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Oral cancer examinations and lesion discovery as reported by U.S. general dentists: Findings from the National Dental Practice-Based Research Network

Psoter, Walter J; Morse, Douglas E; Kerr, Alexander Ross; Tomar, Scott L; Aguilar, Maria L; Harris, D Robert; Stone, Laurence H; Makhija, Sonia K; Kaste, Linda M; Strumwasser, Brett; Pihlstrom, Daniel J; Masterson, Erin E; Meyerowitz, Cyril
General dentists (GDs) have the opportunity to examine their patients for oral premalignancy/malignancy. We estimated the annualized per dentist number of oral lesions suspicious for premalignancy/malignancy discovered by United States (U.S.) general dentists and the annualized per dentist number of histologically-confirmed cancers subsequently diagnosed. Eligible participants were licensed, clinically-active U.S. GDs who were members of the U.S. National Dental Practice-Based Research Network. An a priori sample size of 900 was determined; 2000 GDs were invited to participate; 1,073 completed the study. Self-reported, cross-sectional data were obtained via an online questionnaire during 4/12/2017-8/31/2017 and analyzed. The reported numbers of suspicious oral lesions and histologically-confirmed oral cancer cases diagnosed over the previous six months were quantified. Potential outcome predictors were evaluated as covariates in multivariable analyses. Crude and adjusted statistics were produced by regressing each outcome on each independent variable while assuming a Poisson distribution, log link and utilizing robust standard errors. Eighty-seven percent of dentists reported discovering 1+ lesion suspicious for oral premalignancy/malignancy during the preceding six months. The mean number of suspicious lesions/dentist/year was 9.5; adjusted mean: 9.6. Fifteen percent of participants reported discovering 1+ lesion confirmed as cancer during the same period, 213 confirmed cancer cases/6 months or 426/year. Crude and adjusted mean numbers of histologically-confirmed oral cancers were both 0.4 cancers/dentist/year. Our findings suggest that many U.S. general dentists are actively identifying oral lesions suspicious for premalignancy/malignancy, thereby aiding in the discovery of oral malignancies and representing an important component in the frontline against cancer.
PMID: 31122615
ISSN: 1096-0260
CID: 3902772

World Workshop on Oral Medicine VII: Targeting the oral microbiome Part 2: Current knowledge on malignant and potentially malignant oral disorders

Robledo-Sierra, Jairo; Ben-Amy, Dalit Porat; Varoni, Elena; Bavarian, Roxanne; Simonsen, Janne L; Paster, Bruce J; Wade, William G; Kerr, Ross; Peterson, Douglas E; Frandsen Lau, Ellen
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.
PMID: 31140694
ISSN: 1601-0825
CID: 3902852

World Workshop on Oral Medicine VII: Targeting the microbiome for oral medicine specialists-Part 1. A methodological guide

Varoni, Elena M; Bavarian, Roxanne; Robledo-Sierra, Jairo; Porat Ben-Amy, Dalit; Wade, William G; Paster, Bruce; Kerr, Ross; Peterson, Douglas E; Frandsen Lau, Ellen
Advances in high-throughput sequencing technologies have allowed for a rapid increase in knowledge about the human microbiome in both healthy and diseased states, which is expected to increase our understanding of multifactorial diseases. The World Workshop on Oral Medicine VII chose the microbiome as one of its topics of focus. Part 1 of this review provides updated knowledge in the field of microbiome research, describes the advantages and disadvantages of currently available sequencing technologies, and proposes a seven-step "recipe" for designing and performing studies that is supported by contemporary evidence. Part 2 of this review in a companion paper discusses the results of high-throughput sequencing studies published to date on the microbiota associated with oral mucosal diseases. The goal of this collective enterprise is to encourage more oral medicine specialists to become engaged in multidisciplinary collaborations to investigate the role of the microbiome in relation to oral diseases, which could potentially lead to enhanced diagnosis, risk assessment and treatment of these patients.
PMID: 31140702
ISSN: 1601-0825
CID: 3902882

World Workshop on Oral Medicine VII: Functional pathways involving differentially expressed lncRNAs in oral squamous cell carcinoma

Pentenero, Monica; Bowers, Leah; Jayasinghe, Ruwan; Cheong, Sok Ching; Farah, Camile S; Kerr, Alexander Ross; Alevizos, Ilias
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.
PMID: 31140691
ISSN: 1601-0825
CID: 3902832

World Workshop on Oral Medicine VII: What participants perceive as important

Brailo, Vlaho; McKnight, Patrick; Kerr, Alexander R; Lodi, Giovanni; Lockhart, Peter B
Our objective was to identify which aspects of World Workshop on Oral Medicine (WWOM) participation were perceived as significant for participants' professional development. Online survey was sent to previous WWOM participants. Qualitative analysis of participants' responses to an open-ended question was performed. Fifty-two WWOM participants responded. Nearly three quarters of respondents (72.3%) felt that participation in the WWOM helped their career. A high percentage of respondents (67.3%) provided answers that fell under the domains of international collaboration, followed by personal academic benefits (48%). Overall, the results indicate that WWOM participation played an important role in individual's professional development. We identified aspects of WWOM involvement that the participants perceived as important. This information will be used for the development of an objective instrument for measuring impact of WWOM on participant's professional path.
PMID: 31140692
ISSN: 1601-0825
CID: 3925742

World Workshop on Oral Medicine VII: Editorial [Editorial]

Kerr, Alexander Ross; Greenberg, Martin S; Hodgson, Tim; Jensen, Siri Beier; Lockhart, Peter B; Lodi, Giovanni; Peterson, Douglas E
PMID: 31140695
ISSN: 1601-0825
CID: 3927062

World Workshop on Oral Medicine VII: Clinical evidence of differential expression of lncRNAs in oral squamous cell carcinoma: A scoping review

Pentenero, Monica; Bowers, Leah M; Jayasinghe, Ruwan; Yap, Tami; Cheong, Sok Ching; Kerr, Alexander Ross; Farah, Camile S; Alevizos, Ilias
BACKGROUND:Long non-coding RNAs (lncRNAs) have important roles in regulating gene expression pertaining to cell proliferation, survival, migration and genomic stability. Dysregulated expression of lncRNAs is implicated in cancer initiation, progression and metastasis. OBJECTIVES/OBJECTIVE:To explore, map and summarize the extent of evidence from clinical studies investigating the differential expression of lncRNAs in oral/tongue squamous cell carcinoma. METHODS:PubMed, Scopus and Web of Science were used as search engines. Clinical, full-length, English language studies were included. PRISMA-ScR protocol was used to evaluate and present results. The present scoping review summarizes relationships of the differential expression of lncRNAs with the presence of tumour and with clinicopathological features including survival. RESULTS:Almost half of the investigated transcripts have been explored in more than one study, yet not always with consistent results. The collected data were also compared to the limited studies investigating oral epithelial dysplasia. Data are not easily comparable, first because of different methods used to define what differential expression is, and second because only a limited number of studies performed multivariate analyses to identify clinicopathological features associated with the differentially expressed lncRNAs. CONCLUSIONS:Standard methods and more appropriate data analyses are needed in order to achieve reliable results from future studies.
PMCID:6544174
PMID: 31140697
ISSN: 1601-0825
CID: 4000182

Development of a cytology-based multivariate analytical risk index for oral cancer

Abram, Timothy J; Floriano, Pierre N; James, Robert; Kerr, A Ross; Thornhill, Martin H; Redding, Spencer W; Vigneswaran, Nadarajah; Raja, Rameez; McRae, Michael P; McDevitt, John T
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.
PMID: 31010626
ISSN: 1879-0593
CID: 3819192

Feasibility and acceptance of oral human papillomavirus detection in the dental office: Results from The National Dental Practice-Based Research Network

Rindal, D Brad; Gilbert, Gregg; Carcelén, Claudia; Funkhouser, Ellen; Durand, Emily; Uppgaard, David A; Fellows, Jeff; Ikeda, Jana; Kerr, Alexander Ross; Brar, Branden; Gordan, Valeria V; Agarwal, Sudhir; Barnett, Peter; Pickard, Robert K; Gillison, Maura
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.
PMID: 30691571
ISSN: 1943-4723
CID: 3631312

Incidence and mortality trends in oral and oropharyngeal cancers in China, 2005-2013

Zhang, Li-Wei; Li, Jin; Cong, Xin; Hu, Xiao-Sheng; Li, Dan; Wu, Li-Ling; Hua, Hong; Yu, Guang-Yan; Kerr, Alexander Ross
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.
PMID: 30396144
ISSN: 1877-783x
CID: 3425782