Charlotte S. Schouten, Vittoria Guarda, Thomas M. Stadler, J. Kristian Ikenberg, Martina A. Broglie Däppen
Background
Human papillomavirus (HPV)-16 is the most commonly found HPV-type in HPV-induced oropharyngeal squamous cell carcinomas (OPSCC). The serological response to HPV oncoproteins could be a way to detect HPV-driven OPSCC early. A rapid test for the detection of HPV16 L1 antibodies in blood was developed in 2015 (PrevoCheck).
Methods
Prospectively, we included 42 patients with newly diagnosed head and neck squamous cell carcinomas (HNSCC). Pretreatment venous blood samples were collected and analyzed with PrevoCheck. The results were interpreted by 2 reviewers. Immunohistochemistry with p16 and HPV DNA-PCR testing served as a reference standard.
Results
Sixteen patients had HPV-positive tumors (38.1%). PrevoCheck showed 2 true positives, 26 true negatives, 0 false positives, and 14 false negatives, which resulted in a sensitivity of 12.5% (95% CI: 1.6%–38.4%) at a specificity of 100% (95% CI: 86.8–100). Interobserver agreement showed perfect agreement.
Conclusion
A negative result in a test with a high sensitivity can be used to rule out disease, that is, HPV16-related HNSCC. We found 14 false negative results, resulting in low sensitivity for PrevoCheck. This test does not seem suitable to screen for HPV16-related head and neck cancers.
{"title":"Diagnostic Performance of the PrevoCheck for the Detection of Human Papillomavirus 16-Driven Head and Neck Squamous Cell Carcinoma","authors":"Charlotte S. Schouten, Vittoria Guarda, Thomas M. Stadler, J. Kristian Ikenberg, Martina A. Broglie Däppen","doi":"10.1111/jop.70075","DOIUrl":"10.1111/jop.70075","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Human papillomavirus (HPV)-16 is the most commonly found HPV-type in HPV-induced oropharyngeal squamous cell carcinomas (OPSCC). The serological response to HPV oncoproteins could be a way to detect HPV-driven OPSCC early. A rapid test for the detection of HPV16 L1 antibodies in blood was developed in 2015 (PrevoCheck).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Prospectively, we included 42 patients with newly diagnosed head and neck squamous cell carcinomas (HNSCC). Pretreatment venous blood samples were collected and analyzed with PrevoCheck. The results were interpreted by 2 reviewers. Immunohistochemistry with p16 and HPV DNA-PCR testing served as a reference standard.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sixteen patients had HPV-positive tumors (38.1%). PrevoCheck showed 2 true positives, 26 true negatives, 0 false positives, and 14 false negatives, which resulted in a sensitivity of 12.5% (95% CI: 1.6%–38.4%) at a specificity of 100% (95% CI: 86.8–100). Interobserver agreement showed perfect agreement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A negative result in a test with a high sensitivity can be used to rule out disease, that is, HPV16-related HNSCC. We found 14 false negative results, resulting in low sensitivity for PrevoCheck. This test does not seem suitable to screen for HPV16-related head and neck cancers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 2","pages":"261-266"},"PeriodicalIF":2.3,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513184","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}
Guilherme Iani Pontes, Anna Luíza Damaceno Araújo, Andresa Borges Soares, Saman Warnakulasuriya, André Luis Santana de Freitas, Caroline Gennari Stevão, Marcelo Sperandio, Matheus Cardoso Moraes
Background
Oral leukoplakia (OL) is a potentially malignant disorder of the oral mucosa. Accurate prediction of malignant transformation (MT) remains a clinical challenge. This study aimed to develop and evaluate a machine learning model that integrates histopathological, demographic, and DNA content features to predict MT risk in OL.
Methods
We conducted a retrospective cohort study of 97 OL cases—18 with confirmed MT and 79 non-transformed controls—selected from a larger series. Each case included clinicopathological features, and DNA content data obtained by flow cytometry for cell cycle phases (G1, S-phase, G2 and excess DNA beyond the tetraploid region [4cER]). All cases had a minimum 5-year follow-up or histologically confirmed transformation. A multilayer perceptron (MLP) model was trained on 27 features. Stratified five-fold cross-validation and minority class oversampling (positive filling) were used to improve learning and mitigate data imbalance. Performance was evaluated using accuracy, sensitivity, specificity, F1-score, AUC, and Kaplan–Meier survival analysis.
Results
Significant predictors of MT included 4cER (p = 0.005), G2 phase (p = 0.04), dysplasia grading (p = 0.003), and inflammatory infiltrate (p = 0.01). The optimized model yielded 72% sensitivity, 96% specificity, and an AUC of 85.4%. Survival analysis showed significantly poorer outcomes in the high-risk cases predicted by the model (p < 0.0001).
Conclusion
Integrating DNA content analysis with machine learning provides an objective and clinically useful model to stratify malignant risk in OL, complementing conventional histopathology and supporting personalized patient management.
{"title":"Predicting Malignant Transformation in Oral Leukoplakia: A Multilayer Perceptron Approach Incorporating Clinicopathological Features and DNA Content","authors":"Guilherme Iani Pontes, Anna Luíza Damaceno Araújo, Andresa Borges Soares, Saman Warnakulasuriya, André Luis Santana de Freitas, Caroline Gennari Stevão, Marcelo Sperandio, Matheus Cardoso Moraes","doi":"10.1111/jop.70084","DOIUrl":"10.1111/jop.70084","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oral leukoplakia (OL) is a potentially malignant disorder of the oral mucosa. Accurate prediction of malignant transformation (MT) remains a clinical challenge. This study aimed to develop and evaluate a machine learning model that integrates histopathological, demographic, and DNA content features to predict MT risk in OL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective cohort study of 97 OL cases—18 with confirmed MT and 79 non-transformed controls—selected from a larger series. Each case included clinicopathological features, and DNA content data obtained by flow cytometry for cell cycle phases (G1, S-phase, G2 and excess DNA beyond the tetraploid region [4cER]). All cases had a minimum 5-year follow-up or histologically confirmed transformation. A multilayer perceptron (MLP) model was trained on 27 features. Stratified five-fold cross-validation and minority class oversampling (positive filling) were used to improve learning and mitigate data imbalance. Performance was evaluated using accuracy, sensitivity, specificity, F1-score, AUC, and Kaplan–Meier survival analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant predictors of MT included 4cER (<i>p</i> = 0.005), G2 phase (<i>p</i> = 0.04), dysplasia grading (<i>p</i> = 0.003), and inflammatory infiltrate (<i>p</i> = 0.01). The optimized model yielded 72% sensitivity, 96% specificity, and an AUC of 85.4%. Survival analysis showed significantly poorer outcomes in the high-risk cases predicted by the model (<i>p</i> < 0.0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Integrating DNA content analysis with machine learning provides an objective and clinically useful model to stratify malignant risk in OL, complementing conventional histopathology and supporting personalized patient management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 2","pages":"249-260"},"PeriodicalIF":2.3,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145495891","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}
Francesco Ferella, Letizia Nitro, Fabiana Allevi, Federico Biglioli, Matilde Coccapani, Giovanni Felisati, Giorgia Pugliese, Giorgio Ghilardi, Linda Montavoci, Anna Caretti, Alberto Maria Saibene
Background
Chronic graft-versus-host disease (cGVHD) is a significant complication following hematopoietic cell transplantation, often manifesting with oral lesions that severely impact quality of life. Cytokines such as IL-6, IL-1α, and IL-17 are implicated in inflammation and may serve as biomarkers for disease activity and therapeutic response in cGVHD.
Methods
A prospective monocentric study was conducted on 10 patients with oral cGVHD at San Paolo Hospital, Milan, between April 2023 and January 2024. Salivary and serum levels of IL-6, IL-1α, and IL-17 were measured pre- and post- topical clobetasol treatment for the oral mucosa using enzyme-linked immunoassay (ELISA). Patients underwent clinical assessments for oral pain and dryness using visual analog scales (VAS) and the Oral Mucositis Rating Scale (OMRS). Wilcoxon and Spearman correlation tests were used for statistical analysis.
Results
Significant reductions in serum IL-17 (p = 0.006) and trends towards reduced salivary IL-6 (p = 0.066) were observed post-treatment. No significant changes were found in IL-1α levels. Clinical assessments showed significant improvement in pain and OMRS scores post-therapy (p < 0.05). No correlation was found between cytokine levels and clinical symptoms.
Conclusions
While IL-6 and IL-17 play roles in cGVHD, only IL-17 showed significant reduction after topical steroid therapy. This suggests IL-17's potential as a marker for inflammatory activity in cGVHD. Serum IL-17 may serve as a useful biomarker in oral cGVHD. Future studies with larger cohorts are needed to further validate these findings and explore the role of salivary cytokines in disease monitoring.
{"title":"Salivary and Serum Cytokine Levels in Oral Chronic Graft-Versus-Host Disease: A Longitudinal Study on the Role of IL-6, IL-1α, and IL-17","authors":"Francesco Ferella, Letizia Nitro, Fabiana Allevi, Federico Biglioli, Matilde Coccapani, Giovanni Felisati, Giorgia Pugliese, Giorgio Ghilardi, Linda Montavoci, Anna Caretti, Alberto Maria Saibene","doi":"10.1111/jop.70076","DOIUrl":"10.1111/jop.70076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic graft-versus-host disease (cGVHD) is a significant complication following hematopoietic cell transplantation, often manifesting with oral lesions that severely impact quality of life. Cytokines such as IL-6, IL-1α, and IL-17 are implicated in inflammation and may serve as biomarkers for disease activity and therapeutic response in cGVHD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A prospective monocentric study was conducted on 10 patients with oral cGVHD at San Paolo Hospital, Milan, between April 2023 and January 2024. Salivary and serum levels of IL-6, IL-1α, and IL-17 were measured pre- and post- topical clobetasol treatment for the oral mucosa using enzyme-linked immunoassay (ELISA). Patients underwent clinical assessments for oral pain and dryness using visual analog scales (VAS) and the Oral Mucositis Rating Scale (OMRS). Wilcoxon and Spearman correlation tests were used for statistical analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant reductions in serum IL-17 (<i>p</i> = 0.006) and trends towards reduced salivary IL-6 (<i>p</i> = 0.066) were observed post-treatment. No significant changes were found in IL-1α levels. Clinical assessments showed significant improvement in pain and OMRS scores post-therapy (<i>p</i> < 0.05). No correlation was found between cytokine levels and clinical symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>While IL-6 and IL-17 play roles in cGVHD, only IL-17 showed significant reduction after topical steroid therapy. This suggests IL-17's potential as a marker for inflammatory activity in cGVHD. Serum IL-17 may serve as a useful biomarker in oral cGVHD. Future studies with larger cohorts are needed to further validate these findings and explore the role of salivary cytokines in disease monitoring.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 2","pages":"201-208"},"PeriodicalIF":2.3,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145390587","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}
Wallacy Watson Pereira Melo, Walessa Alana Bragança Aragão, Maria Karolina Martins Ferreira, Vinicius Ruan Neves dos Santos, Leonardo Oliveira Bittencourt, Paulo Fernando Santos Mendes, Deborah Ribeiro Frazão, José Mário Matos-Sousa, Hadassa Helez Neves Ferreira, José Messias Perdigão, Hannah Gil de Farias Morais, Herve Rogez, Roseana de Almeida Freitas, Manoela Domingues Martins, Rafael Rodrigues Lima, Renata Duarte de Souza-Rodrigues
Background
The antineoplastic drugs used in anticancer treatment regimens can induce changes in normal tissues, including salivary glands. This study evaluated the effects of clarified açaí and photobiomodulation (PBM) on the oxidative biochemistry and microstructure of the parotid glands of rats with oral mucositis.
Methods
Male rats (n = 54) were divided into five groups: Negative control (no mucositis); Positive control (mucositis without treatment); PBM; Clarified açaí; and PBM + clarified açaí. Oral mucositis was induced by intraperitoneal injection of 5-fluorouracil on days 0 (60 mg/kg) and 2 (40 mg/kg). On days 3 and 4, bilateral scarification of the buccal mucosa was performed. On days 0 (negative controls), 8 and 10 (other groups), parotid glands were collected. To evaluate oxidative biochemistry, the following analyses were performed: Antioxidant capacity test against peroxyl radicals (ACAP), Lipid Peroxidation Assay (LPO), and Nitric oxide metabolite (NOx). Additionally, histopathological, histomorphometric, and histochemical analyses were performed. Statistical analysis was performed using two-way ANOVA and Tukey's post-test (p < 0.05).
Results
Clarified açaí, alone or associated with photobiomodulation, increased antioxidant levels compared to the positive control on days 8 and 10. Regarding lipid peroxidation and nitric oxide metabolite, the positive control showed higher levels than the other groups. The morphological assessment showed that the clarified açaí and photobiomodulation groups maintained similar structures of the parenchyma, stroma, and acini to the negative control.
Conclusions
The study results demonstrated that clarified açaí and photobiomodulation conferred biochemical and structural protection to the parotid glands against chemotherapy–induced damage.
{"title":"Effects of Clarified Açaí Supplementation and Photobiomodulation on the Parotid Glands of Rats Submitted to Chemotherapy","authors":"Wallacy Watson Pereira Melo, Walessa Alana Bragança Aragão, Maria Karolina Martins Ferreira, Vinicius Ruan Neves dos Santos, Leonardo Oliveira Bittencourt, Paulo Fernando Santos Mendes, Deborah Ribeiro Frazão, José Mário Matos-Sousa, Hadassa Helez Neves Ferreira, José Messias Perdigão, Hannah Gil de Farias Morais, Herve Rogez, Roseana de Almeida Freitas, Manoela Domingues Martins, Rafael Rodrigues Lima, Renata Duarte de Souza-Rodrigues","doi":"10.1111/jop.70072","DOIUrl":"10.1111/jop.70072","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The antineoplastic drugs used in anticancer treatment regimens can induce changes in normal tissues, including salivary glands. This study evaluated the effects of clarified açaí and photobiomodulation (PBM) on the oxidative biochemistry and microstructure of the parotid glands of rats with oral mucositis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male rats (<i>n</i> = 54) were divided into five groups: Negative control (no mucositis); Positive control (mucositis without treatment); PBM; Clarified açaí; and PBM + clarified açaí. Oral mucositis was induced by intraperitoneal injection of 5-fluorouracil on days 0 (60 mg/kg) and 2 (40 mg/kg). On days 3 and 4, bilateral scarification of the buccal mucosa was performed. On days 0 (negative controls), 8 and 10 (other groups), parotid glands were collected. To evaluate oxidative biochemistry, the following analyses were performed: Antioxidant capacity test against peroxyl radicals (ACAP), Lipid Peroxidation Assay (LPO), and Nitric oxide metabolite (NOx). Additionally, histopathological, histomorphometric, and histochemical analyses were performed. Statistical analysis was performed using two-way ANOVA and Tukey's post-test (<i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Clarified açaí, alone or associated with photobiomodulation, increased antioxidant levels compared to the positive control on days 8 and 10. Regarding lipid peroxidation and nitric oxide metabolite, the positive control showed higher levels than the other groups. The morphological assessment showed that the clarified açaí and photobiomodulation groups maintained similar structures of the parenchyma, stroma, and acini to the negative control.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The study results demonstrated that clarified açaí and photobiomodulation conferred biochemical and structural protection to the parotid glands against chemotherapy–induced damage.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 1","pages":"120-132"},"PeriodicalIF":2.3,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.70072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355065","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}
Meng-Nan Cao, Shi-Yang Feng, Chen-Chen Gao, Yang Xiao, Yi-Xin Li, Jie Lei, Kai-Yuan Fu
Background
Excessive subchondral bone resorption is a typical manifestation in the early stage of osteoarthritis. This study is to verify whether and when intervening in subchondral bone could alleviate cartilage degeneration of temporomandibular joint osteoarthritis.
Methods
Disc displacement without reduction was used to induce temporomandibular joint osteoarthritis. Alendronate was administered subcutaneously twice a week at a dosage of 60 μg/kg body weight for 1 week by two intervention methods: early administration (1 day after disc displacement without reduction surgery) and late administration (2 weeks after disc displacement without reduction surgery). Micro-CT was used to assess subchondral bone mass and microstructure. Hematoxylin–eosin staining, toluidine blue staining, tartrate-resistant acid phosphatase staining, immunofluorescence staining, and Western blot were applied to evaluate histopathological changes of the condylar cartilage and subchondral bone.
Results
Early alendronate administration not only prevented subchondral bone resorption in early-stage temporomandibular joint osteoarthritis, but also suppressed chondrocyte apoptosis, cartilage extracellular matrix degeneration, as well as excessive subchondral bone formation of condyle in late-stage temporomandibular joint osteoarthritis. However, late alendronate administration had little effect on either subchondral bone or cartilage degenerative changes.
Conclusions
Early inhibition of subchondral bone resorption could mitigate abnormal subchondral bone formation and condylar cartilage degeneration in late-stage temporomandibular joint osteoarthritis, which might be a promising strategy for temporomandibular joint osteoarthritis treatment.
{"title":"Early Intervention of Subchondral Bone Resorption Mitigates Cartilage Degeneration in TMJOA","authors":"Meng-Nan Cao, Shi-Yang Feng, Chen-Chen Gao, Yang Xiao, Yi-Xin Li, Jie Lei, Kai-Yuan Fu","doi":"10.1111/jop.70073","DOIUrl":"10.1111/jop.70073","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Excessive subchondral bone resorption is a typical manifestation in the early stage of osteoarthritis. This study is to verify whether and when intervening in subchondral bone could alleviate cartilage degeneration of temporomandibular joint osteoarthritis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Disc displacement without reduction was used to induce temporomandibular joint osteoarthritis. Alendronate was administered subcutaneously twice a week at a dosage of 60 μg/kg body weight for 1 week by two intervention methods: early administration (1 day after disc displacement without reduction surgery) and late administration (2 weeks after disc displacement without reduction surgery). Micro-CT was used to assess subchondral bone mass and microstructure. Hematoxylin–eosin staining, toluidine blue staining, tartrate-resistant acid phosphatase staining, immunofluorescence staining, and Western blot were applied to evaluate histopathological changes of the condylar cartilage and subchondral bone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Early alendronate administration not only prevented subchondral bone resorption in early-stage temporomandibular joint osteoarthritis, but also suppressed chondrocyte apoptosis, cartilage extracellular matrix degeneration, as well as excessive subchondral bone formation of condyle in late-stage temporomandibular joint osteoarthritis. However, late alendronate administration had little effect on either subchondral bone or cartilage degenerative changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Early inhibition of subchondral bone resorption could mitigate abnormal subchondral bone formation and condylar cartilage degeneration in late-stage temporomandibular joint osteoarthritis, which might be a promising strategy for temporomandibular joint osteoarthritis treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 1","pages":"133-146"},"PeriodicalIF":2.3,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345679","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}
Oral submucous fibrosis (OSF) is a chronic progressive disease characterized by fibrosis. Panax notoginseng saponins (PNS) are effective components of the traditional Chinese medicine Panax notoginseng and play an important role in the treatment of OSF. However, the underlying mechanism of action for this medicine remains unclear. The aim of this study was to explore the effects of ferroptosis in OSF.
Subjects and Methods
The mice were divided into six groups. Mouth openings were detected. The buccal tissues were harvested for histomorphological analysis, western blot, and RT-qPCR. The cells were harvested for CCK8 detection, western blot, RT-qPCR, TEM, immunofluorescence, fluorescent probe, and colorimetry.
Results
PNS improved mouth opening, alleviated tissue cell damage, and inhibited ferroptosis and fibrosis in OSF rat models. Our study found that ferroptosis is closely related to arecoline-induced OSF and that PNS inhibits ferroptosis by upregulating glutathione peroxidase 4 (GPX4) to alleviate OSF.
Conclusions
The research established OSF in vivo and in vitro, respectively, and the changes in the expression of fibrosis and ferroptosis-related markers in these models were studied to provide a theoretical and experimental basis for the clinical prevention and treatment of OSF.
{"title":"Panax notoginseng Saponins Alleviate OSF by Inhibiting Ferroptosis Through GPX4 Activation","authors":"Xinyue Zhang, Yujie Sun, Chenxi Zhao, Hong Zou, Liang Hu, Lixiang Wen, Qun Tang","doi":"10.1111/jop.70069","DOIUrl":"10.1111/jop.70069","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Oral submucous fibrosis (OSF) is a chronic progressive disease characterized by fibrosis. <i>Panax notoginseng</i> saponins (PNS) are effective components of the traditional Chinese medicine <i>Panax notoginseng</i> and play an important role in the treatment of OSF. However, the underlying mechanism of action for this medicine remains unclear. The aim of this study was to explore the effects of ferroptosis in OSF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Subjects and Methods</h3>\u0000 \u0000 <p>The mice were divided into six groups. Mouth openings were detected. The buccal tissues were harvested for histomorphological analysis, western blot, and RT-qPCR. The cells were harvested for CCK8 detection, western blot, RT-qPCR, TEM, immunofluorescence, fluorescent probe, and colorimetry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PNS improved mouth opening, alleviated tissue cell damage, and inhibited ferroptosis and fibrosis in OSF rat models. Our study found that ferroptosis is closely related to arecoline-induced OSF and that PNS inhibits ferroptosis by upregulating glutathione peroxidase 4 (GPX4) to alleviate OSF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The research established OSF in vivo and in vitro, respectively, and the changes in the expression of fibrosis and ferroptosis-related markers in these models were studied to provide a theoretical and experimental basis for the clinical prevention and treatment of OSF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 1","pages":"107-119"},"PeriodicalIF":2.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251591","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}
Jonas Eichberger, Juliane Schmelzer, Michael Gerken, Christa Buechler, Daniela Schulz, Mathias Fiedler, Stephanie Eckmueller, Josef Maximilian Gottsauner, Richard Bauer, Torsten Eugen Reichert, Florian Weber, Tobias Ettl
Background
The objective of our study was to examine the role of Chemerin, Chemokine like receptor 1 (CMKLR1), receptor activator of nuclear factor kappa-Β ligand (RANKL), and Osteoprotegerin (OPG) in the development of bone-invasive oral squamous cell carcinoma.
Methods
In order to evaluate the presence of these markers at the interface between bone and tumor, immunohistochemical analyses were conducted using tissue microarrays obtained from 164 patients with oral squamous cell carcinoma growing in close contact with jaw bone.
Results
The findings indicate that Chemerin and Osteoprotegerin are notably reduced in tumors that have invaded the bone. Only 21 (32.8%) of pT4a tumors (defined as bone invasive) had a high Osteoprotegerin expression, whereas 36 (66.7%) of pT2 and pT3 tumors demonstrated high expression of Osteoprotegerin (p < 0.001). Similarly, we saw a downregulation of Chemerin in 50 (60.2%) bone invasive oral squamous cell carcinoma samples compared to 28 (35.0%) in non-bone invasive tumors (p = 0.002). In addition, our data indicated a connection between worst pattern of invasion score and less favorable overall and disease-specific survival (p = 0.007 and p = 0.024, respectively).
Conclusions
The findings suggest that Chemerin and Osteoprotegerin have the potential to serve as indicators for bone invasion in oral squamous cell carcinoma, which could have significant implications for diagnosis and treatment approaches.
{"title":"Chemerin, OPG, and WPOI as Markers of Bone Invasion and Prognosis in Oral Squamous Cell Carcinoma","authors":"Jonas Eichberger, Juliane Schmelzer, Michael Gerken, Christa Buechler, Daniela Schulz, Mathias Fiedler, Stephanie Eckmueller, Josef Maximilian Gottsauner, Richard Bauer, Torsten Eugen Reichert, Florian Weber, Tobias Ettl","doi":"10.1111/jop.70068","DOIUrl":"10.1111/jop.70068","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The objective of our study was to examine the role of Chemerin, Chemokine like receptor 1 (CMKLR1), receptor activator of nuclear factor kappa-Β ligand (RANKL), and Osteoprotegerin (OPG) in the development of bone-invasive oral squamous cell carcinoma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In order to evaluate the presence of these markers at the interface between bone and tumor, immunohistochemical analyses were conducted using tissue microarrays obtained from 164 patients with oral squamous cell carcinoma growing in close contact with jaw bone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The findings indicate that Chemerin and Osteoprotegerin are notably reduced in tumors that have invaded the bone. Only 21 (32.8%) of pT4a tumors (defined as bone invasive) had a high Osteoprotegerin expression, whereas 36 (66.7%) of pT2 and pT3 tumors demonstrated high expression of Osteoprotegerin (<i>p</i> < 0.001). Similarly, we saw a downregulation of Chemerin in 50 (60.2%) bone invasive oral squamous cell carcinoma samples compared to 28 (35.0%) in non-bone invasive tumors (<i>p</i> = 0.002). In addition, our data indicated a connection between worst pattern of invasion score and less favorable overall and disease-specific survival (<i>p</i> = 0.007 and <i>p</i> = 0.024, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The findings suggest that Chemerin and Osteoprotegerin have the potential to serve as indicators for bone invasion in oral squamous cell carcinoma, which could have significant implications for diagnosis and treatment approaches.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 1","pages":"87-98"},"PeriodicalIF":2.3,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238906","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}
Denise M. Laronde, Matt Berkowitz, A. Ross Kerr, Erinn M. Hade, Mutita Siriruchatanon, Miriam P. Rosin, Stella K. Kang
Background
Inferring risk for malignant transformation (MT) in patients with lesions diagnosed as mild or moderate oral epithelial dysplasia (low-grade OED) remains challenging. We developed two models assessing the risk of progression to high-grade OED (severe dysplasia or carcinoma in situ) or OSCC in patients with low-grade OED lesions.
Methods
We included demographic, risk habit and clinical data from participants with low-grade OED lesions enrolled in the BC Oral Cancer Prevention Program's Oral Cancer Prediction Longitudinal study. Cox proportional hazard models were fit to estimate the effects of anatomic site and toluidine blue findings and adjusted for confounders, as both are associated with MT in the literature but without a North American-specific cohort analysis. Our primary model included both variables of interest. A secondary model included only anatomic site since toluidine blue is not in widespread use.
Results
Five hundred and thirty-four participants with 605 lesions met final inclusion criteria, with 339 mild and 266 moderate OED at baseline. In the primary model, lesions at a high-risk anatomic site or with positive toluidine blue staining were associated with a 2.6 and 2.4-fold increased risk of progression, respectively. In the second model that did not incorporate toluidine blue, high-risk anatomic site remained a highly associated risk factor (2.7-fold increased risk of progression).
Conclusion
Lesion anatomic site is associated with higher risk of MT for the general practitioner, while a specialist with access to toluidine blue results can assume additional risk associated with positive staining. These models may inform decisions for surveillance and intervention for OED.
{"title":"Clinical Features Associated With Malignant Transformation of Low-Grade Dysplasia","authors":"Denise M. Laronde, Matt Berkowitz, A. Ross Kerr, Erinn M. Hade, Mutita Siriruchatanon, Miriam P. Rosin, Stella K. Kang","doi":"10.1111/jop.70070","DOIUrl":"10.1111/jop.70070","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inferring risk for malignant transformation (MT) in patients with lesions diagnosed as mild or moderate oral epithelial dysplasia (low-grade OED) remains challenging. We developed two models assessing the risk of progression to high-grade OED (severe dysplasia or carcinoma in situ) or OSCC in patients with low-grade OED lesions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included demographic, risk habit and clinical data from participants with low-grade OED lesions enrolled in the BC Oral Cancer Prevention Program's Oral Cancer Prediction Longitudinal study. Cox proportional hazard models were fit to estimate the effects of anatomic site and toluidine blue findings and adjusted for confounders, as both are associated with MT in the literature but without a North American-specific cohort analysis. Our primary model included both variables of interest. A secondary model included only anatomic site since toluidine blue is not in widespread use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Five hundred and thirty-four participants with 605 lesions met final inclusion criteria, with 339 mild and 266 moderate OED at baseline. In the primary model, lesions at a high-risk anatomic site or with positive toluidine blue staining were associated with a 2.6 and 2.4-fold increased risk of progression, respectively. In the second model that did not incorporate toluidine blue, high-risk anatomic site remained a highly associated risk factor (2.7-fold increased risk of progression).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Lesion anatomic site is associated with higher risk of MT for the general practitioner, while a specialist with access to toluidine blue results can assume additional risk associated with positive staining. These models may inform decisions for surveillance and intervention for OED.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 1","pages":"99-106"},"PeriodicalIF":2.3,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.70070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238876","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}
Pemphigus vulgaris is a rare autoimmune blistering condition characterised by mucocutaneous lesions secondary to acantholysis. Assessment of disease activity, severity, and treatment response is crucial for guiding management and research. Multiple clinical scoring systems have been developed for pemphigus vulgaris; however, consensus on their optimal use is lacking. This scoping review aims to identify, evaluate, and summarise the clinical scoring systems used in pemphigus vulgaris, focusing on validity, reliability, and application in clinical practice and research.
Methods
A comprehensive literature search was conducted using electronic databases (PubMed (Medline), Embase, Web of Science, Scopus, and Cochrane Library) as well as grey literature to identify studies describing clinical scoring systems for pemphigus vulgaris. Data on scoring system components, validity, clinical applicability, and limitations were extracted and synthesised.
Results
The review identified several scoring systems, including the Pemphigus Disease Area Index, Autoimmune Bullous Skin Disorder Intensity Score, and other less commonly used tools. Scoring systems varied in design, with key differences noted in assessment domains, including mucosal versus cutaneous involvement, patient-reported outcomes, and usability.
Conclusion
Current clinical scoring systems for pemphigus vulgaris provide frameworks for disease assessment but exhibit variability in scope, validation, and practical implementation. Further development to incorporate emerging biomarkers and quality of life, as well as encompass all clinical subsites, will enhance their utility in guiding patient care and advancing research. This review highlights the need for consensus on a universal scoring system tailored to the multifaceted nature of pemphigus vulgaris.
背景：寻常型天疱疮是一种罕见的自身免疫性水疱，其特征是继发于棘层松解的皮肤粘膜病变。评估疾病活动性、严重程度和治疗反应对指导管理和研究至关重要。多种临床评分系统已开发寻常型天疱疮；然而，对它们的最佳使用还缺乏共识。本综述旨在识别、评估和总结用于寻常型天疱疮的临床评分系统，重点关注有效性、可靠性及其在临床实践和研究中的应用。方法：通过电子数据库（PubMed （Medline）、Embase、Web of Science、Scopus和Cochrane Library）以及灰色文献进行全面的文献检索，以确定描述寻常型天疱疮临床评分系统的研究。提取和综合评分系统组成、有效性、临床适用性和局限性的数据。结果：本综述确定了几种评分系统，包括天疱疮疾病面积指数、自身免疫性大疱性皮肤疾病强度评分和其他不太常用的工具。评分系统在设计上各不相同，在评估领域存在关键差异，包括粘膜与皮肤受累、患者报告的结果和可用性。结论：目前的寻常型天疱疮临床评分系统为疾病评估提供了框架，但在范围、有效性和实际实施方面存在差异。进一步发展纳入新兴生物标志物和生活质量，以及涵盖所有临床亚位点，将增强其在指导患者护理和推进研究方面的效用。这篇综述强调需要共识的普遍评分系统量身定制寻常性天疱疮的多方面性质。
{"title":"Pemphigus Vulgaris Scoring Systems: A Scoping Review","authors":"Sue-Ching Yeoh, Stephen Adelstein, Omar Kujan","doi":"10.1111/jop.70071","DOIUrl":"10.1111/jop.70071","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pemphigus vulgaris is a rare autoimmune blistering condition characterised by mucocutaneous lesions secondary to acantholysis. Assessment of disease activity, severity, and treatment response is crucial for guiding management and research. Multiple clinical scoring systems have been developed for pemphigus vulgaris; however, consensus on their optimal use is lacking. This scoping review aims to identify, evaluate, and summarise the clinical scoring systems used in pemphigus vulgaris, focusing on validity, reliability, and application in clinical practice and research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive literature search was conducted using electronic databases (PubMed (Medline), Embase, Web of Science, Scopus, and Cochrane Library) as well as grey literature to identify studies describing clinical scoring systems for pemphigus vulgaris. Data on scoring system components, validity, clinical applicability, and limitations were extracted and synthesised.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The review identified several scoring systems, including the Pemphigus Disease Area Index, Autoimmune Bullous Skin Disorder Intensity Score, and other less commonly used tools. Scoring systems varied in design, with key differences noted in assessment domains, including mucosal versus cutaneous involvement, patient-reported outcomes, and usability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Current clinical scoring systems for pemphigus vulgaris provide frameworks for disease assessment but exhibit variability in scope, validation, and practical implementation. Further development to incorporate emerging biomarkers and quality of life, as well as encompass all clinical subsites, will enhance their utility in guiding patient care and advancing research. This review highlights the need for consensus on a universal scoring system tailored to the multifaceted nature of pemphigus vulgaris.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 1","pages":"42-60"},"PeriodicalIF":2.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225685","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}
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