough published diagnostic criteria are inconsistent. A precise evidence-based diagnosis is im-portant to differentiate this lesion from others on the oral mucosa with less tendency for cancer progression, and thus establish specific management protocols aimed at the early diagnosis of oral cancer. In this scoping review the published conceptual and diagnostic criteria for prolifera-tive verrucous leukoplakia were comprehensively analyzed, and a conceptual proposal for fu-ture diagnosis is proposed based on current evidence. Proliferative verrucous leukoplakia (PVL) is considered as an oral potentially malignant disorder (OPMD) that presents with a high tendency to recurrence after treatment and has the highest malignant transformation ratio among all OPMD (50%). Evidence-based publications have indicated that the malignant evolution reported is significantly related to the inconsistent diagnostic criteria used in primary-level studies; so, it has been hypothesized that the risk of oral cancer for this disease could even be underestimated. This is important because PVL requires specific management protocols, evidence-based, aimed at the early diagnosis of cancer developing in these lesions. We present a scoping review—a novel approach to mapping the available literature on a given topic to provide an overview of the available research evidence and to highlight possible gaps in the evidence—especially related in our study to the diagnostic aspects of PVL, and to issue a conceptual proposal and diagnostic criteria for PVL. We conclude that PVL is a white, multifocal and progressive lesion with a high malignant transformation rate which is diagnosed mainly around the age of 60 years without any specific histological characterization. We also advise a personal reflection on the level of certainty with which the clinician makes the diagnosis of a particular case of PVL. [ABSTRACT FROM AUTHOR]

Background: The endoscopic appearance of glottic erythroleukoplakias is non-predictive of their histopathology, potentially ranging from keratosis to invasive squamous cell carcinoma (SCC). The aim of this study was to assess a comprehensive workup for the one-step diagnosis and treatment of mid-cord erythroleukoplakias, using CO2 laser excisional biopsy. Methods: We evaluated 147 untreated patients affected by 155 mid-cord erythroleukoplakias submitted to excisional biopsy by subepithelial (Type I) or subligamental cordectomy (Type II), across two academic institutions. Patients were evaluated by preoperative videolaryngostroboscopy, pre- and intraoperative videoendoscopy with biologic endoscopy (narrow band imaging, NBI, or the Storz professional image enhancement system, SPIES), either with or without intraoperative saline infusion into the Reinke's space. Adequacy of treatment was the primary outcome. Results: The histopathologic diagnosis was keratosis in 26 (17%) cases, squamous intraepithelial neoplasia (SIN1-2) in 47 (30%), carcinoma in situ in 21 (14%), and SCC in 61 (39%) patients. The adequacy of treatment across the entire cohort was 89%. The intraoperative saline infusion procedure, facing not clearly suspicious lesions, raised the adequacy of treatment from 60% to 90% (p = 0.006). Conclusions: Excisional biopsy by Type I–II cordectomies, after a comprehensive diagnostic workup, should be accepted as an adequate and cost-effective treatment of unilateral mid-cord glottic erythroleukoplakias. [ABSTRACT FROM AUTHOR]

Photobiomodulation therapy (PBMT) is an effective treatment modality, which has the significant advantage of enhancing a patient's quality of life (QoL) by minimising the side effects of oral cancer treatments, as well as assisting in the management of potentially cancerous lesions. It is important to note that the major evidence-based documentation neither considers, nor tackles, the issues related to the impact of PBMT on tumour progression and on the downregulation of cellular proliferation improvement, by identifying the dose- and time-dependency. Moreover, little is known about the risk of this therapy and its safety when it is applied to the tumour, or the impact on the factor of QoL. The review aimed to address the benefits and limitations of PBMT in premalignant oral lesions, as well as the conflicting evidence concerning the relationship between tumour cell proliferation and the applied dose of photonic energy (fluence) in treating oral mucositis induced by head and neck cancer (H&N) treatments. The objective was to appraise the current concept of PBMT safety in the long-term, along with its latent impact on tumour reaction. This review highlighted the gap in the literature and broaden the knowledge of the current clinical evidence-based practice, and effectiveness, of PBMT in H&N oncology patients. As a result, the authors concluded that PBMT is a promising treatment modality. However, due to the heterogeneity of our data, it needs to undergo further testing in well-designed, long-term and randomised controlled trial studies, to evaluate it with diligent and impartial outcomes, and ensure laser irradiation's safety at the tumour site. [ABSTRACT FROM AUTHOR]

The interleukin-3 receptor alpha chain (IL-3Rα), more commonly referred to as CD123, is widely overexpressed in various hematological malignancies, including acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia, hairy cell leukemia, Hodgkin lymphoma and particularly, blastic plasmacytoid dendritic neoplasm (BPDCN). Importantly, CD123 is expressed at both the level of leukemic stem cells (LSCs) and more differentiated leukemic blasts, which makes CD123 an attractive therapeutic target. Various agents have been developed as drugs able to target CD123 on malignant leukemic cells and on the normal counterpart. Tagraxofusp (SL401, Stemline Therapeutics), a recombinant protein composed of a truncated diphtheria toxin payload fused to IL-3, was approved for use in patients with BPDCN in December of 2018 and showed some clinical activity in AML. Different monoclonal antibodies directed against CD123 are under evaluation as antileukemic drugs, showing promising results either for the treatment of AML minimal residual disease or of relapsing/refractory AML or BPDCN. Finally, recent studies are exploring T cell expressing CD123 chimeric antigen receptor-modified T-cells (CAR T) as a new immunotherapy for the treatment of refractory/relapsing AML and BPDCN. In December of 2018, MB-102 CD123 CAR T developed by Mustang Bio Inc. received the Orphan Drug Designation for the treatment of BPDCN. In conclusion, these recent studies strongly support CD123 as an important therapeutic target for the treatment of BPDCN, while a possible in the treatment of AML and other hematological malignancies will have to be evaluated by in the ongoing clinical studies. [ABSTRACT FROM AUTHOR]