Background: Elucidating the immune cell network is of great significance for understanding the pathogenesis of periodontitis. Flow cytometry is the preferred tool for quantifying the composition of immune cells in the pathological process of inflammation. Perfusion prior to tissue harvesting is necessary for flow cytometric analysis of various tissues. However, whether perfusion is necessary for flow cytometric analysis of murine gingival tissues has never been reported.
Method: Forty-eight mice were randomly divided into four groups: control + non-perfused group, control + perfused group, periodontitis + non-perfused group, and periodontitis + perfused group. Ligation-induced experimental periodontitis was established in periodontitis mice. The circulating blood was perfused out in the perfused groups before harvesting tissue samples. Flow cytometry was used to analyze the composition of immune cells in murine palatal gingival tissues.
Results: Experimental periodontitis induced alveolar bone resorption and inflammatory cell infiltration. Perfusion can successfully remove blood from the vessels of murine periodontal tissues. Flow cytometric analysis showed that there was no significant difference in the proportion of various immune cells in murine gingival tissues between the perfusion groups and the non-perfusion groups.
Conclusion: The present study was the first to use flow cytometry to compare perfused mouse gingiva with non-perfused mouse gingiva and found no significant difference in immune cell composition between the two groups. In addition, this study provides a simple and efficient protocol for the collection and processing of murine gingival tissue, which could provide facilities for understanding the role and mechanism of the immune cell network in periodontal diseases.
{"title":"A Simple and Efficient Method for Analyzing Murine Gingival Immune Cells Using Flow Cytometry: An Animal Study.","authors":"Wenting Jiang, Xuekang Wang, Yiping Wei, Ping Lv, Ying Wang, Wenjie Hu","doi":"10.1111/jop.70074","DOIUrl":"10.1111/jop.70074","url":null,"abstract":"<p><strong>Background: </strong>Elucidating the immune cell network is of great significance for understanding the pathogenesis of periodontitis. Flow cytometry is the preferred tool for quantifying the composition of immune cells in the pathological process of inflammation. Perfusion prior to tissue harvesting is necessary for flow cytometric analysis of various tissues. However, whether perfusion is necessary for flow cytometric analysis of murine gingival tissues has never been reported.</p><p><strong>Method: </strong>Forty-eight mice were randomly divided into four groups: control + non-perfused group, control + perfused group, periodontitis + non-perfused group, and periodontitis + perfused group. Ligation-induced experimental periodontitis was established in periodontitis mice. The circulating blood was perfused out in the perfused groups before harvesting tissue samples. Flow cytometry was used to analyze the composition of immune cells in murine palatal gingival tissues.</p><p><strong>Results: </strong>Experimental periodontitis induced alveolar bone resorption and inflammatory cell infiltration. Perfusion can successfully remove blood from the vessels of murine periodontal tissues. Flow cytometric analysis showed that there was no significant difference in the proportion of various immune cells in murine gingival tissues between the perfusion groups and the non-perfusion groups.</p><p><strong>Conclusion: </strong>The present study was the first to use flow cytometry to compare perfused mouse gingiva with non-perfused mouse gingiva and found no significant difference in immune cell composition between the two groups. In addition, this study provides a simple and efficient protocol for the collection and processing of murine gingival tissue, which could provide facilities for understanding the role and mechanism of the immune cell network in periodontal diseases.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":"191-200"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145390468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: CBD holds substantial promise in medical applications. This review aims to comprehensively analyse the current status of cannabidiol (CBD) in dentistry.
Methods: A systematic search of databases including PubMed-MEDLINE, Scopus, Embase, Cochrane Library, World Intellectual Property Organization (WIPO), European Patent Office (EPO), and the United States Patent and Trademark Office (USPTO) was conducted. Peer-reviewed journal manuscripts focusing on cell studies, clinical trials, and registered patents related to CBD and its derivatives in dentistry were summarised. Inclusion criteria were studies on CBD in dentistry, including original research and patents, published in English between 2013 and mid-2023 (articles) or early 2024 (patents), with full-text availability. Excluded were non-dentistry studies, unpublished or non-peer-reviewed reports, and duplicates using Microsoft Excel. The risk of bias was evaluated using the Cochrane RoB 2 tool. Two observers independently screened the articles for inclusion in the present study to mitigate bias. Cohen's kappa was used to measure inter-rater agreement.
Results: The total number of included studies was 57. Cell-based studies demonstrated CBD's effectiveness in modulating cellular responses and anti-inflammatory properties, especially in oral-origin cells, and its impact on osteogenic differentiation. Research, including clinical trials and patents, has shown CBD's benefits in treating pain and inflammation in the maxillofacial area, notably in conditions such as radiation-induced mucositis. CBD research in dental pain and inflammation is advanced, but studies on CBD's role in regenerative dentistry remain limited.
Conclusion: More studies on the mineralisation of oro-facial structures are necessary to fully understand CBD's role in regenerative dentistry. This study was supported by the Faculty of Dentistry, Chulalongkorn University. This study was registered in the PROSPERO (ID: CRD4201055832) and Open Science Framework (OSF) database (osf.io/z3bd8). The PRISMA guideline was followed to include the relevant full-text papers.
背景:CBD在医学应用方面有着巨大的前景。本文旨在全面分析大麻二酚(CBD)在牙科中的现状。方法:系统检索PubMed-MEDLINE、Scopus、Embase、Cochrane Library、世界知识产权组织(WIPO)、欧洲专利局(EPO)、美国专利商标局(USPTO)等数据库。总结了与牙科CBD及其衍生物相关的细胞研究、临床试验和注册专利的同行评审期刊手稿。纳入标准是2013年至2023年中期(文章)或2024年初(专利)期间以英文发表的CBD在牙科领域的研究,包括原创研究和专利,并提供全文。排除非牙科研究,未发表或未经同行评议的报告,以及使用Microsoft Excel重复的报告。使用Cochrane RoB 2工具评估偏倚风险。两名观察员独立筛选纳入本研究的文章,以减轻偏倚。科恩kappa被用来衡量评分者之间的一致性。结果:纳入的研究总数为57项。基于细胞的研究证明了CBD在调节细胞反应和抗炎特性方面的有效性,特别是在口腔来源的细胞中,以及它对成骨分化的影响。包括临床试验和专利在内的研究表明,CBD在治疗颌面疼痛和炎症方面有好处,尤其是在辐射引起的粘膜炎等疾病中。CBD在牙痛和炎症方面的研究取得了进展,但关于CBD在再生牙科中的作用的研究仍然有限。结论:为了充分了解CBD在再生牙科中的作用,需要对口腔-面部结构的矿化进行更多的研究。这项研究得到了朱拉隆功大学牙科学院的支持。本研究已在PROSPERO (ID: CRD4201055832)和开放科学框架(OSF)数据库(OSF .io/z3bd8)中注册。按照PRISMA指南纳入了相关的全文论文。
{"title":"Therapeutic Potential of Cannabidiol in Dentistry: A Systematic Review From Cellular Mechanisms to Clinical Trials.","authors":"Chatvadee Kornsuthisopon, Ajjima Chansaenroj, Sornkanok Vimolmangkang, Lakshman P Samaranayake, Thanaphum Osathanon","doi":"10.1111/jop.70081","DOIUrl":"10.1111/jop.70081","url":null,"abstract":"<p><strong>Background: </strong>CBD holds substantial promise in medical applications. This review aims to comprehensively analyse the current status of cannabidiol (CBD) in dentistry.</p><p><strong>Methods: </strong>A systematic search of databases including PubMed-MEDLINE, Scopus, Embase, Cochrane Library, World Intellectual Property Organization (WIPO), European Patent Office (EPO), and the United States Patent and Trademark Office (USPTO) was conducted. Peer-reviewed journal manuscripts focusing on cell studies, clinical trials, and registered patents related to CBD and its derivatives in dentistry were summarised. Inclusion criteria were studies on CBD in dentistry, including original research and patents, published in English between 2013 and mid-2023 (articles) or early 2024 (patents), with full-text availability. Excluded were non-dentistry studies, unpublished or non-peer-reviewed reports, and duplicates using Microsoft Excel. The risk of bias was evaluated using the Cochrane RoB 2 tool. Two observers independently screened the articles for inclusion in the present study to mitigate bias. Cohen's kappa was used to measure inter-rater agreement.</p><p><strong>Results: </strong>The total number of included studies was 57. Cell-based studies demonstrated CBD's effectiveness in modulating cellular responses and anti-inflammatory properties, especially in oral-origin cells, and its impact on osteogenic differentiation. Research, including clinical trials and patents, has shown CBD's benefits in treating pain and inflammation in the maxillofacial area, notably in conditions such as radiation-induced mucositis. CBD research in dental pain and inflammation is advanced, but studies on CBD's role in regenerative dentistry remain limited.</p><p><strong>Conclusion: </strong>More studies on the mineralisation of oro-facial structures are necessary to fully understand CBD's role in regenerative dentistry. This study was supported by the Faculty of Dentistry, Chulalongkorn University. This study was registered in the PROSPERO (ID: CRD4201055832) and Open Science Framework (OSF) database (osf.io/z3bd8). The PRISMA guideline was followed to include the relevant full-text papers.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":"177-190"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rairam Fernandes de Aguiar, Denis Francisco Gonçalves de Oliveira, Lucas Moreira de Araújo, Khalil Fernandes Viana, Douglas Matheus Lima Farias, Joyce Magalhães de Barros, Filipe Nobre Chaves, Alexia Nathália Brígido Assef, Thâmara Manoela Marinho Bezerra, Sthefane Gomes Feitosa, Karuza Maria Alves Pereira
Introduction: Methylation of tumor-suppressor gene promoters, particularly p16INK4A, is implicated in oral carcinogenesis. Although associations with oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) have been reported, no systematic review has examined these conditions while assessing evidence certainty. This review evaluated whether p16INK4A promoter methylation is associated with OSCC and OPMD.
Materials and methods: PubMed, Embase, Web of Science, Scopus, Livivo, and Google Scholar were searched. Studies were selected by title/abstract and then full-text review. Eligible studies investigated p16INK4A methylation in OSCC or OPMD with comparator groups. Data were meta-analyzed using random-effects models to obtain pooled odds ratios (OR). Heterogeneity, publication bias, sensitivity analyses, and prediction intervals were assessed. Evidence certainty was rated using GRADE.
Results: Twenty-four studies were included, comprising 1330 OSCC patients, 606 OPMD patients, and 681 healthy controls. Meta-analyses demonstrated a strong association between p16INK4A methylation and OSCC when compared with healthy controls (OR = 11.59; 95% CI = 6.01-22.37; p < 0.0001), with surgical margins (OR = 3.24; 95% CI = 1.86-5.65; p < 0.0001) and with OPMD (OR = 3.72; 95% CI = 2.47-5.59; p < 0.0001). OPMD also showed increased methylation versus healthy controls (OR = 24.8; 95% CI = 7.4-83.14; p < 0.0001).
Conclusions: p16INK4A methylation is strongly associated with OSCC and OPMD; however, due to heterogeneity and low certainty of evidence, these findings should be interpreted cautiously. Further standardized, well-designed studies are needed to clarify the role of p16INK4A methylation in oral carcinogenesis.
Trial registration: International Prospective Register of Systematic Reviews (PROSPERO): CRD42023410477.
肿瘤抑制基因启动子的甲基化,特别是p16INK4A,与口腔癌的发生有关。尽管有报道称口腔鳞状细胞癌(OSCC)和口腔潜在恶性疾病(OPMD)存在相关性,但在评估证据确定性时,尚未有系统的综述对这些疾病进行研究。本综述评估了p16INK4A启动子甲基化是否与OSCC和OPMD相关。资料与方法:检索PubMed, Embase, Web of Science, Scopus, Livivo,谷歌Scholar。通过题目/摘要筛选研究,然后进行全文综述。符合条件的研究用比较组调查了OSCC或OPMD中p16INK4A的甲基化。使用随机效应模型对数据进行meta分析,获得合并优势比(OR)。评估异质性、发表偏倚、敏感性分析和预测区间。证据确定性采用GRADE评分。结果:纳入24项研究,包括1330例OSCC患者,606例OPMD患者和681例健康对照。荟萃分析显示,与健康对照组相比,p16INK4A甲基化与OSCC之间存在很强的相关性(OR = 11.59; 95% CI = 6.01-22.37; p)。结论:p16INK4A甲基化与OSCC和OPMD密切相关;然而,由于证据的异质性和低确定性,这些发现应谨慎解释。需要进一步标准化、精心设计的研究来阐明p16INK4A甲基化在口腔癌变中的作用。试验注册:国际前瞻性系统评价注册(PROSPERO): CRD42023410477。
{"title":"Association of p16<sup>INK4A</sup> Methylation With Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review and Meta-Analysis.","authors":"Rairam Fernandes de Aguiar, Denis Francisco Gonçalves de Oliveira, Lucas Moreira de Araújo, Khalil Fernandes Viana, Douglas Matheus Lima Farias, Joyce Magalhães de Barros, Filipe Nobre Chaves, Alexia Nathália Brígido Assef, Thâmara Manoela Marinho Bezerra, Sthefane Gomes Feitosa, Karuza Maria Alves Pereira","doi":"10.1111/jop.70119","DOIUrl":"https://doi.org/10.1111/jop.70119","url":null,"abstract":"<p><strong>Introduction: </strong>Methylation of tumor-suppressor gene promoters, particularly p16<sup>INK4A</sup>, is implicated in oral carcinogenesis. Although associations with oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) have been reported, no systematic review has examined these conditions while assessing evidence certainty. This review evaluated whether p16<sup>INK4A</sup> promoter methylation is associated with OSCC and OPMD.</p><p><strong>Materials and methods: </strong>PubMed, Embase, Web of Science, Scopus, Livivo, and Google Scholar were searched. Studies were selected by title/abstract and then full-text review. Eligible studies investigated p16<sup>INK4A</sup> methylation in OSCC or OPMD with comparator groups. Data were meta-analyzed using random-effects models to obtain pooled odds ratios (OR). Heterogeneity, publication bias, sensitivity analyses, and prediction intervals were assessed. Evidence certainty was rated using GRADE.</p><p><strong>Results: </strong>Twenty-four studies were included, comprising 1330 OSCC patients, 606 OPMD patients, and 681 healthy controls. Meta-analyses demonstrated a strong association between p16<sup>INK4A</sup> methylation and OSCC when compared with healthy controls (OR = 11.59; 95% CI = 6.01-22.37; p < 0.0001), with surgical margins (OR = 3.24; 95% CI = 1.86-5.65; p < 0.0001) and with OPMD (OR = 3.72; 95% CI = 2.47-5.59; p < 0.0001). OPMD also showed increased methylation versus healthy controls (OR = 24.8; 95% CI = 7.4-83.14; p < 0.0001).</p><p><strong>Conclusions: </strong>p16<sup>INK4A</sup> methylation is strongly associated with OSCC and OPMD; however, due to heterogeneity and low certainty of evidence, these findings should be interpreted cautiously. Further standardized, well-designed studies are needed to clarify the role of p16<sup>INK4A</sup> methylation in oral carcinogenesis.</p><p><strong>Trial registration: </strong>International Prospective Register of Systematic Reviews (PROSPERO): CRD42023410477.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Olga Rusinovich-Lovgach, Zulema Plaza, Mónica Fernández Castro, Carlos Sánchez-Piedra, José Rosas, Victor Martínez-Taboada, Alejandro Olivé, Raul Menor Almagro, Beatriz Rodrígez-Lozano, Angel Garcia-Aparicio, Francisco Javier Lopez Longo, Sara Manrique-Arija, Jesús Alberto Garcia-Vadillo, Susana Gil Barato, Ruth Lopez-Gonzalez, Javier Narvaez García, Carlos Galisteo Lencastre, Jorge Gonzalez-Martin, Fernando Alonso, Jose Luis Andreu
Objective: To identify key clinical and therapeutic predictors of malignancy in a well-characterized, multicenter Spanish cohort of patients with Sjögren's disease (SjD).
Methods: A retrospective, cross-sectional study was conducted using data from the SjögrenSER-TRANS registry, a national cohort of 437 SjD patients from 33 Spanish hospitals who fulfilled the 2002 AECG classification criteria. Clinical, serological, and treatment-related variables were systematically collected. Descriptive statistics were used to summarize demographic and clinical characteristics. Bivariate analysis (chi-squared for categorical variables and t-tests for continuous variables) was performed to identify associations with malignancy (p < 0.05), followed by multivariate logistic regression to determine independent predictors.
Results: Malignancy was identified in 30 patients (6.86%), with gynecological cancers (30%) and lymphomas (23.3%) being the most common types. Independent predictors of malignancy included older age (OR 1.042, 95% CI 1.007-1.079), glandular inflammation (OR 2.888, 95% CI 1.281-6.512), and rituximab use (OR 3.959, 95% CI 1.461-10.730).
Conclusion: This study underscores the role of older age, glandular inflammation, and rituximab use as key risk factors for malignancy in SjD. However, the association with rituximab should be interpreted with caution, as indication bias cannot be ruled out. These findings emphasize the need for improved risk stratification and targeted surveillance strategies to facilitate early detection and enhance malignancy management in clinical practice. Prospective studies are warranted to refine monitoring protocols and optimize patient outcomes.
目的:在一个特征明确的、多中心的西班牙Sjögren’s disease (SjD)患者队列中,确定恶性肿瘤的关键临床和治疗预测因素。方法:采用SjögrenSER-TRANS登记处的数据进行回顾性横断面研究,该登记处是来自33家西班牙医院的437名SjD患者的国家队列,符合2002年AECG分类标准。系统收集临床、血清学和治疗相关变量。描述性统计用于统计人口学和临床特征。进行双变量分析(分类变量为卡方,连续变量为t检验)以确定与恶性肿瘤的关联(p)结果:30例患者(6.86%)发现恶性肿瘤,其中妇科癌症(30%)和淋巴瘤(23.3%)是最常见的类型。恶性肿瘤的独立预测因子包括年龄较大(OR 1.042, 95% CI 1.007-1.079)、腺体炎症(OR 2.888, 95% CI 1.281-6.512)和使用美罗华(OR 3.959, 95% CI 1.461-10.730)。结论:该研究强调了年龄、腺体炎症和使用利妥昔单抗作为SjD恶性肿瘤的关键危险因素的作用。然而,与利妥昔单抗的关联应谨慎解释,因为不能排除适应症偏倚。这些发现强调需要改进风险分层和有针对性的监测策略,以促进早期发现和加强临床实践中的恶性肿瘤管理。前瞻性研究是必要的,以完善监测方案和优化患者的结果。
{"title":"Sjögren's Disease and Cancer: Key Predictors From the Spanish Multicenter SjögrenSER-TRANS Cohort.","authors":"Olga Rusinovich-Lovgach, Zulema Plaza, Mónica Fernández Castro, Carlos Sánchez-Piedra, José Rosas, Victor Martínez-Taboada, Alejandro Olivé, Raul Menor Almagro, Beatriz Rodrígez-Lozano, Angel Garcia-Aparicio, Francisco Javier Lopez Longo, Sara Manrique-Arija, Jesús Alberto Garcia-Vadillo, Susana Gil Barato, Ruth Lopez-Gonzalez, Javier Narvaez García, Carlos Galisteo Lencastre, Jorge Gonzalez-Martin, Fernando Alonso, Jose Luis Andreu","doi":"10.1111/jop.70123","DOIUrl":"https://doi.org/10.1111/jop.70123","url":null,"abstract":"<p><strong>Objective: </strong>To identify key clinical and therapeutic predictors of malignancy in a well-characterized, multicenter Spanish cohort of patients with Sjögren's disease (SjD).</p><p><strong>Methods: </strong>A retrospective, cross-sectional study was conducted using data from the SjögrenSER-TRANS registry, a national cohort of 437 SjD patients from 33 Spanish hospitals who fulfilled the 2002 AECG classification criteria. Clinical, serological, and treatment-related variables were systematically collected. Descriptive statistics were used to summarize demographic and clinical characteristics. Bivariate analysis (chi-squared for categorical variables and t-tests for continuous variables) was performed to identify associations with malignancy (p < 0.05), followed by multivariate logistic regression to determine independent predictors.</p><p><strong>Results: </strong>Malignancy was identified in 30 patients (6.86%), with gynecological cancers (30%) and lymphomas (23.3%) being the most common types. Independent predictors of malignancy included older age (OR 1.042, 95% CI 1.007-1.079), glandular inflammation (OR 2.888, 95% CI 1.281-6.512), and rituximab use (OR 3.959, 95% CI 1.461-10.730).</p><p><strong>Conclusion: </strong>This study underscores the role of older age, glandular inflammation, and rituximab use as key risk factors for malignancy in SjD. However, the association with rituximab should be interpreted with caution, as indication bias cannot be ruled out. These findings emphasize the need for improved risk stratification and targeted surveillance strategies to facilitate early detection and enhance malignancy management in clinical practice. Prospective studies are warranted to refine monitoring protocols and optimize patient outcomes.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F J Mulder, T F B Gielgens, E J de Ruiter, R de Bree, M F C M van den Hout, B Kremer, S M Willems, E J M Speel
Introduction: While the prevalence of microsatellite instability (MSI) is low in the whole head and neck squamous cell carcinoma (HNSCC) population, it has been suggested to be more prominent in tumors of non-smokers. Therefore, the goal of this study was to determine the presence of MSI in a cohort of well-defined HNSCC of non-smokers and non-drinkers (NSND).
Methods: Clinical characteristics and tumor tissue of 119 NSND with HNSCC were retrospectively collected and analyzed for MLH1, PMS2, MSH2, and MSH6 protein expression on tissue microarrays (TMA). In case of negative staining for one of these mismatch repair proteins in the TMA cores, immunohistochemistry (IHC) was repeated on a whole slide section and additional molecular analyses were performed using polymerase chain reaction (PCR) and quantitative PCR (qPCR).
Results: Two cases showed dubious loss of MSH2 expression, one of these with concurrent dubious loss of MSH6 on the TMA. However, MSH2 and MSH6 expression was retained on whole slide sections and PCR and qPCR analyses did not show any mutations, compatible with a microsatellite stable result.
Conclusion: This study shows no single case with MSI in the NSND subgroup of HNSCC. Although a deficient DNA mismatch repair system is a predictive biomarker for response to immune checkpoint inhibitors, we found no evidence to support routine analysis of MSI in HNSCC, also not in the subgroup of NSND.
{"title":"No Evidence of Microsatellite Instability in Head and Neck Squamous Cell Carcinoma of Non-Smokers and Non-Drinkers.","authors":"F J Mulder, T F B Gielgens, E J de Ruiter, R de Bree, M F C M van den Hout, B Kremer, S M Willems, E J M Speel","doi":"10.1111/jop.70120","DOIUrl":"https://doi.org/10.1111/jop.70120","url":null,"abstract":"<p><strong>Introduction: </strong>While the prevalence of microsatellite instability (MSI) is low in the whole head and neck squamous cell carcinoma (HNSCC) population, it has been suggested to be more prominent in tumors of non-smokers. Therefore, the goal of this study was to determine the presence of MSI in a cohort of well-defined HNSCC of non-smokers and non-drinkers (NSND).</p><p><strong>Methods: </strong>Clinical characteristics and tumor tissue of 119 NSND with HNSCC were retrospectively collected and analyzed for MLH1, PMS2, MSH2, and MSH6 protein expression on tissue microarrays (TMA). In case of negative staining for one of these mismatch repair proteins in the TMA cores, immunohistochemistry (IHC) was repeated on a whole slide section and additional molecular analyses were performed using polymerase chain reaction (PCR) and quantitative PCR (qPCR).</p><p><strong>Results: </strong>Two cases showed dubious loss of MSH2 expression, one of these with concurrent dubious loss of MSH6 on the TMA. However, MSH2 and MSH6 expression was retained on whole slide sections and PCR and qPCR analyses did not show any mutations, compatible with a microsatellite stable result.</p><p><strong>Conclusion: </strong>This study shows no single case with MSI in the NSND subgroup of HNSCC. Although a deficient DNA mismatch repair system is a predictive biomarker for response to immune checkpoint inhibitors, we found no evidence to support routine analysis of MSI in HNSCC, also not in the subgroup of NSND.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ivan José Correia-Neto, Alex Franco da Costa, Anna Luíza Damaceno Araújo, Cristina Saldivia-Siracusa, Raísa Sales de Sá, Thiago Martini Pereira, Pablo Agustin Vargas, Alan Roger Santos-Silva, Luiz Paulo Kowalski, Matheus Cardoso Moraes, Marcio Ajudarte Lopes
Objective: This study aimed to develop and evaluate Machine Learning models to predict the malignant transformation (MT) in patients with actinic cheilitis (AC).
Methods: Three hundred forty patients diagnosed with AC (322 in the no MT group, and 18 in the MT group) were carefully documented. The study used the Adaptive Synthetic Sampling to adaptively balance the dataset (322 in the no MT group and 319 in the MT group). Four supervised Machine Learning classifiers (Random Forest, Xtreme Gradient Boosting, Multilayer Perceptron, and Support Vector Machine) were trained and tested using 5-fold cross-validation to correlate inputs (clinical descriptors and demographic data) to outputs (MT). SHAP values were used to identify the most influential predictors of MT.
Results: The Xtreme Gradient Boosting model stood out, achieving 96.72% accuracy, 96.87% sensitivity, 96.57% specificity, 96.61% precision, 96.73% of F1-Score, and 0.9498 AUC. Multilayer Perceptron showed the best sensitivity (98.44%), and Random Forest presented comparable results. In contrast, Support Vector Machine underperformed, with higher values of false negatives and false positives. Across models, ulceration, multifocality, and long-standing lesions were the strongest predictors of MT, while small, asymptomatic, or solitary lesions were associated with lower risk.
Conclusion: The results revealed promising performance metrics for Xtreme Gradient Boosting and Multilayer Perceptron suggesting their potential value as tools in a support system for monitoring AC. Additionally, synthetic data proved constructive in training, enhancing the models' robustness and predictive capabilities.
{"title":"Machine Learning for Predicting Malignant Transformation in Actinic Cheilitis: A Prognostic Support System Based on Demographic and Clinical Descriptors.","authors":"Ivan José Correia-Neto, Alex Franco da Costa, Anna Luíza Damaceno Araújo, Cristina Saldivia-Siracusa, Raísa Sales de Sá, Thiago Martini Pereira, Pablo Agustin Vargas, Alan Roger Santos-Silva, Luiz Paulo Kowalski, Matheus Cardoso Moraes, Marcio Ajudarte Lopes","doi":"10.1111/jop.70113","DOIUrl":"10.1111/jop.70113","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to develop and evaluate Machine Learning models to predict the malignant transformation (MT) in patients with actinic cheilitis (AC).</p><p><strong>Methods: </strong>Three hundred forty patients diagnosed with AC (322 in the no MT group, and 18 in the MT group) were carefully documented. The study used the Adaptive Synthetic Sampling to adaptively balance the dataset (322 in the no MT group and 319 in the MT group). Four supervised Machine Learning classifiers (Random Forest, Xtreme Gradient Boosting, Multilayer Perceptron, and Support Vector Machine) were trained and tested using 5-fold cross-validation to correlate inputs (clinical descriptors and demographic data) to outputs (MT). SHAP values were used to identify the most influential predictors of MT.</p><p><strong>Results: </strong>The Xtreme Gradient Boosting model stood out, achieving 96.72% accuracy, 96.87% sensitivity, 96.57% specificity, 96.61% precision, 96.73% of F1-Score, and 0.9498 AUC. Multilayer Perceptron showed the best sensitivity (98.44%), and Random Forest presented comparable results. In contrast, Support Vector Machine underperformed, with higher values of false negatives and false positives. Across models, ulceration, multifocality, and long-standing lesions were the strongest predictors of MT, while small, asymptomatic, or solitary lesions were associated with lower risk.</p><p><strong>Conclusion: </strong>The results revealed promising performance metrics for Xtreme Gradient Boosting and Multilayer Perceptron suggesting their potential value as tools in a support system for monitoring AC. Additionally, synthetic data proved constructive in training, enhancing the models' robustness and predictive capabilities.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comment on \"COVID-19 Dry Mouth Induced by SARS-CoV-2 Not Binding Directly to ACE2 but Interacting Electrostatically With Lipid Raft in Salivary Glands\".","authors":"Hironori Tsuchiya","doi":"10.1111/jop.70121","DOIUrl":"https://doi.org/10.1111/jop.70121","url":null,"abstract":"","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Importance: Diprosopus is an exceedingly rare craniomaxillofacial dysmorphosis that is considered a subgroup of conjoined twins. This phenotype encompasses a broad spectrum of duplications ranging from partial structures to complete dicephalus. The embryogenesis and mechanism of disease are not well understood. The objective of this investigation was to describe a case of partial dentofacial duplication and to discuss the possible etiology with novel genetic insights thereof.
Observations: A newborn Kazakh boy was referred to the First Affiliated Hospital of Xinjiang Medical University because of a maxillary mass detected on prenatal imaging. Physical examination revealed a unilateral cleft lip and a soft lump around 2.5 cm in diameter with the appearance of an accessory upper lip. He underwent two surgical procedures at 11 months and 4 years of age for definitive treatment. He demonstrated favorable recovery outcomes, maintaining normal speech and oral intake capabilities during long-term follow-up.
Conclusions and relevance: Our preliminary findings and comprehensive literature review suggest that mutations in the PAX7 gene could contribute to the pathogenesis of craniofacial duplication. This hypothesis establishes a previously unrecognized association between specific genetic alterations and the clinical manifestations of this condition, potentially offering a molecular foundation for prenatal diagnostic approaches. The present case provides more profound insights into the disease mechanisms compared to prior reports. Further validation through basic scientific investigations and clinical studies, incorporating comprehensive genetic analyses, will be essential to substantiate this proposed mechanism.
{"title":"Duplicated, Translocated Upper Lip and Maxilla: An Extremely Rare Congenital Craniofacial Anomaly With Novel Genetic Findings.","authors":"Chen-Xi Li, Di-Shu Huang, Zhong-Cheng Gong","doi":"10.1111/jop.70117","DOIUrl":"https://doi.org/10.1111/jop.70117","url":null,"abstract":"<p><strong>Importance: </strong>Diprosopus is an exceedingly rare craniomaxillofacial dysmorphosis that is considered a subgroup of conjoined twins. This phenotype encompasses a broad spectrum of duplications ranging from partial structures to complete dicephalus. The embryogenesis and mechanism of disease are not well understood. The objective of this investigation was to describe a case of partial dentofacial duplication and to discuss the possible etiology with novel genetic insights thereof.</p><p><strong>Observations: </strong>A newborn Kazakh boy was referred to the First Affiliated Hospital of Xinjiang Medical University because of a maxillary mass detected on prenatal imaging. Physical examination revealed a unilateral cleft lip and a soft lump around 2.5 cm in diameter with the appearance of an accessory upper lip. He underwent two surgical procedures at 11 months and 4 years of age for definitive treatment. He demonstrated favorable recovery outcomes, maintaining normal speech and oral intake capabilities during long-term follow-up.</p><p><strong>Conclusions and relevance: </strong>Our preliminary findings and comprehensive literature review suggest that mutations in the PAX7 gene could contribute to the pathogenesis of craniofacial duplication. This hypothesis establishes a previously unrecognized association between specific genetic alterations and the clinical manifestations of this condition, potentially offering a molecular foundation for prenatal diagnostic approaches. The present case provides more profound insights into the disease mechanisms compared to prior reports. Further validation through basic scientific investigations and clinical studies, incorporating comprehensive genetic analyses, will be essential to substantiate this proposed mechanism.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: No studies to date have examined human papillomavirus (HPV) positivity in both odontogenic keratocysts (OKCs) and dentigerous cysts (DCs) or performed HPV genotyping in these lesions. This research aims to compare HPV expression rates in DCs and OKCs to provide insight into the molecular behavior of OKCs.
Methods: Forty DC and forty OKC cases were randomly selected and analyzed for HPV-DNA expression. Positive cases underwent HPV genotyping. Additionally an immunohistochemical staining for p16 was performed for each case.
Results: Due to epithelial integrity loss or inflammation, 18 samples were excluded, leaving 32 DCs and 30 OKCs for evaluation. HPV was detected in five DC cases but absent in all OKC samples. The difference between DC and OKC groups was not statistically significant (p = 0.053). Genotyping identified HPV-16 in four cases and HPV-66 in one.
Discussion: Despite OKCs' aggressive behavior, this study found no significant association between HPV and their pathogenesis. These findings suggest HPV is unlikely to contribute to OKC proliferation or recurrence, underscoring the need for larger studies to clarify its role in odontogenic cysts.
{"title":"Prevalence and Molecular Insights of Human Papillomavirus in Dentigerous Cysts and Odontogenic Keratocysts: A Comparative Study.","authors":"Nelli Agbulut, Mualla Özcan","doi":"10.1111/jop.70118","DOIUrl":"https://doi.org/10.1111/jop.70118","url":null,"abstract":"<p><strong>Background: </strong>No studies to date have examined human papillomavirus (HPV) positivity in both odontogenic keratocysts (OKCs) and dentigerous cysts (DCs) or performed HPV genotyping in these lesions. This research aims to compare HPV expression rates in DCs and OKCs to provide insight into the molecular behavior of OKCs.</p><p><strong>Methods: </strong>Forty DC and forty OKC cases were randomly selected and analyzed for HPV-DNA expression. Positive cases underwent HPV genotyping. Additionally an immunohistochemical staining for p16 was performed for each case.</p><p><strong>Results: </strong>Due to epithelial integrity loss or inflammation, 18 samples were excluded, leaving 32 DCs and 30 OKCs for evaluation. HPV was detected in five DC cases but absent in all OKC samples. The difference between DC and OKC groups was not statistically significant (p = 0.053). Genotyping identified HPV-16 in four cases and HPV-66 in one.</p><p><strong>Discussion: </strong>Despite OKCs' aggressive behavior, this study found no significant association between HPV and their pathogenesis. These findings suggest HPV is unlikely to contribute to OKC proliferation or recurrence, underscoring the need for larger studies to clarify its role in odontogenic cysts.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toniya Raut, Namrata G R Raut, Neetu Jain, Shashi Keshwar, Sunil Shrestha
Background: The dynamic interplay between reactive free radicals (FR) and antioxidants (AO) can lead to either redox homeostasis or oxidative stress. Disruption of redox balance contributes to oxidative stress, a key factor in the pathogenesis of various conditions, notably oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC). At low to moderate levels, FRs trigger adaptive mutations that initiate carcinogenesis and support neoplastic cell survival. In contrast, high concentrations of FRs exert cytotoxic effects, a mechanism exploited in radiotherapy and chemotherapy. Antioxidants counteract FRs, mitigating cellular damage-a benefit demonstrated in several clinical trials involving OPMDs. However, their efficacy in OSCC remains contentious.
Methods and finding: This review explores the multifaceted roles of FRs and AOs in OPMD and OSCC, with emphasis on their contributions to carcinogenesis and therapeutic strategies. Tracking the FR-AO ratio during treatment may offer predictive insights into malignant transformation and facilitate early OSCC detection.
{"title":"Imbalance of Free Radicals and Antioxidants in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma: A Review.","authors":"Toniya Raut, Namrata G R Raut, Neetu Jain, Shashi Keshwar, Sunil Shrestha","doi":"10.1111/jop.70109","DOIUrl":"https://doi.org/10.1111/jop.70109","url":null,"abstract":"<p><strong>Background: </strong>The dynamic interplay between reactive free radicals (FR) and antioxidants (AO) can lead to either redox homeostasis or oxidative stress. Disruption of redox balance contributes to oxidative stress, a key factor in the pathogenesis of various conditions, notably oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC). At low to moderate levels, FRs trigger adaptive mutations that initiate carcinogenesis and support neoplastic cell survival. In contrast, high concentrations of FRs exert cytotoxic effects, a mechanism exploited in radiotherapy and chemotherapy. Antioxidants counteract FRs, mitigating cellular damage-a benefit demonstrated in several clinical trials involving OPMDs. However, their efficacy in OSCC remains contentious.</p><p><strong>Methods and finding: </strong>This review explores the multifaceted roles of FRs and AOs in OPMD and OSCC, with emphasis on their contributions to carcinogenesis and therapeutic strategies. Tracking the FR-AO ratio during treatment may offer predictive insights into malignant transformation and facilitate early OSCC detection.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}