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.

Differences among oral carcinomas arising de novo from those associated with oral potentially malignant disorders: a systematic review and meta-analysis.

OBJECTIVE: To analyze the frequency of sequential oral squamous cell carcinomas (s-OSCC), preceded by oral potentially malignant disorders, and OSCC de novo (OSCC-dn) and explore differences in their clinicopathologic presentations. STUDY DESIGN: A structured electronic search strategy identified studies that analyzed frequency, clinical, biological, demographic, biomarkers, and prognostic features of s-OSCC and OSCC-dn according to PRISMA guidelines in PubMed, Scopus, Cochrane Library, and Google Scholar, up to January 31, 2023. Inclusion criteria were original English, Spanish, Portuguese, French, Italian, and German cross-sectional, cohort, and case-control studies. The quality of studies was assessed using the Agency for Research and Health Quality tool and the Newcastle-Ottawa Scale tool. RESULTS: The final selection included 40 studies. OSCC-dn and s-OSCC represent, respectively, 71% and 29% of cases of OSCC (P = .00), showing a higher percentage of T1 or of T1+T2 in s-OSCC (P < .0001). The association meta-analysis showed OSCC-dn with a significant association. The meta-analysis showed that s-OSCC was significantly associated with smaller tumor size, absence of distant metastases, relapses, male sex, and tumor sites different from tongue; and OSCC-dn was associated with more advanced tumor size, more regional and distant metastases, more advanced stages, and worse survival. CONCLUSIONS: S-OSCC was less frequent than expected. OSCC-dn seems to have specific clinical, biological, and prognostic features. Future perspectives on oral cancer prevention should address novel approaches and alternatives to screening, such as urgent referral of OSCC-dn.

Epidemiology of oral cancer in South and South-East Asia: Incidence and mortality.

INTRODUCTION: This study provides an epidemiological description of cancer in the lip, oral cavity, and oropharynx in the South and South-East Asia region. METHODS: The number of new cases and deaths was extracted from the GLOBOCAN 2020 and the CI5 series. We present age-standardized incidence and mortality rates per 100,000 inhabitants. To assess temporal trends, we estimated the annual percent change. RESULTS: The incidence rates (ASR) for lip and oral cavity cancer in South and South-East Asia were highest in Taiwan (30.2), Sri Lanka (16.5), India (14.8), and Pakistan (13.2) among males. For oropharyngeal cancer, the highest rates were found in Taiwan (4.7), Bangladesh, Sri Lanka, and India (4.3, 2.9, and 2.6, respectively). Incidence rates were consistently higher in males compared to females. Overall, trends in lip and oral cavity cancer incidence were either stable or decreasing in most of the populations evaluated. In India, an increase in rates among males contrasted with a decline among females over the study period. CONCLUSION: Incidence and mortality rates of oral cavity cancer in South and South-East Asia are among the highest globally. Our results suggest an optimistic trend of reduction in oral cavity rates in the region, despite an increase in rates among Indian males.

Oral cancer and oral potentially malignant disorders in patients with Fanconi anemia - A systematic review.

The purpose of the present study was to perform a systematic review focusing on oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) in Fanconi anemia (FA) individuals. Electronic searches were undertaken in five databases supplemented by manual scrutiny and gray literature. Case reports and/or cases series were included. The searches yielded 55 studies describing 112 cases of OSCC (n = 107) and/or OPMD (n = 5) in FA individuals. The mean age at diagnosis of OSCC/OPMD was 27.1 (±9.6) years, and females (51.8 %) were slightly more affected. Ulcer (n = 37) or mass (n = 25) were described as clinical presentations for OSCC and OPMD. White lesions (n = 4) were the most common manifestation in OPMD. Tongue (47.2 %) was the most frequent location. Sixty-one (54.5 %) individuals underwent HSCT. Surgical resection (n = 75) was the main treatment adopted. The estimated rate of OPMD malignant transformation was 1.8 % and recurrences following OSCC excision occurred in 26.8 % of individuals. Overall, at 60 months of follow-up, the probability of survival fell to 25.5 % and at 64 months the probability of recurrence increased to 63.2 %. The present data support the need for strict surveillance of patients with FA, even in the absence of OPMD, for early OSCC detection and reduction of mortality.

Barriers to early diagnosis and management of oral cancer in Latin America and the Caribbean.

OBJECTIVE: This study aimed to explore perceived barriers to early diagnosis and management of oral cancer, as well as potential pathways for improvement in Latin America and the Caribbean (LAC). METHODS: This cross-sectional study used a self-administered online questionnaire created via the Research Electronic Data Capture platform. The survey was distributed to health professionals trained in Oral Medicine, Oral Pathology, Oral and Maxillofacial Surgery, and Dentists with clinical and academic expertise in oral potentially malignant disorder (OPMD) and oral cancer. Data obtained were systematically organized and analyzed descriptively using Microsoft Excel. RESULTS: Twenty-three professionals from 21 LAC countries participated. Major barriers included the limited implementation of OPMD and oral cancer control plans (17.4%), low compulsory reporting for OPMD (8.7%) and oral cancer (34.8%), unclear referral pathways for OPMD (34.8%) and oral cancer (43.5%), and a shortage of trained professionals (8.7%). Participants endorsed the utility of online education (100%) and telemedicine (91.3%). CONCLUSION: The survey highlights major perceived barriers to early diagnosis and management of OPMD and oral cancer in LAC, as well as potential avenues for improvement.

Proliferative verrucous leukoplakia/multifocal leukoplakia in patients with and without oral submucous fibrosis / Leucoplasia verrugosa proliferativa/leucoplasia multifocalen pacientes con y sin fibrosis submucosa oral

Background: Oral submucous fibrosis (OSF) and proliferative verrucous leukoplakia (PVL) are established as oralpotentially malignant disorders. Dual pathology of the two conditions is not commonly encountered in clinicalpractice. This study aims to present a case series of multifocal leukoplakia in patients with and without OSF tooutline the clinical behavior and challenges in the management of this high-risk group in clinical practice.Material and Methods: We retrospectively analyzed cases of six Indian patients (four with OSF) managed over aperiod of 5.5 to 13 years at the Government Dental College, Nagpur. Patient data consisting of age, gender, med-ical history, habits, clinical findings, and biopsy reports were recorded at the initial visit. During follow-up visits,the clinicopathological data were reassessed. When surgical intervention failed to arrest the disease or whensurgery was contraindicated metronomic therapy with Folitrax 15 mg once a week and Celecoxib 100mg twicedaily was initiated.Results: All patients developed PVL after the initial pathology diagnosis of OSF or oral leukoplakia. Initial lesionswere either homogenous or non-homogenous leukoplakia. All patients developed multiple recurrences, regional orsystemic metastasis. Despite thorough interventions, the patients died of, or with the disease.Conclusions: The occurrence of two or more oral potentially malignant disorders poses challenges in patient man-agement and possibly presents a higher risk of malignant transformation. More clinical trials are necessary to as-sess the benefits of metronomic therapy for patients diagnosed with aggressive PVL concurrently found with OSF.(AU)

Adjunctive aids for the detection of oral squamous cell carcinoma and oral potentially malignant disorders: A systematic review of systematic reviews.

This study presents the results of systematic reviews on adjunctive tools in screening and diagnosis of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) and to determine if the current literature supports their use as either an adjunctive tool or replacement of gold standard techniques. Systemic reviews and meta-analysis that evaluated adjunctive tools including chemiluminescence, tissue autofluorescence, tissue fluorescence spectroscopy, vital staining and cytology techniques were systematically examined using AMSTAR II. Twenty-seven systematic reviews were included. Five studies had a low quality of evidence, and nine studies had a critically low quality of evidence. This review found limited evidence to recommend chemiluminescence, tissue autofluorescence tools and vital staining as diagnostic tools, but only serve as clinical adjuncts to conventional oral examination. Cytology techniques and narrow-band imaging may be utilised as a non-invasive diagnostic adjunctive tool for the detection of OSCC and the malignant transformation of OPMD. In conclusion, this paper provides evidence on several types of adjunctive tools and provides recommendations on their use in clinical practice. These tools are considered useful as clinical adjuncts but there is insufficient evidence for their use as a diagnostic tool to replace gold standard conventional oral examination and surgical biopsy.

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.

Mucormycosis of the Mandible and Tongue: A Systematic Scoping Review.

AIM: Mucormycosis is a rare human infection associated with Mucorales, a group of filamentous moulds found in different environmental niches. Its oral manifestations may occur in the mandible and tongue despite being rare. We aimed to systematically review the data on clinical manifestations, risk factors, diagnostic approaches, treatment options, and outcomes of mandibular and tongue mucormycosis. METHODS: An electronic search of articles published between January 1975 and November 2022 in PubMed, Web of Science, and EMBASE databases was performed. A total of 22 articles met the inclusion criteria and reported 27 cases of oral mucormycosis in total. RESULTS: Fourteen patients had mandibular mucormycosis signs unrelated to COVID-19 infection, 6 had SARS-CoV-2-related mandibular mucormycosis, and 6 had manifestations in the tongue. All published case reports during the COVID-19 pandemic were from India. Patient ages ranged from 4 months old to 82 years, and most patients had important comorbidities, such as blood dyscrasias related to immune deficiency and uncontrolled type 2 diabetes mellitus. The signs and symptoms of mandibular and tongue mucormycosis varied from dental pain, loose teeth, and nonhealing sockets to dysphagia and paraesthesia of the lip. Some patients also reported trismus, draining sinus tract, and facial pain. The diagnosis of oral mucormycosis was based on a combination of clinical, radiographic, and histopathologic findings by demonstrating fungal hyphae in tissue specimens. In most cases, mucormycosis was managed with systemic amphotericin B, strict glycaemic control, and aggressive surgical debridement of infected tissue, minimising the progression of the fungal infection and thus improving the survival rate. In some cases, combined antifungal therapy, antibiotic therapy, and chlorhexidine mouthwashes were used successfully. CONCLUSIONS: Recognition of the signs and symptoms by oral care providers is pertinent for the early diagnosis and treatment of tongue and mandibular mucormycosis, and providers should be aware of the possibility of this opportunistic fungal infection in patients with COVID-19. A multidisciplinary approach is recommended for the management of this lethal infection.

Clinical and Psychosocial Impact of Communication about Oral Potentially Malignant Disorders: A Scoping Review.

Delivering bad news has been widely studied in cancer, thus, this scoping review aims to identify the available evidence concerning the communication of oral potentially malignant disorders (OPMDs) and their clinical and psychosocial impacts. A search was performed using electronic databases (Medline/PubMed, Scopus, Embase, and Web of Science) and one grey literature database (Google Scholar). Studies focused on communicating the diagnosis of OPMDs and the patients' perceptions were included. Study selection and data extraction were performed by two authors in a two-phase process. Five publications were included in the qualitative analysis. Differences regarding the study design, population, OPMDs assessed, and outcomes of professional-patient communication were found in each study. Protocols for OPMD communication have not yet been reported and there is a need to standardize strategies as communication skills may provide better clinical outcomes for patients diagnosed with potentially malignant disorders. Although future studies are needed, a brief list recommending the aspects that must be communicated is proposed.

World Workshop on Oral Medicine VIII: Barriers to research in oral medicine: results from a global survey.

OBJECTIVES: To explore factors influencing research interest and productivity and perceived barriers to conducting research in Oral Medicine (OM). METHODS: Invitations to participate in an online survey were e-mailed to a network of international OM practitioners and related professional organizations. Questions captured respondents' demographic/professional variables and gauged research interest, productivity, and perceived barriers to conducting research specifically in OM. Statistical analysis was conducted via descriptive, logistic regression, and multivariate modeling. RESULTS: Five hundred and ninety-three OM practitioners from 55 countries completed the survey, with 54%, 25%, and 21% practicing in high, upper-middle, and lower-middle-income countries, respectively. Eighty-six percent of respondents were interested in conducting research. Age (less interest with an increase in age), working in academia, and practicing in a lower-middle vs high-income country were significant predictors of research interest. Self-reported research productivity was significantly greater among males, those working in academia, and those who graduated from programs that mandated research presentation/publication. Obtaining research funding was a significant barrier among respondents from lower and upper-middle-income countries, whereas finding time for research was a reported barrier by respondents from high-income countries. CONCLUSION: The results of this survey identified perceived barriers to conducting research in OM and highlighted solutions to address such barriers.

An overview of the burden of oral cancer in Sri Lanka and its inequalities in the face of contemporary economic and social malaise.

OBJECTIVES: Over the past several decades, oral cancer has been the most common malignancy among Sri Lankan males and the top 10 cancer among females, disproportionately affecting low socio-economic groups. Sri Lanka is a lower-middle-income developing country (LMIC), currently striking through an economic crisis, and social and political unrest. Occurring at an accessible body site and predominantly attributed to potentially modifiable health-related behaviours, oral cancer should be preventable and controllable. Unfortunately, broader contextual factors that are socio-cultural, environmental, economic, and political and mediated through social determinants of people's lives consistently hinder progress. Many LMICs with a high burden of oral cancer are now gripped by economic crises, consequent social and political unrest, all compounded by reduced public health investments. The aim of this review is to provide a critical commentary on key aspects of oral cancer epidemiology including inequalities, using Sri Lanka as a case study. METHODS: The review synthesizes evidence from multiple data sources, such as published studies, web-based national cancer incidence data, national surveys on smokeless tobacco (ST) and areca nut use, smoking and alcohol consumption, poverty headcount ratios, economic growth, and Gross Domestic Product (GDP) health expenditure. National trends in the oral cancer, ST use, smoking and alcohol consumption in Sri Lanka are identified alongside inequalities. RESULTS: Using these evidence sources, we discuss 'where are we now?', together with the availability, accessibility and affordability of oral cancer treatment services, oral cancer prevention and control programmes, tobacco and alcohol control policies, and finally, outline macroeconomic perspectives of Sri Lanka. CONCLUSIONS: Finally, we speculate, 'where to next?' Our overarching goal of this review is to initiate a critical discourse on bridging the gaps and crossing the divides to tackle oral cancer inequalities in LMIC such as Sri Lanka.

Pan-American prevalence of smokeless tobacco use and association with oral potentially malignant disorders and head and neck cancer: a systematic review and meta-analysis.

OBJECTIVES: To determine the prevalence of smokeless tobacco (SLT) use and its association with oral potentially malignant disorders (OPMDs) and head and neck cancer (HNC) in the Pan-American Health Organization (PAHO) region. STUDY DESIGN: A literature search was conducted across 9 databases and other sources. The eligibility criteria were pediatric (0-18 years old) and adult (19 years and older) populations consuming any type of SLT. Meta-analysis was performed to determine the prevalence of SLT and the association between its use and OPMDs/HNC in the PAHO region; the Grading of Recommendations Assessment, Development, and Evaluation tool was used to verify the certainty of evidence. RESULTS: Fifty-nine studies from 6 PAHO countries were included, of which 51 were also subjected to quantitative analysis. The pooled SLT prevalence of use was 15% (95%CI: 11.93-18.69) overall, 17% (95%CI: 13.25-22.65) in adults, and 11% (95%CI: 8.54-14.78) in the pediatric population. The highest reported SLT prevalence of use was 33.4% (95%CI: 27.17-39.93) in Venezuela. HNC was positively associated with SLT use (OR = 1.98, 95%CI: 1.54-2.55), with a moderate certainty of evidence. Among OPMDs, only leukoplakia reported a positive association with SLT use (OR = 8.38; 95%CI: 1.05-67.25). However, the quality of the evidence was very low. CONCLUSION: A high consumption of SLT use, chewing tobacco and snuff, is reported among the adult population residing in the PAHO region with a positive association with the development of oral leukoplakia and HNC.

Carcinogenic Effects of Areca Nut and Its Metabolites: A Review of the Experimental Evidence.

Oral cancers (OC) are among the most frequent malignancies encountered in Southeast Asia, primarily due to the prevalent habit of betel quid (BQ) and smokeless tobacco use in this region. Areca nut (AN), the primary ingredient in BQ, contains several alkaloids, including arecoline, arecaidine, guvacoline, and guvacine. These have been associated with both the AN abuse liability and carcinogenicity. Additionally, variations in AN alkaloid levels could lead to differences in the addictiveness and carcinogenic potential across various AN-containing products. Recent studies based on animal models and in vitro experiments show cellular and molecular effects induced by AN. These comprise promoting epithelial-mesenchymal transition, autophagy initiation, tissue hypoxia, genotoxicity, cytotoxicity, and cell death. Further, clinical research endorses these undesired harmful effects in humans. Oral submucosal fibrosis, a potentially malignant disease of the oral cavity, is predominantly reported from the geographical areas of the globe where AN is habitually chewed. OC in chronic AN users presents a more aggressive phenotype, such as resistance to anti-cancer drugs. The available evidence on the carcinogenicity of AN based on the findings reported in the recently published experimental studies is discussed in the present review.

Machine learning for detection and classification of oral potentially malignant disorders: A conceptual review.

Oral potentially malignant disorders represent precursor lesions that may undergo malignant transformation to oral cancer. There are many known risk factors associated with the development of oral potentially malignant disorders, and contribute to the risk of malignant transformation. Although many advances have been reported to understand the biological behavior of oral potentially malignant disorders, their clinical features that indicate the characteristics of malignant transformation are not well established. Early diagnosis of malignancy is the most important factor to improve patients' prognosis. The integration of machine learning into routine diagnosis has recently emerged as an adjunct to aid clinical examination. Increased performances of artificial intelligence AI-assisted medical devices are claimed to exceed the human capability in the clinical detection of early cancer. Therefore, the aim of this narrative review is to introduce artificial intelligence terminology, concepts, and models currently used in oncology to familiarize oral medicine scientists with the language skills, best research practices, and knowledge for developing machine learning models applied to the clinical detection of oral potentially malignant disorders.

The carcinogenicity of opium consumption: a systematic review and meta-analysis.

The carcinogenicity of opium consumption was recently evaluated by a Working Group convened by the International Agency for Research on Cancer (IARC). We supplement the recent IARC evaluation by conducting an extended systematic review as well as a quantitative meta-analytic assessment of the role of opium consumption and risk for selected cancers, evaluating in detail various aspects of study quality on meta-analytic findings. We searched the published literature to identify all relevant studies on opium consumption and risk of selected cancers in humans through 31 October, 2022. Meta-relative risks (mRRs) and associated 95% confidence intervals (CIs) were estimated using random-effects models for studies of cancer of the urinary bladder, larynx, lung, oesophagus, pancreas, and stomach. Heterogeneity among studies was assessed using the I2 statistic. We assessed study quality and conducted sensitivity analyses to evaluate the impact of potential reverse causation, protopathic bias, selection bias, information bias, and confounding. In total, 2 prospective cohort studies and 33 case-control studies were included. The overall pooled mRR estimated for 'ever or regular' versus 'never' use of opium ranged from 1.50 (95% CI 1.13-1.99, I2 = 0%, 6 studies) for oesophageal cancer to 7.97 (95% CI 4.79-13.3, I2 = 62%, 7 studies) for laryngeal cancer. Analyses of cumulative opium exposure suggested greater risk of cancer associated with higher opium consumption. Findings were robust in sensitivity analyses excluding studies prone to potential methodological sources of biases and confounding. Findings support an adverse association between opium consumption and cancers of the urinary bladder, larynx, lung, oesophagus, pancreas and stomach.