The majority of patients with OED were smokers. Of these, more were males, non-Caucasians and heavy drinkers. A significantly higher number of OED in NS were in the tongue, whereas a significantly higher number of OED in smokers were in the floor of mouth (FOM). OED in NS showed a greater than 2-fold increase in cancer progression. Strikingly, OED located in the FOM in NS showed a 38-fold increase in cancer progression as compared to those in smokers.

Oral lichen planus is categorized as a potentially malignant condition by the World Health Organization; however, some argue that only lichen planus with dysplasia have malignant potential. Many pathologists call lichen planus with dysplasia "dysplasia with lichenoid mucositis (LM)" or "LM with dysplasia." Previous research has shown that certain high-risk patterns of loss of heterozygosity (LOH) in dysplastic lesions are associated with significantly increased cancer risk. However, LM without dysplasia lacks such molecular patterns, supporting the hypothesis that LM, by itself, is not potentially malignant and that only those with dysplasia have malignant potential. To further investigate the premalignant nature of LM with dysplasia, this study compared the rate of malignant progression of dysplasia with LM with that of dysplasia without LM. Patients from a population-based prospective cohort study with >10 y of follow-up were analyzed. Study eligibility included a histological diagnosis of a primary low-grade dysplasia with or without LM. A total of 446 lesions in 446 patients met the selection criteria; 373 (84%) were classified as dysplasia without LM, while 73 (16%) were classified as dysplasia with LM. Demographic and habit information, clinical information, and outcome (progression) were compared between the 2 groups. Forty-nine of 373 cases of dysplasia (13%) progressed compared to 8% (6/73) of dysplasia with LM. However, the difference was not statistically different ( P = 0.24). The 3- and 5-y rate of progression did not differ between the groups (6.7% and 12.5% for dysplasia without LM and 2.9% and 6.6% for those with LM; P = 0.36). Progression was associated with nonsmoking, location at a high-risk site, and diagnosis of moderate dysplasia regardless of whether LM was present or not. Dysplasia with or without LM had similar cancer risk, and dysplasia should not be discounted in the presence of LM.

Background:The 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 (NCT02581137) in individuals with oral premalignant lesions (OPL) to explore the potential of metformin to target PI3K/mTOR signaling for HNSCC prevention.Methods: Individuals with OPL, otherwise healthy and without diabetes, underwent pre-and posttreatment clinical exam and biopsy. Participants received metformin for 12 weeks (week 1, 500 mg; week 2, 1,000 mg; week 3-12, 2,000 mg daily). Pre-and post-treatment biopsies, saliva, and blood were obtained for biomarker analysis, including immunohistochemical (IHC) assessment of mTOR signaling and exome sequencing.Results: Twenty-three participants were evaluable for response. The clinical response rate (defined as ≥50% reduction in lesion size) was 17%. While lower than the proposed threshold for favorable clinical response, the histologic response rate (improvement in histologic grade) was 60%, including 17% complete responses and 43% partial responses. Logistic regression analysis revealed that when compared to never smokers, current and former smokers had statistically significantly increased histologic responses (p=0.016). Remarkably, a significant correlation existed between decreased mTOR activity (pS6 IHC staining) in the basal epithelial layer of OPL and the histological (p=0.04) and clinical (p=0.01) responses.Conclusions: This is the first phase II trial of metformin in individuals with OPL, providing evidence that metformin administration results in encouraging histological responses and mTOR pathway modulation, thus supporting its further investigation as a chemopreventive agent.

No abstract

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.

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.

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.

Background: The COVID-19 novel coronavirus closed oral health care in Nova Scotia (NS) Canada in March 2020. Preparing for a phased reopening, a knowledge exchange coalition (representing government, academia, hospitals, oral health professions, and regulators) developed return-to-work (RTW) guidelines detailing the augmentation of standard practices to ensure safety for patients, oral health care providers (OHPs), and the community. Using online surveys, this study explored the influence of the RTW guidelines and related education on registered NS OHPs during a phased return to work. Methods: Dissemination of R2W guidelines included website or email communiques and interdisciplinary education webinars that coincided with 2 RTW phases approved by the government. Aligned with each phase, all registered dentists, dental hygienists, and dental assistants were invited to complete an online survey to gauge the influence of the coalition-sponsored education and RTW guidelines, confidence, preparedness, and personal protective equipment use before and after the pandemic. Results: Three coalition-sponsored multidisciplinary webinars hosted 3541 attendees prior to RTW. The response to survey 1 was 41% (881/2156) and to survey 2 was 26% (571/2177) of registrants. Survey 1 (82%) and survey 2 (89%) respondents “agreed/strongly agreed” that R2W guidelines were a primary source for guiding return to practice, and most were confident with education received and had the skills needed to effectively treat patients during the COVID-19 pandemic. Confidence and preparedness improved in survey 2. Gowns/lab coat use for aerosol-generating procedures increased from 26% to 93%, and the use of full face shields rose from 6% to 93% during the pandemic. Conclusions: A multistakeholder coalition was effective in establishing and communicating comprehensive guidelines and web-based education to ensure unified reintegration of oral health services in NS during a pandemic. This multiorganizational cooperation lay the foundation for responses to subsequent waves of COVID-19 and may serve as an example for collaboratively responding to future public health threats in other settings. Knowledge Transfer Statement: The return-to-work strategy that was developed, disseminated, and assessed through this COVID-19 knowledge exchange coalition will benefit oral health practitioners, professional regulators, government policy makers, and researchers in future pandemic planning.