Relationship between aggressive features of oral squamous cell carcinoma and the immunoexpression of CX3CR1, CX3CL1 and ITGAV.

OBJECTIVE: We aimed to describe the association between CX3CR1, CX3CL1, and ITGAV immunoexpression with PNI and adverse oncologic outcomes in patients with OSCC. STUDY DESIGN: Expression CX3CR1, CX3CL1, and ITGAV was assessed by immunohistochemistry in a cohort of 50 paraffin-embedded resections of OSCC. Survival analysis, Cox, and binary logistic regressions were undertaken to determine the impact on patient survival and predictive value for PNI. RESULTS: CX3CL1 positive nerves exhibited a significant association with tumor budding (TB) (P = .043), whereas nerves positive for ITGAV were associated with PNI (P = .021), T3-T4 tumor size (P = .029), and III-IV stage (P = .044). Cases with ITGAV-positive nerves exhibited an odds ratio of 9.603 (P = .008) for PNI, whereas cases with CX3CL1-positive nerves exhibited and odds ratio of 4.682 (P = .033) for TB. A trend toward decreased 5-year overall survival (P = .078) and 5-year disease-specific survival (P = .09) was observed in relation to ITGAV-positive nerves. However, no independent predictors for poor survival were identified. CONCLUSIONS: The expression of ITGAV was associated with PNI and advanced disease, whereas the expression of CX3CL1 was related to TB, suggesting that ITGAV and CX3CL1 are involved in their respective developments. Therefore, further investigations are encouraged to assess the potential utility of targeted therapies against CX3CL1 receptors in OSCC.

Salivary Biomarkers for Oral Cancer Detection: An Exploratory Systematic Review.

Different efforts have been made to find better and less invasive methods for the diagnosis and prediction of oral cancer, such as the study of saliva as a source of biomarkers. The aim of this study was to perform a scoping review about salivary molecules that have been assessed as possible biomarkers for the diagnosis of oral squamous cell carcinoma (OSCC). A search was conducted using EBSCO, PubMed (MEDLINE), Scopus, and Web of Science. The research question was as follows: which molecules present in saliva have utility to be used as biomarkers for the early detection of oral cancer? Sixty-two studies were included. Over 100 molecules were assessed. Most of the markers were oriented towards the early diagnosis of OSCC and were classified based on their ability for detecting OSCC and oral potentially malignant disorders (OPMDs), OSCC outcome prediction, and the prediction of the malignant transformation of OPMDs. TNF-α, IL-1ß, IL-6 IL-8, LDH, and MMP-9 were the most studied, with almost all studies reporting high sensitivity and specificity values. TNF-α, IL-1ß, IL-6 IL-8, LDH, and MMP-9 are the most promising salivary biomarkers. However, more studies with larger cohorts are needed before translating the use of these biomarkers to clinical settings.

Comprehensive insights into the understanding of hypoxia in ameloblastoma.

Hypoxia is characterized by a disparity between supply and demand of oxygen. The association between hypoxia and head and neck tumors is a topic of significant interest. Tumors frequently encounter areas with inadequate oxygen supply, resulting in a hypoxic microenvironment. Ameloblastoma is one of the most common benign odontogenic tumors of the maxillofacial region. It is a slow-growing but locally invasive tumor with a high recurrence rate. The literature has demonstrated the correlation between hypoxia and ameloblastoma, revealing a discernible link between the heightened expression of hypoxic markers in low oxygen conditions. This association is intricately tied to the tumoral potential for invasion, progression, and malignant transformation. Hypoxia profoundly influences the molecular and cellular landscape within ameloblastic lesions. The present review sheds light on the mechanisms, implications, and emerging perspectives in understanding this intriguing association to clarify the dynamic relationship between hypoxia and ameloblastoma.

Orthopantomography Versus Cone Beam Computed Tomography for the Assessment of the Proximity of Posterior Maxillary Apexes with the Maxillary Sinus: A Cross-sectional Study.

BACKGROUND: The lack of knowledge of the relation of the maxillary sinus with the apexes of maxillary posterior teeth can lead to important complications during common dental procedures. This can be avoided using different imaging techniques, such as orthopantomography (OPG) and cone beam computed tomography (CBCT). The present study aims to compare the performance of OPG with CBCT in measuring the vertical distance of the apexes of posterior-superior teeth to the maxillary sinus. METHODS: This study corresponded to a cross-sectional study. OPGs and CBCT scans were obtained from the same individuals, and the qualitative and quantitative vertical distance of the apexes in relation to the maxillary sinus was categorized and measured in mm. RESULTS: A total of 28 pairs of OPGs and CBCT scans from the same patients were obtained. About 381 roots were analysed, which included 89 upper first premolars, 51 upper second premolars, 115 upper first molars, and 126 upper second molars. Projection/protrusion was observed with more frequency in molars, specially 1º molars in both OPG (n= 75, 65.2%) and CBCT (n= 31, 27%); however, 106 more cases (27.9%) were classified as projected in the OPG compared to CBCT (p < 0.05). When comparing the performance of the OPG and CBTC for analysing all roots qualitatively, there was a 57.8% agreement between both techniques. This difference was statistically significant (p <0.0001). Statistically significant differences were also observed when comparing the millimetric differences. CONCLUSION: This study showed that OPG is not an accurate technique to observe the relationship between the maxillary sinus and the apexes of the upper posterior teeth. In those cases where precision is required when performing dental procedures in this area, CBCT should be used. When not available, the clinicians should be aware of the limitations of the OPG and add other complementary techniques.

Comparative in vitro analysis of the antifungal activity of different calcium silicate-based endodontic sealers

Aim: This study aimed to perform an in vitro comparative analysis of the antifungal activity of different calcium silicate-based endodontic sealers against three fungal species. Methods: The antifungal properties of three calcium silicate-based sealers were tested: Bio-C Sealer, Cambiar a Sealer Plus BC, and MTA-Fillapex. Two commonly used sealers were used as controls: AH Plus and Endomethasone. An agar diffusion test was performed to analyze the antifungal activity of the sealers against Candida albicans, Candida glabrata, Candida tropicalis, and a mixed microbial culture medium. The results were analyzed using ANOVA (p <0.05). Results: Endomethasone exhibited the highest inhibition against all strains examined, maintaining a consistent level of inhibition throughout 7 days. MTA-Fillapex demonstrated the best performance among the calcium silicate-based sealers for the three fungal species (p < 0.05), maintaining stable values over the 7 days, surpassing that of Endomethasone. Nevertheless, MTA-Fillapex only exhibited antimicrobial effect against the mixed culture for the first 24 hours, and no antimicrobial activity was observed at 48 hours, being surpassed by all tested sealers (p < 0.05). Conclusion: Of all silicate-based sealers tested, only MTA-Fillapex exhibited promising antifungal activity. Nevertheless, care must be taken when extrapolating these results, as MTA-Fillapex exhibited poor antimicrobial activity when tested in mixed microbial cultures

Human Papillomavirus-Associated Oral Epithelial Dysplasia: Report of 5 Illustrative Cases from Latin America.

BACKGROUND: Human papillomavirus-associated oral epithelial dysplasia (HPV-OED) is a distinct oral epithelial disorder characterized by viral cytopathic changes caused by transcriptionally active high-risk HPV. The aim of the present study was to report 5 additional cases from Latin America. METHODS: Clinical data from five patients with HPV-OED were obtained from the archives of three oral pathology services from Brazil and Chile. All cases were submitted to morphological, p16 expression and in situ hybridization (ISH) for HPV analyses. RESULTS: Four patients were male and one patient was female, with a mean age of 55.4 years. Four patients were HIV seropositive and two were smokers. Three cases affected the buccal mucosa and commissure, one of which had an additional plaque in the soft palate, and one case each occurred on the floor of mouth and lower labial mucosa. Most cases presented as well-demarcated white plaques with a verrucous surface. One case presented multiple lesions ranging from normal to white-colored slightly elevated plaques with a cobblestone surface. Peripheral mucosal pigmentation was observed in two cases. All five cases presented with the characteristic microscopic features of HPV-OED, including severe dysplasia with numerous karyorrhectic and apoptotic cells, full-thickness "block positivity" for p16 and high Ki-67 index (> 90%) sharply demarcated from the adjacent non-dysplastic epithelium. Wide-spectrum DNA ISH-HPV was positive in 4 cases. All patients were treated with conservative surgical excision with no signs of recurrence after a mean of 39-month follow-up. CONCLUSION: This represents the first series of HPV-OED from Latin America; most cases presented as well-demarcated papillary white plaques affecting the buccal mucosa and commissure of HIV-positive middle-aged men, two of them exhibiting peripheral pigmentation caused by reactive melanocytes. The typical microscopic findings of HPV-OED were observed in all cases, which also showed strong p16 positivity in a continuous band through the full thickness of the epithelium and high Ki67.

Aging and oral squamous cell carcinoma development: the role of cellular senescence.

The gradual accumulation and inadequate renewal of senescent cells over time drive organismal aging. Senescent cells undergo altered gene expression and release inflammatory mediators collectively termed the senescence-associated secretory phenotype (SASP), which significantly contributes to a spectrum of age-related disorders, including cancer. In the context of carcinogenesis, the SASP produced by senescent cells has been implicated in the promotion of epithelial cancers, including oral squamous cell carcinoma (OSCC), the most common form of oral cancer. Senescent cells within the tumor microenvironment release factors that amplify the growth and invasiveness of neighboring cancer cells. Senotherapeutics, including senolytics and senomorphics, emerge as promising modalities to target senescent cells and their associated inflammatory factors, thereby opening novel avenues for augmenting the efficacy of cancer treatments. Here, we review the general aspects of cellular senescence, focusing on the relation between senescence-related inflammation with cancer development. We also analyze the available evidence linking cellular senescence with OSCC, highlighting possible clinical applications.

World Workshop on Oral Medicine VIII: Development of a core outcome set for dry mouth: a systematic review of outcome domains for xerostomia.

OBJECTIVE: The purpose of this study was to identify all outcome domains used in clinical studies of xerostomia, that is, subjective sensation of dry mouth. This study is part of the extended project "World Workshop on Oral Medicine Outcomes Initiative for the Direction of Research" to develop a core outcome set for dry mouth. STUDY DESIGN: A systematic review was performed on MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials databases. All clinical and observational studies that assessed xerostomia in human participants from 2001 to 2021 were included. Information on outcome domains was extracted and mapped to the Core Outcome Measures in Effectiveness Trials taxonomy. Corresponding outcome measures were summarized. RESULTS: From a total of 34,922 records retrieved, 688 articles involving 122,151 persons with xerostomia were included. There were 16 unique outcome domains and 166 outcome measures extracted. None of these domains or measures were consistently used across all the studies. The severity of xerostomia and physical functioning were the 2 most frequently assessed domains. CONCLUSION: There is considerable heterogeneity in outcome domains and measures reported in clinical studies of xerostomia. This highlights the need for harmonization of dry mouth assessment to enhance comparability across studies and facilitate the synthesis of robust evidence for managing patients with xerostomia.

World Workshop on Oral Medicine VIII: Development of a core outcome set for dry mouth: a systematic review of outcome domains for salivary hypofunction.

OBJECTIVE: To identify all outcome measures used to assess salivary gland hypofunction (i.e., objective measures used to determine actual changes in saliva quantity or to assess response to treatment of salivary gland hypofunction) and to group these into domains. STUDY DESIGN: A systematic review including clinical trials and prospective or retrospective observational studies involving human participants with dry mouth, with any type of intervention where the objective assessment of salivary gland hypofunction was described. RESULTS: Five hundred fifty-three studies involving 31,507 participants were identified. Most assessed salivary gland hypofunction and xerostomia (68.7%), whereas 31.3% assessed salivary gland hypofunction alone. Most studies investigated the "amount of saliva," and the highest number of outcome measures were within the domain of "clinical/objective signs of salivary gland hypofunction." CONCLUSIONS: Seven domains encompassing 30 outcome measures were identified, confirming the diversity in outcomes and outcome measures used in research regarding salivary gland hypofunction. Identified items will be used in conjunction with those identified regarding xerostomia to create a core outcome set for dry mouth quantification for use in future clinical trials, with the overall goal of improving the standardization of reporting, leading to the establishment of more robust evidence for the management of dry mouth and improving patient care.

Association between second mesiobuccal missed canals and apical periodontitis in maxillary molars of a Chilean subpopulation.

Background: To determine the frequency of missed second mesiobuccal canals (MB2) and apical periodontitis in maxillary molars of a Chilean subpopulation using cone beam computed tomography (CBCT). Material and Methods: Two previously calibrated operators evaluated CBCTs with a total of 588 upper molars, of which 179 endodontically treated molars were selected. Axial tomographic slices were used to study the frequency and association between the presence of apical periodontitis and untreated MB2 canals. Results: Of the 179 endodontically treated molars, 45.78% (84) presented MB2 missed canals. Of the upper molars that presented MB2 missed canals, 70% were associated with apical periodontitis, which was statistically significant (p< 0.0001). Sixty-two corresponded to first molars (74%) and 22 to second molars (26%). Of the first molars, 34 (54.8%) presented with apical periodontitis and MB2 missed canals (p< 0.0001), while 12 (54.4%) of the second molars presented this association (p = 0.081). Conclusions: MB2 missed canals are associated with a high degree of apical periodontitis and may be an important predictor of endodontic prognosis of upper molars. Key words:Endodontics, apical periodontitis, cone beam computed tomography, missed canals, maxillary molars.

World Workshop on Oral Medicine VIII: Development of a core outcome set for dry mouth: a consensus study.

OBJECTIVE: This study aimed to develop a consensus-based core outcome set (COS) to be used in clinical trials assessing dry mouth interventions. STUDY DESIGN: Through 2 systematic literature reviews and interviews with dry mouth patients, we identified relevant outcome domains for dry mouth assessment. A Delphi survey was presented to health care providers attending the American Academy of Oral Medicine annual meeting in Memphis, Tennessee, USA, on May 2022 (n = 104) and 10 dry mouth patients at Cork University Dental School and Hospital, Republic of Ireland. The outcome domains for which no consensus was reached were subsequently discussed in a second consensus process led by a virtual Special Interest Group of 11 oral medicine experts from the World Workshop on Oral Medicine VIII dry mouth working group. RESULTS: After the 2-step consensus process, a consensus was reached for 12 dry mouth outcome domains (i.e., salivary gland flow, signs of hyposalivation, mucosal moisture/wetness, the severity of xerostomia, duration of xerostomia, the overall impact of xerostomia, impact on physical functioning, impact of hyposalivation on general health, impact on social activities, quality of life, the economic impact of dry mouth, patient satisfaction) to be included in the final COS. CONCLUSIONS: We propose a consensus-based COS to assess dry mouth interventions in clinical trials. This COS includes the minimum but mandatory set of domains that all clinical trials evaluating dry mouth treatments should assess.

World Workshop on Oral Medicine VIII: Development of a core outcome set for dry mouth: the patient perspective.

OBJECTIVE: We conducted a qualitative study of patients' perspectives on dry mouth outcomes to explore their personal experiences and investigate which outcomes are most important to them. This work was part of the WONDER initiative (World Workshop on Oral Medicine Outcomes Initiative for the Direction of Research) exploring Core Outcome Measures in Effectiveness Trials. STUDY DESIGN: Using a study-specific topic guide, we conducted digitally recorded, semi-structured interviews of focus groups of patients with dry mouth secondary to Sjögren syndrome and head and neck radiotherapy. We conducted interviews until data saturation had been achieved and evaluated all transcripts for accuracy before we anonymized the data. RESULTS: Two focus groups consisting of 4 participants per group identified 4 distinct themes: (1) impact on oral health and function, (2) social isolation and withdrawal, (3) frustration with dry mouth management, and (4) limited knowledge of the medical community and lack of understanding of family and friends. CONCLUSIONS: The diversity of self-reported outcomes and the complexity of patient perceptions identified in our work may represent additional barriers to successful dry mouth management that should be considered in the design of future clinical trials.

Effect of Ultrasonic Activation on Dentinal Tubule Penetration of Bio-C Temp and Ultracal XS: A Comparative CLSM Assessment.

OBJECTIVE: The aim of this study was to compare the effect of ultrasonic activation (UA) on tubular penetration between Bio-C Temp and Ultracal XS intracanal medicaments. METHODS: Forty single-rooted human premolars were endodontically prepared and divided into 4 experimental groups (n=10): Bio-C Temp, Bio-C Temp+UA, UltraCal XS and UltraCal XS+UA. All medicaments were previously mixed with a specific calcium marker (Fluo-3) and passively injected into the canals. The samples were incubated for 7 days. For each tooth, 1 mm thick sections were obtained from the middle and apical thirds of the canals. The samples were examined by confocal laser scanning microscopy (CLSM) and the depth and area of penetration were determined for each group. The Student t test was used to compare results between groups (p<0.05). RESULTS: UA increased the depth and penetration area of Bio-C Temp and Ultracal XS, showing significant differences in the penetration area of the apical third for Bio-C Temp (p<0.0339). Bio-C Temp presented greater tubular penetration than Ultracal XS, showing significant differences in the depth of penetration in the apical third (p<0.0005), and in the penetration area in the middle (p<0.0016) and apical third (p<0.0339) after UA. CONCLUSION: UA increases tubular penetration (both depth and area) of Bio-C Temp at the apical third but has no significant effect on Ultracal XS. Bio-C Temp has a greater depth and tubular penetration area than Ultracal XS after UA. (EEJ-2023-02-024).