ABSTRACT
OBJECTIVE: Dental regulatory bodies aim to ensure the health and safety of dentists, dental staff patients and the public. An important responsibility during a pandemic is to communicate risk and guidelines for patient care. Limited data exist on the perceptions and experiences of dentists navigating new guidelines for mitigating risk in dental care during the pandemic. The objective of this study was to use a qualitative approach to explore how dentists in Canada experienced and perceived their regulatory bodies' communication about COVID-19 risks and guidelines during the pandemic. METHODS: Participants were Canadian dentists (N = 644) recruited through the email roster of nine provincial dental associations or regulatory bodies. This qualitative analysis was nested within a prospective longitudinal cohort study in which data were collected using online questionnaires at regular intervals from August 2020 to November 2021. To address the objective reported in this paper, a conventional qualitative content analysis method was applied to responses to three open-ended questions included in the final questionnaire. RESULTS: Participants encountered challenges and frustrations amid the COVID-19 pandemic, grappling with diverse regulations and communications from dental bodies. While some bodies offered helpful guidance, many participants felt the need for improved communication on guidelines. Dentists urged for expedited, clearer and more frequent updates, expressing difficulty in navigating overwhelming information. Negative views emerged on the vague and unclear communication of COVID-19 guidelines, contributing to confusion and frustration among participants. CONCLUSION: As COVID-19 persists and in planning for future pandemics, these experiential findings will help guide regulatory bodies in providing clear, timely and practical guidelines to protect the health and safety of dentists, dental staff, patients and the public.
Subject(s)
COVID-19 , Dentists , Humans , Canada/epidemiology , COVID-19/prevention & control , COVID-19/epidemiology , Dentists/psychology , Male , Female , Communication , Adult , Attitude of Health Personnel , Prospective Studies , Practice Guidelines as Topic , Longitudinal Studies , Middle Aged , Surveys and Questionnaires , Qualitative Research , Dental Care , SARS-CoV-2ABSTRACT
OBJECTIVES: Motivations and career outcomes of dental hygienists with baccalaureate degrees have been recently reported; however, few studies have explored Canadian dental hygienists pursuing graduate education. There is limited evidence to inform career outcomes and motivating factors for advanced education, limiting knowledge of how professional outcomes have evolved alongside advancements in graduate program offerings. This study focused on understanding motivating factors to pursue graduate education and the professional outcomes of dental hygienists with graduate degrees. METHODS: This nested online anonymous survey was conducted between November and December 2021 with dental hygienists who graduated from one of four Canadian baccalaureate-level dental hygiene degree programs and had further indicated that they were pursuing or had obtained additional graduate-level education (n = 60). Participants were asked to report on any advanced graduate-level education. Open-ended questions on graduate degree education were analysed through thematic analysis. RESULTS: Motivations for pursuing graduate degrees were influenced by personal and professional preferences. Master's degree recipients cited expanded career opportunities, alternate interests, convenience, and dissatisfaction with/desire to leave clinical practice as major motivators. Doctoral degree holding dental hygienists identified expanded/alternate career opportunities as major motivation but also cited program convenience as an influencer. The availability of distance and flexible programming is a novel finding that positively influences the pursuit of advanced education. CONCLUSION: Dental hygienists are pursuing graduate education to expand their scope of knowledge and create new career opportunities. Graduate degree programs that accommodate work-life balance through flexible and online offerings are very attractive to dental hygienists.
Subject(s)
Dental Hygienists , Motivation , Humans , Dental Hygienists/education , Canada , Education, Graduate , Educational Status , Surveys and QuestionnairesABSTRACT
BACKGROUND: Due to the evolving nature of COVID-19, there is evidence that COVID-19-specific infection prevention and control guideline (IPCG) documents formulated for oral health care settings are also changing rapidly. To better inform future policies, a comprehensive review of all IPCG documents across different phases of restrictions for oral health care practitioners is required. TYPES OF STUDIES REVIEWED: A search was performed for documents shared from March 2020 through January 2022 on websites of oral health regulatory authorities in Canada's 10 provinces and 3 territories. The authors performed a narrative review of the identified IPCG documents for dentists (n = 78) and dental hygienists (n = 57). RESULTS: Overall findings from more than 100 IPCG documents distributed during a period of 23 months revealed that the frequency of these updates differed among jurisdictions and between the 2 oral health care practitioners (ie, dentists and dental hygienists) within the same jurisdiction. The most notable observation was the different face-covering recommendations for dentists and dental hygienists within the same jurisdiction during the same timeframe. A common document was sometimes observed for dentists and dental hygienists, however, most jurisdictions had separate IPCG documents. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The different approaches could have been justified on the basis of prevalence of COVID-19 and availability of personal protective equipment; however, there was a risk of creating confusion about IPCG best practices. The findings of this review will support decision makers when planning future development and dissemination of regulations for all oral health care practitioners.
Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Oral Hygiene , Oral Health , Canada/epidemiology , Personal Protective Equipment , DentistsABSTRACT
A growing body of research associates the oral microbiome and oral cancer. Well-characterized clinical samples with outcome data are required to establish relevant associations between the microbiota and disease. The objective of this study was to characterize the community variations and the functional implications of the microbiome in low-grade oral epithelial dysplasia (OED) using 16S rRNA gene sequencing from annotated archival swabs in progressing (P) and non-progressing (NP) OED. We characterised the microbial community in 90 OED samples - 30 swabs from low-grade OED that progressed to cancer (cases) and 60 swabs from low-grade OED that did not progress after a minimum of 5 years of follow up (matched control subjects). There were small but significant differences between P and NP samples in terms of alpha diversity as well as beta diversity in conjunction with other clinical factors such as age and smoking status for both taxa and functional predictions. Across all samples, the most abundant genus was Streptococcus, followed by Haemophilus, Rothia, and Neisseria. Taxa and predicted functions were identified that were significantly differentially abundant with progression status (all Ps and NPs), when samples were grouped broadly by the number of years between sampling and progression or in specific time to progression for Ps only. However, these differentially abundant features were typically present only at low abundances. For example, Campylobacter was present in slightly higher abundance in Ps (1.72%) than NPs (1.41%) and this difference was significant when Ps were grouped by time to progression. Furthermore, several of the significantly differentially abundant functions were linked to the Campylobacteraceae family in Ps and may justify further investigation. Larger cohort studies to further explore the microbiome as a potential biomarker of risk in OED are warranted.
Subject(s)
Microbiota , Mouth Neoplasms , Cohort Studies , Humans , Child , RNA, Ribosomal, 16S/genetics , Microbiota/genetics , Male , Female , Infant , Child, PreschoolABSTRACT
Background: As discussions about baccalaureate education for dental hygiene continue at national and international levels, examining outcomes of earning a baccalaureate degree in a Canadian context is essential. This study aimed to explore the motivating reasons for pursuing a dental hygiene baccalaureate degree in Canada and the career outcomes of Canadian dental hygiene baccalaureate degree graduates. Methods: Graduates from all 4 Canadian dental hygiene degree programs (N = 262) participated in a cross-sectional online survey between November and December 2021. Survey questions explored motivating reasons for pursuing dental hygiene degree education, educational experiences, employment outcomes, and career satisfaction. A descriptive analysis was performed to report absolute and relative frequencies of responses to each question. Differences between participant characteristics, motivating reasons for pursing a degree, and practice outcomes were assessed. Where applicable, results were compared to the results of the Canadian Dental Hygienists Association's 2019 Job Market and Employment Survey. A thematic analysis was applied to open-ended descriptive responses. Results: Primary motivators included personal satisfaction (77%), status of a degree (75%), increase in employment opportunities (71%), and increase in knowledge base (69%). Respondents (87%) reported that they were satisfied with their educational experiences, and the majority (65%) agreed that a degree should be the minimum entry-level credential for dental hygiene practice in Canada. Primary practice settings were reported as clinical dental hygiene care (80%), educational institutions (9%), community and public health (4%), and other practice settings (7%). A larger proportion reported working in non-clinical settings than those in the national survey (20% and 8%, respectively; p < 0.001). Conclusion: These findings underscore the impact of baccalaureate education on dental hygiene practice in Canada.
Contexte: Étant donné que les discussions sur les études menant à un baccalauréat en hygiène dentaire se poursuivent aux échelles nationales et internationales, il est essentiel d'examiner les résultats de l'obtention d'un baccalauréat dans un contexte canadien. Cette étude visait à explorer les raisons qui motivent la poursuite d'un baccalauréat en hygiène dentaire au Canada et les possibilités de carrière des diplômés canadiens d'un programme de baccalauréat en hygiène dentaire. Méthodologie: Des diplômés des 4 programmes canadiens de baccalauréat en hygiène dentaire (N = 262) ont participé à une enquête ponctuelle en ligne entre novembre et décembre 2021. Les questions de l'enquête ont exploré les raisons motivant la poursuite d'études en hygiène dentaire menant à un baccalauréat, les expériences éducatives, les possibilités d'emploi et la satisfaction par rapport à la carrière. Une analyse descriptive a permis d'établir les fréquences absolues et relatives des réponses à chaque question. Les différences entre les caractéristiques des participants, les raisons motivant l'obtention d'un baccalauréat et les possibilités de la pratique professionnelle ont été évaluées. Le cas échéant, les résultats ont été comparés aux résultats du Sondage sur le marché du travail et de l'emploi de 2019 de l'Association canadienne des hygiénistes dentaires. Une analyse thématique a été appliquée aux réponses descriptives ouvertes. Résultats: Les principaux facteurs de motivation comprenaient la satisfaction personnelle (77 %), le statut d'un baccalauréat (75 %), l'augmentation des possibilités d'emploi (71 %) et l'augmentation de la base de connaissances (69 %). Les répondants (87 %) ont déclaré être satisfaits de leurs expériences éducatives et la majorité (65 %) était d'accord pour dire qu'un baccalauréat devrait être le titre de compétence minimal pour l'admission à la pratique de l'hygiène dentaire au Canada. Les milieux de pratique primaires ont été déclarés comme étant les suivants : soins cliniques en hygiène dentaire (80 %), établissements d'enseignement (9 %), santé communautaire et publique (4 %), et autres milieux de pratique (7 %). Un plus grand nombre de répondants ont déclaré travailler dans des milieux non cliniques que ceux de l'enquête nationale (20 % et 8 %, respectivement; p < 0,001). Conclusion: Ces résultats soulignent l'impact des études menant à un baccalauréat sur la pratique de l'hygiène dentaire au Canada.
Subject(s)
Dental Hygienists , Employment , Humans , Canada , Dental Hygienists/education , Cross-Sectional Studies , SchoolsABSTRACT
Background: Oral health care settings potentially carry a high risk of cross-infection due to close contact and aerosol-generating procedures. There is limited evidence of the impact of COVID-19 among dental hygienists. This longitudinal study aimed to 1) estimate COVID-19 incidence rates among Canadian dental hygienists over a 1-year period; and 2) estimate vaccination rates among Canadian dental hygienists. Methods: A prospective cohort study design was used to collect self-reported COVID-19 status from 876 registered dental hygienists across Canada via an online baseline survey and then 6 follow-up questionnaires delivered between December 2020 and January 2022. Bayesian Poisson and binomial models were used to estimate the incidence rate and cumulative incidence of self-reported COVID-19. Results: The estimated cumulative incidence of COVID-19 in dental hygienists in Canada from December 2020 to January 2022 was 2.39% (95% CrI, 1.49%-3.50%), while the estimated cumulative incidence of COVID-19 in corresponding Canadian provinces was 5.12% (95% CrI, 5.12%-5.13%) during the same period. At last follow-up, 89.4% of participants self-reported that they had received at least 1 dose of a COVID-19 vaccine. Conclusion: The low infection rate observed among Canadian dental hygienists between December 2020 and January 2022 is reassuring to the dental hygiene and general community.
Contexte: Les milieux de soins buccodentaires présentent potentiellement un risque élevé d'infections croisées en raison des contacts étroits et des procédures qui produisent des aérosols. Il y a peu de preuves de l'effet de la COVID-19 chez les hygiénistes dentaires. La présente étude longitudinale visait à 1) estimer les taux d'incidence de la COVID-19 chez les hygiénistes dentaires canadiens sur une période d'un an; et 2) estimer les taux de vaccination chez les hygiénistes dentaires canadiens. Méthodologie: Une méthodologie prospective des cohortes a été utilisée pour recueillir le statut de COVID-19 autodéclaré de 876 hygiénistes dentaires autorisés au Canada par l'intermédiaire d'une enquête initiale en ligne, puis de 6 questionnaires de suivi, distribués entre décembre 2020 et janvier 2022. Des modèles bayésiens de Poisson et binomiaux ont été utilisés pour estimer le taux d'incidence et l'incidence cumulative de la COVID-19 autodéclarée. Résultats: L'incidence cumulative estimée de la COVID-19 chez les hygiénistes dentaires au Canada entre décembre 2020 et janvier 2022 était de 2,39 % (intervalle de crédibilité à 95 %, 1,49 % 3,50 %), alors que l'incidence cumulative estimée de la COVID-19 dans les provinces canadiennes correspondantes était de 5,12 % (intervalle de crédibilité à 95 %, 5,12 % 5,13 %) au cours de la même période. Lors du dernier suivi, 89,4 % des participants ont déclaré avoir reçu au moins une dose du vaccin contre la COVID-19. Conclusion: Le faible taux d'infection constaté chez les hygiénistes dentaires canadiens entre décembre 2020 et janvier 2022 est rassurant pour la communauté d'hygiène dentaire et la communauté générale.
Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , Incidence , COVID-19/epidemiology , Longitudinal Studies , Bayes Theorem , Dental Hygienists , Prospective Studies , Canada/epidemiology , VaccinationABSTRACT
BACKGROUND: In Spring of 2020, due to the COVID-19 pandemic, Canadian provincial dental hygiene regulatory bodies implemented new practice guidelines. Reports of stress, anxiety and conflict experienced by dental hygienists have been linked to miscommunication between oral health regulators at this time. Limited data exists on the perceptions and experiences of dental hygienists navigating new guidelines for dental hygiene care during the pandemic. Therefore, the objective of our study was to explore via descriptive thematic analysis how dental hygienists experienced and perceived: i) dental hygiene practice during the COVID-19 pandemic, and ii) their regulatory body's COVID-19 guidelines. METHODS: Participants were identified through provincial dental hygiene licensing bodies. Online bi-monthly questionnaires were administered to participants (n = 876) from December 2021 to January 2022. Two open-ended questions were asked in the questionnaire. A qualitative descriptive thematic analysis was applied to these two questions. RESULTS: Major themes at baseline relayed challenges related to workplace compliance, patient treatment and communication of practice protocols. Across responses, hygienists confirmed conflicting messaging from regulators and guideline interpretations as stressors impacting their professional practice and satisfaction within the profession. Participant responses at endpoint cited increased satisfaction with regulatory guidelines as the pandemic evolved, yet inconsistencies in regulators' messaging was noted as a prevailing issue. CONCLUSION: Inconsistent guideline messaging reflects an increased need for collaboration amongst oral health care regulators to streamline protocols for practice and reduce interprofessional conflict in pandemic circumstances. A national unified approach is warranted in establishing guidelines for dental hygiene practice in Canada.
Subject(s)
COVID-19 , Pandemics , Humans , Dental Hygienists , Attitude of Health Personnel , Canada/epidemiology , COVID-19/epidemiology , Surveys and QuestionnairesABSTRACT
Background: Burnout syndrome is the result of prolonged occupational stress. The syndrome has 3 dimensions: emotional exhaustion (EE), depersonalization (DP), and reduced personal accomplishment (PA). This study aimed to examine the prevalence of the 3 dimensions of burnout in dental hygienists in Nova Scotia, Canada, (N = 745) as they returned to work during the COVID-19 pandemic following a furlough; to explore the effect of burnout during COVID-19 on dental hygienists' professional lives; and to determine the tools and methods that dental hygienists use to overcome burnout. Methods: In this cross-sectional study, participants were asked to complete an anonymous survey inclusive of demographic information, employment characteristics, the Maslach Burnout Inventory Human Services Survey for Medical Personnel (MBI-HSS [MP]), and 2 open-ended questions. Results: The response rate was 34.9% (n = 260). Approximately one-third (36.2%) of respondents met the criteria for burnout. Contributors to burnout were time, providing dental hygiene care, expectations of dentists, physical and mental health, lack of autonomy, and the COVID-19 pandemic. Reported mechanisms to overcome occupational stress centred on work-life balance, social support networks, working in a positive environment, and physical activity. Discussion: This study took place during the first wave of the COVID-19 pandemic, which may have influenced the rate of burnout among dental hygienists, particularly within the EE domain where scores were twice as high as those reported in pre-COVID-19 studies. Conclusion: Dental hygienists may be at risk for burnout. Recognizing the signs and symptoms of burnout and implementing healthy behaviours may reduce its detrimental effects.
Contexte: La prolongation du stress professionnel entraîne le syndrome de l'épuisement professionnel. Le syndrome comporte 3 volets : l'épuisement émotionnel (ÉÉ), la dépersonnalisation (DP) et la diminution de l'épanouissement personnel (ÉP). La présente étude visait à examiner la prévalence des 3 volets de l'épuisement professionnel chez les hygiénistes dentaires en Nouvelle-Écosse, Canada, (N = 745) à leur retour au travail après avoir eu un congé pendant la pandémie de la COVID-19; à explorer l'effet de l'épuisement professionnel sur la vie professionnelle des hygiénistes dentaires pendant la COVID-19; et à établir quels outils et méthodes les hygiénistes dentaires utilisent pour remédier à l'épuisement professionnel. Méthodologie: Les participants ont été invités à répondre à un sondage anonyme pour cette étude transversale, comprenant les données démographiques, les caractéristiques d'emploi, le sondage Maslach Burnout Inventory Human Services pour le personnel médical (MBI-HSS [PM]) et 2 questions ouvertes. Résultats: Le taux de réponse était de 34,9 % (n = 260). Environ le tiers (36,9 %) des répondants a satisfait aux critères de l'épuisement professionnel. Les facteurs qui y ont contribué étaient le temps, la prestation de soins d'hygiène dentaire, les attentes des dentistes, la santé physique et mentale, le manque d'autonomie et la pandémie de la COVID-19. La conciliation travailvie personnelle, les réseaux de soutien social, travailler dans un environnement positif et l'activité physique étaient cités comme mécanismes qui permettent de surmonter le stress professionnel. Discussion: Cette étude a été effectuée pendant la première vague de la pandémie de la COVID-19, ce qui peut avoir influencé le taux d'épuisement professionnel chez les hygiénistes dentaires, particulièrement en matière d'ÉÉ où les cotes étaient 2 fois plus élevées que celles signalées dans les études d'avant la COVID-19. Conclusion: Les hygiénistes dentaires peuvent être à risque d'épuisement professionnel. Reconnaître les signes et les symptômes de l'épuisement professionnel et mettre en Åuvre des comportements sains peuvent réduire ses effets adverses.
Subject(s)
Burnout, Professional , COVID-19 , Occupational Stress , Burnout, Professional/epidemiology , Burnout, Psychological/epidemiology , COVID-19/epidemiology , Cross-Sectional Studies , Dental Hygienists , Humans , Nova Scotia/epidemiology , Occupational Stress/epidemiology , PandemicsABSTRACT
BACKGROUNDThe aberrant activation of the PI3K/mTOR signaling circuitry is one of the most frequently dysregulated signaling events in head and neck squamous cell carcinoma (HNSCC). Here, we conducted a single-arm, open-label phase IIa clinical trial in individuals with oral premalignant lesions (OPLs) to explore the potential of metformin to target PI3K/mTOR signaling for HNSCC prevention.METHODSIndividuals with OPLs, but who were otherwise healthy and without diabetes, underwent pretreatment and posttreatment clinical exam and biopsy. Participants received metformin for 12 weeks (week 1, 500 mg; week 2, 1000 mg; weeks 3-12, 2000 mg daily). Pretreatment and posttreatment biopsies, saliva, and blood were obtained for biomarker analysis, including IHC assessment of mTOR signaling and exome sequencing.RESULTSTwenty-three participants were evaluable for response. The clinical response rate (defined as a ≥50% reduction in lesion size) was 17%. Although lower than the proposed threshold for favorable clinical response, the histological response rate (improvement in histological grade) was 60%, including 17% complete responses and 43% partial responses. Logistic regression analysis revealed that when compared with never smokers, current and former smokers had statistically significantly increased histological responses (P = 0.016). Remarkably, a significant correlation existed between decreased mTOR activity (pS6 IHC staining) in the basal epithelial layers of OPLs and the histological (P = 0.04) and clinical (P = 0.01) responses.CONCLUSIONTo our knowledge this is the first phase II trial of metformin in individuals with OPLs, providing evidence that metformin administration results in encouraging histological responses and mTOR pathway modulation, thus supporting its further investigation as a chemopreventive agent.TRIAL REGISTRATIONNCT02581137FUNDINGNIH contract HHSN261201200031I, grants R01DE026644 and R01DE026870.
Subject(s)
Gene Expression Regulation, Neoplastic , Leukoplakia, Oral/prevention & control , Metformin/administration & dosage , Mouth Mucosa/metabolism , Precancerous Conditions , TOR Serine-Threonine Kinases/genetics , Administration, Oral , Biopsy , Cell Line, Tumor , Dose-Response Relationship, Drug , Female , Humans , Hypoglycemic Agents/administration & dosage , Leukoplakia, Oral/pathology , Male , Middle Aged , Mouth Mucosa/drug effects , Mouth Mucosa/pathology , RNA, Neoplasm/genetics , Signal Transduction/drug effects , Single-Blind Method , TOR Serine-Threonine Kinases/biosynthesisABSTRACT
Background: Two subtypes of lichenoid mucositis (LM) with oral epithelial dysplasia have been proposed, with differing risks of malignant transformation. However, no research has been done to authenticate this hypothesis. The study objective was to determine whether there are 2 subcategories within this entity, one with primary lichenoid and secondary dysplastic features (L1D2), and the other with primary dysplastic and secondary lichenoid features (D1L2), and to compare the proportion of malignant progression in these groups. Methods: Patients with a diagnosis of lichenoid mucositis with low-grade (mild/moderate) oral epithelial dysplasia, no history of head and neck cancer, and who had at least 5 years of follow-up were eligible to participate in this nested case-control study. Cases (n = 10) were defined as lesions that progressed to severe dysplasia, carcinoma in situ or squamous cell carcinoma; controls (n = 32) were defined as those that did not progress. Immunohistochemistry was performed to assess for basement membrane (BM) degeneration using collagen IV-an integral BM protein. Results: Lesions that progressed to cancer exhibited a similar proportion of BM degeneration at baseline (70%) compared to non-progressors (78%), with no statistically significant difference between groups (p = 0.69). Conclusion: BM degeneration is frequently seen in LM with dysplasia and alone does not appear to be a predictor of malignant progression in lesions with both lichenoid and low-grade dysplastic features. Dysplasia should not be discounted in the presence of LM. Lesions that display any degree of dysplasia warrant clinical follow-up and continued monitoring.
Contexte: Deux sous-types de mucosites lichénoïdes (ML) avec dysplasie épithéliale buccale ont été proposés, avec des risques différents de transformation maligne. Cependant, aucune recherche n'a été faite pour valider cette hypothèse. L'objectif de l'étude était de déterminer s'il y a 2 sous-catégories au sein de cette entité, la première avec des caractéristiques lichénoïdes primaires et dysplasiques secondaires (L1D2), et l'autre avec des caractéristiques dysplasiques primaires et lichénoïdes secondaires (D1L2), et de comparer la proportion de progression maligne dans ces groupes. Méthodologie: Les patients ayant reçu un diagnostic de mucosite lichénoïde avec une dysplasie épithéliale buccale de faible intensité (faible/modérée), qui n'avaient aucun antécédent de cancer de la tête et du cou, et qui avaient eu au moins 5 ans de suivi, étaient admissible à participer à cette étude de cas-témoins emboîtés. Les cas (n = 10) étaient définis comme des lésions qui ont progressé à la dysplasie sévère, un carcinome in situ ou un carcinome squameux; les contrôles (n = 32) étaient définis comme ceux qui n'ont pas progressé. L'immunohistochimie a été effectuée pour évaluer s'il y avait eu une dégénérescence de la membrane basale (MB) en utilisant du collagène IV, une protéine MB intrinsèque. Résultats: Les lésions qui ont évolué en cancer ont présenté une proportion semblable de dégénérescence de MB au début (70 %) par rapport aux non-progresseurs (78 %), et aucune différence statistiquement significative entre les groupes (p = 0,69). Conclusion: La dégénérescence des MB est fréquemment constatée dans les ML avec dysplasie et seule, ne paraît pas être une variable explicative de l'évolution maligne dans les lésions à caractéristiques à la fois lichénoïdes et dysplasiques de faible intensité. Il ne faut pas sous-estimer la dysplasie en présence de ML. Les lésions qui présentent de la dysplasie, peu importe son étendue, exigent un suivi clinique et une surveillance continue.
Subject(s)
Lichen Planus, Oral , Mouth Neoplasms , Mucositis , Basement Membrane , Case-Control Studies , HumansABSTRACT
CD4+ T helper (TH) cells are key regulators in the tumour immune microenvironment (TIME), mediating the adaptive immunological response towards cancer, mainly through the activation of cytotoxic CD8+ T cells. After antigen recognition and proper co-stimulation, naïve TH cells are activated, undergo clonal expansion, and release cytokines that will define the differentiation of a specific effector TH cell subtype. These different subtypes have different functions, which can mediate both anti- and pro-tumour immunological responses. Here, we present the dual role of TH cells restraining or promoting the tumour, the factors controlling their homing and differentiation in the TIME, their influence on immunotherapy, and their use as prognostic indicators.
Subject(s)
Neoplasms/immunology , T-Lymphocytes, Helper-Inducer/immunology , Tumor Microenvironment/immunology , Animals , Cytokines/metabolism , Humans , T-Lymphocytes, Cytotoxic/immunologyABSTRACT
Head and neck squamous cell carcinoma (HNSCC) has a poor survival rate mainly due to late stage diagnosis and recurrence. Despite genomic efforts to identify driver mutations and changes in protein-coding gene expression, developing effective diagnostic and prognostic biomarkers remains a priority to guide disease management and improve patient outcome. Recent reports of previously-unannotated microRNAs (miRNAs) from multiple somatic tissues have raised the possibility of HNSCC-specific miRNAs. In this study, we applied a customized in-silico analysis pipeline to identify novel miRNAs from raw small-RNA sequencing datasets from public repositories. We discovered 146 previously-unannotated sequences expressed in head and neck samples that share structural properties highly characteristic of miRNAs. The combined expression of the novel miRNAs revealed tissue and context-specific patterns. Furthermore, comparison of tumor with non-malignant tissue samples (n = 43 pairs) revealed 135 of these miRNAs as differentially expressed, most of which were overexpressed or exclusively found in tumor samples. Additionally, a subset of novel miRNAs was significantly associated with HPV infection status and patient outcome. A prognostic-model combining novel and known miRNA was developed (multivariate Cox regression analysis) leading to an improved death and relapse risk stratification (log rank p < 1e-7). The presence of these miRNAs was corroborated both in an independent dataset and by RT-qPCR analysis, supporting their potential involvement in HNSCC. In this study, we report the discovery of 146 novel miRNAs in head and neck tissues and demonstrate their potential biological significance and clinical relevance to head and neck cancer, providing a new resource for the study of HNSCC.
ABSTRACT
Recent studies have uncovered microRNAs (miRNAs) that have been overlooked in early genomic explorations, which show remarkable tissue- and context-specific expression. Here, we aim to identify and characterize previously unannotated miRNAs expressed in gastric adenocarcinoma (GA). Raw small RNA-sequencing data were analyzed using the miRMaster platform to predict and quantify previously unannotated miRNAs. A discovery cohort of 475 gastric samples (434 GA and 41 adjacent nonmalignant samples), collected by The Cancer Genome Atlas (TCGA), were evaluated. Candidate miRNAs were similarly assessed in an independent cohort of 25 gastric samples. We discovered 170 previously unannotated miRNA candidates expressed in gastric tissues. The expression of these novel miRNAs was highly specific to the gastric samples, 143 of which were significantly deregulated between tumor and nonmalignant contexts (p-adjusted < 0.05; fold change > 1.5). Multivariate survival analyses showed that the combined expression of one previously annotated miRNA and two novel miRNA candidates was significantly predictive of patient outcome. Further, the expression of these three miRNAs was able to stratify patients into three distinct prognostic groups (p = 0.00003). These novel miRNAs were also present in the independent cohort (43 sequences detected in both cohorts). Our findings uncover novel miRNA transcripts in gastric tissues that may have implications in the biology and management of gastric adenocarcinoma.
Subject(s)
Adenocarcinoma/genetics , Biomarkers, Tumor , MicroRNAs/genetics , Stomach Neoplasms/genetics , Adenocarcinoma/pathology , Adult , Aged , Computational Biology , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , Stomach Neoplasms/pathology , TranscriptomeABSTRACT
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, wherein diagnostic limitations and lack of accurate prognostic factors are important clinical challenges. In this study, we report the discovery of 234 novel miRNAs in non-neoplastic thyroid and PTC samples, obtained from publicly available small RNA sequencing datasets (TCGA and GEO). These sequences were observed to display similar molecular features compared to currently annotated miRNAs. These potentially novel miRNAs presented tissue-specificity and largely decreased expression in PTC compared to non-neoplastic samples. We showed that the disrupted novel miRNAs have diagnostic and prognostic potential, and were associated with BRAF mutation, a frequent alteration related to more aggressive PTC. In conclusion, our results expand the miRNA repertoire in thyroid tissues and highlight the potential biological role and clinical utility of previously unannotated miRNAs.
Subject(s)
MicroRNAs , RNA, Neoplasm , Thyroid Cancer, Papillary , Thyroid Neoplasms , Female , Humans , Male , MicroRNAs/genetics , MicroRNAs/metabolism , Molecular Sequence Annotation , Mutation , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins B-raf/metabolism , RNA, Neoplasm/genetics , RNA, Neoplasm/metabolism , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/metabolism , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/genetics , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathologyABSTRACT
Most Departments of Pathology around the world have a considerable archive of formalin-fixed paraffin-embedded (FFPE) tissue suitable for molecular assessment. This article points out the potential DNA damage that may occur if basic steps are not followed during processing and storage of these samples. Furthermore, it hopes to establish parameters to optimize quality and quantity of DNA extracted from FFPE tissues.
Subject(s)
Tissue Fixation , Humans , Paraffin EmbeddingABSTRACT
Abstract Most Departments of Pathology around the world have a considerable archive of formalin-fixed paraffin-embedded (FFPE) tissue suitable for molecular assessment. This article points out the potential DNA damage that may occur if basic steps are not followed during processing and storage of these samples. Furthermore, it hopes to establish parameters to optimize quality and quantity of DNA extracted from FFPE tissues.
Resumo A maioria dos Departamentos de Patologia em todo o mundo têm um considerável acervo de tecidos embebidos em parafina e fixados em formalina, que são passíveis para análises moleculares. Este artigo apresenta os danos ao DNA que podem ocorrer se passos básicos não forem seguidos durante o processamento e armazenamento destas amostras. Além disso, procura estabelecer parâmetros para otimizar a qualidade e quantidade do DNA extraído de tecidos FFPE.