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Intraoral stents have been provided to minimize acute and chronic toxicities induced by radiotherapy, including oral mucositis, salivary changes, trismus, radiation-related caries, and osteoradionecrosis. However, a systematic review and meta-analysis is necessary to determine their effectiveness.The purpose of this systematic review and meta-analysis was to determine the effectiveness of intraoral stent use and determine whether these prosthetic devices can reduce radiation dosage to nontargeted oral tissues and adverse effects related to head and neck radiation.Two independent reviewers made a systematic search for articles published from January 2010 to March 2020 in 3 databases, supplemented by a manual search. Studies were included if they were clinical trials (randomized controlled trials, both prospective and retrospective), published in English, and evaluated radiation dose and oral adverse side effects (acute or chronic) induced by radiotherapy of participants with and without intraoral stents.The search strategy identified 201 studies; of which, 9 were included. A total of 251 participants were evaluated; of whom, 168 (77.3%) used intraoral stents and 57 (22.7%) were treated with radiotherapy without a prosthetic device. A statistically significant difference was found regarding the use of intraoral stents for preventing oral mucositis (P.001), salivary changes (P=.003), and trismus (P.02). A funnel plot showed asymmetry among the differences of means in all selected studies.Intraoral stents have a positive effect on preventing oral mucositis. Further clinical trials are needed to address the flaws identified in the present systematic review.

We performed a systematic review dedicated to pooling evidence for the associations of clinical features with malignant transformation (MT) and recurrence of 3 oral potentially malignant disorders (OPMDs) (actinic cheilitis [AC], oral leukoplakia [OL], and proliferative verrucous leukoplakia [PVL]).We selected studies that included clinical features and risk factors (age, sex, site, size, appearance, alcohol intake, tobacco use, and sun exposure) of OL, PVL, and AC associated with recurrence and/or MT.Based on the meta-analysis results, non-homogeneous OL appears to have a 4.53 times higher chance of recurrence after treatment. We also found 6.52 higher chances of MT of non-homogeneous OL. Another clinical feature related to higher MT chances is the location (floor of the mouth and tongue has 4.48 higher chances) and the size (OL with200 mmOur study showed that some clinical features may indicate greater chances of recurrence after treatment and MT of OPMD.

Purpose To assess the safety and efficacy of prophylactic extraoral photobiomodulation (PBM) for the prevention of oral and oropharyngeal mucositis (OM) on clinical outcomes and survival in patients with oral cavity and oropharyngeal squamous cell carcinoma (OOPSCC). Methods OOPSCC patients who received radiotherapy (RT) were prospectively randomized to two groups: prophylactic extraoral PBM and placebo. OM grade (NCI), pain (VAS), analgesia, and anti-inflammatory prescriptions were assessed weekly. Quality of life questionnaires (QoL) were performed at the first and last day of RT. Following RT, participants were evaluated quarterly for oncological outcomes follow-up. Results Fifty-five patients met the inclusion criteria. The first occurrence of OM was observed at week 1, for the placebo group (p = 0.014). Later, OM onset and severity was observed for the PBM group, with first occurrence at week 2 (p = 0.009). No difference in severe OM incidence was observed (p > 0.05). Lower mean pain score was noted at week 7 for the PBM group (2.1) compared to placebo group (4.5) (p = 0.009). Less analgesics (week 3; p = 0.009/week 7; p = 0.02) and anti-inflammatory prescription (week 5; p = 0.0346) were observed for the PBM group. Better QoL scores were observed for the PBM group at last day of RT (p = 0.0034). No difference in overall survival among groups was observed in 1 year of follow-up (p = 0.889). Conclusion Prophylactic extraoral PBM can delay OM onset, reduce pain, and reduce analgesic and anti-inflammatory prescription requirements. Extraoral PBM was associated with better QoL. There was no evidence of PBM impact on oncological outcomes. Trial registration TRN:RBR-4w4swx (date of registration: 01/20/2020). Supplementary Information The online version contains supplementary material available at 10.1007/s00520-021-06625-8.

Made available in DSpace on 2022-04-29T08:35:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Background: Fixed drug eruption is a drug reaction characterized by the recurrent occurrence of erosive or ulcerative lesions in skin or mucosa surfaces upon the use of a specific drug. The occurrence of fixed drug eruption in oral mucosa is rare and ill documented. Case report: A 37-year-old woman who presented with recurrent erosive lesions in the palatal marginal gingiva of the upper first molars for 3 consecutive months. In anamnesis and follow-up, the time association with the intake of piroxicam to treat menstrual pain led us to the diagnosis of fixed drug eruption. Conclusion: Piroxicam is a rare culprit drug to fixed drug eruption, especially in oral mucosa. Department of Stomatology AC Camargo Cancer Center Dental School Department of Conservative Dentistry Federal University of Rio Grande do Sul Department of Oral Diagnosis Piracicaba Dental School University of Campinas (UNICAMP) Oral Oncology Center School of Dentistry of Araçatuba São Paulo State University Serviço de Odontologia Oncológica Instituto do Câncer do Estado de São Paulo ICESP-FMUSP Faculdade de Medicina da Universidade de São Paulo Dental School University Brasil Oral Oncology Center School of Dentistry of Araçatuba São Paulo State University

While altered protein glycosylation is regarded a trait of oral squamous cell carcinoma (OSCC), its heterogeneous glycoproteome and dynamics with disease progression remain unmapped. To this end, we here employ an integrated multi-omics approach comprising unbiased and quantitative glycomics and glycoproteomics applied to a valuable cohort of resected tumour tissues from OSCC patients with (n = 19) and without (n = 12) lymph node metastasis. While all tumour tissues displayed uniformN-glycome profiles suggesting relatively stable globalN-glycosylation during lymph node metastasis, glycoproteomics and advanced correlation analysis notably uncovered altered site-specificN-glycosylation and previously unknown associations with several key clinicopathological features. Importantly, focused analyses of the multi-omics data unveiled twoN-glycans and threeN-glycopeptides that were closely associated with patient survival. This study provides novel insight into the complex OSCC tissueN-glycoproteome forming an important resource to further explore the underpinning disease mechanisms and uncover new prognostic glyco-markers for OSCC.TeaserDeep survey of the dynamic landscape of complex sugars in oral tumours paves a way for new prognostic disease markers.

The poor prognosis of head and neck cancer (HNC) is associated with metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision-making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identify nodal metastasis signatures in blood and saliva. We present a proteomic characterization wiring multiple sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures.

Purpose: Radiation caries (RC) is a highly prevalent chronic complication of head and neck radiotherapy (HNRT) and a challenge for clinicians and patients. The present study aimed to assess the impact of RC on the morbidity and mortality outcomes of head and neck squamous cell carcinoma (HNSCC) patients. Methods: Patients were divided into 3 groups: RC (n=20), control (n=20) and edentulous (n=20). Information regarding the number of appointments, dental procedures, osteoradionecrosis (ORN), prescriptions, and hospital admissions werecollected. Mortality outcomes were assessed through disease-free survival (DFS) and overall survival (OS) rates. Results: RC patients required more dental appointments (pConclusion: RC impacts morbidity outcomes for cancer survivors due to increased demand for medication prescriptions, multiple specialized dental appointments, invasive surgical treatments, risk of ORN, and hospital admissions.

Background Plasma cell neoplasms are characterized by the proliferation of a single clone of plasma cells with production of a monoclonal immunoglobulin. They can manifest as a single lesion (plasmacytoma) or as multiple lesions (multiple myeloma). Methods Paraffin-embedded tissue blocks of patients microscopically diagnosed with plasma cell neoplasms in the jaws were retrieved from five pathology files. Data including clinical, radiographic, microscopic and immunohistochemical findings, treatment employed, and follow-up status were retrieved from the pathology reports. Results Fifty-two cases were retrieved (mean age: 59.4 years) without sex predilection. The mandible was the most affected site (67.3%), usually associated with pain and/or paresthesia (53.8%). Lesions in other bones besides the jaws were reported for 24 patients (46.2%). Radiographically, tumors usually presented as poorly defined osteolytic lesions with unilocular or multilocular images, while microscopy revealed diffuse proliferation of neoplastic plasma cells with nuclear displacement and abundant eosinophilic cytoplasm. Two cases were classified as anaplastic, and amyloid deposits were found in two other cases. Immunohistochemistry was positive for plasma cell markers and negative for CD20 and CD3, and monoclonality for kappa light chain predominated. The overall survival rate after 5-years of follow-up was 26.6%. Conclusion Plasma cell neoplasms are aggressive tumors with a poor prognosis and involvement of the jaws may be the first complaint of the patient. Thus, oral pathologists, head and neck surgeons and dentists should be aware of their clinical, radiographic and microscopic manifestations.

Objective The aim of this study was to evaluate the influence of viral load and lymphocyte count on survival of patients who presented with human immunodeficiency virus (HIV)-associated oral Kaposi's sarcoma. Study Design Thirty-one cases (from January 2010 to December 2019) of oral Kaposi's sarcoma in patients with HIV from 2 oral pathology centers in Brazil were reviewed, considering clinical data and correlation of viral load and lymphocyte count with overall survival. Overall survival rates were estimated by a Kaplan-Meier analysis and compared using a log-rank test. The factors introduced stepwise into a Cox proportional hazard model to identify the independent predictors of survival. A P value Results Most of the patients were males (90.3%) with a mean age of 32.4 years (range, 19-58). Hard palate, soft palate, and tongue were the most affected sites. Treatment, viral load >999 copies/mL, CD4+ level ≤200 cells/mm3, CD4+/CD8+ level ≤0.39 cells/mm3, and CD4+ nadir level Conclusions Survival of patients affected by oral HIV-associated Kaposi's sarcoma is influenced by treatment, viral load, CD4+, CD4+/CD8+, and CD4+ nadir count.

To identify and summarize the evidence on the cost-effectiveness of photobiomodulation (PBM) therapy for the prevention and treatment of cancer treatment-related toxicities. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE). Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 1490 studies were identified, and after a two-step review, 4 articles met the inclusion criteria. The included studies analyzed the cost-effectiveness of PBM therapy used in the context of lymphedema for breast cancer and oral mucositis (OM) induced by chemotherapy and radiotherapy. Better outcomes were associated with PBM therapy. The incremental cost-effectiveness ratio ranged from 3050.75 USD to 5592.10 USD per grade 3–4 OM case prevented. PBM therapy cost 21.47 USD per percentage point reduction in lymphedema in comparison with 80.51 USD for manual lymph drainage and physical therapy. There is limited evidence that PBM therapy is cost-effective in the prevention and treatment of specific cancer treatment-related toxicities, namely, OM and breast cancer-related lymphedema. Studies may have underreported the benefits due to a lack of a comprehensive cost evaluation. This suggests a wider acceptance of PBM therapy at cancer treatment centers, which has thus far been limited by the number of robust clinical studies that demonstrate cost-effectiveness for the prevention and treatment of toxicities.

Neuroblastoma is the most common extracranial solid cancer of infancy, occurring mainly in the adrenal gland, with high metastatic potential. However, involvement of the head and neck region is rare. Here, we present two cases of metastatic neuroblastoma of childhood, in which a mandibular swelling was the first sign of disseminated disease. Case 1 describes a 4-year-old boy with a 2-week history of painful swelling in the left mandibular region, body soreness and weakness. Panoramic radiography and computed tomography showed a destructive lesion in the left mandibular ramus. Case 2 describes a 3-year-old boy with a 1-month history of swelling in the right mandibular area. Panoramic radiograph and cone-beam computed tomography showed a destructive lesion in the right body and ramus of the mandible, displacing tooth germs, with the destruction of vestibular and lingual bone cortices. In both cases, microscopic analyses revealed a diffuse proliferation of small, round, and blue cells with hyperchromatic nuclei and scant cytoplasm. While Case 1 was more undifferentiated, Case 2 presented eosinophilic areas suggestive of neuropil. A large immunohistochemical panel was performed, showing expression of neural markers such as CD56, neuron-specific enolase (in Case 2), chromogranin, and synaptophysin. Both lesions presented a high proliferation index (Ki67 > 70% and 80%, respectively). Positron emission tomography-computed tomography revealed ipsilateral adrenal primary lesions in both cases, with multiple bone metastatic lesions. Besides the mandible, multiple sites of the axial and appendicular skeleton were affected. Treatment consisted of induction chemotherapy, adrenalectomy, consolidation chemoradiotherapy, and post-consolidation therapy.

Purpose: This study aimed to characterize the barriers faced by Brazilian dentists to deliver bad news (DBN) about oral and oropharyngeal cancer diagnoses to patients by using a questionnaire based on the guidelines of the SPIKES protocol. Methods: This was an observational cross-sectional study. The questionnaire contained 27 questions based on the SPIKES protocol, which were answered in the SurveyMonkey platform. Results: A total of 186/249 dentists answered the questionnaire. The main specialties reported were 36.02% oral medicine, 21.5% oral pathology, and 9.13% oral and maxillofacial surgery. A total of 44.6% expressed concern about the patient’s emotional reactions, and 46.24% of respondents had never participated in any specific training to communicate bad news. Conclusion: The lack of training and low confidence in dealing with patients’ emotional reactions dentists were considered the greatest barriers to DBNs. Moreover, most dentists who participated in the survey believe that a protocol to guide the communication of bad news would be useful for clinical practice. For those protocols to be used by dentists, training is critical for these protocols to be incorporated by professionals.

Purpose: To characterize oral and oropharyngeal squamous cell carcinoma (OOPSCC) patients with dental needs before cancer treatment and to correlate their baseline characteristics with cancer treatment-related toxicities. Methods: A prospective cohort study that recruited OOPSCC patients referred to the Dental Oncology Service at the Instituto do Câncer do Estado de São Paulo, Brazil, for dental treatment between November/2019 and December/2020. Comorbidities, sociodemographic data, medication in use, treatment-related toxicities and altered laboratory tests results were correlated. Results: 110 patients were included. The most common comorbidities reported and altered laboratory results were respectively hypertension, dyslipidemia, diabetes and C-reactive protein, hemoglobin, and hematocrit. Toxicities were progressive over time. There was no correlation between the comorbidities and cancer treatment-related toxicities. There was a positive correlation between medications in use and oral mucositis (OM) and a negative correlation between medications and dysgeusia. OM was associated with altered laboratory findings, including thyroxine (T4) and free thyroxine (FT4) starting at D15; calcium at D5/10/30; urea at D25/30/33-35; creatinine at D15/30; alkaline phosphatase at D20/25; syphilis at D15/30. Family income and housing were OM predictors. Oral candidiasis (OC) was associated with syphilis and HIV at D20. Conclusion: Laboratory findings including altered T4, FT4, urea, calcium, alkaline phosphatase, creatinine, and syphilis may be useful clinical predictors of OM. Syphilis and HIV may also be considered reliable predictors of OC secondary to OOPSCC treatment. Despite the high frequency of comorbidities and abnormal laboratory results, dental treatment before cancer treatment resulted in no adverse events in our sample.

Made available in DSpace on 2021-06-25T10:47:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Leishmaniasis is a parasitic disease considered an endemic public health problem in developing countries, where it is a reportable disease. Isolated oral manifestation is rare, and its clinical manifestations are variable. In this paper we describe an unusual case of an immunocompetent patient, 57-year-old man with a painless reddish submucosal nodule located on the tongue dorsum. Microscopical analysis showed chronic inflammatory infiltrate with macrophages containing leishmania in cytoplasmic vacuoles. PCR assays confirmed the diagnosis and patient was treated with meglumine antimoniate for 30 days. Absence of the parasite was confirmed by PCR. Thirteen years after treatment, a scar fibrosis persisted on the tongue dorsum. The case reported reveals that leishmaniasis should be considered in the diagnosis of tongue nodules in immunocompetent patients. Oral Oncology Center School of Dentistry São Paulo State University (Unesp), 1193 José Bonifácio St Dental Oncology Service São Paulo State Cancer Institute (ICESP-FMUSP) University of São Paulo Medical School Department of Diagnosis and Surgery São Paulo State University (Unesp) School of Dentistry, 1193 José Bonifácio St Oral Oncology Center School of Dentistry São Paulo State University (Unesp), 1193 José Bonifácio St Department of Diagnosis and Surgery São Paulo State University (Unesp) School of Dentistry, 1193 José Bonifácio St

Evaluate the abundance of the selected targets, alpha-1-antitrypsin (A1AT) and macrophage migration inhibitory factor (MIF), and correlate these findings with the risk of developing severe oral mucositis (OM). Head and neck squamous cell carcinoma (HNSCC) patients submitted to radiotherapy (RT) or chemoradiotherapy (CRT) were assessed. OM grade and pain were evaluated daily during treatment. Two protein targets, A1AT and MIF, were evaluated, using selected reaction monitoring-mass spectrometry (SRM-MS), in whole saliva, collected prior to oncologic treatment. The results obtained from the targeted proteomic analysis were correlated with OM clinical outcomes. A total of 27 patients were included, of whom 21 (77.8%) had locally advanced disease (clinical stage III or IV). Most patients (70.4%) received CRT. OM grades 2 (40.8%) and 3 (33.3%) were the most prevalent during RT with a mean highest reported OM-related pain of 3.22 through the visual analogue scale (VAS). The abundance of A1AT and MIF correlated significantly with severe (grades 3 or 4, p

During the current pandemic scenario, maxillofacial rehabilitation specialists involved with supportive care in cancer must transform its practice to cope with COVID-19 and improve protocols that could quickly return the oral function of complex cancer patients who cannot wait for surgical complex rehabilitation. This includes the role of the maxillofacial prosthodontist for the rehabilitation of surgically treated patients with maxillary cancers by the means of filling obturator prostheses that are considered an optimal scientific-based strategy to reduce hospital stay with excellent pain control, oral function (speech, swallowing, mastication, and facial esthetics), psychologic and quality of life outcomes for the patients following intraoral cancer resection. Therefore, the aim of this commentary was to bring new lights to the strategic use of obturator prostheses for the rehabilitation of oral cancer patients during the COVID-19 pandemic as well as to present a protocol for managing such cases.

To characterize oral sites affected by radiation-induced oral mucositis (OM) and related clinical outcomes in oral cancer patients subjected to prophylactic photobiomodulation therapy (PBMT). This study included advanced oral squamous cell carcinoma (OSCC) patients treated with prophylactic PBMT for OM. The site distribution of OM, OM grading (CTCAE NCI, Version 4.0, 2010), OM-related pain (VAS), analgesic protocol (WHO Analgesic Ladder), and use of enteral nutrition were evaluated weekly during treatment. Data analysis was performed using descriptive statistics expressed as median values and percentages. A total of 145 OSCC patients were included. OM most frequently affected the lateral border of the tongue (44.1%), buccal mucosa (37.2%), and labial mucosa (33.8%). Keratinized oral mucosa sites, including the tongue dorsum (6.21%), retromolar trigone (8.3%), and hard palate (2.76%), were less frequently affected. Peak OM scores were observed at weeks 5, 6, and 7, with severe OM (NCI grades 3 and 4) rates of 11%, 20%, and 25%, respectively. The cumulative occurrence of severe OM was 23%, which developed as early as week 3 and as late as week 7. The highest mean value of OM-related pain (2.7) was observed at the sixth week, and 13.8% of the patients required feeding support. This study showed, compared with studies that did not provide PBMT, reduced severity of mucositis, reduced pain and analgesic use, and reduced tube feeding in patients treated with PBMT. OM involving keratinized and non-keratinized surfaces should be included in the prophylactic PBMT to reduce severe OM in future studies.

Background The aim of this work was to evaluate the microscopic characteristics through polarized light microscopy, scanning electron microscopy and the mineral content of circumpulpal dentin of irradiated (IT) and non-irradiated teeth (NIT), with deep caries that reached the root canal. Material and methods A total of 25 IT were analyzed macroscopically, and radiographed. 5 NIT were used as controls. Two 100-μm-thick sections, per specimen, were evaluated in a polarized light microscopy and a scanning electron microscope. Demographics and clinical data were collected. Results The results did not demonstrate distinct morphology of the IT compared with NIT. Mineral content values by weight percentage of Ca and P were also similar, corresponding to 66.65% and 33.21% in the IT and 66.60% and 33.29% in the NIT. The Ca/P ratio did not show statistical differences between groups being respectively 2.74 and 2.72, in the IT and NIT (p> 0.05). Conclusions Radiotherapy does not change morphology and mineral content of circumpulpal dentin in IT. Key words:Root canal, radiation-related caries, polarization microscopy, scanning electron microscopy, radiotherapy, oral neoplasms, dentin.

To evaluate cancer treatment-related toxicities in young head and neck cancer (HNC) patients.A total of 44 patients were included in the present retrospective cohort study, which was designed to access oral toxicities of cancer treatment in young ( 45 years of age, Group I, n = 22) and old ( 58 years of age, Group II, n = 22) HNC patients with similar tumor stage and treatment protocols. Oral mucositis (OM), xerostomia, dysphagia, dysgeusia, trismus, and radiodermatitis were assessed during days 7th, 21st, and 35th of head and neck radiotherapy (HNRT) according to previously validated scales (World Health Organization criteria and the National Cancer Institute and Common Terminology Criteria for Adverse Events version 4.0).Patients from both groups showed high incidence and severity of oral toxicities by the end of the HNRT with OM (81.9% (Group I); 63.6% (Group II)) and xerostomia (72.6% (Group I); 77.2% (Group II)) being the most prevalent toxicities. No differences regarding xerostomia, dysphagia, dysgeusia, and radiodermatitis incidences or severity could be observed between groups. However, higher incidences and severity of OM at 21st and 35th fractions (odds ratio = 2.22 and 5.71, respectively) and trismus at 21st and 35th fractions (odds ratio = 6.17 and 14.5, respectively) were observed throughout the treatment in young patients when compared to older patients (p 0.01 and p 0.05, respectively).Young HNC patients are more affected by cancer treatment-related OM and trismus despite the similarities in clinical staging and treatment protocols with elderly patients.

Radiation-related caries (RRC) is a disease with a high potential for destruction of the dentition, which impairs quality of life in head-and-neck (HN) cancer (HNC) patients who undergo radiotherapy. In light of the recently described “clustering of oral symptoms theory,” the present systematic review (PROSPERO CRD42019132709) aims to assess HN and gastrointestinal (GI) symptom clusters among HNC patients and discusses how these indirect effects of cancer therapy play a pivotal role in the pathophysiology of RRC. The search was performed at PubMed, Scopus, and Embase and resulted in 11 studies that met the inclusion criteria. Data extraction was performed with respect to the presence of HN/GI symptom clusters among HNC patients. The methodological data of the studies included were assessed using the MAStARI and GRADE instruments. The most prevalent reported HN symptoms were dysphagia, xerostomia, and pain. Taste alterations and fatigue were also commonly reported by the patients. Loss of appetite and weight loss were regularly reported in the studies, as well as nausea and vomiting. The results of the present study suggest that HNC treatment generates clusters of oral symptoms, leading to dietary changes, impaired oral hygiene, enamel fragility, and a highly cariogenic oral environment, which may impact the risk for RRC. A better understanding of oral symptom clustering could be of considerable clinical significance for the oral health and quality of life of HNC patients. Therefore, contemporary protocols of RRC prevention must take this broader treatment scenario of symptom clusters such as oral side effects into account.

Teeth with poor prognosis are generally recommended to be extracted prior to head and neck radiotherapy (RT) to reduce the risk of developing osteoradionecrosis (ORN), although controversies have been reported. The present systematic review aimed to determine whether tooth extraction prior to head and neck RT may be associated with a reduced risk of developing ORN compared to dental extraction during or after RT.The review protocol was registered in PROSPERO (CRD42021241631). The review was reported according to the PRISMA checklist and involved a comprehensive search of PubMed, Scopus, Embase, Cochrane Library, LILACS, and Web of Science, in addition to the gray literature. The selection of studies was performed in two phases by two reviewers independently. The risk of bias of individual studies was analyzed using the Joanna Briggs Institute checklist for cross-sectional studies, and the certainty of evidence was assessed using the GRADE tool.Twenty-eight observational studies were included in the qualitative synthesis, which showed substantial heterogeneity regarding the association between the timing of tooth extraction and ORN development. Twenty-seven of 28 studies were pooled in a meta-analysis that demonstrated a significant association between an increased risk of ORN and post-RT tooth extraction (odds ratio: 1.98; 95% CI: 1.17-3.35; p = 0.01).It was confirmed with moderate certainty that dental extractions should be performed prior to the start of head and neck RT to reduce the risk of ORN.

High-risk (HR) human papillomavirus (HPV) infection is recognized as a primary etiologic factor of anogenital cancers and more recently of a subgroup of oropharyngeal squamous cell carcinomas (OPSCC). The incidence of HPV-related OPSCC has increased dramatically in several developed countries in the past 3 decades and is currently the most common cancer caused by HR-HPV in the United States and Germany, surpassing cervical cancer. Consequently, the patient's demographic and clinicopathologic profile has shifted to nonsmoking and nondrinking younger men with higher schooling level and with a history of multiple oral sex partners. Patients with HPV-related OPSCC often show better treatment outcomes and higher survival rates than their HPV-unrelated counterparts, which has led to a change in tumor staging for HPV-related cases. HPV vaccination is emerging as an effective primary prevention strategy, and systematic screening of HPV DNA in blood and salivary oral rinse samples of HR patients is being examined to determine if it may provide a surveillance method and support early diagnosis of HPV-related OPSCC. In this context, a narrative review was conducted to provide an overview of the state-of-the-art of HPV-related OPSCC, including epidemiology, risk factors, clinicopathologic and molecular features, screening, prevention, management, and prognosis.

This review outlines the historical perspective, status, and future challenges of oral medicine (stomatology) in Brazil based on the records of the Brazilian Society of Stomatology and Oral Pathology (SOBEP) and the Brazilian Federal Dental Council as well as expert evidence input from academic leaders from 3 different generations of Brazilian oral medicine specialists. The beginning of oral medicine in Brazil dates to 1969, followed by the organization of SOBEP in 1974; however, official recognition as an independent specialty was achieved more recently within the Brazilian Federal Dental Council in 1992. After a 50-year maturation period of oral medicine in Brazil in terms of specialty crystallization across dentistry, medicine, and research, it is now time to follow the historical trends of the specialty internationally and establish a standard curriculum at a post-graduate level that will lead to uniformity of training for oral medicine in Brazil.

SUMMARYThe poor prognosis of head and neck cancer (HNC) is associated with the presence of metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identified a nodal metastasis signature in the blood and saliva. In summary, we present the deepest proteome characterization wiring multiple sampling sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures.

Photobiomodulation therapy (PBMT) has been considered an effective method for preventing and managing certain cancer-related toxicities in head and neck cancer (HNC) patients treated with radiotherapy and chemotherapy. However, the potential effects of PBMT on pain control and analgesia resulting from these toxicities is still controversial. The aim of this systematic review was to compile available evidence of the effects of PMBT on pain control and reduced use of analgesics in HNC patients. We searched three indexed databases: MEDLINE/PubMed, Embase, and Scopus. The databases were reviewed up to and including December 2018. Only human clinical studies in English language were selected. Information was only available for mucositis and radiodermatitis. Fifteen out of 1112 studies met the inclusion criteria (14 for oral mucositis (OM) and 1 for radiodermatitis). From the 14 studies involving the prevention and treatment of OM, 10 had the study subjects compared to a placebo group. Of these 10 studies, all but 1 showed statistically significant difference related to pain control favoring the PBMT group. The study that compared PBMT with other treatment modality showed better results in pain control with PBMT. It appears that PBMT application frequency and potency impact on pain control. The only study involving the prevention and treatment of radiodermatitis was compared to placebo arm and showed statistically significant difference related to pain control favoring the PBMT group. Seven studies compared the need of analgesic medication between PBMT and placebo groups. Of these, five studies showed that the use of analgesic medication was significantly higher in the placebo group. The current evidence supports that PBMT is effective in pain control resulting from OM and radiodermatitis and may also reduce the need for analgesics. The evidence is not yet available of the effects of PBMT in other HNC treatment-related toxicities.

Photobiomodulation therapy (PBMT), also known as low-level laser therapy (LLLT), has been increasingly used for the treatment of toxicities related to cancer treatment. One of the challenges for the universal acceptance of PBMT use in cancer patients is whether or not there is a potential for the light to stimulate the growth of residual malignant cells that evaded oncologic treatment, increasing the risk for tumor recurrences and development of a second primary tumor. Current science suggests promising effects of PBMT in the prevention and treatment of breast cancer-related lymphedema and oral mucositis, among other cancer treatment toxicities. Nevertheless, this seems to be the first systematic review to analyze the safety of the use of PBMT for the management of cancer-related toxicities. Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 27 articles met the search criteria. Selected studies included the use of PBMT for prevention and treatment of oral mucositis, lymphedema, radiodermatitis, and peripheral neuropathy. Most studies showed that no side effects were observed with the use of PBMT. The results of this systematic review, based on current literature, suggest that the use of PBMT in the prevention and management of cancer treatment toxicities does not lead to the development of tumor safety issues.

Background Radiation-related caries (RRC) is one of the most significant oral toxicities of head and neck radiotherapy (HNRT); however, the potential of radiation to directly cause harmful dentin and pulpal effects and impair response to caries progression is controversial. Material and Methods Therefore, the aim of this study was to characterize the reactions of the dentin-pulp complex in teeth affected by RRC. Patients and methods: Twenty-two carious teeth extracted from 22 head and neck cancer (HNC) patients were divided into control (conventional caries; n=11) and irradiated (RRC; n=11) groups and paired matched by dental homology, clinical patterns of caries progression following the Post-Radiation Dental Index (PRDI) and microscopic depth of carious invasion. Histopathological characteristics based on morphological hierarchy, cell populations of dental pulp, blood vessels, neural elements, extracellular matrix components, inflammation, patterns of carious invasion and reactionary dentin presence were evaluated by optical light microscopy and histomorphometry. Results Mean PRDI scores were 3.2 for the control group and 3.8 for the irradiated group. Dentin demineralization patterns were also similar between the groups and the mean depths of demineralization were 1,158.58µm and 1,056.89µm for the control and irradiated groups, respectively. Conclusions Pulp histopathological changes and dentin reaction patterns were similar between groups and varied according to the PRDI scores and carious lesions depth. Dentin and pulp reactions are highly preserved in RRC teeth. Key words:Cancer, radiotherapy, radiation-related caries, teeth, pulp.

Validation studies of whole slide imaging (WSI) systems produce evidence regarding digital microscopy (DM). This systematic review aimed to provide information about the performance of WSI devices by evaluating intraobserver agreement reported in previously published studies as the best evidence to elucidate whether DM is reliable for primary diagnostic purposes. In addition, this review delineates the reasons for the occurrence of discordant diagnoses. Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 13 articles were included. The total sample of 2145 had a majority of 695 (32.4%) cases from dermatopathology, followed by 200 (9.3%) cases from gastrointestinal pathology. Intraobserver agreements showed an excellent concordance, with values ranging from 87% to 98.3% (κ coefficient range 0.8-0.98). Ten studies (77%) reported a total of 128 disagreements. The remaining three studies (23%) did not report the exact number and nature of disagreements. Borderline/challenging cases were the most frequently reported reason for disagreements (53.8%). Six authors reported limitations of the equipment and/or limited image resolution as reasons for the discordant diagnoses. Within these articles, the reported pitfalls were as follows: difficulties in the identification of eosinophilic granular bodies in brain biopsies; eosinophils and nucleated red blood cells; and mitotic figures, nuclear details, and chromatin patterns in neuropathology specimens. The lack of image clarity was reported to be associated with difficulties in the identification of microorganisms (e.g., Candida albicans, Helicobacter pylori, and Giardia lamblia). However, authors stated that the intraobserver variances do not derive from technical limitations of WSI. A lack of clinical information was reported by four authors as a source for disagreements. Two studies (15.4%) reported poor quality of the biopsies, specifically small size of the biopsy material or inadequate routine laboratory processes as reasons for disagreements. One author (7.7%) indicated the lack of immunohistochemistry and special stains as a source for discordance. Furthermore, nine studies (69.2%) did not consider the performance of the digital method-limitations of the equipment, insufficient magnification/limited image resolution-as reasons for disagreements. To summarize the pitfalls of digital pathology practice and better address the root cause of the diagnostic discordance, we suggest a Categorization for Digital Pathology Discrepancies to be used in further validations studies. Among 99 discordances, only 37 (37.3%) had preferred diagnosis rendered by means of WSI. The risk of bias and applicability concerns were judged with the QUADAS-2. Two studies (15.4%) presented an unclear risk of bias in the sample selection domain and 2 (15.4%) presented a high risk of bias in the index test domain. Regarding applicability, all studies included were classified as a low concern in all domains. The included studies were optimally designed to validate WSI for general clinical use, providing evidence with confidence. In general, this systematic review showed a high concordance between diagnoses achieved by using WSI and conventional light microscope (CLM), summarizes difficulties related to specific findings of certain areas of pathology-including dermatopathology, pediatric pathology, neuropathology, and gastrointestinal pathology-and demonstrated that WSI can be used to render primary diagnoses in several subspecialties of human pathology.

Objectives Ameloblastoma is an odontogenic epithelial tumour with a low expression of mismatch repair system components. We aimed to investigate the methylation status of the genes MSH2, MSH3 and MSH6 (MutS group) in conventional ameloblastomas. Materials and methods The ameloblastoma and dental follicle samples (n = 10 each) were collected from 20 different patients. Each ameloblastoma sample was sectioned into two fragments: one was paraffin-embedded while the other one, likewise the dental follicle samples, was fixed in RNAlater and frozen at -196°C. All frozen samples were investigated for the MutS genes methylation levels, using the enzymatic restriction digestion and quantitative real-time PCR (qPCR) assay. The ameloblastoma paraffin-embedded samples were submitted to immunohistochemical reactions for MutS proteins detection and digitally quantification. Correlation analyses were performed between the immunohistochemical results and the respective gene methylation percentage. Results There are no significant differences between the MutS genes methylation levels in the ameloblastoma and the dental follicle. However, a strong negative correlation was found between MSH2 and MSH6 gene methylation status and their respective proteins expressions evaluated by immunohistochemistry. Conclusion Our results show that the genes methylations is in part responsible for decreasing the expression of MSH2 and MSH6 genes in ameloblastoma.