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.

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.

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 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.

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.

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).

Tobacco Use, Attitudes, Knowledge, and Perception About Smoking Cessation Counseling Among Brazilian Dental Students: a Cross-Sectional Study.

The aim of this study was to evaluate the prevalence of tobacco use, exposure to secondhand smoke, and knowledge and perception about smoking cessation counseling among dental students in Brazil. A cross-sectional study was performed at the School of Dentistry, Universidade Federal de Pernambuco, Brazil. The Global Health Professions Student Survey (GHPSS) research instrument was used. In the second half of 2017, students from the 5th to the 10th semester were recruited to answer the anonymous and self-administered survey in classrooms. The data were tabulated and analyzed, and information about the variables was presented using descriptive statistics. The association between the variables was determined through the Chi-square test and binary logistic regression. Two hundred and twenty-four students answered the survey. More than 40% of the students had tried cigarettes at least once and 8.9% were current smokers. About 28% of the participants reported having been exposed to secondhand smoke in their home and 57.1% in other environments. Most students recognized that they are role models for society and believed they should receive training in smoking cessation counseling. However, only 12.5% of the students reported having received some formal training in this subject. In conclusion, although dental students are aware of the harmful effects of tobacco, there is still a lack of training in smoking prevention and control among these future professionals.

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

Abstract: 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.

Impact of Saliva and Cariogenic Microbiota on the Chemotherapy-Induced Oral Mucositis in Oncopediatric Patients: A Preliminary Longitudinal Study.

This study aims to evaluate the salivary parameters and cariogenic microbiota of pediatric oncological patients and their correlation with severe oral mucositis (SOM). A preliminary longitudinal study included patients in the age range from 4 to 18 years (n = 26), with diagnosis of primary cancer, who were followed up before and after time intervals of two, five, and ten weeks of induction chemotherapy. Oral mucosa examinations were performed by means of the modified Oral Assessment Guide (OAG) by calibrated examiners (κ > 0.70). Saliva analysis (unstimulated saliva flow (USF), clinical saliva viscosity (CSV), and pH) and microbiological (total Streptococcus (TS) and Streptococcus of the mutans group (SMG)) tests were performed using unstimulated saliva. The data were analyzed by the Wilcoxon and Spearman Correlation tests (α = 5%). The patients were predominantly of the female sex (n = 15; 57.7%), adolescents (n = 15; 57.7%), and patients with hematological tumors (n = 21; 80.8%). SOM was more frequent in the tenth week (n = 7; 28.6%). The values of USF, CSV, pH, TS, and SMG were not changed by the institution of chemotherapy (p > 0.05). These values were correlated with SOM and the time, TS and SMG, and CSV and SMG. The salivary and microbiological parameters investigated did not influence the severity of oral mucositis in the pediatric patients oncological..

The effectiveness and acceptability of a portable pediatric sialometer: A new technique for saliva collection.

OBJECTIVE: To compare the effectiveness and acceptability of a newly developed pediatric sialometer as an alternative to the conventional spitting method. METHODS: A clinical study was carried out with healthy children (G1; n = 30) and oncological children (G2; n = 30). A newly developed pediatric sialometer was compared to the traditional spitting method to determine unstimulated salivary flow (mL/min), with a one-hour wash out period between sample collections. A semi-structured questionnaire was applied to G1 and G2 using the Facial Anxiety Scale to evaluate the device's acceptability. The children's behavior was also observed throughout saliva collection. The data were analyzed by Mann-Whitney U, Wilcoxon, Student's t and Chi-Square tests (α = 5%). RESULTS: There was no significant difference between groups and methods (P > 0.05). However, the saliva collected with the pediatric sialometer was clearer and had less apparent contamination. The device characteristics were rated positively, with high acceptability even among children with more difficult conditioning (G2) (P > 0.05). CONCLUSION: The newly developed pediatric sialometer presented herein can be an alternative option for saliva collection in pediatric dentistry, with good reproducibility and acceptability by children.

Oral Mucositis in Pediatric Oncology Patients: A Nested Case-Control to a Prospective Cohort.

This study aimed to evaluate the factors associated with the occurrence of severe oral mucositis (SOM) in pediatric oncology patients during the chemotherapeutic treatment. This is a nested case-control to a prospective cohort that monitored 105 patients for 10 consecutive weeks after the beginning of the chemotherapy treatment. Logistic regression was used to identify the factors associated with SOM, by group of malignancy (hematologic or solid tumors) (Sig.=5%). To patients with hematologic tumors were found factors associated with SOM in two weeks of treatment: in the 6th week (increase in frequency of chemotherapy doses (OR=3.02)) and in the 7th week (female sex (OR=21.28); and increase in frequency of chemotherapy doses (OR=2.51)); and to patients with solid tumors were found factors associated with SOM in five weeks of treatment: in the 1st week (female sex (OR=14.43); age increase (OR=1.24)); in the 2nd week (Miscellany (OR=6.39)); in the 5th week (Antimetabolites (OR=17.44); Miscellany (OR=45.42); and platelets reduction (OR=1.12)); in the 6th week (creatinine increase (OR=1.63)); and in the 7th week (creatinine increase (OR=2.39)). For patients with hematologic tumors, to be female, and the increase in the frequency of chemotherapy doses increased the risk for SOM and for patients with solid tumors, to be female, the increase in age and in level blood concentration of creatinine, the reduction in number of platelets and the use of chemotherapy with miscellany and antimetabolites agents were associated with an increase in risk for occurrence of SOM.

Oral Mucositis in Pediatric Oncology Patients: A Nested Case-Control to a Prospective Cohort

Abstract This study aimed to evaluate the factors associated with the occurrence of severe oral mucositis (SOM) in pediatric oncology patients during the chemotherapeutic treatment. This is a nested case-control to a prospective cohort that monitored 105 patients for 10 consecutive weeks after the beginning of the chemotherapy treatment. Logistic regression was used to identify the factors associated with SOM, by group of malignancy (hematologic or solid tumors) (Sig.=5%). To patients with hematologic tumors were found factors associated with SOM in two weeks of treatment: in the 6th week (increase in frequency of chemotherapy doses (OR=3.02)) and in the 7th week (female sex (OR=21.28); and increase in frequency of chemotherapy doses (OR=2.51)); and to patients with solid tumors were found factors associated with SOM in five weeks of treatment: in the 1st week (female sex (OR=14.43); age increase (OR=1.24)); in the 2nd week (Miscellany (OR=6.39)); in the 5th week (Antimetabolites (OR=17.44); Miscellany (OR=45.42); and platelets reduction (OR=1.12)); in the 6th week (creatinine increase (OR=1.63)); and in the 7th week (creatinine increase (OR=2.39)). For patients with hematologic tumors, to be female, and the increase in the frequency of chemotherapy doses increased the risk for SOM and for patients with solid tumors, to be female, the increase in age and in level blood concentration of creatinine, the reduction in number of platelets and the use of chemotherapy with miscellany and antimetabolites agents were associated with an increase in risk for occurrence of SOM.

Resumo Este estudo objetivou avaliar os fatores associados com a ocorrência de mucosite oral grave (SOM) em pacientes pediátricos oncológicos durante o tratamento quimioterápico. Trata-se de um estudo de caso-controle aninhado a uma coorte prospectiva que monitorou 105 pacientes por 10 semanas consecutivas após o início do tratamento quimioterápico. Regressão logística foi utilizada para identificar os fatores associados com a MOG, por grupo de malignidade (tumores hematológicos ou sólidos) (Sig.=5%). Para pacientes com tumores hematológicos foram encontrados fatores associados com a MOG em duas semanas de tratamento: na 6ª semana (aumento na frequência de doses de quimioterapia (OR=3,02)) e na 7ª semana (sexo feminino (OR=21,28); e aumento na frequência de doses de quimioterapia (OR=2,51)); e para pacientes com tumores sólidos foram encontrados fatores associados com MOG em cinco semanas de tratamento: na 1ª semana (sexo feminino (OR=14,43), aumento na idade (OR=1,24)); na 2ª semana (Miscelânea (OR=6,39)); na 5ª semana (Antimetabólitos (OR=17,44); Miscelânea (OR=45,42); e redução de plaquetas (OR=1,12)); na 6ª semana (aumento na creatinina (OR=1,63)); e na 7ª semana (aumento na creatinina (OR=2,39)). Para pacientes com tumores hematológicos, ser do sexo feminino e o aumento na frequência de doses de quimioterapia aumentou o risco para MOG; e, para pacientes com tumors sólidos, ser do sexo feminino, o aumento na idade e nos níveis de concentração sanguínea de creatinina, a redução no número de plaquetas e o uso de quimioterapia com agentes das classes Miscelânea e Antimetabólitos estiveram associados com o aumento no risco para a ocorrência de MOG.

Differences between the oral changes presented by patients with solid and hematologic tumors during the chemotherapeutic treatment.

OBJECTIVE: This study sought to identify the differences between the oral changes presented by patients with solid and hematologic tumors during chemotherapeutic treatment. METHODOLOGY: This is an observational, prospective and quantitative study using direct documentation by follow-up of 105 patients from 0 to 18 years using the modified Oral Assessment Guide (OAG). Of the 105 patients analyzed, 57 (54.3%) were boys with 7.3 years (±5.2) mean age. Hematologic neoplasms accounted for 51.4% of all cases. RESULTS: Voice, lips, tongue, and saliva changes were not significantly different (p>0.05) between patients with solid or hematologic tumors and during the follow-up. From the 6th until the 10th week of chemotherapeutic treatment alterations in swallowing function, in the mucous membrane (buccal mucosa and palate), in the labial mucosa, and in the gingiva occurred and were distributed differently between the two tumors groups (p<0.05). The main alterations were observed in patients with hematologic tumors. CONCLUSION: It was concluded that the oral changes during the chemotherapeutic treatment occurred especially in swallowing function, in the mucous membrane, in the labial mucosa and in the gingiva, and these alterations were found mainly in patients with hematologic tumors.

Differences between the oral changes presented by patients with solid and hematologic tumors during the chemotherapeutic treatment

Abstract Objective: This study sought to identify the differences between the oral changes presented by patients with solid and hematologic tumors during chemotherapeutic treatment. Methodology: This is an observational, prospective and quantitative study using direct documentation by follow-up of 105 patients from 0 to 18 years using the modified Oral Assessment Guide (OAG). Of the 105 patients analyzed, 57 (54.3%) were boys with 7.3 years (±5.2) mean age. Hematologic neoplasms accounted for 51.4% of all cases. Results: Voice, lips, tongue, and saliva changes were not significantly different (p>0.05) between patients with solid or hematologic tumors and during the follow-up. From the 6th until the 10th week of chemotherapeutic treatment alterations in swallowing function, in the mucous membrane (buccal mucosa and palate), in the labial mucosa, and in the gingiva occurred and were distributed differently between the two tumors groups (p<0.05). The main alterations were observed in patients with hematologic tumors. Conclusion: It was concluded that the oral changes during the chemotherapeutic treatment occurred especially in swallowing function, in the mucous membrane, in the labial mucosa and in the gingiva, and these alterations were found mainly in patients with hematologic tumors.