Agata Baczynska, Umar Rehman, Shireen S. Gohari, Kelly Chu, Mohammad Sohaib Sarwar, Peter A. Brennan
{"title":"Bridging the Health Literacy Gap for Patients With Oral Cancer: Readability Enhancement With AI Chatbots","authors":"Agata Baczynska, Umar Rehman, Shireen S. Gohari, Kelly Chu, Mohammad Sohaib Sarwar, Peter A. Brennan","doi":"10.1111/jop.70158","DOIUrl":"10.1111/jop.70158","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Early diagnosis is crucial in improving oral cancer outcomes. Patient education materials support timely recognition and management. However, these resources are often written above recommended reading levels, beyond patients' health literacy and limiting accessibility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To assess the readability of available patient information on oral cancer by the NHS, to evaluate three large language models (LLMs; ChatGPT, Claude and Gemini) in simplifying texts while preserving their content, and to propose an improved leaflet based on UK materials, expert review and LLM adjustment to match average UK reading levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Materials were collected from NHS-affiliated websites. Original and LLM-simplified texts were assessed using validated readability tools (FRES, FKGL, GFI, CLI and SMOG). Content fidelity was assessed using character 3–5-g cosine, sentence-content retention and latent semantic analysis (LSA). An expert review was applied to the proposed leaflet.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LLM-revisions significantly improved readability across all five indices (<i>p</i> < 0.0001). Mean FRES of original texts was 66.4 ± 7.7, while Claude (81.6 ± 6.2) was the only model to surpass the 80 benchmark. Semantic similarity to source text remained high (LSA means 0.97 ± 0.04, 0.94 ± 0.09 and 0.96 ± 0.08; character 3–5-g cosine 0.85 ± 0.05, 0.80 ± 0.08 and 0.82 ± 0.08 for respective models). Baseline readability of the proposed leaflet was comparable to NHS materials (FRES 65.7); Claude increased this to 81.2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>LLM-based simplification enhanced readability while preserving content fidelity. This approach can help enhance accessibility, particularly for populations disproportionately affected by oral cancer. With human oversight, it could be adopted at the policy level to standardise patient education and reduce health literacy disparities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 8","pages":"936-945"},"PeriodicalIF":2.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.70158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148226076","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}
{"title":"Adjuvant Immune Checkpoint Inhibitors in Head and Neck Cancer: A Meta-Analysis of Phase III Trials","authors":"Wala Ben Kridis, Afef Khanfir","doi":"10.1111/jop.70153","DOIUrl":"10.1111/jop.70153","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This meta-analysis evaluates the efficacy and safety of adjuvant immune checkpoint inhibitors (ICIs), specifically nivolumab and pembrolizumab, when combined with standard chemoradiotherapy (CRT) in patients with resected locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Despite the potential of ICIs in improving survival outcomes, variability in patient responses and adverse event profiles remains a challenge.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were pooled from two Phase III randomized controlled trials, NIVOPOSTOP and KEYNOTE-689, involving 1394 high-risk patients with advanced disease, positive surgical margins, and extranodal extension. The primary endpoints were disease-free survival (DFS) and overall survival (OS). Secondary endpoints included treatment-related adverse events. Hazard ratios (HR) and corresponding 95% confidence intervals (CI) were calculated for survival outcomes, and risk ratios (RR) for adverse events. Subgroup analyzes were performed based on PD-L1 expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The addition of ICIs to CRT resulted in significant improvements in DFS (HR: 0.75, 95% CI: 0.65–0.87) and OS (HR: 0.74, 95% CI: 0.65–0.85), representing a 25% reduction in the risk of recurrence and a 26% reduction in the risk of death. Subgroup analysis showed a greater benefit for patients with PD-L1 expression (CPS ≥ 1), with a pooled HR of 0.66 (95% CI: 0.49–0.88). Adverse events were more frequent with ICIs, with 81% of patients reporting any-grade adverse events and 42.9%–44.6% experiencing Grade 3 or higher events. The incidence of immune-related adverse events was significantly higher in the immunotherapy groups (<i>p</i> = 0.008), with notable increases in hypothyroidism and immune-mediated toxicities. Treatment discontinuation due to adverse events occurred in 12.4%–17.7% of patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Adjuvant ICIs significantly improve survival outcomes in high-risk patients with resected LA-HNSCC, especially in case of CPS ≥ 1, but are associated with an increased risk of adverse events, particularly immune-related toxicities. These findings support the integration of ICIs into postsurgical treatment regimens, though careful patient selection and monitoring are essential. Further research is needed to optimize treatment regimens and manage toxicities effectively.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 8","pages":"865-872"},"PeriodicalIF":2.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147973178","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":"Rapamycin Targets Cancer Stem Cells to Decrease Cisplatin Resistance in a Head and Neck Cancer Mouse Xenograft Model","authors":"Khin Swe Hlaing, Aung Phyo Shan, Eakapong Tamboon, Asada Leelahavanichkul, Panomwat Amornphimoltham","doi":"10.1111/jop.70156","DOIUrl":"10.1111/jop.70156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cisplatin is a common chemotherapeutic agent for advanced head and neck squamous cell carcinoma (HNSCC), but treatment success is often limited by resistance. Cancer stem cells (CSCs) are known contributors to this cisplatin chemoresistance in HNSCC. The mechanistic target of rapamycin (mTOR) pathway, which is frequently dysregulated in HNSCC, plays a crucial role via the PI3K/AKT/mTOR axis in maintaining CSC populations and promoting cancer proliferation. However, the specific effects of combining rapamycin, an mTOR pathway inhibitor, with chemotherapeutic agents on CSC maintenance and overall tumorigenicity remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We examined CSC gene expression in HNSCC cell lines (HSC4, SCC25, OT-1109) and evaluated the therapeutic potential of combining rapamycin, an mTOR pathway inhibitor, with cisplatin on CSC using a cell viability assay. The combination was further evaluated in an HSC4 mouse xenograft model. Tumor volume and animal weight were monitored throughout treatment. Xenograft tissue analysis via immunohistochemistry assessed stem cell markers (CD133 and ALDH1A1), proliferation markers (Ki-67), and mTOR pathway inhibition (pS6).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Administration of low-dose cisplatin enriched the CD133<sup>+</sup> cell population but failed to decrease the tumor mass in HNSCC xenografts. In contrast, the combination of cisplatin and rapamycin significantly impeded tumor growth and minimized toxicity, concurrently reducing the population of CD133<sup>+</sup> tumor cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that rapamycin enhances the mechanistic efficacy of cisplatin by specifically targeting and reducing cisplatin-induced stemness (CD133<sup>+</sup> CSC population). This study proposes a viable combination therapy for HNSCC involving an mTOR inhibitor and a platinum-based drug to overcome CSC-mediated resistance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 8","pages":"926-935"},"PeriodicalIF":2.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205166","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}
Till Nicke, Fleming Wolf-Eli Michelsen, Jan-Raphael Schäfer, Jonas Wuester, Marc Christian Metzger, Rainer Schmelzeisen, Gian Kayser, Andreas Weber-Steinhilber, Joachim Georgii, Johannes Lotz, Leonard Simon Brandenburg
{"title":"Sample-Efficient Transfer Learning for Histopathological Detection of HNSCC.","authors":"Till Nicke, Fleming Wolf-Eli Michelsen, Jan-Raphael Schäfer, Jonas Wuester, Marc Christian Metzger, Rainer Schmelzeisen, Gian Kayser, Andreas Weber-Steinhilber, Joachim Georgii, Johannes Lotz, Leonard Simon Brandenburg","doi":"10.1111/jop.70181","DOIUrl":"https://doi.org/10.1111/jop.70181","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with increasing incidence. Histopathological assessment remains the diagnostic gold standard, but is labor-intensive and affected by a growing shortage of specialized pathologists. Limited availability of annotated data poses a major challenge for AI-based support tools in digital pathology.</p><p><strong>Methods: </strong>We evaluated the transfer performance of a domain-specific foundation model, Tissue Concepts, compared to standard ImageNet pretraining for HNSCC detection in histopathological whole slide images. A multicentric, retrospective dataset comprising digitized H&E-stained slides from The Cancer Imaging Archive was used (390 slides, 268 HNSCC cases, 112 patients). Tumor regions were annotated by expert pathologists. Model representations were assessed without task-specific fine-tuning using a standardized classifier probe. Sample efficiency was investigated on patch-based and patient-based levels to estimate the number of annotated cases required for robust performance.</p><p><strong>Results: </strong>The foundation model consistently outperformed ImageNet pretraining across all experiments. On a patch-based level, Tissue Concepts achieved substantially higher discrimination performance with minimal training data (AUROC = 0.70 vs. = 0.50 using only 1 patch). On a patient-based level, the foundation model reached robust performance with a limited number of annotated cases (AUROC = 0.90 with 10 cases), whereas ImageNet-based representations showed slightly inferior performance despite substantially larger training sets (AUROC = 0.87 with 50 cases). Performance improvements plateaued beyond 10 cases, indicating diminishing returns with additional annotations.</p><p><strong>Conclusion: </strong>Domain-specific foundation models enable competitive HNSCC detection under annotation-scarce conditions. However, performance depends on the representativeness of annotated cases and tumor heterogeneity across anatomical sites and institutions. Further multicenter and prospective studies are required to assess generalizability and integration into routine histopathological workflows.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864922","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":"TOP2A Drives Oral Squamous Cell Carcinoma Initiation and Progression Through Activation of the TGF-β2/Smad Signaling Pathway.","authors":"Xueying Zhang, Shaohong Zhang, Chong Chen, Shuhan Zhou, Huiming Yu, Wei Zhang","doi":"10.1111/jop.70178","DOIUrl":"https://doi.org/10.1111/jop.70178","url":null,"abstract":"<p><strong>Objective: </strong>TOP2A has been implicated in the progression of multiple malignancies; however, its clinical significance and biological role in OSCC remain poorly understood. This study aimed to comprehensively investigate the expression, prognostic value, biological functions, and molecular mechanisms of TOP2A in OSCC through an integrative, multilevel approach that combined multi-cohort bioinformatics analyses, clinical immunohistochemical validation, and both in vitro and in vivo functional experiments.</p><p><strong>Methods: </strong>Multi-cohort bioinformatics analyses were first performed to evaluate TOP2A expression, prognostic relevance, and potential downstream signaling pathways. These findings were further validated using clinical OSCC specimens by IHC and western blot analysis. The biological functions of TOP2A were assessed through a panel of in vitro functional assays and in vivo xenograft models. Mechanistically, the involvement of the TGF-β2/Smad pathway was examined by integrating transcriptomic profiling with pathway validation and functional rescue experiments using TGF-β2 overexpression.</p><p><strong>Results: </strong>TOP2A is aberrantly overexpressed in OSCC, and it was associated with shortened overall survival in affected individuals. TOP2A silencing impaired cell proliferation, invasion, migration, and promoted apoptosis, whereas in vivo it inhibited tumor growth. In addition, TOP2A can activate the TGF-β2/Smad pathway and promote the biological behavior of OSCC cells by this pathway.</p><p><strong>Conclusions: </strong>These findings suggest that TOP2A is upregulated in OSCC and may promote tumor progression via the TGF-β2/Smad signaling pathway. Our results support TOP2A as a potential prognostic biomarker and therapeutic target in OSCC.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865113","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}
Julius Hirsch, Keskanya Subbalekha, Chatpong Tangmanee, Christian Stoll, Poramate Pitak-Arnnop
{"title":"Evaluation of GPT-5, a Large Language Model, in Replicating German Clinical Practice Guideline Recommendations in Oral Oncology: A Cross-Sectional Concordance Study","authors":"Julius Hirsch, Keskanya Subbalekha, Chatpong Tangmanee, Christian Stoll, Poramate Pitak-Arnnop","doi":"10.1111/jop.70140","DOIUrl":"10.1111/jop.70140","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Artificial intelligence (AI) technologies, particularly large language models (LLMs) such as ChatGPT, are increasingly utilised in medical education and clinical information retrieval. Nevertheless, their capacity to accurately reproduce recommendations from established clinical practice guidelines (CPGs) has not been thoroughly examined. The present study evaluated the concordance between responses generated by GPT-5 and recommendations contained in German CPGs addressing oral potentially malignant disorders (OPMDs) and oral carcinomas (OCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cross-sectional analytical comparison was performed between GPT-5 outputs and German CPG recommendations available as of October 2025. Individual guideline statements were entered verbatim into GPT-5, which was asked to confirm or reject the statements. To assess methodological robustness, inverted versions of the same statements were additionally tested. GPT-5 was accessed through the free version without internet connectivity to ensure that responses originated solely from the model's internal training data. Accuracy was defined as the proportion of correctly classified statements. Concordance between guideline content and model responses was quantified using Cohen's 𝝹.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two German CPGs comprising 111 recommendations were included: the S2k guideline for OPMDs (15 recommendations) and the S3 guideline for OCs (96 recommendations). GPT-5 correctly affirmed all authentic recommendations and rejected all inverted statements. Agreement between guideline statements and GPT-5 responses was perfect when the original recommendations were analysed (𝝹 = 1.0) and remained very high when both original and inverted statements were evaluated jointly (𝝹 = 0.96). The majority of references cited within the guidelines were published in English (> 93%) and originated from outside Germany (> 77%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>When guideline recommendations were presented verbatim, GPT-5 demonstrated complete concordance with German oral oncology CPGs. These findings indicate that the model is capable of recognising and retrieving established guideline information. However, this experimental design evaluates recognition of existing statements rather than autonomous clinical reasoning. At present, LLMs should therefore be regarded primarily as educational and informational tools rather than a replacement for expert clinical judgement in oral oncology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 7","pages":"856-860"},"PeriodicalIF":2.3,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674234","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}
Ida Andersson Cronblad, Cathrine Elise Warvik, Inger-Heidi Bjerkli, Sonja Eriksson Steigen, Lars Uhlin-Hansen, Synnøve Norvoll Magnussen, Elin Hadler-Olsen, Anna Maria Wirsing
{"title":"Lymphatic Vessel Density or Area Are Not Reliable Prognostic Factors in Oral Cancer","authors":"Ida Andersson Cronblad, Cathrine Elise Warvik, Inger-Heidi Bjerkli, Sonja Eriksson Steigen, Lars Uhlin-Hansen, Synnøve Norvoll Magnussen, Elin Hadler-Olsen, Anna Maria Wirsing","doi":"10.1111/jop.70148","DOIUrl":"10.1111/jop.70148","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oral tongue squamous cell carcinomas (OTSCC) frequently metastasise via lymphatic vessels, thus lymphangiogenesis may enhance tumour cell dissemination by increasing tumour-lymphatic interactions. The prognostic significance of lymphatic vessel density (LVD) and lymphatic vessel area (LVA) in OTSCC remains inconclusive. This study aimed to evaluate the association of tumour-associated LVD and LVA with clinical outcomes and pathological characteristics in a homogenous OTSCC cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed tumour samples from 121 OTSCC patients using D2-40 immunohistochemical staining to visualise lymphatic vessels. We calculated mean LVD and LVA from five peritumoural hotspots per tumour and examined their relationships to clinical-pathological data including 5-year disease-specific survival (DSS) using cross-tabulation, Kaplan–Meier, and Cox regression analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>High LVD was more prevalent in well/moderately differentiated compared to poorly differentiated tumours (78.1% and 45.5%, respectively, <i>p</i> = 0.017). No significant associations were found between LVD or LVA and other clinical-pathological variables. Neither low LVD nor LVA significantly impacted 5-year DSS in univariate (HR = 0.65 CI: 0.32, 1.31; HR = 0.69, 95% CI: 0.34, 1.40, respectively) or multivariate analyses (HR = 0.75, 95% CI: 0.32, 1.76; HR = 0.54, 95% CI: 0.23, 1.25, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>LVD and LVA did not predict prognosis in this OTSCC cohort. Further standardised studies investigating lymphatic vessels within the tumour microenvironment are necessary to better understand their role and potential prognostic significance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 7","pages":"837-847"},"PeriodicalIF":2.3,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774336","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":"Prognostic Significance of CD105-Assessed Angiogenesis in Relation to Survival and Clinicopathological Features of Oral Squamous Cell Carcinoma","authors":"Amol Ramchandra Gadbail, Minal Chaudhary, Satyajit Ashok Tekade, Alka Hande, Monal Yuwanati, Pranali Nimonkar, Shailesh M. Gondivkar, Sachin Sarode","doi":"10.1111/jop.70142","DOIUrl":"10.1111/jop.70142","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of this study was to determine the clinical significance of mean vascular density (MVD) using the expression of CD105 (endoglein) to predict the 3- and 5-year survival rates of oral squamous cell carcinoma (OSCC), as well as assess its value for predicting clinical outcomes of OSCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 217 OSCC patients treated surgically between 2010 and 2015 were included. Immuno-histochemistry for CD105 was performed, and MVD was quantified. The correlations of MVD with histopathological (HSPL) grade, the clinical Tumor Node Metastasis (TNM) stage, nodal status and survival were analyzed. Multivariate Cox proportional hazards regression analysis was also performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The MVD significantly increased with increasing HSPL grade from well-differentiated OSCC to poorly-differentiated OSCC (<i>p</i> < 0.001). MVD was significantly increased for advanced-stage TNM cases (III/IV) and metastatic cases when compared to early-stage and non-metastatic tumors (<i>p</i> < 0.001). Survival analysis revealed an inverse relationship between MVD and both three- and five-year disease-free survival. Patients with low MVD had the highest disease-free survival (3 years: 96.2%, 5 years: 92.7%), whereas those with high MVD had poor survival (3 years: 34.0%, 5 years: 27.9%). Multivariate Cox regression analysis confirmed MVD and HSPL grade as independent prognostic factors for overall survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>An elevated MVD by CD105 expression is strongly correlated with aggressive HSPL features, stage, nodal metastasis, and poor prognosis in OSCC. In addition to prognostic information, CD105 has the potential to be a target for anti-angiogenic strategies in OSCC indicating its potential use in clinical risk stratification and planning.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 7","pages":"805-811"},"PeriodicalIF":2.3,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729335","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":"Transcriptome Analysis and Histological Validation Identified the HO-1-u-1 Cell Line as a Model for Perineural Invasion in Oral Squamous Cell Carcinoma","authors":"Taisuke Hani, Tomoo Kudo, Toshiki Nishimura, Yuuichi Soeno","doi":"10.1111/jop.70143","DOIUrl":"10.1111/jop.70143","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Perineural invasion (PNI) is a pathological feature of oral squamous cell carcinoma (OSCC) that is associated with a poor prognosis. However, the molecular mechanisms remain poorly understood. The aim of this study was to establish an in vivo model to explore PNI in OSCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed an integrated analysis of The Cancer Genome Atlas transcriptome data from tongue squamous cell carcinoma (TSCC) and floor of the mouth squamous cell carcinoma (FOMSCC) by the presence of PNI and identified differentially expressed genes (DEGs). We also performed xenografts of five OSCC cell lines (OSC19, OSC20, HSC2, KOSC2, and HO-1-u-1) into nude mouse tongues and assessed PNI histology. Furthermore, transcriptome profiles of the cell lines were analyzed to identify cell line-specific genes associated with PNI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among OSCCs, PNI cases were more prevalent in TSCC and FOMSCC. Expression analysis detected 103 DEGs in TSCC and 401 in FOMSCC. In TSCC, 42.2% of the DEGs were non-coding RNAs, whereas DEGs in FOMSCC were predominantly protein-coding genes enriched in pathways related to muscle contraction and fibrosis. Xenograft analysis revealed that HO-1-u-1 uniquely exhibited a nerve-directed invasion phenotype. Transcriptome analysis of OSCC cell lines demonstrated that HO-1-u-1 was enriched in neural- and glial-related pathways, consistent with its neurotropic behavior in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our transcriptome analysis suggested that different pathways might drive PNI in TSCC and FOMSCC, depending on their origin. We also demonstrated that HO-1-u-1 is a unique OSCC cell line with strong neurotropic properties and a valuable xenograft model for OSCC PNI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 7","pages":"812-821"},"PeriodicalIF":2.3,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729316","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":"Fragmented Thresholds, Unified Vision: Advancing Salivary Diagnostics for OSCC and OPMD","authors":"Hichem Moulahoum, Faezeh Ghorbanizamani","doi":"10.1111/jop.70141","DOIUrl":"10.1111/jop.70141","url":null,"abstract":"<div>\u0000 \u0000 <p>Salivary diagnostics for oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) have advanced significantly, yet clinical translation remains limited. A key barrier is the lack of harmonized thresholds for candidate biomarkers, ranging from cytokines to genetic and epigenetic markers, across studies. This variability undermines biosensor calibration, impedes algorithmic integration, and restricts the scalability of AI and eHealth tools. Paradoxically, saliva is well-established in systemic disease diagnostics but remains undervalued in oral oncology. Recent initiatives, such as COST Action CA21140—INTERCEPTOR, are working to intercept oral carcinogenesis through collaborative innovation in molecular diagnostics and surveillance technologies. This letter calls for standardized protocols, multicenter validation, and digital integration to unlock saliva's full potential as a frontline diagnostic fluid. By addressing biomarker variability and embracing cross-sector collaboration, the field can move toward clinically actionable, digitally enabled solutions for early detection and monitoring of OSCC and OPMD.</p>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 7","pages":"729-731"},"PeriodicalIF":2.3,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690299","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}