Mapping Conformational Changes in the Saliva Proteome Potentially Associated with Oral Cancer Aggressiveness.

Diverse proteomics-based strategies have been applied to saliva to quantitatively identify diagnostic and prognostic targets for oral cancer. Considering that these targets may be regulated by events that do not imply variation in protein abundance levels, we hypothesized that changes in protein conformation can be associated with diagnosis and prognosis, revealing biological processes and novel targets of clinical relevance. For this, we employed limited proteolysis-mass spectrometry in saliva samples to explore structural alterations, comparing the proteome of healthy control and oral squamous cell carcinoma (OSCC) patients with and without lymph node metastasis. Thirty-six proteins with potential structural rearrangements were associated with clinical patient features including transketolase and its interacting partners. Moreover, N-glycosylated peptides contribute to structural rearrangements of potential diagnostic and prognostic markers. Altogether, this approach utilizes saliva proteins to search for targets for diagnosing and prognosing oral cancer and can guide the discovery of potential regulated sites beyond protein-level abundance.

Barriers to early diagnosis and management of oral cancer in Latin America and the Caribbean.

OBJECTIVE: This study aimed to explore perceived barriers to early diagnosis and management of oral cancer, as well as potential pathways for improvement in Latin America and the Caribbean (LAC). METHODS: This cross-sectional study used a self-administered online questionnaire created via the Research Electronic Data Capture platform. The survey was distributed to health professionals trained in Oral Medicine, Oral Pathology, Oral and Maxillofacial Surgery, and Dentists with clinical and academic expertise in oral potentially malignant disorder (OPMD) and oral cancer. Data obtained were systematically organized and analyzed descriptively using Microsoft Excel. RESULTS: Twenty-three professionals from 21 LAC countries participated. Major barriers included the limited implementation of OPMD and oral cancer control plans (17.4%), low compulsory reporting for OPMD (8.7%) and oral cancer (34.8%), unclear referral pathways for OPMD (34.8%) and oral cancer (43.5%), and a shortage of trained professionals (8.7%). Participants endorsed the utility of online education (100%) and telemedicine (91.3%). CONCLUSION: The survey highlights major perceived barriers to early diagnosis and management of OPMD and oral cancer in LAC, as well as potential avenues for improvement.

To extract or not extract teeth prior to head and neck radiotherapy? A systematic review and meta-analysis.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

DNA methylation status of MutS genes in ameloblastoma.

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.

Impact of head and neck radiotherapy on the longevity of dental adhesive restorations: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Established restorative protocols for patients after head and neck radiotherapy are lacking, increasing the failure rates of dental adhesive restorations. PURPOSE: The purpose of this systematic review and meta-analysis was to analyze the evidence regarding the impact of head and neck radiotherapy on the longevity of dental adhesive restorations. MATERIAL AND METHODS: A search was performed using PubMed, Scopus, and Embase in May 2018 (updated in November 2020). Data extraction was performed regarding the percentage of restoration failure among dental adhesive materials, including glass ionomer cements, resin-modified glass ionomer cements, and composite resins. Risk of bias was assessed by the meta-analysis of statistics assessment and review instrument (MAStARI). Confidence in cumulative evidence was evaluated by the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) protocol. RESULTS: Four studies met the inclusion criteria. All included studies were classified as having a moderate risk of bias and reported results regarding class V restorations. Overall, composite resins presented lower failure rates at 2 years (30%) when compared with resin-modified glass ionomer (41%) and glass ionomer cements (57%). Meta-analysis showed that the risk of failure with glass ionomer cements was greater than with resin-modified glass ionomer cements (RR: 1.71, P<.001). Composite resins presented lower risk of failure when compared with glass ionomer (RR: 2.29, P<.001) and resin-modified glass ionomer cements (RR: 1.30, P=.03). Three studies reported results regarding fluoride compliance, which had a negative effect on the survival rates of glass ionomer and resin-modified glass ionomer cements and a positive effect on composite resin restorations. CONCLUSIONS: The results suggest that composite resin restorations associated with fluoride gel compliance seems to be the best alternative for restoring class V lesions in patients after head and neck radiotherapy. However, the results showed moderate certainty of evidence, which justifies the need for more randomized clinical trials regarding this subject.

Plasmacytoma and plasma cell myeloma affecting the jaws: A multi-institutional collaborative study.

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, tumours 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 tumours 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.

Salivary alpha-1-antitrypsin and macrophage migration inhibitory factor may be potential prognostic biomarkers for oncologic treatment-induced severe oral mucositis.

AIMS: 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). MATERIALS AND METHODS: 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. RESULTS: 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 < 0.02) compared with moderate-low (grades 1 or 2, p < 0.04) OM grade. CONCLUSIONS: There is a correlation between the abundance of salivary A1AT and MIF and oncologic treatment-induced OM. The correlation of MIF expression with severe OM appears to be compatible with its physiological pro-inflammatory role. These results open up great possibilities for the use of salivary MIF and A1AT levels as prognostic markers for effective therapeutic interventions, such as photobiomodulation therapy, patient-controlled analgesia, or personalized medicaments.

Strategic use of obturator prostheses for the rehabilitation of oral cancer patients during the COVID-19 pandemic.

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.

Management of intraoral stents for radiotherapy during COVID-19 pandemic.

Radiotherapy is being performed in many situations as a curative approach for head and neck cancer instead of surgery due to the current novel coronavirus disease (COVID-19) pandemic. A recent publication reported that even hypofractionation was being conducted in order to reduce the daily exposure of both patients and the medical staff involved in cancer therapies. As a result, dental teams may be requested more frequently than usual to fabricate intraoral stents (IOS). Given that IOS may be a potential source of COVID-19 contagion, the main purpose of the present correspondence is to offer a guide on how health professionals may be safely presented in the room, on the management of the IOS and also how to sanitize the stents.

Dental treatment needs in hospitalized cancer patients: a retrospective cohort study.

PURPOSE: The objectives of this study were to describe the distribution and the clinicopathological features of the most common causes for dental treatment needs during the hospitalization of cancer patients. METHODS: A retrospective cohort study of 2664 hospitalized cancer patients that analyzed the main dental treatment needs and dental procedures performed from January 2010 to December 2017. RESULTS: A total of 2664 medical patients were included in this study. Non-Hodgkin lymphoma (17.2%) was the most common cancer type, followed by leukemia (14.8%), and oral and oropharyngeal squamous cell carcinoma (10.5%). The most common reasons for patients' hospitalization were chemotherapy protocols (18.8%), monitoring head and neck surgeries (9.7%), and febrile neutropenia (9.6%). The main motivation for the medical team to request dental evaluation was oral mucositis (22.8%) followed by oral pain or toothache (10.8%) and fungal, viral oral infections or traumatic oral lesions (9.9%). The dental treatment needs most observed were pain due to oral mucositis (17%), dental treatment prior to radiotherapy (RT), chemotherapy (CT) or bisphosphonate therapy (BP) (10.8%), teeth extractions (6.5%), and prophylactic photobiomodulation therapy (6.3%), whereas the most common dental treatments performed were oral hygiene protocols (30.2%), photobiomodulation therapy (prophylactic and curative) (21.7%), and dental treatment prior to cancer treatment initiation (RT, CT, and BP) (9.5%). CONCLUSION: This study can be considered original in the oncologic context, providing new information about the most frequent dental treatment needs among a large population of hospitalized cancer patients.

The impact of radiation caries in the quality of life of head and neck cancer patients.

PURPOSE: The objective of this multicentre study was to verify the relationship between the scores of quality of life (QoL) and the decayed, missing and filled teeth (DMFT) and radiation caries (RC) in patients treated with radiation therapy (RT) for head and neck cancer, and through this to determine if RC is capable of causing a significant decrease in the QoL. METHODS: One hundred patients were divided into 2 groups: patients with at least 1 year of RT completion who developed RC (study group, n = 50); and patients with at least 1 year of RT completion who did not develop RC (control group, n = 50). All patients answered the Brazilian-Portuguese version of the University of Washington quality of life (UW-QoL) questionnaire, which was divided into physical and social-emotional functioning domains and evaluated the DMFT index score. RESULTS: The mean score of QoL was 927.2 in the control group and 878.1 in the study group (P = 0.24). The mean score of DMFT was 30.5 in the study group and 20.7 in the control group (P = 0.001). The items recreation and saliva, which belong to the physical function domain, showed a statistically significant difference between the study and control groups (P = 0.031 and P = 0.047, respectively). Saliva was the item with the higher number of patient complaints in both groups. CONCLUSION: RC had a negative impact on the QoL of HNC patients.

Postradiation Matrix Metalloproteinase-20 Expression and Its Impact on Dental Micromorphology and Radiation-Related Caries.

Recent evidence suggests that head-and-neck radiotherapy (HNRT) increases active forms of matrix metalloproteinase-20 (MMP-20) in human tooth crowns, degrading the dentin-enamel junction (DEJ) and leading to enamel delamination, which is a pivotal step in the formation of radiation-related caries (RRC). Additional participation of enzymatic degradation of organic matrix components in caries progression was attributed to MMP-20 in dentin. Therefore, the current study tested the hypothesis that MMP-20 is overexpressed in the DEJ, dentin-pulp complex components, and carious dentin of post-HNRT patients, leading to detectable micromorphological changes to the enamel and dentin. Thirty-six teeth were studied, including 19 post-HNRT specimens and 17 nonirradiated controls. Optical light microscopy was used to investigate the micromorphological components of the DEJ, dentin-pulp complex components, and carious dentin. The samples were divided into 2 subgroups: nondemineralized ground sections (n = 20) and demineralized histological sections (n = 16). In addition, immunohistochemical analysis using the immunoperoxidase technique was conducted to semiquantitatively assess MMP-20 expression in the DEJ, dentin-pulp complex components, and carious dentin. No apparent damage to the DEJ microstructure or other dentin-pulp complex components was observed and no statistically significant differences were detected in MMP-20 expression (p > 0.05) between the irradiated and control groups. This study rejected the hypothesis that MMP-20 is overexpressed in the DEJ, dentin-pulp complex components, and carious dentin of post-HNRT patients, leading to detectable micromorphological changes. Hence, direct effects of radiation may not be regarded as an independent factor to explain aggressive clinical patterns of RRC.

Evaluation of use of acrylic resin-based surgical guide in the function and quality of life provided by mandibular prostheses with microvascular free fibula flap: A four-year, randomized, controlled trial.

STATEMENT OF PROBLEM: The correct positioning of the microvascular-free fibula flap (MFFF) is essential for satisfactory mandibular reconstruction. However, the effect of acrylic resin-based surgical guides on prosthetic rehabilitations has not yet been properly investigated. PURPOSE: The purpose of this randomized clinical trial was to evaluate whether intraoral and extraoral acrylic resin-based surgical guides improve anatomic, functional, esthetic, and quality of life (QoL) results for dental prosthetic rehabilitation with MFFF. MATERIAL AND METHODS: Participants subjected to mandibular reconstruction with MFFF were selected and randomly distributed into 2 groups, control (Co; using conventional surgery) and acrylic resin-based surgical guides (Sg). Functional parameters related to prosthetic rehabilitation and QoL were evaluated by interviews and an oral health impact profile (OHIP)-14 questionnaire. Functional parameters and questionnaire scores were subjected to statistical analysis: the likelihood ratio and the Fisher exact and Mann-Whitney U tests (α=.05). RESULTS: Of 40 participants, 18 were rehabilitated, 10 with tooth-tissue-supported partial removable dentures and 8 with implant prostheses. In Sg, the study measured an enhancement in functional parameters and revealed a significant improvement in QoL (P=.020). CONCLUSIONS: The guides proposed directly improved mandibular reconstruction. Functional aspects may be improved by allowing good intermaxillary relationships and posterior dental rehabilitation. Functional success is directly dependent on soft tissue status and the quality of its reconstruction. Soft tissue evaluation is important before dental rehabilitation.

Reported physical examination methods for screening of oral cancer and oral potentially malignant disorders: a systematic review.

OBJECTIVE: This systematic review aimed to describe the method followed during physical examination and the anatomical structures of the head and neck assessed in screening for oral cancer and oral potentially malignant disorders (OPMDs). STUDY DESIGN: An extensive literature search was carried out using MEDLINE/PubMed, EMBASE, Scopus, LILACS, Web of Science, Cochrane databases, and gray literature. The risk of bias was available in all papers included. RESULTS: Of 9,688 records identified, 27 were included in this review, reporting data from 356,250 individuals screened and distributed across 11 countries. Most of these (n = 19) were based on 1 round of screening conducted by a dental professional or other health care workers. Most screening programs included visual inspection and palpation of the lips, oral cavity, and the most visible oropharyngeal sites, but the descriptions reported were imprecise. Additional inspection and palpation of the neck (submental, submandibular, cervical, and supraclavicular regions) to assess for the presence of swellings and any palpable neck nodes were also performed in 15 programs. CONCLUSION: In conclusion, there was considerable heterogeneity in the method of physical examination in screening programs for oral cancer and OPMDs among the included studies.

The impact of radiation caries on morbidity and mortality outcomes of head and neck squamous cell carcinoma patients.

AIMS: Radiation caries (RC) is a highly prevalent and chronic complication of head and neck radiotherapy (HNRT) and presents 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 AND RESULTS: Patients were divided into three groups: (1) RC (n = 20), (2) control (n = 20), and (3) edentulous (n = 20). Information regarding the number of appointments, dental procedures, osteoradionecrosis (ORN), prescriptions, and hospital admissions were collected. Mortality outcomes were assessed through disease-free survival (DFS) and overall survival (OS) rates. RC patients required more dental appointments (p < .001), restorations (p < .001), extractions (p = .001), and antibiotic and analgesic prescriptions (p < .001). Kaplan-Meier subgroup analyses showed a significantly increased risk of ORN in RC compared to edentulous patients (p = .015). RC patients presented lower DFS rates (43.2 months) than the control and edentulous groups (55.4 and 56.1 months, respectively). CONCLUSIONS: RC impacts morbidity outcomes among cancer survivors due to increased demand for medication prescriptions, multiple specialized dental appointments, invasive surgical treatments, increased risk of ORN, and increased need for hospital admissions.

Prospective Cohort Study Identifies Medical Predictors of Treatment-Related Oral Toxicities in Oral and Oropharyngeal Cancer Patients.

The dental treatment of patients with oral cavity and oropharyngeal squamous cell carcinoma (OOPSCC) may be challenging for dentists. This study aimed to characterize systemic changes in patients with OOPSCC undergoing dental treatment prior to cancer therapy, with a specific focus on laboratory assessments. The primary objectives included identifying potential adverse events, such as infections or bleeding, resulting from dental procedures. Additionally, the study aimed to correlate baseline patient characteristics with treatment-related toxicities. This was a prospective cohort study that included 110 OOPSCC patients referred to the Dental Oncology Service at São Paulo State Cancer Institute, Brazil, between November/2019 and December/2020. Comorbidities, sociodemographic data, medication in use, cancer treatment-related toxicities, and altered laboratory tests results were correlated. The most common comorbidities and altered laboratory results were hypertension, dyslipidemia, diabetes, as well as elevated levels of C-reactive protein, hemoglobin, and hematocrit. Toxicities exhibited a progressive pattern over time, encompassing oral mucositis (OM), xerostomia, dysphagia, dysgeusia, trismus, and radiodermatitis. No correlation between comorbidities and cancer treatment-related toxicities, a positive correlation between medications in use and OM, and a negative correlation between medications and dysgeusia were found. OM was associated with altered thyroxine (T4) and free thyroxine (FT4), calcium, urea, creatinine, alkaline phosphatase, and syphilis. Family income and housing were OM predictors. Altered T4/FT4/urea/calcium/alkaline phosphatase/creatinine/syphilis may be useful clinical predictors of OM. Despite the elevated prevalence of comorbidities and abnormal laboratory findings, dental treatment prior to cancer treatment yielded no adverse events.

The first case report of metastatic rectal adenocarcinoma to the oral vestibule in a young woman.

BACKGROUND: The available literature regarding metastasis to the oral cavity from colorectal cancer, especially rectal cancer, is currently limited. With this in mind, we aimed to report the first case of rectal adenocarcinoma metastasis to the oral vestibule. CASE REPORT: A 36-year-old Caucasian female with a 17-months history of rectal adenocarcinoma and several metastases was referred to the Dental Oncology Service due to a nodular swelling in the oral cavity. Intraoral examination showed a large, painless nodule with superficial necrosis on the right side of the mandibular vestibule. An incisional biopsy was performed, and the microscopic analysis demonstrated an infiltrative tumor characterized by islands of malignant epithelial cells with a columnar appearance and tubular pattern. The epithelial component presented pseudoductal structures resemble intestinal mucosa, which exhibited intraluminal secretion. The neoplastic cells were immunoreactive for CDX2 and Cytokeratin 20, and negative for Cytokeratin 7. Therefore, the final diagnosis of metastatic rectal adenocarcinoma was established. Unfortunately, the patient died 23 months after the diagnosis of the primary tumor. CONCLUSION: The study highlights that metastases to the oral cavity should be considered in the differential diagnosis of large reactive lesions affecting young patients, especially in the setting of a patient history of cancer.

Awareness of the risk of radiation-related caries in patients with head and neck cancer: A survey of physicians, dentists, and patients.

OBJECTIVES: Radiation-related caries (RRC) is one of the most aggressive complications of radiotherapy (RT) in survivors of head and neck cancer (HNC). Lack of RRC awareness may contribute to the occurrence of this oral cavity complication. RRC may be considered a "forgotten oral complication" by patients with HNC, oncologists, and dentists. The present study aimed to assess the level of awareness of RRC among physicians, dentists, and patients. STUDY DESIGN: Physicians (group 1, G1), dentists (group 2, G2), and patients with HNC undergoing RT (group 3, G3) answered questionnaires concerning their awareness of RRC. Physicians (G1) were divided into group 1A (oncological experience) and group 1B (general physicians/other specialties). Dentists (G2) were divided into group 2A (oncological experience) and group 2B (general dentists/other specialties). Personalized questionnaires were designed for each group. RESULTS: Recruitment was as follows: physicians (n = 124): 1A (n = 64), 1B (n = 60); dentists: (n = 280), 2A (n = 160), 2B (n = 120). In addition, 58 patients answered the questionnaire. In terms of RRC awareness, 46.77% of physicians, 81.78% of dentists, and 24.13% of patients had some knowledge of the problem. CONCLUSION: Patient awareness of RRC was poor. The heterogeneity of answers among physicians and dentists suggests an opportunity to improve patient education and prevention of this serious oral complication of RT.

Oral lesions in patients with SARS-CoV-2 infection: could the oral cavity be a target organ?

Several viruses transmitted through saliva, such as herpes simplex virus, cytomegalovirus, and Zika virus, are capable of infecting and replicating in the oral mucosa, leading to painful oral ulcers. Few studies have described the oral manifestations of coronavirus disease 2019 (COVID-19). There is growing evidence that angiotensin-converting enzyme 2 (ACE2), the main host cell receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed on the epithelial cells of the tongue and of the salivary glands, which may explain the development of dysgeusia in patients with COVID-19. Hence, it is important to understand if SARS-CoV-2 can infect and replicate in oral keratinocytes and fibroblasts, causing oral ulcerations and superficial necrosis. Here, we report a series of 8 cases of COVID-19 infection, with oral necrotic ulcers and aphthous-like ulcerations which developed early in the course of disease after the development of dysgeusia and affected the tongue, lips, palate, and oropharynx. A short review of the literature regarding the important role of ACE2 in SARS-CoV-2 cellular entry is also provided, bringing new insights into oral keratinocytes and minor salivary glands as potential targets.

Meta-omics analysis indicates the saliva microbiome and its proteins associated with the prognosis of oral cancer patients.

Saliva is a biofluid that maintains the health of oral tissues and the homeostasis of oral microbiota. Studies have demonstrated that Oral squamous cell carcinoma (OSCC) patients have different salivary microbiota than healthy individuals. However, the relationship between these microbial differences and clinicopathological outcomes is still far from conclusive. Herein, we investigate the capability of using metagenomic and metaproteomic saliva profiles to distinguish between Control (C), OSCC without active lesion (L0), and OSCC with active lesion (L1) patients. The results show that there are significantly distinct taxonomies and functional changes in L1 patients compared to C and L0 patients, suggesting compositional modulation of the oral microbiome, as the relative abundances of Centipeda, Veillonella, and Gemella suggested by metagenomics are correlated with tumor size, clinical stage, and active lesion. Metagenomics results also demonstrated that poor overall patient survival is associated with a higher relative abundance of Stenophotromonas, Staphylococcus, Centipeda, Selenomonas, Alloscordovia, and Acitenobacter. Finally, compositional and functional differences in the saliva content by metaproteomics analysis can distinguish healthy individuals from OSCC patients. In summary, our study suggests that oral microbiota and their protein abundance have potential diagnosis and prognosis value for oral cancer patients. Further studies are necessary to understand the role of uniquely detected metaproteins in the microbiota of healthy and OSCC patients as well as the crosstalk between saliva host proteins and the oral microbiome present in OSCC.