Image collection and annotation platforms to establish a multi-source database of oral lesions.

OBJECTIVE: To describe the development of a platform for image collection and annotation that resulted in a multi-sourced international image dataset of oral lesions to facilitate the development of automated lesion classification algorithms. MATERIALS AND METHODS: We developed a web-interface, hosted on a web server to collect oral lesions images from international partners. Further, we developed a customised annotation tool, also a web-interface for systematic annotation of images to build a rich clinically labelled dataset. We evaluated the sensitivities comparing referral decisions through the annotation process with the clinical diagnosis of the lesions. RESULTS: The image repository hosts 2474 images of oral lesions consisting of oral cancer, oral potentially malignant disorders and other oral lesions that were collected through MeMoSA® UPLOAD. Eight-hundred images were annotated by seven oral medicine specialists on MeMoSA® ANNOTATE, to mark the lesion and to collect clinical labels. The sensitivity in referral decision for all lesions that required a referral for cancer management/surveillance was moderate to high depending on the type of lesion (64.3%-100%). CONCLUSION: This is the first description of a database with clinically labelled oral lesions. This database could accelerate the improvement of AI algorithms that can promote the early detection of high-risk oral lesions.

Management of oral potentially malignant disorders.

Patients with oral potentially malignant disorders (OPMDs), including oral leukoplakia and erythroplakia, proliferative verrucous leukoplakia, oral submucous fibrosis, and oral lichen planus/lichenoid lesions, can be challenging to manage. A small proportion will undergo cancer development and determining a patient's cancer risk is key to making management decisions. Yet, our understanding of the natural history of OPMDs has not been fully elucidated, and a precision approach based on the integration of numerous predictive markers has not been validated by prospective studies. Evidence-based health promotion by clinicians and healthcare systems is not embraced universally. Medical and surgical interventions evaluated by rigorous research measuring important endpoints, such as cancer development, mortality, or survival, are difficult and expensive to run. Most of these studies employ non-ideal surrogate endpoints and have deep methodologic flaws. Diagnostic criteria for enrolling research subjects are not uniform, and patients with the highest risk for cancer development comprise small proportions of those enrolled. Few studies explore quality of life and patient preferences. It is time to rethink how we approach the management of these patients, across each OPMD, and considering the healthcare infrastructure and cost-effectiveness. Global networks with well-characterized patient populations with OPMDs and well-designed interventional trials using validated outcome measures are needed.

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

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.

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

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.

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

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: 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.

World Workshop on Oral Medicine VI: a systematic review of medication-induced salivary gland dysfunction: prevalence, diagnosis, and treatment.

OBJECTIVES: Medication-induced salivary gland dysfunction (MISGD) causes significant morbidity resulting in decreased quality of life. This systematic review assessed the literature on the prevalence, diagnosis, treatment, and prevention of MISGD. MATERIALS AND METHODS: Electronic databases were searched for articles related to MISGD through June 2013. Four independent reviewers extracted information regarding study design, study population, interventions, outcomes, and conclusions for each article. Only papers with acceptable degree of relevance, quality of methodology, and strength of evidence were retained for further analysis. RESULTS: There were limited data on the epidemiology of MISGD. Furthermore, various methods were used to assess salivary flow rate or xerostomia. Preventive and therapeutic strategies included substitution of medications, oral, or systemic therapy with sialogogues, use of saliva substitutes or of electro-stimulating devices. Although there are promising approaches to improve salivary gland function, most studies are characterized by small numbers and heterogeneous methods. CONCLUSIONS: Physicians and dentists should identify the medications associated with xerostomia and salivary gland dysfunction through a thorough medical history. Preferably, health care providers should measure the unstimulated and stimulated whole salivary flow rates of all their patients so that these values can be used as a baseline to rate the complaints of patients who subsequently claim to experience xerostomia or salivary gland dysfunction as well as the possibilities of effectively treating this condition. CLINICAL RELEVANCE: MISGD remains a major burden for the population. This systematic review provides a contemporary in-depth description of the diagnosis and treatment of MISGD.

Mapping the legacy of the world workshop on oral medicine: a 35-year global bibliometric analysis.

OBJECTIVE: This study utilized bibliometric methodologies to explore the body of research presented at the World Workshop on Oral Medicine (WWOM) over the past 35 years. METHODS: A systematic tracking of articles across 8 editions of WWOM was conducted using databases such as Web of Science, Scopus, and PubMed. Comprehensive bibliographic analysis and data visualization were executed through Bibliometrix, Rstudio, and VOSviewer, facilitating an in-depth examination of citation metrics and collaborative networks. RESULTS: The investigation revealed that WWOM, held in 6 cities spanning four countries and addressing 33 distinct topics, demonstrated an annual citation growth rate of 8.29%, with an average of 49.31 citations per article. Notably, WWOM IV garnered the highest number of citations (1,342), reaching its peak in 2021 with 365 citations. Key contributors to the most-cited articles include Al-Hashimi, Dawes, and Syrjänen et al. Since its inception, the workshops have engaged 505 faculty members from 37 nations, with significant participation from the Americas and Europe, notably the United States and the United Kingdom, which also led in terms of publications. Network analysis delineated 6 country clusters, underscoring robust connections between the US and the UK. Co-authorship analysis revealed 18 clusters involving 267 authors. CONCLUSION: The influence of the WWOM on the field of oral medicine is clearly demonstrated by the outcomes of its publications, reflecting a collaborative effort to enhance comprehension and treatment modalities for patients with oral diseases. The study's findings provide insights into future research directions within the WWOM legacy.

World Workshop on Oral Medicine VIII: barriers to research in oral medicine: lessons learned from a bibliometric analysis of the oral potentially malignant disorders literature.

OBJECTIVE: This study aimed to assess the impact of oral medicine (OM) practitioners on the literature regarding oral potentially malignant disorders (OPMDs), focusing on oral leukoplakia. STUDY DESIGN: Using a bibliometric approach on the Scopus database until September 1, 2022, the top 100 cited articles were analyzed for article type, subtopic, specialty contributions, author metrics, and keywords. The Bibliometrix package for R and VOSviewer were used to evaluate interactions and generate science maps. RESULTS: OM practitioners, comprising 39% of contributors, played a significant role in studies related to nomenclature and screening of OPMDs. Notably, 4 OM specialists ranked among the most prolific authors, demonstrating denser collaboration with OM co-authors compared to other cancer specialists. However, there was a scarcity of OPMD management studies authored by OM practitioners. CONCLUSIONS: Despite the paucity of OM practitioners, the findings underscored the substantial contribution of OM practitioners in developing OPMD nomenclature and classification, emphasizing the need for increased collaboration with cancer specialists to conduct comprehensive clinical trials for OPMD management. The study highlights the importance of standardized criteria in OPMDs research for better data comparison and encourages further efforts from the OM scientific community.

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.

World Workshop on Oral Medicine VIII: Development of a core outcome set for dry mouth: a systematic review of outcome domains for salivary hypofunction.

OBJECTIVE: To identify all outcome measures used to assess salivary gland hypofunction (i.e., objective measures used to determine actual changes in saliva quantity or to assess response to treatment of salivary gland hypofunction) and to group these into domains. STUDY DESIGN: A systematic review including clinical trials and prospective or retrospective observational studies involving human participants with dry mouth, with any type of intervention where the objective assessment of salivary gland hypofunction was described. RESULTS: Five hundred fifty-three studies involving 31,507 participants were identified. Most assessed salivary gland hypofunction and xerostomia (68.7%), whereas 31.3% assessed salivary gland hypofunction alone. Most studies investigated the "amount of saliva," and the highest number of outcome measures were within the domain of "clinical/objective signs of salivary gland hypofunction." CONCLUSIONS: Seven domains encompassing 30 outcome measures were identified, confirming the diversity in outcomes and outcome measures used in research regarding salivary gland hypofunction. Identified items will be used in conjunction with those identified regarding xerostomia to create a core outcome set for dry mouth quantification for use in future clinical trials, with the overall goal of improving the standardization of reporting, leading to the establishment of more robust evidence for the management of dry mouth and improving patient care.

World Workshop on Oral Medicine VIII: Development of a core outcome set for dry mouth: a systematic review of outcome domains for xerostomia.

OBJECTIVE: The purpose of this study was to identify all outcome domains used in clinical studies of xerostomia, that is, subjective sensation of dry mouth. This study is part of the extended project "World Workshop on Oral Medicine Outcomes Initiative for the Direction of Research" to develop a core outcome set for dry mouth. STUDY DESIGN: A systematic review was performed on MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials databases. All clinical and observational studies that assessed xerostomia in human participants from 2001 to 2021 were included. Information on outcome domains was extracted and mapped to the Core Outcome Measures in Effectiveness Trials taxonomy. Corresponding outcome measures were summarized. RESULTS: From a total of 34,922 records retrieved, 688 articles involving 122,151 persons with xerostomia were included. There were 16 unique outcome domains and 166 outcome measures extracted. None of these domains or measures were consistently used across all the studies. The severity of xerostomia and physical functioning were the 2 most frequently assessed domains. CONCLUSION: There is considerable heterogeneity in outcome domains and measures reported in clinical studies of xerostomia. This highlights the need for harmonization of dry mouth assessment to enhance comparability across studies and facilitate the synthesis of robust evidence for managing patients with xerostomia.

World Workshop on Oral Medicine VIII: Development of a core outcome set for dry mouth: a consensus study.

OBJECTIVE: This study aimed to develop a consensus-based core outcome set (COS) to be used in clinical trials assessing dry mouth interventions. STUDY DESIGN: Through 2 systematic literature reviews and interviews with dry mouth patients, we identified relevant outcome domains for dry mouth assessment. A Delphi survey was presented to health care providers attending the American Academy of Oral Medicine annual meeting in Memphis, Tennessee, USA, on May 2022 (n = 104) and 10 dry mouth patients at Cork University Dental School and Hospital, Republic of Ireland. The outcome domains for which no consensus was reached were subsequently discussed in a second consensus process led by a virtual Special Interest Group of 11 oral medicine experts from the World Workshop on Oral Medicine VIII dry mouth working group. RESULTS: After the 2-step consensus process, a consensus was reached for 12 dry mouth outcome domains (i.e., salivary gland flow, signs of hyposalivation, mucosal moisture/wetness, the severity of xerostomia, duration of xerostomia, the overall impact of xerostomia, impact on physical functioning, impact of hyposalivation on general health, impact on social activities, quality of life, the economic impact of dry mouth, patient satisfaction) to be included in the final COS. CONCLUSIONS: We propose a consensus-based COS to assess dry mouth interventions in clinical trials. This COS includes the minimum but mandatory set of domains that all clinical trials evaluating dry mouth treatments should assess.

World Workshop on Oral Medicine VIII: Development of a core outcome set for dry mouth: the patient perspective.

OBJECTIVE: We conducted a qualitative study of patients' perspectives on dry mouth outcomes to explore their personal experiences and investigate which outcomes are most important to them. This work was part of the WONDER initiative (World Workshop on Oral Medicine Outcomes Initiative for the Direction of Research) exploring Core Outcome Measures in Effectiveness Trials. STUDY DESIGN: Using a study-specific topic guide, we conducted digitally recorded, semi-structured interviews of focus groups of patients with dry mouth secondary to Sjögren syndrome and head and neck radiotherapy. We conducted interviews until data saturation had been achieved and evaluated all transcripts for accuracy before we anonymized the data. RESULTS: Two focus groups consisting of 4 participants per group identified 4 distinct themes: (1) impact on oral health and function, (2) social isolation and withdrawal, (3) frustration with dry mouth management, and (4) limited knowledge of the medical community and lack of understanding of family and friends. CONCLUSIONS: The diversity of self-reported outcomes and the complexity of patient perceptions identified in our work may represent additional barriers to successful dry mouth management that should be considered in the design of future clinical trials.

English and Spanish oral cancer information on the internet: a pilot surface quality and content evaluation of oral cancer web sites.

OBJECTIVE: Oral and pharyngeal cancers are responsible for over 7600 deaths each year in the United States. Given the significance of the disease and the fact that many individuals increasingly rely on health information on the Internet, it is important that patients and others can access clear and accurate oral cancer information on the Web. The objective of this study was threefold: (a) develop an initial method to evaluate surface and content quality of selected English- and Spanish-language oral cancer Web sites; (b) conduct a pilot evaluation; and (c) discuss implications of our findings for dental public health. METHODS: We developed a search strategy to find oral cancer sites frequented by the public using Medline Plus, Google, and Yahoo in English and Spanish. We adapted the Information Quality Tool (IQT) to perform a surface evaluation and developed a novel tool to evaluate site content for 24 sites each in English and Spanish. RESULTS: English-language sites had an average IQT score of 76.6 (out of 100) and an average content score of 52.1 (out of 100). Spanish-language sites had an average IQT score of 50.3 and an average content score of 25.6. CONCLUSIONS: The study produced a quality assessment of oral cancer Web sites useful for clinicians and patients. Sites provided more information on clinical presentation, and etiology, and risk factors, than other aspects of oral cancer. The surface and quality of Spanish-language sites was low, possibly putting Hispanic populations at a disadvantage regarding oral cancer information on the Web.

Oral submucous fibrosis: a contemporary narrative review with a proposed inter-professional approach for an early diagnosis and clinical management.

Oral Submucous fibrosis (OSMF) has traditionally been described as "a chronic, insidious, scarring disease of the oral cavity, often with involvement of the pharynx and the upper esophagus". Millions of individuals are affected, especially in South and South East Asian countries. The main risk factor is areca nut chewing. Due to its high morbidity and high malignant transformation rate, constant efforts have been made to develop effective management. Despite this, there have been no significant improvements in prognosis for decades. This expert opinion paper updates the literature and provides a critique of diagnostic and therapeutic pitfalls common in developing countries and of deficiencies in management. An inter-professional model is proposed to avoid these pitfalls and to reduce these deficiencies.

Cues used by dentists in the early detection of oral cancer and oral potentially malignant lesions: findings from the National Dental Practice-Based Research Network.

OBJECTIVE: The aim of this study was to assess the influence of clinical cues on risk assessment of cancer-associated mucosal abnormalities. STUDY DESIGN: We differentiated lesions with a low risk from those with a high risk for premalignancy or malignancy by using 4 cues: (1) color, (2) location, (3) induration, and (4) pain on exploration. Combinations of color and location were presented through 8 photographs, with induration and pain status variably presented in the standardized history and physical findings. This created 16 clinical scenarios (vignettes) that were permutations of the 4 cues. Three questions assessed the extent to which each cue was used in obtaining a clinical impression as to whether a lesion was benign, premalignant, or malignant. RESULTS: Completed vignette questionnaires were obtained from 130 of 228 invited dentists, (two-thirds males; 79% white; mean age 52 years; average weekly hours of practice 33 hours). Only 40% of the responding dentists had statistically significant decision policies to assign a clinical diagnosis of a lesion as benign, premalignant, or malignant. Lesion location and color were the 2 dominant cues. As a cue, induration was used as a cue by more of the respondents in determining a clinical diagnosis of malignancy, and pain was infrequently used as a cue. CONCLUSIONS: Many dentists do not to have a decision strategy for the clinical diagnosis and risk stratification of oral potentially malignant lesions.

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

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: 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.

Evaluation and Management of Oral Potentially Malignant Disorders.

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.

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

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: 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.