Therapeutic Advances and Challenges for the Management of HPV-Associated Oropharyngeal Cancer.

The use of conventional chemotherapy in conjunction with targeted and immunotherapy drugs has emerged as an option to limit the severity of side effects in patients diagnosed with head and neck cancer (HNC), particularly oropharyngeal cancer (OPC). OPC prevalence has increased exponentially in the past 30 years due to the prevalence of human papillomavirus (HPV) infection. This study reports a comprehensive review of clinical trials registered in public databases and reported in the literature (PubMed/Medline, Scopus, and ISI web of science databases). Of the 55 clinical trials identified, the majority (83.3%) were conducted after 2015, of which 77.7% were performed in the United States alone. Eight drugs have been approved by the FDA for HNC, including both generic and commercial forms: bleomycin sulfate, cetuximab (Erbitux), docetaxel (Taxotere), hydroxyurea (Hydrea), pembrolizumab (Keytruda), loqtorzi (Toripalimab-tpzi), methotrexate sodium (Trexall), and nivolumab (Opdivo). The most common drugs to treat HPV-associated OPC under these clinical trials and implemented as well for HPV-negative HNC include cisplatin, nivolumab, cetuximab, paclitaxel, pembrolizumab, 5-fluorouracil, and docetaxel. Few studies have highlighted the necessity for new drugs specifically tailored to patients with HPV-associated OPC, where molecular mechanisms and clinical prognosis are distinct from HPV-negative tumors. In this context, we identified most mutated genes found in HPV-associated OPC that can represent potential targets for drug development. These include TP53, PIK3CA, PTEN, NOTCH1, RB1, FAT1, FBXW7, HRAS, KRAS, and CDKN2A.

Digital resources in the monitoring of patients with cleft lip and palate: protocol for a scoping review.

INTRODUCTION: Cleft lip and/or palate (CL+/-P) is a congenital malformation affecting the lip and palate, requiring long-term treatment due to potential associated complications. For this reason, it is important for the patient to be continuously monitored and followed for health promotion and prevention, as well as improving the quality of life. The aim of this scoping review protocol is to identify and map the available evidence regarding the application of digital resources and technologies in the monitoring and follow-up of patients with CL+/-P. METHODS AND ANALYSIS: This scoping review protocol follows the guidelines recommended by the Joanna Briggs Institute Manual, employing the PCC acronym (Patient/Concept/Context). Searches will be conducted, in May 2024, of PubMed, Web of Science, Scopus, Latin American and Caribbean Health Sciences Literature, ScienceDirect, as well as grey literature indexed in ProQuest Open Access Dissertations & Theses and Google Scholar. The review will consider all types of published studies, including grey literature, in English, Portuguese and Spanish languages, and will consider studies regardless of publication date. Exclusions will apply to studies that do not address the use of digital resources and technologies in CL+/-P monitoring and follow-up. ETHICS AND DISSEMINATION: As this is a scoping review, no ethics committee approval is required. After completion, the plan is to publish results in scientific journals on craniofacial malformations. STUDY REGISTRATION: Open Science Framework, DOI:10.17605/OSF.IO/Y6AG8.

Oral Lymphatic Malformations: A 21-Year Retrospective Study in a Single Institution.

Introduction. Oral lymphatic malformations are uncommon lesions. This study assessed the clinicopathological and sociodemographic features of oral lymphatic malformations in a Brazilian oral pathology service. Methods. Between 2000 and 2021, all oral lymphatic malformations diagnosed in a single oral pathology service were selected for the study. Clinical data, such as age, sex, site of the lesion, clinical presentation, diagnosis clinical, and the type of biopsy were recorded from the patient's clinical charts. Results. From 7554 oral lesions, 17 (0.22%) were oral lymphatic malformations. This lesion similarly affected both sexes, and the mean age of the patients was 16.5 years. The tongue was the most common site (n = 13; 76%). The mean size of the lesions was 17 mm. Oral lymphatic malformations were asymptomatic for 29% of the patients. Clinically, most lesions appeared as a reddish, sessile nodule, with a pebbly surface. In addition, the clinical and histopathological diagnoses agreed for most lesions (n = 11; 64%). The type of biopsy performed was excisional in 41% of lesions. Conclusions. In summary, oral lymphatic malformations present a low prevalence among the oral lesions diagnosed in an oral pathology service. Moreover, they affect equally both sexes, especially young patients, and usually appear as an asymptomatic or symptomatic nodular swelling on the tongue.

Telehealth in oral medicine: A cross-sectional evaluation based on a mobile application.

BACKGROUND: Teledentistry is considered a good tool in the diagnostic process. In oral medicine, there is a low number of trained professionals and dentists have difficulty in diagnosing and treating oral lesions. OBJECTIVE: We aimed to perform a cross-sectional evaluation based on the mobile application for oral diagnosis using a mobile application in a Brazilian State. METHODS: This is a retrospective, cross-sectional, observational study of the data of the "Telehealth in Stomatology in Paraíba" carried out between May 2021 and November 2022. RESULTS: The app has a team of 16 consultants (Ph.D. professors, postgraduate students, residents, and dentists). In addition, there are 289 registered professionals, with a mean age of 33.7 years, predominantly female (70.2%), working in primary care (79.2%), and general practitioners (42.6%). Regarding the cases, the app has 194 cases, and reactive lesions are the most suggested hypotheses reported by dentists (24.5%) and consultants (22.3%). We had an overall concordance rate of 64.1%. CONCLUSION: The application is easily accessible and has an assistance network that helps with early diagnosis. In addition, it has good coverage with users in more than 50% of the cities in the state. Thus, applications that provide specialized care to distant areas are important for better public health.

Antimicrobial effect and the mechanical and surface properties of a self-disinfecting and a chlorhexidine-incorporated Type IV dental stone.

STATEMENT OF PROBLEM: Stone casts are subject to contamination, but whether disinfectants incorporated into the stone are effective is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the antimicrobial activity and the mechanical and surface properties of self-disinfecting gypsum (SDG) and gypsum mixed with 2% chlorhexidine (GCHX). MATERIAL AND METHODS: Antimicrobial action was evaluated using the diffusion-disk technique on Streptococcus aureus and Candida albicans 1 hour and 24 hours after pouring the gypsum. The groups were SDG, GCHX, a positive control (PC) of gypsum mixed with distilled water, and a negative control (NC) of filter paper disk soaked with 2% chlorhexidine; n=8. Inhibition halos were measured using the ImageJ software program and statistically analyzed using the repeated measures mixed ANOVA with time×group interaction. Compressive strength (CS) in MPa and surface roughness (SR) in µm (parameters: Ra - roughness average; and Sa - 3-dimensional (3D) arithmetic mean of the surface profile) tests were performed to characterize the specimens (evaluated groups: SDG, GCHX, and PC; n=10). CS data were analyzed by a 2-way ANOVA with time×group interaction, and SR data by a 1-way ANOVA (α=.05). RESULTS: For S aureus, there were differences between GCHX and SDG at 1 hour and 24 hours (P<.05), but no significant differences were found for C albicans (P>.05). GCHX was better than PC, except for C albicans, and showed a reduction in CS when compared with PC and SDG (P<.05) at all time intervals. The SR of GCHX increased (Ra:1.76, Sa:2.08) when compared with PC (Ra:0.89, Sa:1.12) and SDG (Ra:1.03, Sa:1.35) (Ra: P<.004 and Sa: P<.001). CONCLUSIONS: The antimicrobial activity of GCHX against S aureus was better than that of SDG, but neither had an effect against C albicans. As for CS and SR, GCHX presented a decrease in properties when compared with PC and SDG but was within the American Dental Association #25 specification values.

Oral Mucositis in Children with Leukemia Undergoing Chemotherapy: A Case Series

ABSTRACT Objective: To report nine cases of pediatric patients with Acute Lymphoid Leukemia (ALL) or Acute Myeloid Leukemia who developed severe oral mucositis (SOM) at the first week of chemotherapy. Material and Methods: The cases were selected from a sample of 105 children followed for 10 consecutive weeks. Hematological and personal data were obtained from the patient's medical records. The oral cavity was examined weekly using the modified Oral Assessment Guide. Results: More of the patients were male (55.6%), had black/brown skin (55.6%), with ALL (66.7%), and the mean age was 5.55. Two patients had values below normal for leukocytes, platelets, and creatinine over the follow-up. However, all patients showed changes in the normality of hematological data in most weeks. The most used chemotherapeutic agents were aracytin, etoposide, and methotrexate, known for their high stomatotoxic potential. Patients had 2 to 6 (mean of 4) episodes of SOM and 4 to 7 (mean of 5.5) episodes of OM. One patient at week 7, one patient at week 5, and one patient at weeks 2 and 10 did not have OM. Saliva (84 times) and lips (44 times) were the most affected items. Conclusion: The patients showed oscillations in the severity of oral mucositis and hematological parameters over the follow-up. All patients were exposed to stomatotoxic drugs during the initial phase of cancer treatment.

Implications and Emerging Therapeutic Avenues of Inflammatory Response in HPV+ Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinomas (HNSCC) are a heterogeneous group of malignancies which have shown exponential incidence in the last two decades especially due to human papillomavirus (HPV) infection. The HPV family comprises more than 100 types of viruses with HPV16 and HPV18 being the most prevalent strains in HNSCC. Literature data reveal that the mutation profile as well as the response to chemotherapy and radiotherapy are distinct among HPV+ versus HPV-negative tumors. Furthermore, the presence of the virus induces activation of an immune response, in particular the recruitment of specific antiviral T lymphocytes to tumor sites. These T cells when activated produce soluble factors including cytokines and chemokines capable of modifying the local immune tumor microenvironment and impact on tumor response to the treatment. In this comprehensive review we investigated current knowledge on how the presence of an HPV can modify the inflammatory response systemically and within the tumor microenvironment's immunological responses, thereby impacting on disease prognosis and survival. We highlighted the research gaps and emerging approaches necessary to discover novel immunotherapeutic targets for HPV-associated HNSCC.

Impact of COVID-19 on dental practice and anxiety among increased risk group dentists: A cross-sectional study.

BACKGROUND: The likelihood of infection with SARS-COV-2 (COVID-19) in the dental office is considered high. OBJECTIVES: Assessing the impact of the COVID-19 on dental practices and anxiety levels in risk group Brazilian dentists. METHODS: A cross-sectional study was performed using an online questionnaire. The data obtained were analyzed using the IBM SPSS 25.0 software (Pearson's Chi-square association test, multivariate logistic regression, and Poisson multiple regression), with subsequent calculation of the odds ratio at a 95% confidence interval, with a significance level of 5%. RESULTS: Responses of 578 dentists distributed in all regions of Brazil were collected. Most of the dentists were female, with an average age of 35. Of the participants, 23.4% were part of the increased risk group for COVID-19. The professionals who belonged to the increased risk group had a greater chance of not feeling prepared to perform consultations (OR = 1.67) and were not performing any procedures during the pandemic (OR = 2.03). Belonging to the increased risk group did not influence anxiety levels among the dentists. The factors associated with increased anxiety were being female, being younger, working in the southeastern region of the country, being afraid of contracting COVID-19 while working, and being concerned for one's professional future. CONCLUSIONS: The pandemic has had a negative impact on the professional practice of individuals at risk, but the level of anxiety was like professionals who were not part of the increased risk group for COVID-19.

Evaluation of the economic impact of COVID-19 on Brazilian private dental clinics: A cross-sectional study.

BACKGROUND: The changes in dental care in the face of the COVID-19 pandemic resulted in the need for greater financial investment by dentists in biosafety measures and increase in the costs of dental consultations. OBJECTIVE: To evaluate the economic impact of the COVID-19 pandemic on dental practices in private clinics in Brazil. METHODS: A cross-sectional study was carried out, using an online questionnaire indexed in Google Forms, and distributed among dentists. The data obtained were analyzed using the IBM SPSS 25.0 software, evaluating the factors associated with strong or very strong impact on the participants' income and the factors that motivated the dentists to look for a credit line. Multiple logistic regression models were constructed to identify the associated factors. Variables with p < 0.05 were considered statistically significant. RESULTS: Most participants were female, with a median age of 35 years. Dentists who are most concerned about their professional future (OR = 3.134; 95% CI: 1.804-5.445), who have longer office hours (OR = 2.056; 95% CI: 1.198-3.529), who had the greatest impact on the flow of patients (OR = 16.358; 95% CI: 9.408-28.443) and in need of investing in infrastructure (OR = 1.756; 95% CI: 1.014-3.041), had the greatest impact on monthly earnings. CONCLUSIONS: The pandemic and the new biosafety recommendations for care during this period had a negative impact on the income of Brazilian dental offices and increased the chance of seeking credit to alleviate the financial deficit.

Impact of COVID-19 on Oral Healthcare for Oncopediatric Patients: The Setting in a Reference Hospital in Northeast Brazil

Abstract Objective: To describe the impact of the COVID-19 pandemic on dental care provided to pediatric cancer patients assisted in a referral hospital. Material and Methods: This is an observational, retrospective study based on secondary data extracted from worksheets of dental procedures for patients aged between 0 and 19 years assisted in the pediatric oncology sector of a hospital in João Pessoa, PB, Brazil. Dental procedures performed by the interdisciplinary team of researchers from August 2018 to February 2020 (19 months prior to the pandemic) and from April 2020 to October 2021 (19 months during the pandemic) were totaled and compared. A descriptive analysis of the data was performed. Results: There was a reduction of 80.2% in dental interventions implemented in the sector during the pandemic, with the number of procedures decreasing from 6,210 (the period before the pandemic) to 1,229 (during the pandemic). Most procedures in both periods were performed for patients assisted in beds, for whom there was a reduction of care provided for 81.2% from 5,275 to 994 procedures. Dental procedures in the outpatient clinic decreased by 74.9%, from 935 to 235. Conclusion: The COVID-19 pandemic negatively impacted dental care provided to pediatric oncology patients by restricting dental procedures to emergency demands, compromising performance prevention and health promotion actions.

Self-regulated learning perception of undergraduate dental students during the COVID-19 pandemic: A nationwide survey in Brazil.

BACKGROUND: This study aimed to evaluate the perception of self-regulated learning of Brazilian undergraduate dental students during the COVID-19 pandemic. MATERIAL AND METHODS: A nationwide cross-sectional survey was conducted. Data were collected in 2020, through an anonymous self-administered virtual questionnaire, which comprised an initial section related to the students' sociodemographic data, category of educational institution where they enrolled, and the possible impacts of COVID-19 pandemic on family income, teaching activities (maintained remotely or totally suspended), and self-perception of academic performance during e-learning. The second part comprising 31 questions related to the adapted Self-Regulated Learning Perception Scale (SRLPS). For statistical analysis, Student's t-test of independent samples, Kruskal-Wallis, and Mann-Whitney U test were used, considering a significance of 5%. RESULTS: From 779 students, 425 (54.6%) reported distance learning activities during the pandemic, and 354 (45.4%) experienced complete interruption of teaching activities. Students with good performance during e-learning were more skilled in self-regulated learning when compared to those who reported regular (p = 0.026), bad (p = 0.000), and very bad (p = 0.000) performance. In addition, students who stated a good performance during e-learning were more skilled in self-regulated learning than those with fully suspended teaching activities (p = 0.000). CONCLUSIONS: E-learning performance of undergraduate dental students during COVID-19 pandemic influenced the self-regulated learning perception. In addition, the pandemic negatively impacted the self-regulated learning of students who experimented full suspension of teaching activities. Changes in family's income did not affect their self-regulated learning. Key words:Dental education, community health, e-learning, learning, pandemics.

Effect of the incorporation of silica blow spun nanofibers containing silver nanoparticles (SiO2/Ag) on the mechanical, physicochemical, and biological properties of a low-viscosity bulk-fill composite resin.

OBJECTIVE: This work aimed at producing silica-blow-spun nanofibers containing silver nanoparticles (SiO2/Ag) and investigating the effect of their incorporation in different proportions, with or without pre-treatment with a silane coupling agent, on the mechanical, physicochemical, and biological properties of a commercial composite low-viscosity bulk-fill resin. METHODS: The production of SiO2/Ag nanofibers was confirmed by transmission electron microscopy (TEM) and energy dispersive X-ray analysis (EDX). A portion of the produced nanofibers was silanized. Scanning electronic microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), contact angle measurements, and agar diffusion tests against Streptococcus mutans were used to verify the differences between silanized and non-silanized nanofibers. Different proportions (0.5 wt% and 1 wt%) of silanized (SiO2/Ag-0.5S and SiO2/Ag-1S) and non-silanized (SiO2/Ag-0.5NS and SiO2/Ag-1NS) nanofibers were incorporated into the bulk-fill composite (Opus Bulk Fill Flow, FGM). A commercial composite was used as the control. Evaluation of the color parameters (L*, a*, and b*), radiopacity, contact angle, antimicrobial activity, Vickers microhardness, surface roughness (Sa and Sq), flexural strength, and SEM of the fractured surfaces were performed. The data were analyzed using the Mann-Whitney U test (fiber morphology), Kruskal-Wallis tests, with Dunn's post hoc test (antimicrobial activity of the specimen against S. mutans), Student's t-test (disk diffusion), one-way ANOVA and Tukey (color, radiopacity, and contact angle), and two-way ANOVA and Tukey (microhardness, surface roughness, and flexural strength) tests. All statistical analyses were performed at a significance level of 1% (α = 0.01). RESULTS: Porous nanometric SiO2/Ag fibers were successfully produced. The silanization process, confirmed by FTIR, increased the diameter and contact angle and reduced the growth inhibition halos of the nanofibers (p < 0.01). After the incorporation of nanofibers into the dental composite, all color parameters were altered in all the experimental groups (p < 0.01). All the groups presented adequate radiopacity values. No statistical difference was observed in the contact angles of the experimental composites (p > 0.01). The lowest microbial counts were obtained in the SiO2/Ag-0.5S group; although no significant difference was observed with the control group (p < 0.01). The SiO2/Ag-1S, SiO2/Ag-0.5S, and SiO2/Ag-0.5NS groups exhibited higher microhardness after 30 d of immersion in water (p < 0.01). The surface roughness (Sa-µm) resembled that of the control at baseline, except for the SiO2/Ag-1NS group. For the baseline evaluation of flexural strength, all the experimental groups exhibited lower values than the control, except for SiO2/Ag-0.5NS and SiO2/Ag-0.5S, but after 30 d of immersion in water, there was no difference (p < 0.01). SIGNIFICANCE: The incorporation of 0.5% wt. of silanized nanofibers in the commercial composite (SiO2/Ag-0.5S) seemed to be promising, especially for its greater inhibition of S. mutans, adequate roughness, and flexural strength, in addition to high hardness, even after aging in water.

Chitosan/PCL nanoparticles can improve anti-neoplastic activity of 5-fluorouracil in head and neck cancer through autophagy activation.

Head and neck squamous cell carcinoma (HNSCC), a prevalent cancer worldwide, has a high incidence of loco-regional dissemination, frequent recurrence, and lower 5-year survival rates. Current gold standard treatments for advanced HNSCC rely primarily on radiotherapy and chemotherapy but with limited efficacy and significant side effects. In this study, we characterized a novel 5-fluorouracil (5-FU) carrier composed of chitosan solution (CS) and polycaprolactone (PCL) microparticles (MPs) in HNSCC preclinical models. The designed MPs were evaluated for their size, morphology, drug entrapment efficiency (EE%) and in vitro drug release profile. The anti-cancer activity of 5-FU-loaded particles was assessed in HNSCC human cell lines (CAL27 and HSC3) and in a preclinical mouse model (AT84) utilizing cell proliferation and survival, cell motility, and autophagy endpoints. The results demonstrated a 38.57 % in 5-FU entrapment efficiency associated with reduced 5-FU in vitro release up to 96 h post-exposure. Furthermore, CS-decorated PCL MPs were able to promote a significant inhibition of cancer cell proliferation based on the metabolic and colony formation assays, in comparison to controls. In contrast, CS-decorated PCL MPs did not influence the pharmacological efficacy of 5-FU to inhibit in vitro cancer cell migration. Last, cell protein analysis revealed a significant increase of autophagy and cell death evaluated by LC3-II expression and PARP1 cleavage, respectively. In summary, these results support the potential utility of CS-decorated PCL MPs as an effective 5-FU-delivery carrier to improve HNSCC therapeutic management.

Potential link between SARS-CoV-2 and Kawasaki disease: importance of dentists for the diagnosis.

Kawasaki disease (KD) is a vasculitis with predilection for coronary arteries. Due to a lack of reliable confirmatory laboratory tests, the diagnosis of KD is based on a characteristic pattern of clinical findings that appear in a typical temporal sequence. The diagnostic criteria have been periodically modified and the American Heart Association has proposed the most recent guidelines for its diagnosis. However, patients may have incomplete or atypical forms of KD and diagnosis can often be difficult. Because oropharyngeal manifestations are a common and important feature for diagnosing KD and recent studies have hypothesized a possible association between KD and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in this review we highlight the importance of dentists in the diagnosis of KD and its potential association with SARS-CoV-2.

Is there an association between rheumatoid arthritis and bone changes in the temporomandibular joint diagnosed by cone-beam computed tomography? A systematic review and meta-analysis.

OBJECTIVES: Evaluate the relation of rheumatoid arthritis (RA) and bone changes in the temporomandibular joint diagnosed by cone-beam computed tomography (CBCT). MATERIALS AND METHODS: This systematic review and meta-analysis were recorded in the PROSPERO database, using the CRD42020153246 protocol. The electronic searches were performed in the following databases: Pubmed, Scopus, Web of Science, Lilacs, Cochrane, and Open Grey. Cross-sectional studies that evaluated patients with RA with bone changes in the temporomandibular joint diagnosed by CBCT, without language restriction or publication date, were included. Meta-analysis was performed in Stata Software (StataCorp, TX, USA, version 12.0), using the metan, and a random effects model, and the risk of different bone alterations occurring in adults with and without arthritis was estimated using odds ratios (ORs) as a pooled measure of effect. Forest plots were used to present the isolated and the pooled effects (ORs and 95% CI). RESULTS: Six studies were used for qualitative synthesis and 2 studies for quantitative synthesis. All studies diagnosed higher prevalence changes in the bone structures of the TMJ of RA patients, described as erosion, flattening, sclerosis, and osteophytes. Meta-analysis showed that the chance of bone changes occurring in components of the TMJ is greater in individuals who have RA. CONCLUSION: There is an association between RA and bone changes in TMJ structures diagnosed through CBCT, as RA patients were more likely to have osteoarthritic changes in this joint. CLINICAL RELEVANCE: Understanding the existence of an association between bone alterations in TMJ and RA can assist in the management of patients.

Efficacy of essential oil of cinnamon for the treatment of oral candidiasis: A randomized trial.

AIM: It was analyzed the efficacy of mouthwash and spray containing essential oil (EO) of Cinnamomum zeylanicum Blume for the treatment of oral candidiasis. METHODS AND RESULTS: A randomized, controlled, and blinded clinical trial was conducted with 36 individuals (probabilistic sample) with oral candidiasis who were divided into two treatment groups: C. zeylanicum (0.5 mg/mL), n = 18; nystatin (100,000IU/mL), n = 18. The efficacy of the products was evaluated by two parameters: (a) clinical evolution recorded by calibrated examiners (Kappa = 0.822) according to Newton's classification and (b) reduction of colony-forming units/mL. Mycological and clinical parameters were analyzed before and at 15 days after treatment. Clinical examination of the mucosa showed that C. zeylanicum (p < 0.0339) and nystatin (p < .0139) had efficacy, resulting in a reduction of signs and symptoms (Mann-Whitney test). Mycological analysis showed that C. zeylanicum caused a reduction of 61% and 33% of Candida spp., isolates oral mucosa and dentures, respectively. Candida tropicalis strains were eliminated after C. zeylanicum, in both sites. The participants reported a pleasant taste and few product-related complaints. CONCLUSION: C. zeylanicum EO and nystatin exhibited clinical efficacy, according to the Newton classification, and reducing in Candida spp. The clinical trial has been registered (Registration number: NBR-33s6 × 5, ensaiosclinicos.gov.br).