Faculty Bibliography

Long non-coding RNAs (lncRNA) modulate gene expression at the epigenetic, transcriptional and post-transcriptional levels and are involved in tumorigenesis. They can form complex secondary and tertiary structures and have been shown to act as precursors, enhancers, reservoirs and decoys in the complex endogenous RNA network. They were first reported in relation to oral squamous cell carcinoma (OSCC) in 2013. Here, we summarise the functional roles and pathways of the most commonly studied lncRNAs in OSCC. Existing research demonstrates the involvement of lncRNA within pivotal pathways leading to the development and spread of OSCC, including interactions with key cancer-associated microRNAs such as miR-21. The number of studies on lncRNA and OSCC remains limited in this new field. As evidence grows, the tissue-specific expression patterns of lncRNAs should further advance our understanding of the altered regulatory networks in OSCC and possibly reveal new biomarkers and therapeutic targets.

OBJECTIVE:The World Workshop on Oral Medicine VII chose the oral microbiome as a focus area. Part 1 presents the methodological state of the science for oral microbiome studies. Part 2 was guided by the question: What is currently known about the microbiome associated with oral squamous cell carcinoma and potentially malignant disorders of the oral mucosa? MATERIALS AND METHODS/METHODS:A scoping review methodology was followed to identify and analyse relevant studies on the composition and potential functions of the oral microbiota using high-throughput sequencing techniques. The authors performed searches in PubMed and EMBASE. After removal of duplicates, a total of 239 potentially studies were identified. RESULTS:Twenty-three studies on oral squamous cell carcinoma, two on oral leukoplakia and four on oral lichen planus were included with substantial differences in diagnostic criteria, sample type, region sequenced and sequencing method utilised. The majority of studies focused on bacterial identification and recorded statistically significant differences in the oral microbiota associated with health and disease. However, even when comparing studies of similar methodology, the microbial differences between health and disease varied considerably. No consensus on the composition of the microbiomes associated with these conditions on genus and species level could be obtained. Six studies on oral squamous cell carcinoma had included in silico predicted microbial functions (genes and/or pathways) and found some similarities between the studies. CONCLUSIONS:Attempts to reveal the microbiome associated with oral mucosal diseases are still in its infancy, and the studies demonstrate significant clinical and methodological heterogeneity across disease categories. The immense richness and diversity of the microbiota clearly illustrate that there is a need for additional methodologically comparable studies utilising deep sequencing approaches in significant cohorts of subjects together with functional analyses. Our hope is that following the recipe as outlined in our preceding companion paper, that is Part 1, will enhance achieving this in the future and elucidate the role of the oral microbiome in oral squamous cell carcinoma and potentially malignant disorders of the oral mucosa.

OBJECTIVES/OBJECTIVE:The diagnosis and management of oral cavity cancers are often complicated by the uncertainty of which patients will undergo malignant transformation, obligating close surveillance over time. However, serial biopsies are undesirable, highly invasive, and subject to inherent issues with poor inter-pathologist agreement and unpredictability as a surrogate for malignant transformation and clinical outcomes. The goal of this study was to develop and evaluate a Multivariate Analytical Risk Index for Oral Cancer (MARIO) with potential to provide non-invasive, sensitive, and quantitative risk assessments for monitoring lesion progression. MATERIALS AND METHODS/METHODS:A series of predictive models were developed and validated using previously recorded single-cell data from oral cytology samples resulting in a "continuous risk score". Model development consisted of: (1) training base classification models for each diagnostic class pair, (2) pairwise coupling to obtain diagnostic class probabilities, and (3) a weighted aggregation resulting in a continuous MARIO. RESULTS AND CONCLUSIONS/CONCLUSIONS:Diagnostic accuracy based on optimized cut-points for the test dataset ranged from 76.0% for Benign, to 82.4% for Dysplastic, 89.6% for Malignant, and 97.6% for Normal controls for an overall MARIO accuracy of 72.8%. Furthermore, a strong positive relationship with diagnostic severity was demonstrated (Pearson's coefficient = 0.805 for test dataset) as well as the ability of the MARIO to respond to subtle changes in cell composition. The development of a continuous MARIO for PMOL is presented, resulting in a sensitive, accurate, and non-invasive method with potential for enabling monitoring disease progression, recurrence, and the need for therapeutic intervention of these lesions.

BACKGROUND:Oral human papillomavirus (HPV) infection is the principal underlying cause of a dramatic increase in oropharyngeal cancer. Dentistry can play an important role in developing clinical algorithms for secondary prevention. METHODS:The authors conducted this cross-sectional pilot study with practices of The National Dental Practice-Based Research Network. The authors evaluated the feasibility and acceptability of screening and testing procedures as judged by practitioners and patients. The authors used tablet devices for patient screening, obtaining consent, and administering a confidential oral HPV risk factor survey. RESULTS:Most patients (85%) were comfortable being asked about their cigarette use and their sexual behavior (69%) and were interested in participating again (79%). More than 90% of practitioners were comfortable with study procedures except the extra time required for patient participation (75% comfortable). There were no problems with oral rinse collection as reported by patients or practitioners. CONCLUSIONS:It is feasible in community dental offices to collect oral rinses for HPV detection and to ask patients explicit questions about sexual history when using a tablet device for confidentiality. PRACTICAL IMPLICATIONS/CONCLUSIONS:Discussing high-risk types of HPV and appropriately assessing that risk are a challenge for oral health care professionals. These results are positive from a research perspective but do not address the advisability of routine HPV screening in dentistry.

BACKGROUND:Oral and oropharyngeal cancers are among the most common cancers globally. This study aimed to assess the incidence and mortality trends of oral and oropharyngeal cancers in China between 2005 and 2013. METHODS:Estimates of national trends of oral and oropharyngeal cancers were based on the data from Chinese Cancer Registry Annual Reports. The crude incidence rates of oral and oropharyngeal cancers between 2015 and 2035 were evaluated. The age-standardized rate was based on the world standard population. RESULTS:It was estimated that 285,857 new cases and 132,698 deaths were related to oral and oropharyngeal cancers in China between 2005 and 2013, with mouth and tongue cancers being the most frequently diagnosed and the leading causes of death among all oral and oropharyngeal cancers. The incidence rates of oral and oropharyngeal cancer fluctuated from 1.69 to 1.89 per 100,000 person-years, and the mortality rate showed an increasing trend, ranging from 0.77 and 0.84 per 100,000 person-years. Males were more susceptible than females to oral and oropharyngeal cancers. The incidence and mortality rates of oral and oropharyngeal cancers were significantly higher in urban regions. The crude incidence rates of oral cancers are projected to increase from 2.26 to 3.21 per 100,000 person-years over the next 20 years in China. CONCLUSION/CONCLUSIONS:The incidence of oral and oropharyngeal cancers fluctuated, whereas the mortality rate showed an upward trend from 2005 to 2013. A heavier burden from oral and oropharyngeal cancers is predicted in the next two decades in China.

Evidence-based reviews of drugs causing medication-induced salivary gland dysfunction, such as xerostomia (sensation of oral dryness) and subjective sialorrhea are lacking. To compile a list of medicaments that influence salivary gland function, electronic databases were searched for relevant articles published up to June 2013. A total of 269 papers out of 3,867 records located satisfied the inclusion criteria (relevance, quality of methodology, strength of evidence). A total of 56 active substances with a higher level of evidence and 50 active substances with a moderate level of evidence of causing salivary gland dysfunction are described in this article. While xerostomia was a commonly reported outcome, the objective effect on salivary secretion was rarely measured. Xerostomia was, moreover, mostly reported as a negative side effect instead of the intended effect of that drug. A comprehensive list of medications having documented effects on salivary gland function or symptoms was compiled, which may assist practitioners in assessing patients who complain of dry mouth while taking medications

Introduction Photobiomodulation (PBM Therapy) formerly known as Low Level Laser Therapy (LLLT) is an effective treatment for reducing the incidence and severity of oral mucositis (OM) after high dose chemotherapy and/or radiotherapy. However, reported PBM irradiation parameters, dose per point, number of treatment points or treatment intervals vary widely Objectives To systematically review randomized clinical trials (RCTs), summarise the PBM parameters and detain the most effective treatment regimen. Methods Online databases were searched for RCTs comparing efficacy of PBM verses controls for prevention or treatment cancer therapy induced OM. Papers were scored for quality and effect size for the primary outcome, irradiation parameters and dose were compared with outcomes. Results There was lots of mistakes and missing treatment data (i.e. laser wavelength ranges, power, beam sizes, energy applied and treatment duration) on the reported data, however the majority of the randomized clinical trials reported positive effects: PBM reduced pain, onset of OM, and improved overall quality of life of the patients that received PBM. Conclusions Although no precise conclusion can be drawn due to a large variation on the reported data, PBM used for OM confidently recommend an optimal treatment guideline for this condition

OBJECTIVE:We aimed to characterize proliferative verrucous leukoplakia (PVL) from a clinical and histopathologic standpoint and suggest an updated classification. SUBJECTS AND METHODS/METHODS:Records of patients seen at three oral medicine centers with a clinical diagnosis of PVL were reviewed for clinical and histopathologic features, and malignant transformation (MT). RESULTS:There were 42 patients (median age: 69 years [range:36-88]; 35 females). 12.2% were current smokers. Family history of cancer was present in 43.7% of patients. Partial demarcation of lesion margins was present in 31.3% of lesions, followed by verrucous (27.5%), smooth (22.7%,) erythematous (22.3%), and fissured (18.3%) appearance. Large and contiguous, and multi-site and noncontiguous lesions, comprised 57.1% (24/42) and 35.7% (15/42) of PVL cases, respectively. 19.1% had prominent erythema (erythroleukoplakia). The most common histopathologic diagnosis at first visit was hyperkeratosis without dysplasia (22/42; 56.4%). MT occurred in 71.4% patients after a median of 37 months [range:1-210] from initial visit; erythroleukoplakia exhibited MT in 100% of cases. CONCLUSION/CONCLUSIONS:The generic term "proliferative leukoplakia (PL)" may be more appropriate than PVL because 18.3% were fissured and 22.7% erythematous. We also propose the term proliferative erythroleukoplakia to more accurately describe the subset of PL with prominent erythema, which had the highest MT rate.

Oral potentially malignant disorders (OPMDs) refer to epithelial lesions and conditions with an increased risk for malignant transformation; oral leukoplakia is the most commonly encountered. Overall, OPMDs have a low risk for malignant transformation, yet the challenge is the difficulty to reliably identify and predict which patients with OPMDs are at the highest risk for malignant transformation. Future research is needed to elucidate the molecular aspects of OPMDs, to improve current diagnostic strategies, leading to personalized management.