Mapping oral medicine (stomatology) & oral and maxillofacial pathology international organizations: a scoping review of global data and historical analysis.

OBJECTIVES: To describe the historical evolution and dissemination of the Oral Medicine and Oral and Maxillofacial Pathology international societies and associations across the globe, and to provide insights into their significant contributions toward oral health promotion. STUDY DESIGN: This review was conducted in accordance with the JBI Scoping Review Methodology Group guidance. The reporting followed the Preferred Reporting Items for Systematic Reviews extension for Scoping Reviews (PRISMA-ScR). RESULTS: Search strategy was applied to 5 databases (MEDLINE/PubMed, Scopus, Embase, Web of Science, Latin American and Caribbean Health Sciences (LILACS)) and grey literature (Google Scholar, Open Grey and ProQuest), as well as additional sources, such as organization websites. Eighty-nine sources were included in this review. Forty-six professional associations/societies were identified, of which 39 represented a country or geopolitical region, 2 represented continents, 2 represented multinational organizations and 3 multinational study groups. CONCLUSIONS: Documentation of the historical establishment and development of Oral Medicine and Oral and Maxillofacial Pathology organizations worldwide is limited and describing these processes remains challenging. Analysis of global data reveals heterogeneous development and distribution, resulting in disparities in accessibility and standardization. Further efforts toward oral health promotion should be implemented.

Decalcification-free technique on the analysis of dental pulp tissue: histological and immunohistochemical analysis.

BACKGROUND: Histological techniques are essential for the microscopic study and investigation of the human dental pulp. The aim of this study was to evaluate the impact of decalcification-free technique by examining dental pulp morphology by histological staining with haematoxylin and eosin and immunohistochemistry. MATERIALS AND METHODS: The sample consisted of 30 healthy third molars extracted for orthodontic indication, the pulp tissue was obtained by removing the mineralized tissues, separating the enamel and dentine and by marking with a flexible diamond disc on the coronal surface and longitudinal axis of the root. These guides made it possible to separate the fragments and obtain the pulp tissue for fixation and staining with H&E and subsequent immunohistochemistry with CD34 and S-100 antibodies. RESULTS: The technique showed preservation of pulp morphology with adequate preservation of microscopic structures. No alterations in tissue viability were observed. The staining allowed an accurate assessment of vascular and nervous components by means of CD34 and S-100 markers, respectively. CONCLUSIONS: This technique allows preservation of pulp tissue, maintaining viable tissue for histological analysis and immunohistochemistry tests, as well as reducing sample processing time.

The Frequency of Risk Factors for Cleft Lip and Palate in Mexico: A Systematic Review.

BACKGROUND: Cleft lip and palate is an anomaly that affects both women and men. It is considered to be among the most frequent congenital abnormalities and is related to modifications in chromosomal DNA and multiple genetic alterations. This anomaly can also be associated with various environmental factors, such as tobacco and alcohol consumption, medication use, and exposure to different environmental and industrial toxic substances. The objective of this study was to document the frequency of risk factors related to cleft lip and palate through a systematic review of Mexican studies. METHODS: In this systematic review, a bibliographic search was conducted following PRISMA guidelines in the databases Scielo, ScienceDirect, PubMed, and EBSCO. Keywords related to cleft lip and palate, epidemiology, and risk factors were used. In all, 3 independent reviewers (J.A.S.L., S.L.V., and N.M.F.) selected and evaluated a total of 17 articles included in this analysis, achieving a coefficient of κ = 0.84. RESULTS: The analysis revealed that the highest frequency of conducted studies was in the State of Mexico. The most common risk factors identified were environmental, pharmacological, consumption habits, and gynecological factors. CONCLUSIONS: Identifying the main risk factors for cleft lip and palate in the Mexican population will enable the implementation of preventive measures aimed at reducing exposure to these factors. Additionally, early intervention can improve the quality of life for individuals affected by this condition.

Association between fluoride intake from drinking water and severity of dental fluorosis in Northern and Western Mexico: systematic review and meta-analysis.

BACKGROUND: Dental fluorosis (DF) is caused by excessive exposure to fluoride during odontogenesis and leads to various changes in the development of tooth enamel. Some regions in Mexico are considered endemic fluorosis zones due to the high fluoride content in drinking water. The objective of this study was to perform a systematic review and meta-analysis to identify the association between the concentration of fluoride in drinking water and the severity of dental fluorosis in northern and western Mexico. METHODS: This protocol was registered in the PROSPERO database (ID: CRD42023401519). The search for information was carried out in the PubMed/Medline, Scopus, SpringerLink, and Google Scholar databases between January 2015 and October 2023. The overall relative risk was calculated using the inverse of variance approach with the random effects method. The RoB 2.0 tool was used to construct risk plots. RESULTS: Eleven articles were analyzed qualitatively, and most of the included studies presented at least one level of DF severity; six articles were analyzed quantitatively, dividing them into two regions. In North region it was observed a higher prevalence of severe TF cases, corresponding to ≥ TF 5 category (4.78) [3.55, 6.42]. In the West region, most of the included studies presented a higher prevalence of less severe cases, corresponding to ≤ TF 4, in comparison with the North region (0.01) [0.00, 0.52], interpreted as a protective effect. CONCLUSION: The concentrations of fluorides in drinking water are reportedly high in these regions and are directly related to the severity of dental fluorosis experienced by the inhabitants. In the Northern region exists a major concentration of fluoride in drinking water compared with the Western region as well as a prevalence of higher severity cases of dental fluorosis.

Correlation between Vascularity and Advancing Histological Grades of Oral Submucous Fibrosis with a Plausible Role in Malignisation: Systematic review of a persisting matter of conflict.

Objectives: This study aimed to quantify the vascularity in histological grades of oral submucous fibrosis (OSMF) and to determine if there is any connection between vasculogenesis and malignisation. Recent studies show no significant change in vascularity as the stage advances as opposed to the conventional concept. Methods: A comprehensive database search until December 2022 was conducted for published articles on vascularity in OSMF following preferred reporting items for systematic reviews and meta-analyses guidelines. Results: A total of 98 articles were screened of which 13 were included for systematic evaluation. The study included 607 cases, with a definite predilection for the male gender. Of the 13 studies, 11 evaluated mean vascular density. In more than half of the studies, the vascularity decreased as the stage advanced. Similar results were obtained for endothelial cells/µm2, mean vascular area percentage and mean vascular area. Conclusion: The present review supports the prevailing concept that vascularity decreases with the advancement of the OSMF stage. This denies the systemic absorption of carcinogens into the circulation with resultant longer exposure of compromised epithelium and malignisation.

Targeted therapies in ameloblastomas and amelobastic carcinoma-A systematic review.

Targeted therapy has the potential to be used in the neoadjuvant setting for odontogenic tumors, reducing the morbidities associated with major surgery. In this regard, the aim of this study was to summarize the current evidence on the different forms of targeted therapy, effectiveness, and drawbacks of this course of treatment. Four databases were searched electronically without regard to publication date or language. Grey literature searches and manual searches were also undertaken. Publications with sufficient clinical data on targeted therapy for odontogenic tumors were required to meet the criteria for eligibility. The analysis of the data was descriptive. A total of 15 papers comprising 17 cases (15 ameloblastomas and 2 ameloblastic carcinomas) were included. Numerous mutations were found, with BRAF V600E being most common. Dabrafenib was the most utilized drug in targeted therapy. Except for one case, the treatment reduced the size of the lesion (16/17 cases), showing promise. Most of the adverse events recorded were mild, such as skin issues, voice changes, abnormal hair texture, dry eyes, and systemic symptoms (e.g., fatigue, joint pain, and nausea). It is possible to reach the conclusion that targeted therapy for ameloblastoma and ameloblastic carcinoma may be a useful treatment strategy, based on the findings of the included studies.

Classificatory updates in verrucous and cuniculatum carcinomas: Insights from the 5th edition of WHO-IARC head and neck tumor classification.

The International Agency for Research on Cancer (IARC) and World Health Organization (WHO) collaboratively produce the 'WHO Blue Books' essential tools standardizing the diagnostic process for human cancers. Regular updates in this classification accommodate emerging molecular discoveries, advances in immunohistochemical techniques, and evolving clinical insights. The 5th edition of the WHO/IARC classification of head and neck tumors refines the 'Oral Cavity and Mobile Tongue' chapter, including sections for non-neoplastic lesions, epithelial tumors, and tumors of uncertain histogenesis. Notably, the epithelial tumors section is rearranged by tumor behavior, starting with benign squamous papillomas and progressing through potentially malignant oral disorders to oral squamous cell carcinoma (OSCC). The section on OSCC reflects recent information on epidemiology, pathogenesis, and histological prognostic factors. Noteworthy is the specific categorization of verrucous carcinoma (VC) and carcinoma cuniculatum (CC), both associated with the oral cavity and distinct in clinical and histologic characteristics. This classification adjustment emphasizes the oral cavity as their predominant site in the head and neck. Designating specific sections for VC and CC aims to provide comprehensive insights into these unique subtypes, elucidating their clinical features, distinct histological characteristics, prevalence, significance, and clinical relevance. By categorizing these subtypes into specific sections, the 5th edition of the WHO classification aims to provide a more nuanced and detailed account, enhancing our understanding of these specific variants within the broader spectrum of head and neck tumors.

Differential effects of coverslip-induced hypoxia and cobalt chloride mimetic hypoxia on cellular stress, metabolism, and nuclear structure.

Hypoxia has profound effects on cell physiology, both in normal or pathological settings like cancer. In this study, we asked whether a variant of coverslip-induced hypoxia that recapitulates the conditions found in the tumor microenvironment would elicit similar cellular responses compared to the well established model of cobalt chloride-induced hypoxia. Comparable levels of nuclear HIF-1α were observed after 24 h of coverslip-induced hypoxia or cobalt chloride treatment in CAL-27 oral squamous carcinoma cells. However, cellular stress levels assessed by reactive oxygen species production and lipid droplet accumulation were markedly increased in coverslip-induced hypoxia compared to cobalt chloride treatment. Conversely, mitochondrial ATP production sharply decreased after coverslip-induced hypoxia but was preserved in the presence of cobalt chloride. Coverslip-induced hypoxia also had profound effects in nuclear organization, assessed by changes in nuclear dry mass distribution, whereas these effects were much less marked after cobalt chloride treatment. Taken together, our results show that coverslip-induced hypoxia effects on cell physiology and structure are more pronounced than mimetic hypoxia induced by cobalt chloride treatment. Considering also the simplicity of coverslip-induced hypoxia, our results therefore underscore the usefulness of this method to recapitulate in vitro the effects of hypoxic microenvironments encountered by cells in vivo.

Clinicopathological features of myofibromas and myofibromatosis affecting the oral and maxillofacial region: A systematic review.

BACKGROUND: Myofibromas are rare benign neoplasms composed of myoid cells and myofibroblasts. This study aimed to systematically review case reports and a series of myofibromas (MF) and myofibromatosis (MFT) occurring in the oral and maxillofacial regions in order to describe their main clinicopathological features. METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic searches were conducted in 2023 in four databases: MEDLINE/PubMed, Web of Science, Scopus, and EMBASE. A manual search and a search in the grey literature were also conducted. The lesions were classified as MF or MFT according to their original report. RESULTS: A total of 169 cases were included in this systematic review. Men were slightly more affected, with a painless nodule. When occurring in soft tissue, MF usually developed in the gingiva (mean age:29.23 ± 21.93 years) and when it was intra-osseous, it occurred more frequently in the posterior mandible (mean age:14.33 ± 15.62 years). MFT occurred mainly in the mandible and was predominantly described as well-circumscribed masses of spindle cells organized in fascicles with a prominent vascular activity in a hemangiopericytoma-like pattern. The lesions were mainly positive for smooth muscle actin and vimentin immunomarkers. Surgical excision was the treatment of choice in the majority of cases and recurrence was observed in only three cases. CONCLUSION: MF and MFT affect more men, with an indolent clinical course. Intra-osseous tumors and MFT seem to occur more frequently in younger individuals. These lesions seem to have a good prognosis and low recurrence.

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.

Comprehensive insights into the understanding of hypoxia in ameloblastoma.

Hypoxia is characterized by a disparity between supply and demand of oxygen. The association between hypoxia and head and neck tumors is a topic of significant interest. Tumors frequently encounter areas with inadequate oxygen supply, resulting in a hypoxic microenvironment. Ameloblastoma is one of the most common benign odontogenic tumors of the maxillofacial region. It is a slow-growing but locally invasive tumor with a high recurrence rate. The literature has demonstrated the correlation between hypoxia and ameloblastoma, revealing a discernible link between the heightened expression of hypoxic markers in low oxygen conditions. This association is intricately tied to the tumoral potential for invasion, progression, and malignant transformation. Hypoxia profoundly influences the molecular and cellular landscape within ameloblastic lesions. The present review sheds light on the mechanisms, implications, and emerging perspectives in understanding this intriguing association to clarify the dynamic relationship between hypoxia and ameloblastoma.

Riesgo de transformación maligna de las lesiones verrucopapilares orales

Objetivos: evaluar el riesgo potencial maligno mediante la tinción de azul de toluidina y gradificación displásica de las lesiones verrucopapilares de la cavidad oral (LVPO). Materiales y métodos: Se identificaron pacientes con LVPO localizados en la cavidad oral, se les aplicó azul de toluidina y posteriormente se evaluó los cambios displásicos para finalmente gradificarlos histopatológicamente en ausente, bajo o alto riesgo de transformación maligna. Pacientes que se negaron a la tinción con AT, no aceptaron la biopsia escisional o el tejido no poseía coilocitos, daño citopático asociado a la presencia del virus papiloma humano fueron eliminados del estudio. Resultados: se incluyeron 34 pacientes con LVPO, 4 con tinción positiva al AT (3 fueron considerados intensos y 1 leve). Conclusiones: las LVPO pueden emitir una tinción positiva al azul de toluidina así como presentar una variedad heterogenea de cambios displásicos arquitecturales y citológicos evaluados histopatologicamente, que en la totalidad de las muestras, de acuerdo al sistema binario, son clasificadas como riesgo leve de transformación maligna.

Objetivos: Avaliar o risco de potencial maligno através da coloração com azul de toluidina e da classificação displásica das lesões verrucopapilares da cavidade oral (LVPO). Materiais e métodos: Foram identificados pacientes com LVPO POVE localizados na cavidade oral nos quais foi aplicado azul de toluidina e posteriormente avaliadas as alterações displásicas para finalmente serem classificadas histopatologicamente como ausentes, baixo ou alto risco de transformação maligna. Os pacientes que recusaram a coloração com azul de toluidina AT, não aceitaram a biópsia excisional ou o tinha tecido insuficiente, presença de coilócitos ou dano citopático associado ao papilomavírus humano foram eliminados do estudo. Resultados: Foram incluídos 34 pacientes com LVPO, dos quais 4 foram interpretados como tendo coloração positiva para azul de toluidina AT positiva, sendo 3 considerados intensos e 1 leve. Conclusões: A LVPO pode emitir coloração positiva para azul de toluidina, bem como apresentar uma variedade heterogênea de alterações arquitetônicas e citológicas displásicas avaliadas histopatologicamente, que em todas as amostras, segundo o sistema binário, são classificadas como leve risco de transformação maligna.

Objectives: to evaluate the risk of malignant potential through toluidine blue staining and dysplastic grading of verrucous papillary lesions of the oral cavity (VPLO). Materials and methods: patients with VPLO located in the oral cavity were identified to whom toluidine blue was applied and dysplastic changes were subsequently evaluated and graded histopathologically as absent, low or high risk of malignant transformation. Patients who refused toluidine blue staining, did not accept excisional biopsy or had insufficient tissue, or the tissue lack of presence of koilocytes, damage associated with the presence of human papilloma virus were eliminated from the study. Results: Thirty-four patients with VPLO were included, of which 4 were found to have positive toluidine blue staining. Of these, 3 cases were considered intense and 1 was mild. Conclusions: VPLO may emit a positive stain to toluidine blue as well as present a heterogeneous variety of architectural and cytological dysplastic changes evaluated histopathologically, which in all samples, according to the binary system, are classified as low risk of malignant transformation.

Oral squamous cell carcinomas and oral potentially malignant disorders: A Latin American study.

OBJECTIVE: To determine the frequency of oral squamous cell carcinoma (OSCC) associated or not with oral potentially malignant disorders (OPMD), and the epidemiological profile and traditional risk factors in Latin America. METHODS: A retrospective observational study was conducted in 17 Latin American centres. There were included cases of OSCC, analysing age, gender, OSCC and their association with previous OPMD. Clinicopathological variables were retrieved. The condition of sequential-OSCC versus OSCC-de novo (OSCC-dn) was analysed concerning the aforementioned variables. Quantitative variables were analysed using Student's t-test, and qualitative variables with chi-square. RESULTS: In total, 2705 OSCC were included with a mean age of 62.8 years old. 55.8% were men. 53.75% of the patients were smokers and 38% were common drinkers. The lateral tongue border was the most affected site (24.65%). There were regional variations in OPMD, being leukoplakia the most frequent. Of the overall 2705 OSCC cases, 81.4% corresponded to OSCC-dn, while s-OSCC were 18.6%. Regarding lip vermillion SCC, 35.7% corresponded to de novo lip SCC and 64.3% were associated with previous OPMD. CONCLUSIONS: In Latin America, OSCC-dn seems to be more frequent with regional variations of some clinical and histopathological features. Further prospective studies are needed to analyse this phenomenon.

Contributions of viral oncogenes of HPV-18 and hypoxia to oxidative stress and genetic damage in human keratinocytes.

Infection with high-risk human papillomaviruses like HPV-16 and HPV-18 is highly associated with the development of cervical and other cancers. Malignant transformation requires viral oncoproteins E5, E6 and E7, which promote cell proliferation and increase DNA damage. Oxidative stress and hypoxia are also key factors in cervical malignant transformation. Increased levels of reactive species of oxygen (ROS) and nitrogen (RNS) are found in the hypoxic tumor microenvironment, promoting genetic instability and invasiveness. In this work, we studied the combined effect of E5, E6 and E7 and hypoxia in increasing oxidative stress and promoting DNA damage and nuclear architecture alterations. HaCaT cells containing HPV-18 viral oncogenes (HaCaT E5/E6/E7-18) showed higher ROS levels in normoxia and higher levels of RNS in hypoxia compared to HaCaT parental cells, as well as higher genetic damage in hypoxia as measured by γH2AX and comet assays. In hypoxia, HaCaT E5/E6/E7-18 increased its nuclear dry mass and both cell types displayed marked heterogeneity in nuclear dry mass distribution and increased nuclear foci. Our results show contributions of both viral oncogenes and hypoxia to oxidative stress, DNA damage and altered nuclear architecture, exemplifying how an altered microenvironment combines with oncogenic transformation to promote tumor progression.

Correlation of Bony Invasion With Nodal Metastasis, Pattern of Invasion and Survival in Oral Squamous Cell Carcinoma: A Retrospective Analysis of 122 Primary Cases From Oral Cancer Centre of South India.

Background Oral squamous cell carcinoma (OSCC) is considered to be the most common epithelial malignant neoplasm of the oral cavity. Despite advancements in diagnosis and therapeutics the clinical outcome of the disease has not improved much which may be attributed to tumor biology and heterogeneity. Bone invasion by cancer cells is currently staged as a moderately advanced disease. However, many low-grade carcinomas such as verrucous carcinoma and carcinoma cuniculatum show body invasion but less nodal metastases and better overall survival. The present study was orchestrated to analyze if bone invasion in OSCC has any impact on regional nodal metastases and survival. Materials and methods A total of 122 cases of OSCC who underwent excision and neck dissection were retrieved and included. These cases were then divided into two study groups. Group I comprised 56 OSCC cases with bone involvement and 66 cases with no bony involvement. The bone invasion was correlated with nodal metastases, survival and pattern of invasion. Statistical analysis was done using SPSS software (IBM Corp., Armonk, NY, USA). Results There was no statistically significant correlation between bone invasion with either nodal metastases or pattern of invasion, however, the worst pattern of invasion (WPOI)-4,5 showed a statistically higher incidence of nodal involvement in OSCC. No statistical difference was noted in overall survival between the two groups. Conclusion The worst pattern of invasion and not bone involvement, depicts nodal metastases in OSCC and thus, deserves consideration while staging and treatment planning.

Artificial Intelligence for Image Analysis in Oral Squamous Cell Carcinoma: A Review.

Head and neck tumor differential diagnosis and prognosis have always been a challenge for oral pathologists due to their similarities and complexity. Artificial intelligence novel applications can function as an auxiliary tool for the objective interpretation of histomorphological digital slides. In this review, we present digital histopathological image analysis applications in oral squamous cell carcinoma. A literature search was performed in PubMed MEDLINE with the following keywords: "artificial intelligence" OR "deep learning" OR "machine learning" AND "oral squamous cell carcinoma". Artificial intelligence has proven to be a helpful tool in histopathological image analysis of tumors and other lesions, even though it is necessary to continue researching in this area, mainly for clinical validation.

Mechanical profile of human keratinocytes expressing HPV-18 oncogenes.

During tumorigenesis, the mechanical properties of cancer cells change markedly, with decreased stiffness often accompanying a more invasive phenotype. Less is known about the changes in mechanical parameters at intermediate stages in the process of malignant transformation. We have recently developed a pre-tumoral cell model by stably transducing the immortalized but non-tumorigenic human keratinocyte cell line HaCaT with the E5, E6 and E7 oncogenes from HPV-18, one of the leading causes of cervical cancer and other types of cancer worldwide. We have used atomic force microscopy (AFM) to measure cell stiffness and to obtain mechanical maps of parental HaCaT and HaCaT E5/E6/E7-18 cell lines. We observed a significant decrease in Young's modulus in HaCaT E5/E6/E7-18 cells measured by nanoindentation in the central region, as well as decreased cell rigidity in regions of cell-cell contact measured by Peakforce Quantitative Nanomechanical Mapping (PF-QNM). As a morphological correlate, HaCaT E5/E6/E7-18 cells displayed a significantly rounder cell shape than parental HaCaT cells. Our results therefore show that decreased stiffness with concomitant perturbations in cell shape are early mechanical and morphological changes during the process of malignant transformation.