{"title":"GPAT3 Promotes Oral Squamous Cell Carcinoma Invasion by Reprogramming Lipid Metabolism.","authors":"Zixian Li, Zhiheng Yang, Xiren Wang, Qiuya Yu, Shu Xia, Huiling Li, Yanhong Ni, Zhiyong Wang, Xiaofeng Huang","doi":"10.1111/jop.70188","DOIUrl":"https://doi.org/10.1111/jop.70188","url":null,"abstract":"<p><strong>Background: </strong>Although Glycerol-3-phosphate acyltransferase 3 (GPAT3)-mediated lipid metabolic reprogramming has been recognized as a driver of tumor progression, its prognostic significance and underlying mechanisms in oral squamous cell carcinoma (OSCC) remain to be fully elucidated.</p><p><strong>Methods: </strong>This retrospective study included 77 primary OSCC samples, expression pattern of GPAT3 and the prognostic value were analyzed by immunohistochemistry. In vitro functional experiments included cell viability and cell migration. Gene and protein expressions was analyzed via immunofluorescence staining, flow cytometry, RT-PCR, and western blotting. Lipids profiles were determined by mass spectrometry.</p><p><strong>Results: </strong>GPAT3 was broadly expressed in tumor cells, fibroblast-like cells, and tumor-infiltrating lymphocytes, with significantly higher expression at the invasive tumor front than in the tumor center. Elevated GPAT3 expression was positively correlated with adverse clinical outcomes and poor prognosis. In vitro experiments showed that both GPAT3 knockdown and overexpression markedly altered OSCC cell proliferation and migration. GPAT3 inhibition reduced the levels of several phospholipids, including Cer, PS, PE, and PC, accompanied by decreased expression of the invasion-related proteins p-FAK and p-Myosin II.</p><p><strong>Conclusion: </strong>GPAT3 regulates the invasive behavior of OSCC by mediating lipid metabolic reprogramming, serving as a biomarker for the clinical prognosis of OSCC patients.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170997","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}
Lilianny Querino Rocha de Oliveira, Everton Freitas de Morais, Cintia Eliza Marques, Bruno Cesar da Costa, Fábio Haach Téo, Tuula Salo, Ricardo D Coletta, Sabrina Daniela Silva Wurzba
{"title":"SLC7A3 Expression Is Associated With Migration, Invasion, and Survival in Oral Squamous Cell Carcinoma.","authors":"Lilianny Querino Rocha de Oliveira, Everton Freitas de Morais, Cintia Eliza Marques, Bruno Cesar da Costa, Fábio Haach Téo, Tuula Salo, Ricardo D Coletta, Sabrina Daniela Silva Wurzba","doi":"10.1111/jop.70190","DOIUrl":"https://doi.org/10.1111/jop.70190","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) is an aggressive malignancy with limited prognostic biomarkers, in which metabolic reprogramming contributes to tumor progression. Amino acid transporters of the solute carrier family have emerged as key regulators of cancer biology; however, the role of solute carrier family 7 member 3 (SLC7A3), a cationic amino acid transporter involved in arginine uptake, remains poorly characterized in OSCC.</p><p><strong>Methods: </strong>SLC7A3 expression was evaluated using RNA expression data from the Cancer Genome Atlas OSCC cohort (TCGA-OSCC), and protein levels were assessed by immunohistochemistry in a tissue microarray comprising 67 OSCC samples matched with normal oral tissue and 18 metastatic lymph nodes. Associations with clinicopathological features and survival were analyzed using chi-squared tests, Kaplan-Meier curves, and Cox regression. Functional assays, including cell cycle, apoptosis, migration, and invasion analyses, were performed in HSC3 cells following SLC7A3 knockdown.</p><p><strong>Results: </strong>In TCGA-OSCC, SLC7A3 mRNA levels were significantly lower in tumors than in nontumor tissues (p = 0.017), with no association with disease-specific or disease-free survival. At the protein level, SLC7A3 was significantly upregulated in tumors (p = 0.007), and high expression was associated with early clinical stage (p = 0.007) and improved disease-specific survival, remaining significant in multivariate Cox analysis (HR: 0.18, 95% CI: 0.07-0.50, p = 0.001). Functionally, SLC7A3 knockdown did not alter cell cycle distribution or apoptosis but significantly increased OSCC cell migration and invasion.</p><p><strong>Conclusion: </strong>High SLC7A3 protein levels were associated with OSCC cell migration and invasion and improved disease-specific survival, suggesting its potential as an indicator of tumor aggressiveness and a promising prognostic potential.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127906","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":"Adverse Oral and Salivary Effects Associated With Glucagon-Like Peptide-1 Receptor Agonists: Clinical Insights.","authors":"Gerardo Gilligan, Federico Garola, Vivian Petersen Wagner, Manoela Domingues Martins","doi":"10.1111/jop.70191","DOIUrl":"https://doi.org/10.1111/jop.70191","url":null,"abstract":"<p><strong>Background: </strong>The expanding use of glucagon-like peptide-1 receptor agonists and the dual incretin agonist tirzepatide for Type 2 diabetes mellitus and obesity has drawn attention to potential oral and salivary adverse effects. This short communication summarizes the available evidence, discusses potential mechanisms, and highlights implications for oral medicine practice.</p><p><strong>Methods: </strong>A narrative synthesis of published case reports, pharmacovigilance findings, and indirect experimental evidence was undertaken to discuss reported manifestations, biological plausibility, and existing knowledge gaps.</p><p><strong>Results: </strong>Reported manifestations include xerostomia, hyposalivation, dysgeusia, oral mucosal discomfort, burning sensations, and throat-related symptoms. Proposed mechanisms include modulation of cyclic adenosine monophosphate-dependent signaling in salivary acinar cells, altered autonomic regulation of salivary secretion, and dehydration secondary to gastrointestinal adverse events. Reduced salivary protection combined with gastric acid exposure from reflux or vomiting may increase susceptibility to dental erosion, although a direct association with these therapies has not been established. Sporadic immune-mediated mucocutaneous reactions and facial soft-tissue changes associated with rapid weight loss have also been described. Evidence remains limited and largely indirect.</p><p><strong>Conclusion: </strong>Potential oral and salivary adverse effects warrant clinical awareness, careful medication history-taking, assessment of salivary function, and individualized preventive care. Systematic reporting and focused clinical and experimental studies are needed to clarify causality, frequency, and underlying mechanisms.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127912","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}
Samaneh Fattahi, Solmaz Maleki Dizaj, Mina Yekani, Maria Bahramian, Ayla Bahramian, Mohammad Yousef Memar
{"title":"Biocompatibility and Antifungal Effects of Chitosan Nanoparticles Loaded With Nystatin and Carvacrol Against Candida albicans","authors":"Samaneh Fattahi, Solmaz Maleki Dizaj, Mina Yekani, Maria Bahramian, Ayla Bahramian, Mohammad Yousef Memar","doi":"10.1111/jop.70174","DOIUrl":"10.1111/jop.70174","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nanocarrier-based drug delivery systems enable the co-administration of antifungal agents, enhancing pharmacological efficacy and creating synergistic effects. This study aimed to evaluate the biocompatibility and antifungal properties of chitosan nanoparticles co-loaded with nystatin and carvacrol against <i>Candida albicans</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Chitosan nanoparticles were synthesized and loaded with nystatin and carvacrol. Their antifungal activity was evaluated by determining the minimum inhibitory concentration (MIC) and checkerboard synergy assays, while antibiofilm activity was measured using a microtiter plate crystal violet assay. Biocompatibility was assessed through hemolysis testing of human red blood cells (HRBCs) and MTT cytotoxicity assays on human foreskin fibroblasts (HFF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The nanoparticles exhibited an average hydrodynamic diameter of 70 ± 1.2 nm with favorable polydispersity (0.21 ± 0.03). The MIC of co-loaded nanoparticles was significantly lower than that of single-drug loaded nanoparticles, and checkerboard assays confirmed strong synergy (FICI 0.16–0.5). Sub-MIC concentrations markedly reduced biofilm formation. At 1000 μg/mL, drug-loaded nanoparticles induced < 5% hemolysis, compared with 15.7% ± 2.7% for blank chitosan nanoparticles. HFF cell viability exceeded 90% across concentrations up to 1000 μg/mL at 24–72 h.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Co-loading nystatin and carvacrol into chitosan nanoparticles yielded a synergistic antifungal and antibiofilm effect against <i>C. albicans</i>, coupled with excellent hemocompatibility and minimal cytotoxicity, highlighting its potential as a topical therapeutic for oral candidiasis particularly where resistance to azoles is rising. Further in vivo studies are warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 9","pages":"1052-1064"},"PeriodicalIF":2.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706785","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}
Merva Soluk-Tekkesin, Keith David Hunter, Ronell Bologna-Molina, Kelly Magliocca, Liam Robinson, Akinyele Olumuyiwa Adisa, Jiang Li, Elizabeth Ann Bilodeau, Haizal Mohd Hussaini, Madhu Shrestha, Ricardo Santiago Gomez, Willie van Heerden, Wanninayake Mudiyanselage Tilakaratne
{"title":"Response to: “Sclerosing Odontogenic Carcinoma: Why Is It Difficult to Diagnose With Confidence?”","authors":"Merva Soluk-Tekkesin, Keith David Hunter, Ronell Bologna-Molina, Kelly Magliocca, Liam Robinson, Akinyele Olumuyiwa Adisa, Jiang Li, Elizabeth Ann Bilodeau, Haizal Mohd Hussaini, Madhu Shrestha, Ricardo Santiago Gomez, Willie van Heerden, Wanninayake Mudiyanselage Tilakaratne","doi":"10.1111/jop.70167","DOIUrl":"10.1111/jop.70167","url":null,"abstract":"","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 9","pages":"980-982"},"PeriodicalIF":2.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456083","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}
Cristóbal L. Aravena-Ávila, Javiera F. Santander-Sandoval, César Rivera
{"title":"Clinical–Psychological Characteristics and Clonazepam Outcomes in Burning Mouth Syndrome: A Systematic Review Based on the SWiM Approach","authors":"Cristóbal L. Aravena-Ávila, Javiera F. Santander-Sandoval, César Rivera","doi":"10.1111/jop.70164","DOIUrl":"10.1111/jop.70164","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Burning mouth syndrome (BMS) is a chronic pain disorder frequently associated with clinical and psychological comorbidities, the treatment of which continues to represent a therapeutic challenge. Clonazepam is widely used in its management, although reported results vary depending on the route of administration. This review mapped how clinical–psychological characteristics were reported across clonazepam studies and explored whether outcome patterns differed by administration route within a synthesis without meta-analysis (SWiM) framework.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic review was carried out in accordance with the PRISMA 2020 guidelines and the SWiM framework. We searched PubMed, Scopus, and Web of Science for studies up to October 2025, including clinical and observational studies evaluating the use of clonazepam in people with BMS. Therapeutic response was defined as a ≥ 30% reduction in baseline symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 20 studies (<i>n</i> = 1042 patients; 85% women; mean age: 62 years). Patients presented with frequent systemic comorbidities, such as high blood pressure, diabetes mellitus, and thyroid disorders, along with a high prevalence of anxiety and depression. Eleven studies evaluated topical clonazepam, eight the systemic route, and one a mixed regimen. Using a vote-counting approach, topical clonazepam reported a ≥ 30% reduction in pain in 9 of 11 studies and ≥ 50% in 5 of 11; however, the studies showed substantial heterogeneity in diagnostic criteria, design, dosage, duration of treatment, pain assessment tools, and methodological quality. In this context, the results should be interpreted as a descriptive synthesis and not as definitive comparative evidence between routes of administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Topical clonazepam showed a more consistent trend toward clinically meaningful symptom improvement; however, comparative effectiveness and phenotype-related effect modification cannot be inferred from the available evidence. Clinical–psychological characteristics could constitute a relevant element in therapeutic decision-making, although their value as a predictive guide requires confirmation in future studies with standardized methodologies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 9","pages":"994-1007"},"PeriodicalIF":2.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376025","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":"Sclerosing Odontogenic Carcinoma: Why Is It Difficult to Diagnose With Confidence?","authors":"Fumio Ide, Shinnichi Sakamoto, Michiko Nishimura, Yuji Miyazaki, Takashi Muramatsu, Kentaro Kikuchi","doi":"10.1111/jop.70170","DOIUrl":"10.1111/jop.70170","url":null,"abstract":"","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 9","pages":"977-979"},"PeriodicalIF":2.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562493","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}
Vitor Simbalista Teixeira Soares, Anna Luíza Damaceno Araújo, Ivan José Correia-Neto, Cristina Saldivia-Siracusa, Raísa Sales de Sá, Hugo Abritta Reis, Ayrton da Costa Ganem Filho, André Carlos Ponce de Leon Ferreira de Carvalho, Thierry Urruty, Paulo Rogério Ferreti Bonan, Nathalia Rodrigues Gomes, Felipe Paiva Fonseca, Pablo Agustin Vargas, Alan Roger Santos-Silva, Luiz Paulo Kowalski, Matheus Cardoso Moraes, Marcio Ajudarte Lopes
{"title":"EffiSegNet: Advances in Automated Segmentation of Actinic Cheilitis and Lip Squamous Cell Carcinoma in Clinical Photographs","authors":"Vitor Simbalista Teixeira Soares, Anna Luíza Damaceno Araújo, Ivan José Correia-Neto, Cristina Saldivia-Siracusa, Raísa Sales de Sá, Hugo Abritta Reis, Ayrton da Costa Ganem Filho, André Carlos Ponce de Leon Ferreira de Carvalho, Thierry Urruty, Paulo Rogério Ferreti Bonan, Nathalia Rodrigues Gomes, Felipe Paiva Fonseca, Pablo Agustin Vargas, Alan Roger Santos-Silva, Luiz Paulo Kowalski, Matheus Cardoso Moraes, Marcio Ajudarte Lopes","doi":"10.1111/jop.70176","DOIUrl":"10.1111/jop.70176","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Actinic cheilitis (AC) is a potentially malignant oral disorder linked to lip squamous cell carcinoma (LSCC). Clinical diagnosis is hindered by lesion heterogeneity. While AI tools have shown promise in oral lesion detection and diagnosis, image segmentation remains underexplored. This study developed and externally validated a deep learning segmentation model for digital photographs of lip lesions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 489 clinical photographs from one institution were used for training/internal testing, and 82 external images from two independent institutions (UFPB and UFMG) served as external validation. EffiSegNet‑B0 used Image Net‑pretrained EfficientNet‑B0 encoder, with stage features aggregated via Ghost Modules. Manual segmentation masks comprised the clinically affected lip region and were used as ground truth. Performance was assessed using accuracy, sensitivity (recall), precision, Dice Similarity Coefficient (DSC) and intersection over union (IoU).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The model achieved high accuracy (> 95%) on both internal and external datasets. DSCs were 0.888 (95% CI: 0.871–0.904) for internal test and 0.875 (95% CI: 0.862–0.888) for external validation, while IoU values were 0.802 (95% CI: 0.777–0.828) and 0.782 (95% CI: 0.763–0.801), respectively. No performance decline was observed on external validation data. The model remained robust to lesion variations (ulceration, crusting, and keratinization).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>EffiSegNet-B0 demonstrated high accuracy and adaptability in segmenting lip lesions, reinforcing its potential for clinical image analysis applications. The proposed model generalizes well across different institutions and lesion phenotypes, consistently extracting the complete region of interest. This proof-of-concept study supports its promise as a tool for automated lip lesion segmentation in heterogeneous clinical settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 9","pages":"1073-1080"},"PeriodicalIF":2.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.70176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diele Carine Barreto Arantes, Lucas Monteiro Delgado, Marília de Marco Pinto Paiva dos Santos, Saman Warnakulasuriya, Marcelo Sperandio
{"title":"Predicting Malignant Transformation in Oral Epithelial Dysplasia: A Systematic Comparison of Artificial Intelligence-Based Risk Models and Pathologist-Based Microscopy","authors":"Diele Carine Barreto Arantes, Lucas Monteiro Delgado, Marília de Marco Pinto Paiva dos Santos, Saman Warnakulasuriya, Marcelo Sperandio","doi":"10.1111/jop.70168","DOIUrl":"10.1111/jop.70168","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/Aims</h3>\u0000 \u0000 <p>Risk prediction models (RPMs) based on histopathological analysis of oral epithelial dysplasia (OED) are increasingly used to stratify patients with oral potentially malignant disorders (OPMDs) and support personalized management. This systematic review and meta-analysis evaluated artificial intelligence (AI)-based models compared with conventional human microscopy for predicting malignant transformation (MT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 32 studies published between 1998 and 2026 were included (9 AI-based and 23 human-based), focusing on OED in oral leukoplakia (OL), erythroleukoplakia, and erythroplakia. AI approaches addressed prediction or prognostic tasks using machine learning (ML), deep learning (DL), or hybrid methods, with multilayer perceptron and random forest among the most frequently used algorithms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Meta-analysis demonstrated strong discriminative performance for AI models (pooled odds ratio [OR] = 12.64; 95% CI: 5.65–28.26; <i>I</i><sup>2</sup> = 57%). Human evaluation also confirmed a significant association between OED and MT (OR = 3.42; 95% CI: 2.07–5.68), with substantial heterogeneity (<i>I</i><sup>2</sup> = 85%). AI-based models showed higher specificity and more consistent performance, while sensitivity remained comparable to human assessment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overall, AI-based RPMs demonstrate promising and more reliable discriminative ability, primarily by improving decision precision rather than detection rates. However, further standardization, external validation, and larger multicentric datasets are required for clinical implementation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 9","pages":"1019-1033"},"PeriodicalIF":2.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.70168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adriely Primo da Silva, Beatriz Gomes Carreira Sartori, Carolina de Barros Gigliotti Vendramini, Adauto José Ferreira Nunes, Maria Renata Sales Nogueira
{"title":"Correlation Between Prognostic Indicators, HPV Status, and Cancer Stem Cell Markers in a Population of Human Tongue Carcinomas","authors":"Adriely Primo da Silva, Beatriz Gomes Carreira Sartori, Carolina de Barros Gigliotti Vendramini, Adauto José Ferreira Nunes, Maria Renata Sales Nogueira","doi":"10.1111/jop.70175","DOIUrl":"10.1111/jop.70175","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oral squamous cell carcinoma (OSCC) is a significant public health issue. While tobacco and alcohol are established risk factors, the role of human papillomavirus (HPV) in oral carcinogenesis remains debated. Cancer stem cells (CSCs) are implicated in tumor aggressiveness and therapy resistance. This study investigated the correlation between HPV infection, CSC marker expression (CD44, CD98, ALDH1), and clinicopathological parameters in tongue SCCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective cohort of 1047 OSCC cases (2013–2018) was reviewed. From 452 tongue SCCs, 83 formalin-fixed paraffin-embedded specimens were randomly selected. HPV DNA detection was performed using qPCR with generic and type-specific primers (HPV 6, 11, 16, 18). Immunohistochemical expression of CD44, CD98, and ALDH1 was evaluated and quantified using digital image analysis (IHC Profiler). Statistical analyses included Kaplan–Meier survival curves, Kruskal-Wallis, Chi-square, and Spearman correlation tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HPV DNA was detected in 2/83 cases (2.4%): one HPV16-positive and one with co-infection (HPV6/18). CD44 expression was ubiquitously high, with no significant difference between -High and -Positive categories (<i>p</i> > 0.9999), but both were significantly higher than -Low and -Negative scores (<i>p</i> < 0.0001). ALDH1 exhibited a focal staining pattern. The ALDH1-High score was significantly less frequent than -Positive and -Low scores (<i>p</i> < 0.01) and showed a significant positive correlation with both advanced clinical stage (Spearman r: 0.5062; <i>p</i> = 0.0007) and higher tumor grade (Spearman r: 0.3352; <i>p</i> = 0.0322). CD98 was not detected. An inverse correlation was observed between HPV and clinical staging (Spearman r: −0.2377; <i>p</i> = 0.0305); however, due to the low number of HPV-positive cases, this finding must be interpreted with caution.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest a distinct CSC expression profile in this cohort, characterized by ubiquitous CD44 expression and a rare but highly aggressive ALDH1-High subpopulation, concomitant with low HPV detection. The strong positive correlation of ALDH1-High score with advanced stage and grade highlights its potential role as a key driver of tumor aggression, warranting further investigation as a prognostic marker.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 9","pages":"1065-1072"},"PeriodicalIF":2.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.70175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}