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.
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.
Objectives
To describe the genetic variants that may be associated with the development of head and neck cancer (HNC) and functionally validating the molecular implications.
Materials and Methods
A ...prospective observational study was carried out on a family of 3 generations in which 3 members had developed HNC. Peripheral blood sample was taken in a routine procedure for exome sequencing in one relative and genotyping in the remaining twelve relatives. For the functional analysis all‐trans retinoic acid (atRA) was extracted from saliva and serum and measured using ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS). The presence of HPV‐DNA.
Results
None of the patients smoked or consumed alcohol. The presence of HPV DNA was not detected in any of the biopsied samples. A total amount of 6 members out of 13 (46.15%) carried out the same mutation of CYP26B1 (2p13.2; G>T). The mean plasma concentration of atRA was 3.3109 ± 1.4791 pg/mL for the study family and 4.7370 ± 1.5992 pg/mL for the controls (p = 0.042).
Conclusion
Lower levels of atRA were confirmed in the study family, which may open the way to the possible relationship between the polymorphism CYP26B1 (2p13.2; G>T) and HNC.
The sentinel node biopsy (SNB) is highly protocolized in other cancers, however, this is not the case for oral squamous cell carcinoma patients, hence our objective was to evaluate the different ...protocols published. A specific study protocol was designed and subsequently registered on PROSPERO (Ref. CRD42021279217). Twenty‐three articles were included in the meta‐analysis. The grouped sensitivity of the SNB was 82% (95% CI: 0.74–0.88), and the grouped specificity was 100% (95% CI: 0.99–1.00). The use of other radiotracers other than pre‐operative lopamidol showed higher values of sensitivity of 82.80% (95% CI: 76.90%–87.50%; p < 0.001). The use of the blue dye stain showed higher sensitivity values of 85.60% (95% CI: 71.90%–93.20%), compared to sensitivity values of 77.50% when it was not used (95% CI: 69.10%–84.20%) (p < 0.001). Diagnostic rates are variable and they were significantly better when 99mTc was used in all its variations and accompanied by the blue dye staining.
By using a meta-analytical approach, this study aimed to analyse the diagnostic capacity of protein-based biomarkers in saliva for the differential diagnosis of oral potentially malignant disorders ...(OPMDs) and oral squamous cell carcinoma (OSCC) from healthy individuals as control group (HCG).Articles on protein-based biomarkers in saliva, which provided quantitative expression in individuals with clinical and histopathological diagnosis of OPMD or oral leukoplakia (OL) were considered eligible. Searches were conducted in eight electronic databases. The methodological quality was assessed using the Quality Assessment of Diagnostic Studies tool (QUADAS-2). Functional analysis was also performed. Meta-analyses were performed using the OpenMeta tool (Analyst).Meta-analysis was possible for 4 of the 11 biomarkers studied. Only the carcinoembryonic antigen (CEA) and the soluble fragment of cytokeratin 19 (CYFRA21) were significant for the OSCC/OPMD subgroup, both with a very low heterogeneity. CEA had an OE = 25.854 (CI95%: 13.215-38.492, p< 0.001, I2 = 0) and CYFRA21 had an OE = 9.317 (CI95%: 9.014-9.619, p< 0.001, I2 = 0). For the OPMD/HCG subgroup, only CYFRA21 was significant, with an OE = 3.679 (CI95%: 0.663-6.696, p= 0.017) although with high heterogeneity (I2 = 91.24).The CEA and CYFRA21 markers proved very useful when differentiating OSCC from OPMD. The CYFRA21 was the only protein that was capable of distinguishing between OPMD and healthy controls.
The aim of this study is 1) to obtain the area and volumes of the maxillary sinuses in patients affected by clinically unilateral sinus pathology by comparing the results to the contralateral sinus ...and 2) to determine the importance of the volumetric measures when diagnosing the percentage of sinus obliteration. A single-centre observational retrospective clinical study was conducted in 214 patients with clinically unilateral sinus pathologies. Linear (mm), area (mm2) and volume (mm3) measurements were taken from Cone Beam Computed Tomography (CBCT) images of the affected sinus as well as from the contralateral ones. Histopathological study was performed using haematoxylin/eosin and PAS or Groccot stains. The lesions were classified into non-specific sinusitis, polyps, inverted papilloma, fungal sinusitis, cysts, mucocele and other lesions. Chi-squared test, ANOVA for independent samples and Pearson test were used for the statistical analysis. A total of 100 sinuses were measured in 50 patients (28 men and 22 women, with an age of 43.6 years (SD = 18.3), 50 pathological and 50 healthy contralateral sinuses. The three-dimensional occupation volume of the affected sinuses was 97.1 mm.sup.3 (62.5%) vs. 40.6 mm.sup.3 (22.8%) in the healthy ones (p0.0001). The medial-lateral width of the sinus in the frontal plane was significantly higher in the cysts group (32.4 mm, CI: 23-41.8 mm). In medical terms, the global percentage of occupation determined using the classic manual determination method does not differ from the three-dimensional percentage calculated using specific complex software.
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.
: 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.
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 (
< 0.01), Hippo signaling pathway (
< 0.01), and Transforming growth factor-beta (TGF-beta) signaling pathway (
< 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 (
< 0.001) were miR-137, miR-125b-2, miR-26c, and miR-1304.
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.
DNA damage is accumulated in the cells over time as the result of both exogenous and endogenous factors. The objective of this study was to analyze the immunohistochemical expression of the repair ...proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC).
Paraffin blocks were selected from the archives of the Laboratory of Hospital Clinico Universitario de Santiago de Compostela, Spain. The sample was composed of 16 cases of OL without dysplasia, 14 cases of OL with dysplasia, and 15 cases of OSCC. The patients' clinical data were collected and immunohistochemical analysis was performed for MLH1, MSH2, MRE11, and XRCC1. The data were submitted to the χ2 and the Kruskal-Wallis (P≤0.05) tests.
MSH2 was overexpressed in OSCC (P=0.020) and was positive in 100% of patients with OL with dysplasia or OSCC (P=0.019). Positivity for MLH1 was significantly associated with comorbidity (P=0.040), especially in patients who presented with 2 or more pathologies (P=0.028). XRCC1 positivity was also associated with comorbidity (P=0.039). No significant associations were found for the MRE11A expression. Although the simultaneous positivity for the 4 markers was observed in presence of comorbidities (P=0.006).
This study supports the effect of the overexpression of MSH2 protein in samples of OL with dysplasia and OSCC, most notably in patients who present with comorbidities and negativity for OL without dysplasia.
Background: Nearly two decades have passed since a paradoxical reaction in the orofacial region to some bone modifying agents and other drugs was recognized, namely medication-related osteonecrosis ...of the jaw (MRONJ). Purpose: The aim of this manuscript was to critically review published data on MRONJ to provide an update on key terminology, concepts, and current trends in terms of prevention and diagnosis. In addition, our objective was to examine and evaluate the therapeutic options available for MRONJ. Methods: The authors perused the most relevant literature relating to MRONJ through a search in textbooks and published articles included in several databases for the years 2003–2021. Results and conclusions: A comprehensive update of the current understanding of these matters was elaborated, addressing these topics and identifying relevant gaps of knowledge. This review describes our updated view of the previous thematic blocks, highlights our current clinical directions, and emphasizes controversial aspects and barriers that may lead to extending the accumulating body of evidence related to this severe treatment sequela.
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.
To begin, 29 OL and 10 normal oral mucosa (NOM) biopsies were retrieved for FD analysis of the epithelial (
) and the connective (
) tissue.
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,
= 0.0031). There were no differences in relation to dimc. Significant differences were observed between the non-dysplasia vs. high-grade (
= 0.0156) and low-grade vs. high-grade (
= 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 (
= 0.003).
FD at the level of the epithelium may be used as a diagnostic tool in OL.
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