Detection of prognostic biomarkers and application in clustering patients with oral squamous cell carcinoma, according to the risk of relapse

Most head and neck cancers derive from the mucosal epithelium of the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC), accounting for over 600,000 new cases diagnosed per year and of these, more than 300.000 new cases annually are reported to take origin from the surface of the oral mucosa. Current evidence supports that these subsites exhibit distinctive molecular and clinical behaviors, leading to an "anatomical bias" both for research and clinical decision-making. Oral squamous cell carcinoma (OSCC), in particular involving oral tongue (OTSCC) is the most common malignancy of the head and neck region, characterized by a high rate of local and regional recurrences, which strongly decreases patients’ survival rates. The American Joint Committee on Cancer (AJCC) staging system is the standard tool used to classify oncological patients and predict their clinical outcomes. Despite advancements in patients’ prognostic stratification, the 8th edition of AJCC fails to identify patients characterized by early relapse and poor prognosis. Currently, no prognostic biomarkers have been validated to stratify these patients and their risk of recurrence and death. This scenario calls for the investigation of biomarkers from basic research combined with bioinformatics to clinical and routine diagnostic application in a translational pathway. This project aimed to investigate prognostic biomarkers in HNSCC, OSCC and OTSCC, 4 by different approaches, such as reviews and meta-analysis, histopathology, and bioinformatics. This is to highlight possible histopathologic and genetic biomarkers to be integrated in future staging systems in a precision medicine environment. Different histopathologic features were tested, such as tumour budding, eosinophils infiltration, lymph-vascular invasion, perineural invasion, lymphocytes infiltration, and tumour-stroma ratio. This investigation led to the development of promising and easy to be assessed histopathologic biomarkers, such as immune-phenotype, thresholds, and improved staging systems. Furtherly, a new prognostic classification system was developed based on TP53 gene mutations. In conclusion, the heterogeneous background of HNSCC, including OSCC and, OTSCC emerged, and new prognostic biomarkers were proposed to be furtherly evaluated in other cohorts for routine translational application in the aim of precision medicine

Facial scanning technologies in the era of digital workflow: A systematic review and network meta-analysis.

PURPOSE The aim of this network meta-analysis is to evaluate the accuracy of various face-scanning technologies in the market, with respect to the different dimensions of space (x, y, and z axes). Furthermore, attention will be paid to the type of technologies currently used and to the best practices for high-quality scan acquisition. MATERIAL AND METHODS The review was conducted following the PRISMA guidelines and its updates. A thorough search was performed using the digital databases MEDLINE, PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials by entering research lines or various combinations of free words. The main keywords used during the search process were "photogrammetry", "laser scanner", "optical scanner", "3D, and "face". RESULTS None of the included technologies significantly deviated from direct anthropometry. The obtained mean differences in the distances between the considered landmarks range from 1.10 to -1.74 mm. CONCLUSION Limiting the movements of the patient and scanner allows for more accurate facial scans with all the technologies involved. Active technologies such as laser scanners (LS), structured light (SL), and infrared structured light (ISL) have accuracy comparable to that of static stereophotogrammetry while being more cost-effective and less time-consuming

Oral Mucosa and Nails in Genodermatoses: A Diagnostic Challenge

Genodermatoses represent a group of uncommon, hereditary, single-gene skin disorders, characterized by multisystem involvement, heterogeneous clinical manifestations and different degrees of morbidity and mortality. Some genodermatoses may have oral mucosa and nail involvement, since the oral cavity and cutaneous organ system, including nails, share a close embryologic origin. Nail disorders can manifest with nail hypoplasia or nail hypertrophy. Clinical pictures of affected oral mucosa can be extremely heterogeneous, ranging from asymptomatic papules to painful blisters, leukokeratosis, oral papillomas and fibromas to oral potentially malignant disorders and cancerous lesions. Oral mucosa and nails pathological features may occur synchronously or not and are usually associated with other systemic and skin manifestations. In some cases, oral mucosa and nails diseases may be distinct and constitute the principal sign of the genetic disorder, in other cases they represent only a part of the puzzle for the confirmation of the diagnosis. Continued awareness of the correlation between oral mucosa and nails findings can help physicians to diagnose genodermatosis in a timely manner, allowing more effective clinical management and prevention and/or early detection of complications. This article provides an overview of all specific genodermatoses affecting both oral mucosa and nails. Moreover, the correlation between teeth and nails is summarized in tabular form

Predictive value of CDKN2A/p16INK4a expression in the malignant transformation of oral potentially malignant disorders: Systematic review and meta-analysis

[Abstract] Background: Management of oral potentially malignant disorders (OPMDs) is still challenging. Despite the diagnostic ascertainment by bioptic examination, this method is poorly informative of the prognosis and subsequent malignant transformation. Prognosis is based on histological findings by grading of dysplasia. Immunohistochemical expression of p16INK4a has been investigated in different studies, with controversial results. In this scenario, we systematically revised the current evidence about p16INK4a immunohistochemical expression and the risk of malignization of OPMDs. Material and methods: After a proper set of keywords combination, 5 databases were accessed and screened to select eligible studies. The protocol was previously registered on PROSPERO (Protocol ID: CRD42022355931). Data were obtained directly from the primary studies as a measure to determine the relationship between CDKN2A/P16INK4a expression and the malignant transformation of OPMDs. Heterogeneity and publication bias were investigated by different tools, such as Cochran’s Q test, Galbraith plot and Egger and Begg Mazumdar’s rank tests. Results: Meta-analysis revealed a twofold increased risk to malignant development (RR = 2.01, 95% CI = 1.36–2.96 - I2 = 0%). Subgroup analysis did not highlight any relevant heterogeneity. Galbraith plot showed that no individual study could be considered as an important outlier. Conclusion: Pooled analysis showed that p16INK4a assessment may arise adjunct tool to dysplasia grading, leading to an optimized determination of the potential progression to cancer of OPMDs. The p16INK4a overexpression analysis by immunohistochemistry techniques has a multitude of virtues that may facilitate its incorporation in the day-to-day prognostic study of OPMDs

Predictive value of CDKN2A/p16INK4a expression in the malignant transformation of oral potentially malignant disorders: Systematic review and meta-analysis

Background Management of oral potentially malignant disorders (OPMDs) is still challenging. Despite the diagnostic ascertainment by bioptic examination, this method is poorly informative of the prognosis and subsequent malignant transformation. Prognosis is based on histological findings by grading of dysplasia. Immunohistochemical expression of p16INK4a has been investigated in different studies, with controversial results. In this scenario, we systematically revised the current evidence about p16INK4a immunohistochemical expression and the risk of malignization of OPMDs. Material and methods After a proper set of keywords combination, 5 databases were accessed and screened to select eligible studies. The protocol was previously registered on PROSPERO (Protocol ID: CRD42022355931). Data were obtained directly from the primary studies as a measure to determine the relationship between CDKN2A/P16INK4a expression and the malignant transformation of OPMDs. Heterogeneity and publication bias were investigated by different tools, such as Cochran's Q test, Galbraith plot and Egger and Begg Mazumdar’s rank tests. Results Meta-analysis revealed a twofold increased risk to malignant development (RR = 2.01, 95% CI = 1.36–2.96 - I2 = 0%). Subgroup analysis did not highlight any relevant heterogeneity. Galbraith plot showed that no individual study could be considered as an important outlier. Conclusion Pooled analysis showed that p16INK4a assessment may arise adjunct tool to dysplasia grading, leading to an optimized determination of the potential progression to cancer of OPMDs. The p16INK4a overexpression analysis by immunohistochemistry techniques has a multitude of virtues that may facilitate its incorporation in the day-to-day prognostic study of OPMDsS

Oral lichen planus in children: An Italian case series

Oral lichen planus usually occurs in adults; there are no clear data regarding the incidence and the clinical features of oral lichen planus in children. This paper reports clinical findings, treatments, and outcomes of 13 Italian patients with oral lichen planus in childhood diagnosed between 2001 and 2021. The most common finding was keratotic lesions with reticular or papular/plaque-like patterns, confined to the tongue in seven patients. Although oral lichen planus in childhood is rare and the malignant transformation index is unknown, specialists must be aware of its characteristics and oral mucosal lesions must be correctly diagnosed and managed

Pyrosequencing analysis of O-6-methylguanine-DNA methyltransferase methylation at different cut-offs of positivity associated with treatment response and disease-specific survival in Isocitrate Dehydrogenase-wildtype grade 4 glioblastoma

The O-6-methylguanine-DNA methyltransferase (MGMT) gene is a critical guardian of genomic integrity. MGMT methylation in diffuse gliomas serves as an important determinant of patients’ prognostic outcomes, more specifically in glioblastomas (GBMs). In GBMs, the absence of MGMT methylation, known as MGMT promoter unmethylation, often translates into a more challenging clinical scenario, tending to present resistance to chemotherapy and a worse prognosis. A pyrosequencing (PSQ) technique was used to analyze MGMT methylation status at different cut-offs (5%, 9%, and 11%) in a sample of 78 patients diagnosed with IDH-wildtype grade 4 GBM. A retrospective analysis was provided to collect clinicopathological and prognostic data. A statistical analysis was used to establish an association between methylation status and treatment response (TR) and disease-specific survival (DSS). The patients with methylated MGMT status experienced progressive disease rates of 84.6%, 80%, and 78.4% at the respective cut-offs of 5%, 9%, and 11%. The number was considerably higher when considering unmethylated patients, as all patients (100%), regardless of the cut-off, presented progressive disease. Regarding disease-specific survival (DSS), the Hazard Ratio (HR) was HR = 0.74 (0.45–1.24; p = 0.251); HR = 0.82 (0.51–1.33; p = 0.425); and HR = 0.79 (0.49–1.29; p = 0.350), respectively. Our study concludes that there is an association between MGMT unmethylation and worse TR and DSS. The 9% cut-off demonstrated a greater potential for patient survival as a function of time, which may shed light on the future need for standardization of MGMT methylation positivity parameters in PSQ

Salivary biomarkers in burning mouth syndrome: A systematic review and meta-analysis

The objective of this systematic review was to evaluate which salivary biomarkers are altered in patients with burning mouth syndrome (BMS) compared to a control group (CG). A comprehensive literature search was conducted in four databases. Case– control studies evaluating salivary biomarkers in BMS patients were included. Risk of bias was assessed using the Newcastle-Ottawa tool. RevMan was used for metaanalysis. Seventeen studies were selected. The included studies collected 54 different biomarkers. Of these biomarkers, only three (cortisol, α-amylase, and dehydroepiandrosterone) were analyzed in three or more studies. Dehydroepiandrosterone obtained contradictory results among the studies. However, cortisol and α-amylase levels were found to be higher in BMS patients. Cortisol was the only biomarker which could be included for meta-analysis. Cortisol levels were significantly higher in the BMS group compared to the CG (Mean Difference = 0.39; 95% CI [0.14–0.65]; p = 0.003). In conclusion, different studies investigated salivary biomarkers in patients with BMS compared to a CG, with controversial results. Meta-analysis, confirmed by trial-sequential analysis, showed how cortisol levels were significantly higher in BMS. Cortisol emerges as an interesting salivary biomarker in BMS, but future properly designed studies are needed to evaluate its role in diagnosis and/or response to treatment