Efficacy of topical agents in oral mucositis prevention: Systematic review and network meta-analysis.

BACKGROUND: Oral mucositis (OM) is considered one of the most common side effects of patients undergoing cancer therapy. OM prevention plays a crucial role in the effectiveness of cancer treatment and the patient's quality of life. Different preventive treatments have been proposed in clinical trials, however with inconclusive results. MATERIALS AND METHODS: A systematic review search was conducted in PubMed, Scopus, Web of Science, and Cochrane Database to answer the PICO question: in cancer patients, do specific topical agents compared to standard treatments or placebo reduce the onset and severity of oral mucositis? The risk of bias was assessed, and a network meta-analysis was conducted. RESULTS: Of 2913 results, 30 randomized clinical trials were considered suitable for inclusion. A total of 2564 patients were analyzed, of which 1284 belonged to the test group and 1280 belonged to the control group. Natural products were the most used, followed mainly by antimicrobial agents, coating agents, and basic oral care measures. Topical sucralfate resulted in the most powerful intervention for the OM prevention (OR = 0.04, 95%C.I. = 0.01-0.25, p-value = 0.001). CONCLUSION: Due to its cytoprotective action, low cost, ease of administration, and safety, sucralfate could become a potential ally to prevent the onset of OM during cancer therapy.

Self-reported allergy to penicillin and clindamycin administration may be risk factors for dental implant failure: A systematic review, meta-analysis and delabeling protocol.

OBJECTIVE: Growing evidence is highlighting the inefficacy of clindamycin as an effective substitute to amoxicillin in patients self-reporting a penicillin allergy. The hypothesis is that implant failure is higher in these patients, when compared to patients receiving penicillin. To test this hypothesis, a systematic review and meta-analysis was undertaken and a protocol for delabeling penicillin allergic patients was presented. MATERIALS AND METHODS: A systematic review was undertaken by searching across three different databases, namely PubMed, Scopus and Web of Science. RESULTS: Out of 572 results, four studies were eligible to be included. Fixed-effects meta-analysis showed a higher number of failed implants in patients who were administered clindamycin, because of a self-reported allergy to penicillin. Results showed that these patients are over three times more likely (OR = 3.30, 95% C.I. 2.58-4.22, p-value < .00001) to undergo implant failure with an average cumulative proportion of 11.0% (95% C.I. 3.5-22.0%) versus 3.8% (95% C.I. 1.2-7.7%) of patients not requiring clindamycin and administered amoxicillin. A protocol for penicillin allergy delabeling is proposed. CONCLUSIONS: Current evidence is still limited and based on retrospective observational studies, it is difficult to state if penicillin allergy, clindamycin administration or a combination of both is responsible for the current trends and reported findings.

Quantitative proteomics in medication-related osteonecrosis of the jaw: A proof-of-concept study.

OBJECTIVE: Medication-related osteonecrosis of the jaw (MRONJ) is a paradoxical effect associated with bone-modifying agents (BMAs) and other drugs. Currently, no valuable diagnostic or prognosis biomarkers exist. The goal of this research was to study MRONJ-related salivary proteome. MATERIALS AND METHODS: This case-control aimed to study salivary proteome in MRONJ versus control groups (i) formed from BMAs consumers and (ii) healthy individuals to unravel biomarkers. Thirty-eight samples of unstimulated whole saliva (18 MRONJ patients, 10 BMA consumers, and 10 healthy controls) were collected. Proteomic analysis by SWATH-MS coupled with bioinformatics analysis was executed. RESULTS: A total of 586 proteins were identified, 175 proteins showed significant differences among MRONJ versus controls. SWATH-MS revealed differentially expressed proteins among three groups, which have never been isolated. These proteins had distinct roles including cell envelope organization, positive regulation of vesicle fusion, positive regulation of receptor binding, or regulation of low-density lipoprotein particle clearance. Integrative analysis prioritized 3 proteins (MMP9, AACT, and HBD). Under receiver-operating characteristic analysis, this panel discriminated MRONJ with a sensitivity of 90% and a specificity of 78.9%. CONCLUSION: These findings may inform a novel biomarker panel for MRONJ prediction or diagnosis. Nonetheless, further research is needed to validate this panel.

Critical update, systematic review, and meta-analysis of oral erythroplakia as an oral potentially malignant disorder.

BACKGROUND: Oral erythroplakia has been classically considered as the potentially malignant disorder with the highest rate of malignant development into squamous cell carcinoma. This critical systematic review and meta-analysis aim to estimate the malignant development rate of oral erythroplakia and identify the associated risk factors. METHODS: We performed a bibliographic search in PubMed, Scopus, Web of Science, Embase, and LILACS, with keywords "erythroplakia," "erythroplasia," "malignant transformation," "malignant development," "malignization," "carcinogenesis," "oral cancer," "oral squamous cell carcinoma," "mouth neoplasm," and "prognosis." Meta-analysis was conducted using a random-effects model. RESULTS: Ten observational studies with 441 patients met the inclusion criteria, whose mean malignant development rate was 12.7% and with a mean follow-up period of patients of 6.66 years. In the initial biopsy, 42.8% of oral erythroplakia were already squamous cell carcinoma. The buccal mucosa was the most frequent location of oral erythroplakia, but the floor of the mouth was the most common site of malignant development. All patients who underwent malignant development showed epithelial dysplasia on the initial diagnostic biopsy. CONCLUSION: Overall malignant development rate of OE in the meta-analysis was 19.9%. We could not associate any specific clinicopathological feature with the malignant development. The presence of epithelial dysplasia in the initial biopsy remains the worst prognostic factor. Further observational studies on OE are needed, with well-established diagnostic criteria and good clinical follow-up, in order to identify the true risk of malignant development of oral erythroplakia and the related risk factors.

Malignant development of proliferative verrucous/multifocal leukoplakia: A critical systematic review, meta-analysis and proposal of diagnostic criteria.

BACKGROUND: Proliferative verrucous/multifocal leukoplakia (PVML) is an oral potentially malignant disorder (OPMD) that exhibits high rates of malignant development (MD). This study aimed to analyse the risk of MD of PVML, as well as to investigate the possible risk factors associated with its malignization. METHODS: A bibliographical search of the PubMed, Embase, Web of Science, and Scopus databases was conducted. PVML MD rates were calculated as a pooled proportion, and the risk factors were calculated as risk ratios, using fixed and random models based on the presence of heterogeneity. RESULTS: From a total of 417 records, 16 articles were retrieved for inclusion. The subgroup analysis revealed a higher MD rate in the studies that were conducted in America, and, likewise, said studies involved a longer follow-up time (>6 years). There was a non-significant lower risk of malignization among males. A negative correlation was observed between MD and the year in which the studies were published. CONCLUSIONS: The pooled MD of PVML was 65.8% (95% CI: 55.3-76.2, p < 0.001). Prospective studies of PVML must be designed using simple and universal clinical diagnostic criteria to be able to make an early diagnosis of this important OPMD and acknowledge the frequency of MD.

Caspase 3 and Cleaved Caspase 3 Expression in Tumorogenesis and Its Correlations with Prognosis in Head and Neck Cancer: A Systematic Review and Meta-Analysis.

Head and neck cancer (HNC) is an ascending and agressive disease. The search for new molecular markers is emerging to solve difficulties in diagnosis, risk management, prognosis and effectiveness of treatments. Proteins related to apoptotic machinery have been identified as potential biomarkers. Caspase 3 is the main effector caspase and has a key role in apoptosis. The objective of this systematic review and meta-analysis is to review studies that analyze changes in Caspase 3 and Cleaved Caspase 3 expression both in oral premalignant disorders (OPMD) as well as in head and neck cancer (HNC). This study also proposes to review the prognostic values associated with HNC according to the expression of Caspase 3. Medline (via PubMed), EMBASE, Scopus, Cochrane, Web of Science and Grey Literature Database were screened from inception to june of 2022 and 18 studies were selected and 8 were included in the prognostic meta-analysis. Results related to the comparison of Caspase 3 expression demonstrated similar expression of Caspase 3 in HNC, with an average of 51.9% (9.5-98.1) showing high/moderate expression compared to 45.7% (14.6-84.7) in OPMD. Of interest, Cleaved Caspase 3 resulted incresed in HNC when compared with OPMD, being 73.3% (38.6-88.3) versus 22.9% (7.1-38.7). Pooled Fixed effect of HR values (95% CI) for OS related to Caspase 3 IHC expression in HNC patients was 1.48 (95% CI 0.95-2.28); also, the rate of heterogeneity was low, as revealed by I2 = 31%. For DFS was 1.07 (95% CI 0.79-1.45) with I2 = 0% and DSS showed a HR of 0.88 (95% CI 0.69-1.12) with I2 = 37%. Caspase 3 and Cleaved Caspase 3 expression could be linked with malignancy progression, but the expression of Caspase 3 did not influence the prognosis of patients with HNC.

Awareness Levels of the Link Between Oropharyngeal Cancer and HPV Infection Among Spanish Women: a Hospital-Based Cross-sectional Study.

Several observational studies have demonstrated the increased awareness of human papillomavirus (HPV) as an etiological factor of oropharyngeal cancers (OPCs). The incidence of OPCs has increased in recent times, particularly among younger women, and the efficacy of the HPV vaccine in preventing these cancers has gained attention among the medical community. The aim of this study was to explore the health literacy of Spanish adult women regarding factors associated with HPV and its link to OPCs, as well as their awareness of the HPV vaccination. A survey was distributed to 508 women, and 409 (70.5%) were considered as valid participants. The majority of the participants were Caucasian (97.8%) with a mean age of 44.1 ± 11.6. Out of all the participants, only 48.9% women identified HPV as a possible etiology of OPC. The most common sources of information regarding this association were the internet (31.3%), video media (28.9%), and healthcare professionals (28.9%), whereas 16.1% of the participants reported that they had obtained information from three or more sources. The average number of correct answers in the 16-item survey which was used to determine the participants' knowledge of HPV-related diseases was 8.7 ± 4.2, and the average number of correct answers in the 6-item survey regarding the usefulness of the HPV vaccination was 3.3 ± 1.6. According to bivariate models, the variables associated with a poorer level of awareness were related mainly to education (p < 0.001), sexual behavior (p < 0.001), and employment status (p < 0.001). This study contributes toward the discovery of the previously unforeseen psychosocial burden of HPV and its related diseases among Spanish women.

DNA Methylation by Bisulfite Next-Generation Sequencing for MLH1 and MGMT in Oral Squamous Cell Carcinomas and Potentially Malignant Disorders: An Integrative Analysis towards Field Cancerization.

Background and Objectives: MGMT methylation is a well-described biomarker in several solid tumors and MLH1 seems to occur in the initial stages of oral carcinogenesis. The aims of this study were to evaluate MHL1 and MGMT methylation levels in oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs), and to integrate this information with The Cancer Genome Atlas (TCGA) database. Materials and Methods: To determine the percentage of gene methylation in MLH1 and MGMT, pyrosequencing analysis was conducted. Samples were divided as follows: (1) patients diagnosed with OSCC (N = 16); (2) patients with OPDM who developed OSCC in the same location (N = 47); and (3) patients with OPDM who developed OSCC in a different location (N = 22). As a validation cohort in this study, data from The Cancer Genomic Atlas (TCGA) database, particularly regarding Head and Neck Squamous Cell Carcinoma, was used. Results: Overall MLH1 methylation levels of 8.6 ± 11.5% and 8.1 ± 9.2% for MGMT were obtained. With regard to MHL1, the OSCC presented the highest degree of methylation with 9.3 ± 7.3% (95%CI 5.1-13.6), and with regards to MGMT, the simultaneous malignancy group presented the highest degree of methylation with 10 ± 13.5% (95%CI 6-10), although no significant differences were found between the groups (p = 0.934 and p = 0.515, respectively). The estimated survival was higher for MGMT methylated cases (19.1 months, 95%CI 19.1-19.1) than for unmethylated cases (9.4 months, 95%CI 6-12.8), but not statistically significant. Conclusions: Our results did not show a correlation between MGMT and MLH1 methylation and any clinicopathological feature or survival in our institutional cohort. MLH1 methylation was present mainly in OSCC, whilst MGMT in OPMD represented a modest contribution to field cancerization, with an overall consistency with the TCGA database.

Association between periodontal disease and inflammatory bowel disease: a systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review was to investigate the association between periodontal disease (PD) and inflammatory bowel disease (IBD), and its two major forms Crohn's disease (CD) and ulcerative colitis (UC). MATERIALS AND METHODS: We searched articles in PubMed/MEDLINE, Web of Science, and LILACS published until March 2020. Observational studies evaluating the coexistence of PD in IBD and reported values of clinical periodontal parameters, or radiographic bone loss; and IBD diagnosis established by clinical, radiological, endoscopic and histological criteria were deemed eligible. RESULTS: A total of 9 studies were included (33,216 individuals). Only one study reported longitudinal data on IBDs onset in patients with PD. Several case-control studies reported coexistence. Meta-analysis showed that the presence of PD was associated with IBD (2.78 [95%CI 1.36-5.69]). PD was strongly associated both with CD (3.41 [95%CI 1.36-8.56]) and UC (3.98 [95%CI 2.02-7.87]). CONCLUSION: This review presents clear evidence for an association between PD and IBDs. Future studies should avoid non-longitudinal designs and focus on addressing direction. PD screening may be included in the multidisciplinary management of IBD patients. The mere theoretical possibility that PD may predispose to IBDs may be of key significance due to the rising incidence of diseases.

Metabolic syndrome and masticatory hypofunction: a cross-sectional study.

The objective of this paper is to clarify the rate of abdominal obesity (AO), waist-to-height ratio (WHtR), metabolic syndrome (MetS) and determine the relationship with the masticatory capacity (MC) in terms of total functional tooth units (t-FTU) in a representative sample of older Spanish adults. This cross-sectional study included 544 adult subjects aged 50 or over, who were prospectively selected and who had participated in a survey conducted in a primary dental care service in a Public Oral Health Service in Spain. Anthropometric, clinical variables and t-FTUs were obtained through a calibrated and well-established protocol. Univariate and multivariate binary and multinomial logistic regression analyses were developed. With regards to the t-FTU or MC, it was poor in 60.3%, good in 17.6%, and complete in 22.1% of the sample. The univariate odss ratio (OR) for MetS and AO increased as the MC decreased and as the age group increased. With regards to gender, women presented with an OR of 5.56 (CI 95% 3.70-8.38). With regards to the WHtR-a3 (WHtR grouped into three categories), the univariate ORs were all significant for morbid obesity compared to the healthy group, with a risk of 6.86 (CI 95% 3.23-14.58) for patients with poor MC compared to those with complete MC. Masticatory hypofunctionality could be associated with the presence of MetS. Clinical relevance: The number of t-FTUs is directly related to AO.

Association between periodontitis and medication-related osteonecrosis of the jaw: A systematic review and meta-analysis.

Consensus has yet to be reached about the prevention and treatment of medication-related osteonecrosis of the jaw (MRONJ), which is a treatment sequela of several antiresorptive therapies and other pharmaceutical interventions. Several epidemiologic studies have identified periodontal disease (PD) as a risk factor for this outcome. Thus, the objective of this systematic review and meta-analysis was to investigate this association and its magnitude. A systematic search in MEDLINE via PubMed, Scopus and ISI Web of Science, and a meta-analysis were undertaken. Observational studies that gathered information regarding prefixed definitions for both outcomes were selected, and the relevant information was then extracted, and their risk of bias was evaluated using the Newcastle-Ottawa Scale. The protocol of the study was registered on PROSPERO (CRD42019125646). The initial search yielded 757 eligible records, of which 12 were deemed adequate for inclusion (5 cohort studies and 7 case-control studies). On a random-effects meta-analysis, the risk of PD in MRONJ-affected sites compared with at-risk non-affected patients was significantly greater, with a risk ratio of 2.75 (95% CI: 1.67-4.52). Nonetheless, from a pooled analysis of three standardized periodontal measures (ie plaque index, clinical attachment loss and probing depth) no significant results were obtained. MRONJ appears to be associated with an increase in prevalence of PD. The direction of this association, and the factors influencing it must be investigated using further prospective data, and likewise, the possibility for using periodontal therapy as a prevention strategy must be looked into. Periodontal screening needs to be made an indispensable requisite for clinicians in order to establish a correct multidisciplinary approach in MRONJ.

Prognostic value of CAIX expression in oral squamous cell carcinoma: a systematic review and meta-analysis.

Carbonic anhydrase IX (CAIX) is a hypoxia-related protein considered as a predictor for oral squamous cell carcinoma (OSCC) biological behaviour. Nevertheless, this prognostic value is still yet to be validated. We aim to quantify prognostic significance of CAIX overexpression in OSCC by meta-analysis. We performed searches in MEDLINE, EMBASE, SCOPUS, WOS, WHO'S databases, CPCI, and OATD from inception to August 2019. Overall survival (OS), disease-free survival (DFS), locoregional control (LC), and disease-specific survival (DSS) were considered as outcomes of interest. Overall 18 studies were included. CAIX overexpression was associated with worse OS (hazard ratio [HR] = 1.45 95% confidence interval [CI] 1.17-1.80) and DFS (HR = 1.98 95% CI 1.18-3.32). To the contrary, it was neither associated with LC (HR = 1.01 95% CI 0.50-2.02) nor with DSS (HR = 1.35 95% CI 0.78-2.33). Heterogeneity was negligible in all analyses except for DSS. Small studies effect was not significant for OS and DFS. This study shows that immunohistochemical CAIX assessment is a useful OSCC prognostic biomarker.

Validity, reliability and optimisation of the TOPICOP questionnaire for oral lichen planus.

Objectives: Due to their anti-inflammatory and immunosuppressive effects, topical corticosteroids (TCs) are commonly used for the treatment of patients with oral lichen planus (OLP) with an erosive or ulcerative component. It has been suggested that many of these patients may suffer from fear or anxiety as a result of prolonged treatment with TCs. The objective of this study was twofold: (1) to optimise a patient reported outcome measure (PROM) in order to explore this feature, and (2) to evaluate this PROM in the treatment of OLP patients.Methods: A group of qualitative researchers adapted the TOPICOP questionnaire in order for it to be used as a PROM for OLP via structural equation modelling (SEM) and internal consistency (IC) analysis. Consequently, 34 patients with symptomatic OLP who were undergoing treatment with TCs completed a questionnaire and underwent a clinical assessment.Results: SEM presented an adequate fit (RMSA = 0.07, CFI = 0.94 and WRMR = 1.18), as well as a high IC (α = 0.81). A total of 16 patients (47.1%) reported TCs phobia. The receiver operating characteristic analysis (ROC) revealed that a TOPICOP value ≥50% predicted the presence of TCs phobia with a sensitivity of 93% and a specificity of 100%.Conclusions: The optimised TOPICOP scale proved valuable as a PROM in OLP. TCs phobia can be a real consideration in OLP, nonetheless, it does not appear to be an impediment to treatment adherence.

Identification of Prognosis Associated microRNAs in HNSCC Subtypes Based on TCGA Dataset.

Background and Objectives: Head and Neck Squamous Cell Carcinoma (HNSCC) includes cancers from the oral cavity, larynx, and oropharynx and is the sixth-most common cancer worldwide. MicroRNAs are small non-coding RNAs for which altered expression has been demonstrated in pathological processes, such as cancer. The objective of our study was to evaluate the different expression profile in HNSCC subtypes and the prognostic value that one or several miRNAs may have. Materials and Methods: Data from The Cancer Genome Atlas Program-Head and Neck Squamous Cell Carcinoma (TCGA-HNSCC) patients were collected. Differential expression analysis was conducted by edge R-powered TCGAbiolinks R package specific function. Enrichment analysis was developed with Diana Tool miRPath 3.0. Kaplan-Meier survival estimators were used, followed by log-rank tests to compute significance. Results: A total of 127 miRNAs were identified with differential expression level in HNSCC; 48 of them were site-specific and, surprisingly, only miR-383 showed a similar deregulation in all locations studied (tonsil, mouth, floor of mouth, cheek mucosa, lip, tongue, and base of tongue). The most probable affected pathways based on miRNAs interaction levels were protein processing in endoplasmic reticulum, proteoglycans in cancer (p < 0.01), Hippo signaling pathway (p < 0.01), and Transforming growth factor-beta (TGF-beta) signaling pathway (p < 0.01). The survival analysis highlighted 38 differentially expressed miRNAs as prognostic biomarkers. The miRNAs with a greater association between poor prognosis and altered expression (p < 0.001) were miR-137, miR-125b-2, miR-26c, and miR-1304. Conclusions: In this study we have determined miR-137, miR-125b-2, miR-26c, and miR-1304 as novel powerful prognosis biomarkers. Furthermore, we have depicted the miRNAs expression patterns in tumor patients compared with normal subjects using the TCGA-HNSCC cohort.

Evaluation of a new tricalcium phosphate for guided bone regeneration: an experimental study in the beagle dog.

This study compared the in vivo behavior of two biomaterials, xenograft (Bio-Oss®) and alloplastic tricalcium phosphate (Sil-Oss®), vs a control (no biomaterial) in beagle dogs treated with guided bone regeneration (GBR). Six male adult beagle dogs were included. The third and fourth mandibular premolars and first mandibular molars (3P3, 4P4 and 1M1) on both sides were extracted. After 12 weeks of healing, Straumann implants (3.3 × 8 mm) were placed, performing standardized defects (3.3 × 6 mm) in the vestibular aspect of the alveolar bone. The defects were surgically treated by randomized placement of xenograft (Bio-Oss®), alloplastic tricalcium phosphate (Sil-Oss®) or no biomaterial and covered with a resorbable collagen membrane (BioGide®). After an additional 12-week healing period, the lower jaws were dissected. Total area regenerated in the region of interest, total volume, bone to implant contact in the regenerated area, and volumetric changes were measured through histological, histomorphometrical and microcomputed tomography (microCT) techniques. The negative control group showed bone ingrowth inside the defect, with a partial collapse of the buccal bone. This was not observed in the biomaterial-treated groups. Defects treated with the xenograft showed 51.40% (SD 19.83) newly mineralized tissue, while those treated with alloplastic tricalcium showed 62.54% (SD 11.54) newly mineralized tissue; the control showed 71.52% (SD 6.46). Alloplastic tricalcium phosphate modified with monetite and zinc showed similar features in alveolar regeneration of defects to those treated with the xenograft or conventional GBR, but it showed an ideally higher rate of new mineralized tissue formation and accelerated resorption.

Dissecting the Proton Transport Pathway in Oral Squamous Cell Carcinoma: State of the Art and Theranostics Implications.

Cancer cells overexpress proton exchangers at the plasma membrane in order acidify the extracellular matrix and maintain the optimal pH for sustaining cancer growth. Among the families of proton exchangers implicated in carcinogenesis, carbonic anhydrases (CAs), monocarboxylate transporters (MCTs), Na+/H+ exchangers (NHEs), sodium bicarbonate cotransporters (NBCs), and vacuolar ATPases (V-ATPases) are highlighted. Considerable research has been carried out into the utility of the understanding of these machineries in the diagnosis and prognosis of several solid tumors. In addition, as therapeutic targets, the interference of their functions has contributed to the discovery or optimization of cancer therapies. According to recent reports, the study of these mechanisms seems promising in the particular case of oral squamous cell carcinoma (OSCC). In the present review, the latest advances in these fields are summarized, in particular, the usefulness of proton exchangers as potential prognostic biomarkers and therapeutic targets in OSCC.

State of art of micronuclei assay in exfoliative cytology as a clinical biomarker of genetic damage in oral carcinogenesis: A systematic review and meta-analysis.

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy, often preceded by oral potentially malignant disorders (OPMDs). Currently, no clinical biomarker exists to predict malignancy, necessitating OPMD follow-up. Habits and environmental factors, such as smoking, and alcohol consumption, influence OSCC onset. Increased micronuclei (MNs) formation has been observed in the development of OSCC. Non-invasive diagnostic tests like exfoliative cytology offer painless and regular monitoring options. This study evaluates the impact of tobacco, alcohol, and pesticide exposure on MNs occurrence in exfoliative cytology-collected oral mucosal cells, assessing their potential as non-invasive biomarker for OSCC development prediction and monitoring in high-risk patients. Despite results from this meta-analysis supporting the existence of a stepwise increase from controls to patients with OPMD to OSCC, the translation of these findings into clinical practice is limited due to intra- and inter-individual heterogeneity, as well as methodological variability in MNs quantification. Various factors contribute to this heterogeneity, including demographic variables, methodological variability of different laboratories, staining techniques, sample collection location, and patient characteristics. All these points were discussed to provide further insights and improve standardization for future studies.

Overexpression of E-Cadherin Is a Favorable Prognostic Biomarker in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Oral squamous cell carcinoma (OSCC) is characterized by poor survival, mostly due to local invasion, loco-regional recurrence, and metastasis. Given that the weakening of cell-to-cell adhesion is a feature associated with the migration and invasion of cancer cells, different studies have explored the prognostic utility of cell adhesion molecules such as E-cadherin (E-cad). This study aims to summarize current evidence in a meta-analysis, focusing on the prognostic role of E-cad in OSCC. To find studies meeting inclusion criteria, Scopus, Web of Science, EMBASE, Medline, and OpenGrey databases were systematically assessed and screened. The selection process led to 25 studies, which were considered eligible for inclusion in the meta-analysis, representing a sample of 2553 patients. E-cad overexpression was strongly associated with longer overall survival (OS) with Hazard Ratio (HR) = 0.41 95% confidence interval (95% CI) (0.32-0.54); p < 0.001 and disease-free survival with HR 0.47 95% CI (0.37-0.61); p < 0.001. In terms of OS, patients with tongue cancer experienced better survivability when expressing E-cad with HR 0.28 95% CI (0.19-0.43); p < 0.001. Globally, our findings indicate the prognostic role of the immunohistochemical assessment of E-cad in OSCC and its expression might acquire a different role based on the oral cavity subsites.

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 OPMDs.

Increased Plasmatic Levels of Exosomes Are Significantly Related to Relapse Rate in Patients with Oral Squamous Cell Carcinoma: A Cohort Study.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is characterized by an immunosuppressive tumor microenvironment. Their plasma-derived exosomes deliver immunomodulatory molecules and cargo that correlate significantly with clinical parameters. This study aims to assess the exosomal profile as a potential tool for early detection of relapse and long-term outcomes in OSCC patients undergoing conventional therapy. METHODS: 27 OSCC patients with a median 38-month follow-up were included in this study. The relationship between NTA-derived parameters and clinical pathological parameters was examined, and receiver operating characteristic (ROC) curves were utilized to evaluate the diagnostic efficacy of these values in detecting cancer relapse. RESULTS: Plasmatic levels of exosomes prior to surgery showed a drastic reduction after surgical intervention (8.08E vs. 1.41 × 109 particles/mL, p = 0.006). Postsurgical concentrations of exosomes were higher in patients who experienced relapse compared to those who remained disease-free (2.97 × 109 vs. 1.11 × 109 particles/mL, p = 0.046). Additionally, patients who relapsed exhibited larger exosome sizes after surgery (141.47 vs. 132.31 nm, p = 0.03). Patients with lower concentrations of exosomes prior to surgery demonstrated better disease-free survival compared to those with higher levels (p = 0.012). ROC analysis revealed an area under the curve of 0.82 for presurgical exosome concentration in identifying relapse. CONCLUSIONS: Presurgical exosomal plasmatic levels serve as independent predictors of early recurrence and survival in OSCC. All in all, our findings indicate that the detection of peripheral exosomes represents a novel tool for the clinical management of OSCC, with potential implications for prognosis assessment.