Assessing bias in the causal role of HPV in oral cancer: A systematic review and meta-analysis.

OBJECTIVE: High-risk human papillomaviruses (HPV) are an established cause of oropharyngeal cancer. Their relationship with oral cancer remains unclear with detection ranging from 0% to 100%. HPV DNA detection or evidence of exposure alone is insufficient to conclude causality. This systematic review assesses the extent of bias in studies of HPV detection in cancers of the oral cavity. METHODS: PubMed, Ovid MEDLINE, EMBASE, and PsycInfo databases were searched for observational studies reporting the effect of HPV in oral cavity specific cancers. RESULTS: All 15 included studies presented HPV DNA detection or serum HPV-antibodies, none included mRNA E6/E7 analysis. Cases with oral cancer had 5.36 times (95% CI 3.29-8.72) higher odds of having HPV detected compared to controls. The odds of HPV detection were higher in cell-based (OR 6.93; 95% CI 0.82-58.55) and tissue samples (OR 5.28; 95% CI 3.41-8.18) than blood-based samples (OR 3.36; 95% CI 1.53-7.40). CONCLUSION: When cancer site is clearly differentiated between oropharynx and oral cavity, 12 studies showed strong association between HPV and oral cancer, but the available estimates lack internal validity due to inconsistent measurements, high confounding, and lack of gold standard testing. There is not high-quality evidence to conclude a causal relationship of HPV with oral cancer.

Confocal microscopy in oral cancer and oral potentially malignant disorders: A systematic review.

OBJECTIVE: To systematically identify and summarise current research on the utility of confocal microscopy in oral squamous cell carcinoma and oral epithelial dysplasia in oral potentially malignant disorders. METHODS: Databases Medline, Embase, Evidence-Based Medicine, and Web of Science were searched with articles screened and included if their primary objective was the use of a confocal microscope in diagnosis of oral cancer or epithelial dysplasia, in vivo or ex vivo. RESULTS AND DISCUSSION: Twenty-eight relevant studies were identified of which 21 studies included oral squamous cell carcinoma specimens. Fifteen studies included in vivo use. The studies included both qualitative and fluorescence confocal microscope and reflectance confocal microscope analysis along with quantitative analysis of carcinoma and dysplasia. Thirteen studies reported the predictive value of their confocal device in the diagnosis of dysplasia and carcinoma. The quantitative software-based studies show promise in objectifying the diagnostic process for identifying abnormalities within the microstructure of the oral mucosa. CONCLUSIONS: There was heterogeneity in the criteria for diagnosis of dysplasia and oral squamous cell carcinoma with experience levels of assessors impacting method efficacy. Both qualitative and quantitative confocal assessment methodologies have been explored, the latter highlighting the potential of future machine-augmented diagnostic precision.

Adhesion of Denture Characterizing Composites to Heat-Cured, CAD/CAM and 3D Printed Denture Base Resins.

PURPOSE: To measure the adhesion of the denture characterizing composite to heat-cured, CAD/CAM and 3D printed denture base resins. METHODS AND MATERIALS: Two different denture characterizing composites with different viscosities (SR Nexco; high viscosity (SR) and Kulzer Cre-active; low viscosity (K)) and three denture base resins (Heat cure, CAD-milled and 3D printed) were investigated. 60 beams (25 × 4 × 3 mm) were fabricated for each denture base resin; 30 were bonded to SR and 30 to K to form a beam 50 × 4 × 3 mm. These were further divided (n = 10/group) to simulate the effects of 0, 6, and 12 months intraorally via thermocycling. The beams were subjected to a 4-point bend test using the chevron-notched beam method. Fracture toughness K1C (MPa ·m1/2 ) and flexural bond strength (MPa) were calculated. All specimens were analyzed for the mode of failure under the light microscope and selected specimens under scanning electron microscope. Results were statistically analyzed using ANOVA (SPSS Ver 25). RESULTS: The mean K1C was highest for the SR composite bonded to the heat-cured denture resin group (0.28 ± 0.11), followed by CAD/CAM (0.18 ± 0.04) and 3D printed groups (0.23 ± 0.16). Differences were not statistically significant (p = 0.268). Within each group, aging showed no statistical significance between the mean K1C and flexural bond strength (p = 0.209). The mean K1C for the K composites bonded to the three different denture bases were significantly lower compared to the SR group (p < 0.001). The mean K1C for the heat-cured denture resin group was (0.21 ± 0.1), followed by CAD/CAM (0.13 ± 0.04) and 3D printed groups (0.03 ± 0.02). Within each of the K group, aging showed a statistical significance for both the mean K1C and flexural bond strength (p = 0.002). CONCLUSION: The high viscosity SR showed significantly higher K1C and flexural bond strength to the lower viscosity K when bonded to heat-cured, CAD-milled and 3D printed denture base resins. Heat-cured denture base resins produced the highest K1C and flexural bond strength when bonded to two different types of characterizing composites.

Patient satisfaction with esthetics, phonetics, and function following implant-supported fixed restorative treatment in the esthetic zone: A systematic review.

OBJECTIVE: To determine patient satisfaction with esthetics, phonetics, and function following implant-supported fixed restorative treatment in the esthetic zone by measuring the Oral Health Related Quality of Life (OHRQoL). MATERIALS AND METHODS: This systematic review follows the "Preferred reporting items for systematic review and meta-analysis protocols" (PRISMA-P) 2015 statement. Studies were searched in the databases Ovid, PubMed, Web of Science, Scopus, and the Cochrane Library. The quality of the studies included in the review was scored using the GRADE system. The impact of the findings was analyzed by calculating effect size and standardization of results across different OHRQoL measurements was achieved by calculating the percentage equivalent. RESULTS: A total of 13 studies were selected to be included in his systematic review after application of the inclusion criteria. A total of six studies recorded pre- and post-treatment OHRQoL results, while the remaining seven studies provided only post-treatment results. CONCLUSIONS: This review concluded that implant-supported fixed restorations in the esthetic zone have an overall positive impact on OHRQoL. However, patient satisfaction from this treatment reduced as the number of missing teeth replaced by implants was increased. CLINICAL SIGNIFICANCE: When implant-supported fixed restorations are being planned in the esthetic zone, dentists need to consider the patient's perception and the subsequent impact of these restorations on the patient's quality of life. Clinicians can be assured that patient OHRQoL will increase; however, clinicians should also keep in mind the importance of the gingival frame. Furthermore, they should be aware of the challenges when planning cases with larger numbers of implants in the esthetic zone as this could lead to a lowering of a patient QoL.

Bond Strength of Denture Teeth to Heat-Cured, CAD/CAM and 3D Printed Denture Acrylics.

PURPOSE: To establish the fracture toughness (K1C ) and flexural bond strength of commercially available denture teeth to heat cured, CAD/CAM and 3D printed denture-based resins (DBRs). MATERIALS AND METHODS: Three types of DBRs (Heat cure, CAD-milled and 3D printed) and four different types of commercial denture teeth (Unfilled PMMA, double cross-linked PMMA, PMMA with nanofillers and 3D printed resin teeth) were investigated. DBR and epoxy embedded denture teeth (n = 30 per group) specimen beams (25 × 4 × 3 mm) were fabricated. The testing ends of all the specimens were surface treated, bonded and processed according to manufacturer's instructions. Twenty specimens were thermal cycled to simulate the effects of 6 and 12 months intraorally. A 4-point bend test, using the chevron-notched beam method was done and K1C (MPa ·m1/2 ) and flexure bond strength (MPa) were calculated. All specimens were analysed for the mode of failure under the light microscope and selected specimens under scanning electron microscope. Results were statistically analysed using ANOVA (SPSS Ver 24). RESULTS: The mean K1C was the highest for the teeth bonded to the heat-cured DBR group (1.09 ± 0.24), followed by CAD/CAM (0.43 ± 0.05) and 3D printed groups (0.17 ± 0.01). Differences were statistically significant (p < 0.01). Within each group, aging showed statistically significantly lower values but no statistical significance between the mean K1C and flexural bond strength (p = 0.36). The dominant mode of failure was cohesive in the CAD/CAM groups and adhesive in the heat-cured and 3D printed groups. CONCLUSION: Teeth bonded to heat-cured DBRs produced the highest K1C .The bond strength decreased significantly with aging. Teeth bonded to CAD/CAM and 3D printed DBRs showed significantly lower bond strength, with no significant influence of aging.

Acquisition and annotation in high resolution in vivo digital biopsy by confocal microscopy for diagnosis in oral precancer and cancer.

Introduction: Scanned fibre endomicroscopes are full point-scanning confocal microscopes with submicron lateral resolution with an optical slice thickness thin enough to isolate individual cell layers, allow active positioning of the optical slice in the z-axis and collection of megapixel images. Here we present descriptive findings and a brief atlas of an acquisition and annotation protocol high resolution in vivo capture of oral mucosal pathology including oral squamous cell carcinoma and dysplasia using a fluorescence scanned fibre endomicroscope with 3 topical fluorescent imaging agents: fluorescein, acriflavine and PARPi-FL. Methods: Digital biopsy was successfully performed via an acquisition protocol in seventy-one patients presenting for investigation of oral mucosal abnormalities using a miniaturized, handheld scanned fibre endoscope. Multiple imaging agents were utilized and multiple time points sampled. Fifty-nine patients had a matched histopathology correlating in location with imaging. The images were annotated back to macrographic location using a purpose-built software, MouthMap™. Results: Acquisition and annotation of cellular level resolved images was demonstrated with all 3 topical agents. Descriptive observations between clinically or histologically normal oral mucosa showed regular intranuclear distance, a regular nuclear profile and fluorescent homogeneity. This was dependent on the intraoral location and type of epithelium being observed. Key features of malignancy were a loss of intranuclear distance, disordered nuclear clustering and irregular nuclear fluorescence intensity and size. Perinuclear fluorescent granules were seen in the absence of irregular nuclear features in lichenoid inflammation. Discussion: High resolution oral biopsy allows for painless and rapid capture of multiple mucosal sites, resulting in more data points to increase diagnostic precision. High resolution digital micrographs can be easily compared serially across multiple time points utilizing an annotation software. In the present study we have demonstrated realization of a high-resolution digital biopsy protocol of the oral mucosa for utility in the diagnosis of oral cancer and precancer..

A Systematic Review of MicroRNA Signatures Associated with the Progression of Leukoplakia with and without Epithelial Dysplasia.

Oral cancer is a significant public health issue, being the eighth most common cancer worldwide with over 300,000 cases diagnosed annually. Early diagnosis and adequate management of oral potentially malignant disorders (OPMDs) before transformation into oral squamous cell carcinoma (OSCC) is critical to reduce deaths, morbidity, and to improve overall prognosis. MicroRNAs (miRNAs) are small noncoding RNAs involved in the post-transcriptional regulation of protein expression and implicated in the control of numerous cellular pathways and impacting physiological, developmental, and pathological processes. Dysregulation of miRNAs has been reported in many cancers and has been demonstrated to play a critical role in cancer initiation, progression, apoptosis, invasion and metastasis. This systematic review provides a comprehensive summary of the prevailing literature on miRNA signatures in OPMDs, specifically leukoplakia with or without oral epithelial dysplasia, and their utility in predicting malignant transformation into OSCC. Eighteen articles describing 73 unique and differentially expressed microRNAs met the criteria for inclusion in this review. We reviewed the characteristics and methodology for each of these studies and assessed the sensitivity and specificity of the studied miRNAs in predicting malignant transformation. This systematic review highlights the significant interest in miRNAs and their tremendous potential as prognostic markers for predicting the malignant transformation of OPMDs into OSCC.

Evaluation of surface roughness, hardness and elastic modulus of nanoparticle containing light-polymerized denture glaze materials.

STATEMENT OF PROBLEM: The surface hardness and roughness of different glaze materials for denture base acrylic resins have not been well reported. PURPOSE: The purpose of the study was to measure the surfaces hardness, elastic modulus and surface roughness of 5 different light-polymerized glaze materials for poly methyl methacrylate (PMMA) denture base materials. MATERIAL AND METHODS: A total of 210 PMMA resin specimens (10 × 5 × 2 mm) were prepared (30 per group); control group was untreated, group 1 was surface treated with conventional pumice and high shine paste; group 2 to 6 specimens were glaze coated with different commercially available denture glaze materials. 20 specimens out of 30 underwent thermocycling to simulate 6 months and 12 months in vivo. Nanoindentation was performed to measure the surface hardness and elastic modulus. Surface roughness was quantitatively analysed using surface metrology software and qualitatively analysed under scanning electron microscope (SEM). Collected data was statistically analysed using SPSS version 24. RESULTS: The mean surface hardness of tested specimens ranged from 0.33 ±0.09 GPa to 0.68 ±0.10 GPa. Specimens coated with Optiglaze produced statistically higher surface hardness compared to other groups (P< 0.01). Aging of 6 months and 12 months was found to have no statistical significance for all groups' surface hardness values. For elastic modulus, specimens coated with Nanovarnish produced statistically higher values compared to other groups (P= 0.03). Thermocycling showed no influence on the elastic modulus of specimens. The mean surface roughness of all groups ranged from 0.16 ±0.01 to 0.30 ±0.02 µm with no statistical significance between groups (P= 0.67). However, under SEM analysis, surfaces showed increased roughness over time. CONCLUSIONS: Statistically significant differences in surface hardness and elastic modulus were found among the different types of surface coated denture acrylic resins. Silica-nanoparticle containing surface coatings produced the highest surface hardness and elastic modulus, however there was no statistical significance found in aging for 6 and 12 months. Contrary to expectations, the surface roughness did not have a significant increase in all groups over time, despite changes observed under SEM. CLINICAL IMPLICATIONS: This study will contribute to our understanding of surface glazed PMMA acrylic resin denture materials and how it improves the surface strength. This research can help dental clinicians and technicians select the most effective polishing and coating material for the dentures.

Mechanical properties of human oral mucosa tissues are site dependent: A combined biomechanical, histological and ultrastructural approach.

AIM: To investigate load-deformation properties of Thiel-embalmed human oral mucosa tissues and to compare three different anatomical regions in terms of mechanical, histological and ultrastructural characteristic with focus on the extracellular matrix. MATERIALS AND METHODS: Thirty specimens from three different regions of the oral cavity: attached gingiva, buccal mucosa and the hard palate were harvested from two Thiel-embalmed cadavers. Mechanical properties were obtained, combining strain evaluation and digital image correlation in a standardised approach. Elastic modulus, tensile strength, strain at maximum load and strain to failure were computed and analysed statistically. Subsamples were also analysed using scanning electron microscopy (SEM) and histological analysis. RESULTS: The highest elastic modulus of 37.36 ± 17.4 MPa was found in the attached gingiva group, followed by the hard palate and buccal mucosa. The elastic moduli of attached gingiva differed significantly to the buccal mucosa (p = .01) and hard palate (p = .021). However, there was no difference in the elastic moduli between the buccal mucosa and hard palate (p > .22). The tensile strength of the tissue samples ranged from 1.54 ± 0.5MPa to 3.81 ± 0.9 MPa, with a significant difference between gingiva group and buccal mucosa or hard palate (p = .001). No difference was found in the mean tensile strength between the buccal mucosa and hard palate (p = .92). Ultrastructural imaging yielded a morphological basis for the various mechanical properties found intraorally; the attached gingiva showed unidirectional collagen fibre network whereas the buccal mucosa and hard palate showed multi-directional network, which was more prone to tension failure and less elasticity. CONCLUSION: This is the first study assessing the various morphological-mechanical relationships of intraoral soft tissues, utilising Thiel-embalmed tissues. The findings of this study suggest that the tissues from different intraoral regions showed various morphological-mechanical behaviour which was also confirmed under the SEM and in the histological analysis.

The cooling efficiency of different dental high-speed handpiece coolant port designs.

The study investigated the cooling efficiency of different numbers of water coolant ports on high-speed handpieces (HSH) under cooling conditions used in clinical practice. Twenty-four groove cuts with water on and nine cuts without water were made on extracted human premolars using three HSHs with different port configurations. Thermocouples were placed in the pulp chambers and temperature changes were recorded with 1-, 3- and 4-coolant port handpieces. Cooling rate was calculated for each coolant port design system. Temperature changes were statistically analysed with Kruskal-Willis Test. All three sample groups resulted in a net temperature decrease during the cutting period with water turned on. There was a pattern of increased cooling rate with increasing number of coolant ports (1-port: -4.27 (±0.94) °C, 3-port: -4.66 (±2.90) °C, 4-port: -5.03 (±1.08) °C). The difference was not statistically significant (p = 0.681). Calculations of cooling rate showed a higher cooling rate with an increase in the number of ports (1-port: 46.13 × 10-4 K-1, 3-port: 51.36 × 10-4 K-1, 4-port: 56.32 × 10-4 K-1). In the dry tooth preparation samples, all resulted in a net increase in temperature (1-port: 4.43 (±3.30) °C, 3-port: 5.13 (±3.27) °C, 4-port: 2.87 (±2.97) °C). All the three water coolant port configurations showed effective cooling of the tooth during cutting and decreased pulpal temperature with no statistical difference. There are HSH designs with varying numbers of coolant ports available in the market for clinicians. The results of the current study could potentially aid clinicians in making a decision while choosing between different dental handpieces.

Real-time pulp temperature change at different tooth sites during fabrication of temporary resin crowns.

AIM: To record the pulp temperature at different tooth sites during fabrication of two different temporary crown systems. METHODOLOGY: Two temporary crown systems were investigated; a conventional direct fabricated and a preformed thermoplastic resin system. Extracted caries-free human teeth (incisor, premolar and molar) were prepared for full coverage ceramic restoration with roots sectioned below the cemento-enamel junction. Thermocouple wires were secured at the surface of crown material, the cut dentine and inside the pulp cavity. Provisional crowns (n = 10/group) from each system were formed prior to placement in a water bath of 37 °C to simulate pulpal temperature. Temperatures were recorded using a K-type thermocouple data logger to collect the mean and peak temperature during crown fabrication. Statistical analysis was carried out on all tested groups and heat flow was calculated. RESULTS: For direct fabricated crowns, the mean rise in pulpal temperature recorded was 0.1 °C with the mean temperature range of 37.3 °C-37.8 °C. For the preformed thermoplastic crowns, the mean rise in pulpal temperature recorded was 37.3 °C-45.1 °C. The increase in temperature was significantly higher (6.5 °C for the incisor group, 7.5 °C for the premolar group, and 6.7 °C for the molar group). For both crown systems, the temperature difference between the three different sites; pulp, crown and tooth surface showed a statistical difference (P < 0.01). CONCLUSIONS: The direct fabrication system showed minimal temperature changes within the teeth, while the preformed thermoplastic fabrication system showed larger temperature change in the teeth.