Pub Date : 2025-11-21DOI: 10.1016/j.oraloncology.2025.107792
Chia Yuen Chong , Richard J. Young , Annette M. Lim , Angela Pizzolla , Christopher M. Angel , Mathias Bressel , Matthew Magarey , Benjamin Dixon , Benjamin Solomon , Danny Rischin
Background
CD103+ intratumoral immune cell (ITIC) abundance in Human Papillomavirus associated Oropharyngeal Cancer (HPVOPC) primary tumors in patients treated with chemoradiation conveys an excellent prognosis, but data is lacking for nodal expression and surgical cohorts. High programmed death-ligand 1 (PD-L1) expression predicts immunotherapy response, but its prognostic significance and correlation with CD103+ expression in HPVOPC is unknown.
Methods
Immunohistochemistry to evaluate CD103+ ITIC abundance > 30 % and PD-L1 Combined Positive Score (CPS) > 20 % in primary tumors and lymph nodes in 114 surgically treated HPVOPC patients. Findings were correlated with clinicopathological and outcome data.
Results
High CD103+ ITIC abundance (>30 %) in 14.5 % of primary tumors (16/110) and 14.3 % (11/77) of lymph nodes. High PD-L1 CPS (>20 %) in 38.3 % (41/107) of primaries, and 36.3 % (28/77) of nodes. Discordant rates between primaries and nodes for CD103+ ITIC and PD-L1 CPS were 15 % and 29 % respectively. 5-year failure free survival (FFS) was 100 % and 83 % in patients with high and low CD103+ ITIC abundance primary tumors, (95 % CI: 72–91; p = 0.161). 5-year FFS was 98 % and 79 % (p = 0.033) in patients with high and low PD-L1 CPS primary tumors. Lymph node CD103+ ITIC abundance and PD-L1 CPS did not appear to be prognostic for survival.
Conclusions
This study highlights the discordance in CD103+ ITIC and PD-L1 expression between primaries and nodes, favorable results in high CD103+ ITIC abundance HPVOPC in a surgical cohort consistent with outcomes in chemoradiation cohorts, and promising results suggesting that high PD-L1 CPS in HPVOPC also identifies patients with an excellent prognosis.
{"title":"Evaluating CD103+ intratumoral immune cell abundance and PD-L1 CPS in primary tumors versus lymph nodes in Human papillomavirus associated oropharyngeal Cancer","authors":"Chia Yuen Chong , Richard J. Young , Annette M. Lim , Angela Pizzolla , Christopher M. Angel , Mathias Bressel , Matthew Magarey , Benjamin Dixon , Benjamin Solomon , Danny Rischin","doi":"10.1016/j.oraloncology.2025.107792","DOIUrl":"10.1016/j.oraloncology.2025.107792","url":null,"abstract":"<div><h3>Background</h3><div>CD103<sup>+</sup> intratumoral immune cell (ITIC) abundance in Human Papillomavirus associated Oropharyngeal Cancer (HPVOPC) primary tumors in patients treated with chemoradiation conveys an excellent prognosis, but data is lacking for nodal expression and surgical cohorts. High programmed death-ligand 1 (PD-L1) expression predicts immunotherapy response, but its prognostic significance and correlation with CD103<sup>+</sup> expression in HPVOPC is unknown.</div></div><div><h3>Methods</h3><div>Immunohistochemistry to evaluate CD103<sup>+</sup> ITIC abundance > 30 % and PD-L1 Combined Positive Score (CPS) > 20 % in primary tumors and lymph nodes in 114 surgically treated HPVOPC patients. Findings were correlated with clinicopathological and outcome data.</div></div><div><h3>Results</h3><div>High CD103<sup>+</sup> ITIC abundance (>30 %) in 14.5 % of primary tumors (16/110) and 14.3 % (11/77) of lymph nodes. High PD-L1 CPS (>20 %) in 38.3 % (41/107) of primaries, and 36.3 % (28/77) of nodes. Discordant rates between primaries and nodes for CD103<sup>+</sup> ITIC and PD-L1 CPS were 15 % and 29 % respectively. 5-year failure free survival (FFS) was 100 % and 83 % in patients with high and low CD103<sup>+</sup> ITIC abundance primary tumors, (95 % CI: 72–91; <em>p</em> = 0.161). 5-year FFS was 98 % and 79 % (<em>p</em> = 0.033) in patients with high and low PD-L1 CPS primary tumors. Lymph node CD103<sup>+</sup> ITIC abundance and PD-L1 CPS did not appear to be prognostic for survival.</div></div><div><h3>Conclusions</h3><div>This study highlights the discordance in CD103<sup>+</sup> ITIC and PD-L1 expression between primaries and nodes, favorable results in high CD103<sup>+</sup> ITIC abundance HPVOPC in a surgical cohort consistent with outcomes in chemoradiation cohorts, and promising results suggesting that high PD-L1 CPS in HPVOPC also identifies patients with an excellent prognosis.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"171 ","pages":"Article 107792"},"PeriodicalIF":3.9,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-20DOI: 10.1016/j.oraloncology.2025.107788
Jérôme R. Lechien
Background
The learning curve for Transoral Robotic Surgery (TORS) in head and neck cancer (HNC) management remains incompletely characterized despite its increasing adoption. This systematic review evaluated the learning curves and required case volume for achieving proficiency and identified factors influencing the learning process.
Methods
Two investigators conducted a PubMed, Scopus, and Cochrane Library systematic review for studies investigating the surgical, functional, oncological and learning curve outcomes related to the implementation of TORS in HNC surgery using the PRISMA statement. The bias analysis was conducted with the MINORS.
Results
Of the 102 identified studies, 9 studies met our inclusion criteria, including 792 (82.1 %) male patients. TORS learning curve was primarily investigated on cT2N1 oropharyngeal cancer. The number of requested cases to achieve inflexion point in performing TORS varied by outcome measures but globally ranges from 25 to 50 cases. The mean MINORS was 8.8 ± 1.8 There was substantial heterogeneity across studies for the definition and criteria used to determine the learning process/inflexion point. No study detailed the surgeon experience and features. Two studies described the training program applied to surgeons before starting the study.
Conclusion
TORS proficiency case numbers remain unclear due to study heterogeneity, non-standardized endpoints, and variable definitions. Estimates range 20–50 cases for operative outcomes; long-term results require higher volumes. Future prospective studies are needed to standardize learning definitions and analyze how surgeon-specific factors (experience, age, prior training) impact TORS learning curves.
{"title":"Learning process of transoral robotic surgery for head and neck cancers: a scoping review","authors":"Jérôme R. Lechien","doi":"10.1016/j.oraloncology.2025.107788","DOIUrl":"10.1016/j.oraloncology.2025.107788","url":null,"abstract":"<div><h3>Background</h3><div>The learning curve for Transoral Robotic Surgery (TORS) in head and neck cancer (HNC) management remains incompletely characterized despite its increasing adoption. This systematic review evaluated the learning curves and required case volume for achieving proficiency and identified factors influencing the learning process.</div></div><div><h3>Methods</h3><div>Two investigators conducted a PubMed, Scopus, and Cochrane Library systematic review for studies investigating the surgical, functional, oncological and learning curve outcomes related to the implementation of TORS in HNC surgery using the PRISMA statement. The bias analysis was conducted with the MINORS.</div></div><div><h3>Results</h3><div>Of the 102 identified studies, 9 studies met our inclusion criteria, including 792 (82.1 %) male patients. TORS learning curve was primarily investigated on cT2N1 oropharyngeal cancer. The number of requested cases to achieve inflexion point in performing TORS varied by outcome measures but globally ranges from 25 to 50 cases. The mean MINORS was 8.8 ± 1.8 There was substantial heterogeneity across studies for the definition and criteria used to determine the learning process/inflexion point. No study detailed the surgeon experience and features. Two studies described the training program applied to surgeons before starting the study.</div></div><div><h3>Conclusion</h3><div>TORS proficiency case numbers remain unclear due to study heterogeneity, non-standardized endpoints, and variable definitions. Estimates range 20–50 cases for operative outcomes; long-term results require higher volumes. Future prospective studies are needed to standardize learning definitions and analyze how surgeon-specific factors (experience, age, prior training) impact TORS learning curves.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"171 ","pages":"Article 107788"},"PeriodicalIF":3.9,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/j.oraloncology.2025.107784
Min Li, Yingchun Zhou, Ming Cai
{"title":"Letter to the Editor: A phase II clinical trial of paclitaxel-carboplatin as neoadjuvant therapy followed by surgery in patients with locally advanced head and neck squamous cell carcinoma","authors":"Min Li, Yingchun Zhou, Ming Cai","doi":"10.1016/j.oraloncology.2025.107784","DOIUrl":"10.1016/j.oraloncology.2025.107784","url":null,"abstract":"","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"171 ","pages":"Article 107784"},"PeriodicalIF":3.9,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In oral cavity cancers, tumors invading the bone marrow of the mandible or maxilla have traditionally been classified as T4a in the TNM staging system. This study evaluated the impact of bone invasion on T classification and survival in patients with squamous cell carcinoma of the oral cavity.
Materials and methods
We retrospectively reviewed and restaged 2,143 patients treated between 2001 and 2019. Bone invasion was categorized as no bone invasion, non-mandibular canal (MC) bone marrow invasion, or MC invasion. Disease-specific survival (DSS) was the primary endpoint. Prognostic performance was assessed using Kaplan–Meier analysis and Cox proportional hazards models. Discriminative ability was evaluated with Harrell’s concordance index (C-index) and calibration analysis.
Results
Among 505 T4a tumors, 271 (53.7%) were classified as T4a solely due to bone marrow invasion, and their survival outcomes were comparable to those of T3 tumors. In multivariate analysis, MC invasion was independently associated with worse DSS, whereas non-MC bone marrow invasion was not. Based on these findings, we developed two revised versions of the MC-T classification for oral tumors, replacing bone marrow invasion with MC invasion as a T4a criterion in the 8th edition UICC/AJCC T classification. Both MC-T classifications showed superior prognostic discrimination, with higher C-indices than the original system.
Conclusions
Patients with T4a oral tumors classified solely by bone marrow invasion had survival outcomes similar to those with T3 tumors. The proposed MC-T classification improves prognostic accuracy by more effectively stratifying T4a tumors.
背景与目的:在口腔癌中,侵袭下颌骨或上颌骨髓的肿瘤在TNM分期系统中传统上被归类为T4a。本研究评估骨浸润对口腔鳞状细胞癌患者T分类和生存的影响。材料和方法:我们对2001年至2019年期间接受治疗的2143例患者进行了回顾性研究和再治疗。骨侵犯分为无骨侵犯、非下颌管(MC)骨髓侵犯和下颌管侵犯。疾病特异性生存(DSS)是主要终点。采用Kaplan-Meier分析和Cox比例风险模型评估预后。采用Harrell’s concordance index (C-index)和校正分析评价辨别力。结果505例T4a肿瘤中有271例(53.7%)仅因骨髓侵袭被归为T4a,其生存结局与T3肿瘤相当。在多变量分析中,MC侵袭与DSS恶化独立相关,而非MC骨髓侵袭与DSS恶化无关。基于这些发现,我们制定了两个修订版本的口腔肿瘤MC-T分类,在第8版UICC/AJCC T分类中以MC侵袭取代骨髓侵袭作为T4a标准。两种MC-T分类均具有较好的预后判别能力,其c指数均高于原分类系统。结论:单纯以骨髓侵袭分类的T4a口腔肿瘤患者的生存结局与T3肿瘤相似。提出的MC-T分类通过更有效地对T4a肿瘤进行分层,提高了预后准确性。
{"title":"T4a classification for oral cancer using mandibular canal invasion instead of bone marrow invasion in the TNM staging system","authors":"Masaya Okura , Nobuhiro Yamakawa , Mitsunobu Otsuru , Takumi Hasegawa , Yusuke Yokota , Shin Rin , Hironori Sakai , Shin-ichi Yamada , Eiji Hirai , Yuichi Ashikaga , Kozo Yamamoto , Michihiro Ueda , Tadaaki Kirita , Masahiro Umeda , Masaya Akashi , Hiroshi Kurita , Yoichi Ohiro , Tomofumi Naruse , Souichi Yanamoto , Japan Oral Oncology Group JOOG","doi":"10.1016/j.oraloncology.2025.107771","DOIUrl":"10.1016/j.oraloncology.2025.107771","url":null,"abstract":"<div><h3>Background and purpose</h3><div>In oral cavity cancers, tumors invading the bone marrow of the mandible or maxilla have traditionally been classified as T4a in the TNM staging system. This study evaluated the impact of bone invasion on T classification and survival in patients with squamous cell carcinoma of the oral cavity.</div></div><div><h3>Materials and methods</h3><div>We retrospectively reviewed and restaged 2,143 patients treated between 2001 and 2019. Bone invasion was categorized as no bone invasion, non-mandibular canal (MC) bone marrow invasion, or MC invasion. Disease-specific survival (DSS) was the primary endpoint. Prognostic performance was assessed using Kaplan–Meier analysis and Cox proportional hazards models. Discriminative ability was evaluated with Harrell’s concordance index (C-index) and calibration analysis.</div></div><div><h3>Results</h3><div>Among 505 T4a tumors, 271 (53.7%) were classified as T4a solely due to bone marrow invasion, and their survival outcomes were comparable to those of T3 tumors. In multivariate analysis, MC invasion was independently associated with worse DSS, whereas non-MC bone marrow invasion was not. Based on these findings, we developed two revised versions of the MC-T classification for oral tumors, replacing bone marrow invasion with MC invasion as a T4a criterion in the 8th edition UICC/AJCC T classification. Both MC-T classifications showed superior prognostic discrimination, with higher C-indices than the original system.</div></div><div><h3>Conclusions</h3><div>Patients with T4a oral tumors classified solely by bone marrow invasion had survival outcomes similar to those with T3 tumors. The proposed MC-T classification improves prognostic accuracy by more effectively stratifying T4a tumors.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"171 ","pages":"Article 107771"},"PeriodicalIF":3.9,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145506328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-10DOI: 10.1016/j.oraloncology.2025.107775
Annu Singh , Teeradon Treechairusame , Edward Christopher Dee , Joseph M. Huryn , Cherry L. Estilo , Nancy Y. Lee
{"title":"Reply to the comment on “Osteoradionecrosis as a complication following post-operative intensity-modulated radiation therapy or proton therapy for oral cavity cancers","authors":"Annu Singh , Teeradon Treechairusame , Edward Christopher Dee , Joseph M. Huryn , Cherry L. Estilo , Nancy Y. Lee","doi":"10.1016/j.oraloncology.2025.107775","DOIUrl":"10.1016/j.oraloncology.2025.107775","url":null,"abstract":"","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"171 ","pages":"Article 107775"},"PeriodicalIF":3.9,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-10DOI: 10.1016/j.oraloncology.2025.107768
Cecelia M. Hidalgo , Gabriel A. Hernandez-Herrera , Courtney N. Day , Felicia Olawuni , Chadi N. Abdel-Halim , Kathryn M. Van Abel , David M. Routman , Linda X. Yin
Purpose
De-escalation trials in human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV + OPSCC) have led to variable institutional treatment algorithms. It is unclear whether treatment options are offered equally throughout the United States. This study assesses how social determinants of health (SDOH), and treatment facility type impact access to surgery and/or high-quality radiotherapy (RT) for HPV + OPSCC.
Results
Among 6,458 patients, the median age was 62, 93.1 % were White, and 79.2 % had no significant comorbidities. Patients with the highest education, income, and private insurance (p ≤ 0.002 for all) underwent more surgery. Patients with lower education and income presented with more advanced disease (each p < 0.001). Care at academic facilities was the strongest predictor of surgery for early-stage disease (aOR:6.17, 95 % CI:3.74–10.18, p < 0.001) and was more likely to result in a margin-negative resection (p = 0.017). Delays in TTI were highest among Black patients, uninsured patients, patients with low socioeconomic status (SES), and patients receiving care at academic facilities (p ≤ 0.011 for all). Patients with significant comorbidities were more likely to experience delays in TTA (p = 0.018) and TTC (p = 0.036). There were no differences in delays in TTA or TTC based on treatment facility.
Conclusions
SDOH affect access to surgery for HPV + OPSCC, with patients of low SES presenting with more advanced disease. Among early-stage cases, access to surgery is significantly greater at academic facilities, which offer superior surgical outcomes. Treatment completion times are comparable between academic and community facilities, suggesting that poor surgical candidates should pursue care at the facility offering the fastest treatment initiation and completion.
{"title":"Access to surgery and high-quality radiotherapy for human papillomavirus related oropharynx cancer","authors":"Cecelia M. Hidalgo , Gabriel A. Hernandez-Herrera , Courtney N. Day , Felicia Olawuni , Chadi N. Abdel-Halim , Kathryn M. Van Abel , David M. Routman , Linda X. Yin","doi":"10.1016/j.oraloncology.2025.107768","DOIUrl":"10.1016/j.oraloncology.2025.107768","url":null,"abstract":"<div><h3>Purpose</h3><div>De-escalation trials in human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV + OPSCC) have led to variable institutional treatment algorithms. It is unclear whether treatment options are offered equally throughout the United States. This study assesses how social determinants of health (SDOH), and treatment facility type impact access to surgery and/or high-quality radiotherapy (RT) for HPV + OPSCC.</div></div><div><h3>Results</h3><div>Among 6,458 patients, the median age was 62, 93.1 % were White, and 79.2 % had no significant comorbidities. Patients with the highest education, income, and private insurance (p ≤ 0.002 for all) underwent more surgery. Patients with lower education and income presented with more advanced disease (each p < 0.001). Care at academic facilities was the strongest predictor of surgery for early-stage disease (aOR:6.17, 95 % CI:3.74–10.18, p < 0.001) and was more likely to result in a margin-negative resection (p = 0.017). Delays in TTI were highest among Black patients, uninsured patients, patients with low socioeconomic status (SES), and patients receiving care at academic facilities (p ≤ 0.011 for all). Patients with significant comorbidities were more likely to experience delays in TTA (p = 0.018) and TTC (p = 0.036). There were no differences in delays in TTA or TTC based on treatment facility.</div></div><div><h3>Conclusions</h3><div>SDOH affect access to surgery for HPV + OPSCC, with patients of low SES presenting with more advanced disease. Among early-stage cases, access to surgery is significantly greater at academic facilities, which offer superior surgical outcomes. Treatment completion times are comparable between academic and community facilities, suggesting that poor surgical candidates should pursue care at the facility offering the fastest treatment initiation and completion.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"171 ","pages":"Article 107768"},"PeriodicalIF":3.9,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-09DOI: 10.1016/j.oraloncology.2025.107742
Rose Doerfler , Jie Chen , Carl Kim , Joshua D. Smith , Micah Harris , Krishna B. Singh , Brian Isett , Rebekah E. Dadey , Daniel D. Brown , Adrian V. Lee , Xuefeng Wang , Matthew E. Spector , Seungwon Kim , Shaum Sridharan , Kevin Contrera , Katelyn Smith , Carly Reeder , Maureen Lyons , Jianhua Luo , Silvia Liu , Riyue Bao
Patient-derived organoids (PDOs) emerge as advanced 3D ex vivo New Approach Methodologies (NAM) preclinical models, offering significant advantages over traditional cell lines and monolayer cultures for therapeutic development. In this study, we established PDOs from surgically resected fresh tissues of human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) across anatomical sites, tumor T-categories, and sample types. These PDOs faithfully recapitulate the tumor’s pathology, mutational profile, and drug response. To enable rapid classification of PDO identity, we developed a new convolutional neural network (CNN) model, TransferNet-PDO, which accurately distinguished tumor versus normal PDOs in culture using digital histopathology images (AUC ≥ 0.88). PDOs maintained stable cultures and were cryopreserved between passages 5 and 12. Immunohistochemistry (IHC) staining (PanCK, p63, Cytokeratin 13, Ki67) confirmed squamous phenotype and histologic aggression of the original tumor. For tumors harboring TP53 mutations by whole-exome sequencing (WES), PDOs retained the corresponding p53 functional status as confirmed by IHC (enhanced or loss of protein expression). Somatic mutational landscape revealed that PDOs preserved driver somatic mutations, copy number variations (CNVs), and clonal architecture including low-prevalence subclones. Drug sensitivity assessment of PDOs showed that cisplatin reduced cell viability, whereas cetuximab and lenvatinib had minimal effects. Chemoradiation led to greater tumor organoid killing compared to radiation or chemotherapy alone. This study presents an integrated HNSCC PDO platform combining tissue biobanking, organoid establishment, multiomics characterization, functional drug screening, and AI-driven histopathologic classification, providing a comprehensive and scalable system for translational cancer research.
{"title":"Integrating artificial intelligence-driven digital pathology and genomics to establish patient-derived organoids as new approach methodologies for drug response in head and neck cancer","authors":"Rose Doerfler , Jie Chen , Carl Kim , Joshua D. Smith , Micah Harris , Krishna B. Singh , Brian Isett , Rebekah E. Dadey , Daniel D. Brown , Adrian V. Lee , Xuefeng Wang , Matthew E. Spector , Seungwon Kim , Shaum Sridharan , Kevin Contrera , Katelyn Smith , Carly Reeder , Maureen Lyons , Jianhua Luo , Silvia Liu , Riyue Bao","doi":"10.1016/j.oraloncology.2025.107742","DOIUrl":"10.1016/j.oraloncology.2025.107742","url":null,"abstract":"<div><div>Patient-derived organoids (PDOs) emerge as advanced 3D ex vivo New Approach Methodologies (NAM) preclinical models, offering significant advantages over traditional cell lines and monolayer cultures for therapeutic development. In this study, we established PDOs from surgically resected fresh tissues of human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) across anatomical sites, tumor T-categories, and sample types. These PDOs faithfully recapitulate the tumor’s pathology, mutational profile, and drug response. To enable rapid classification of PDO identity, we developed a new convolutional neural network (CNN) model, TransferNet-PDO, which accurately distinguished tumor <em>versus</em> normal PDOs in culture using digital histopathology images (AUC ≥ 0.88). PDOs maintained stable cultures and were cryopreserved between passages 5 and 12. Immunohistochemistry (IHC) staining (PanCK, p63, Cytokeratin 13, Ki67) confirmed squamous phenotype and histologic aggression of the original tumor. For tumors harboring TP53 mutations by whole-exome sequencing (WES), PDOs retained the corresponding p53 functional status as confirmed by IHC (enhanced or loss of protein expression). Somatic mutational landscape revealed that PDOs preserved driver somatic mutations, copy number variations (CNVs), and clonal architecture including low-prevalence subclones. Drug sensitivity assessment of PDOs showed that cisplatin reduced cell viability, whereas cetuximab and lenvatinib had minimal effects. Chemoradiation led to greater tumor organoid killing compared to radiation or chemotherapy alone. This study presents an integrated HNSCC PDO platform combining tissue biobanking, organoid establishment, multiomics characterization, functional drug screening, and AI-driven histopathologic classification, providing a comprehensive and scalable system for translational cancer research.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"171 ","pages":"Article 107742"},"PeriodicalIF":3.9,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145489953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-08DOI: 10.1016/j.oraloncology.2025.107774
Araceli Diez-Fraile , Lies Pottel , Philippe Lamoral , Tom De Backer , Christophe Spaas , Raf Van Hoeyweghen , Tom Vauterin , Catherine Dick , Johan Abeloos , Joke De Ceulaer
{"title":"Age and surgical complexity outperform preoperative Geriatric-8 for 30-day major complications in older head and neck cancer","authors":"Araceli Diez-Fraile , Lies Pottel , Philippe Lamoral , Tom De Backer , Christophe Spaas , Raf Van Hoeyweghen , Tom Vauterin , Catherine Dick , Johan Abeloos , Joke De Ceulaer","doi":"10.1016/j.oraloncology.2025.107774","DOIUrl":"10.1016/j.oraloncology.2025.107774","url":null,"abstract":"","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"171 ","pages":"Article 107774"},"PeriodicalIF":3.9,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}