Pub Date : 2025-12-02DOI: 10.1016/j.oraloncology.2025.107790
Sarah C. Nyirjesy , Yana Al-Inaya , Selena Zhang , Omar A. Karadaghy , Derrick T. Lin , Daniel G. Deschler , Allen L. Feng , Mark A. Varvares , Adam S. Fisch , Daniel L. Faden , Jeremy D. Richmon
Second primary tumors after HPV-associated oropharyngeal squamous cell carcinoma (HPV + OPSCCa) are generally assumed to share the same HPV status as the index lesion, and current pathology guidelines discourage repeat HPV testing in recurrent disease. We retrospectively reviewed records from a tertiary academic center (2010–2024) to identify patients with a history of HPV + OPSCCa who subsequently developed an HPV-independent second primary head and neck squamous cell carcinoma. HPV status was determined by p16 immunohistochemistry, high-risk HPV DNA PCR, or RNA in situ hybridization. Eleven patients developed metachronous HPV-independent malignancies, representing an incidence of 2.5 %. The median interval between tumors was 8.8 years (range, 3.2–16.0 years). Second primaries most often arose in the contralateral base of tongue (55 %) or oral cavity (27 %). All patients had received definitive or adjuvant radiation for the initial tumor, and 73 % received concurrent chemotherapy. Four patients (36 %) reported a smoking history >10 pack-years. Most tumors at both time points were T1 or T2, but node-positive disease was more frequent in first primaries (82 % vs 18 %). Two patients developed a third HPV-independent primary tumor. These findings demonstrate that biologically discordant second primary head and neck cancers can emerge years after HPV + OPSCCa, challenging the assumption of HPV concordance and underscoring the need for long-term surveillance and reconsideration of repeat HPV testing in this population.
HPV相关口咽鳞状细胞癌（HPV + OPSCCa）后的第二原发肿瘤通常被认为与指数病变具有相同的HPV状态，目前的病理指南不鼓励在复发性疾病中重复HPV检测。我们回顾性地回顾了一个三级学术中心（2010-2024）的记录，以确定有HPV + OPSCCa病史的患者，这些患者随后发展为不依赖HPV的第二原发性头颈部鳞状细胞癌。通过p16免疫组织化学、高危HPV DNA PCR或RNA原位杂交检测HPV状态。11例患者发生异时性不依赖hpv的恶性肿瘤，发生率为2.5%。肿瘤之间的中位间隔为8.8年（范围3.2-16.0年）。第二原发牙最常发生在对侧舌根（55%）或口腔（27%）。所有患者都接受了初始肿瘤的最终或辅助放疗，73%的患者接受了同期化疗。4例患者（36%）报告吸烟史（10包年）。两个时间点的大多数肿瘤都是T1或T2，但淋巴结阳性疾病在首次原发时更为常见（82%对18%）。两名患者发展为第三个不依赖hpv的原发肿瘤。这些发现表明，生物学上不一致的第二原发性头颈癌可能在HPV + OPSCCa发生数年后出现，这挑战了HPV一致性的假设，并强调了在这一人群中进行长期监测和重新考虑重复HPV检测的必要性。
{"title":"Incidence of HPV-independent second primary malignancies following treatment of HPV-associated malignancy","authors":"Sarah C. Nyirjesy , Yana Al-Inaya , Selena Zhang , Omar A. Karadaghy , Derrick T. Lin , Daniel G. Deschler , Allen L. Feng , Mark A. Varvares , Adam S. Fisch , Daniel L. Faden , Jeremy D. Richmon","doi":"10.1016/j.oraloncology.2025.107790","DOIUrl":"10.1016/j.oraloncology.2025.107790","url":null,"abstract":"<div><div>Second primary tumors after HPV-associated oropharyngeal squamous cell carcinoma (HPV + OPSCCa) are generally assumed to share the same HPV status as the index lesion, and current pathology guidelines discourage repeat HPV testing in recurrent disease. We retrospectively reviewed records from a tertiary academic center (2010–2024) to identify patients with a history of HPV + OPSCCa who subsequently developed an HPV-independent second primary head and neck squamous cell carcinoma. HPV status was determined by p16 immunohistochemistry, high-risk HPV DNA PCR, or RNA in situ hybridization. Eleven patients developed metachronous HPV-independent malignancies, representing an incidence of 2.5 %. The median interval between tumors was 8.8 years (range, 3.2–16.0 years). Second primaries most often arose in the contralateral base of tongue (55 %) or oral cavity (27 %). All patients had received definitive or adjuvant radiation for the initial tumor, and 73 % received concurrent chemotherapy. Four patients (36 %) reported a smoking history >10 pack-years. Most tumors at both time points were T1 or T2, but node-positive disease was more frequent in first primaries (82 % vs 18 %). Two patients developed a third HPV-independent primary tumor. These findings demonstrate that biologically discordant second primary head and neck cancers can emerge years after HPV + OPSCCa, challenging the assumption of HPV concordance and underscoring the need for long-term surveillance and reconsideration of repeat HPV testing in this population.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"172 ","pages":"Article 107790"},"PeriodicalIF":3.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669487","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 : 2025-12-01DOI: 10.1016/j.oraloncology.2025.107795
Elif Baran , Melissa Lee , Pabiththa Kamalraj , Irene Karam , Ian Poon , Andrew Bayley , Kevin M. Higgins , Danny J. Enepekides , Kelvin K.W. Chan , Ambika Parmar , Martin Smoragiewicz , Antoine Eskander
Objective
The objectives were to (1) conduct an electronic health records (EHRs) review of oropharyngeal cancer patients, (2) determine EHR stage documentation rates, and (3) compare staging accuracy within EHRs and by Cancer Center Coders.
Methods
Retrospective analysis of oropharyngeal cancer patients seen between January 1, 2010, and August 1, 2020, at a tertiary care center. Two experts reviewed EHRs to determine tumour (T), nodal (N), metastatic (M) and overall cancer stages. EHR staging documentation was abstracted and accuracy was reported in comparison to expert staging. Cancer Center Coders independently captured cancer staging, and accuracy was reported in comparison to expert staging.
Results
803 patients were included. EHR stage documentation rates were 80 %, 78 %, 16 %, and 16 % for T, N, M, and overall stage, respectively. Average annual concordance (SD) between expert review and Cancer Center Coders were 65.6 %(5.0), 67.0 %(5.4), 90.7 %(4.9), 65.8 %(11.9) for T, N, M and overall stage, respectively. Concordance (SD) between expert review and EHR stage were 65.6%(8.6), 58.5 %(7.8), 9.3 %(3.8) and 13.6 %(7.5) for T, N, M and overall stage, respectively. In a sub-cohort of patients with only chart-documented staging, concordance (SD) rates were 80.9 %(5.4), 74.1 %(5.6), 58.0 %(16.3) and 78.2 %(15.0) for T, N, M and overall cancer stages.
Conclusion
EHR stage documentation rates were good for T and N stages, however poor for M and overall cancer stages. Staging accuracy was moderate-to-good when comparing staging from expert reviews to staging by Cancer Center Coders and clinicians. Quality improvement interventions may improve accuracy and frequency of HNC staging, thus improving patient outcomes.
目的：(1)对口咽癌患者进行电子健康记录（EHR）审查，(2)确定EHR分期记录率，(3)比较EHR和癌症中心编码员的分期准确性。方法回顾性分析2010年1月1日至2020年8月1日在某三级医疗中心就诊的口咽癌患者。两位专家审查了电子病历，以确定肿瘤(T)、淋巴结(N)、转移(M)和总体癌症分期。对EHR分期文件进行了抽象，并报告了与专家分期相比的准确性。癌症中心编码员独立捕获癌症分期，与专家分期相比，准确性被报道。结果共纳入803例患者。EHR分期记录率分别为T、N、M和总分期的80%、78%、16%和16%。专家评审与Cancer Center Coders的年平均一致性（SD）分别为65.6%（5.0）、67.0%（5.4）、90.7%（4.9）、65.8%（11.9）。专家评价与EHR分期的一致性（SD）分别为65.6%（8.6）、58.5%（7.8）、9.3%（3.8）和13.6%（7.5）。在仅记录分期的患者亚队列中，T、N、M和总体癌症分期的一致性（SD）率分别为80.9%（5.4%）、74.1%（5.6%）、58.0%（16.3%）和78.2%（15.0%）。结论ehr分期记录率在T期和N期较好，而在M期和总癌期较差。当比较专家评价和癌症中心编码员和临床医生的分期时，分期准确性为中等至良好。质量改善干预可以提高HNC分期的准确性和频率，从而改善患者的预后。
{"title":"Cancer stage documentation and accuracy: Single-center retrospective study on oropharyngeal cancers","authors":"Elif Baran , Melissa Lee , Pabiththa Kamalraj , Irene Karam , Ian Poon , Andrew Bayley , Kevin M. Higgins , Danny J. Enepekides , Kelvin K.W. Chan , Ambika Parmar , Martin Smoragiewicz , Antoine Eskander","doi":"10.1016/j.oraloncology.2025.107795","DOIUrl":"10.1016/j.oraloncology.2025.107795","url":null,"abstract":"<div><h3>Objective</h3><div>The objectives were to (1) conduct an electronic health records (EHRs) review of oropharyngeal cancer patients, (2) determine EHR stage documentation rates, and (3) compare staging accuracy within EHRs and by Cancer Center Coders.</div></div><div><h3>Methods</h3><div>Retrospective analysis of oropharyngeal cancer patients seen between January 1, 2010, and August 1, 2020, at a tertiary care center. Two experts reviewed EHRs to determine tumour (T), nodal (N), metastatic (M) and overall cancer stages. EHR staging documentation was abstracted and accuracy was reported in comparison to expert staging. Cancer Center Coders independently captured cancer staging, and accuracy was reported in comparison to expert staging.</div></div><div><h3>Results</h3><div>803 patients were included. EHR stage documentation rates were 80 %, 78 %, 16 %, and 16 % for T, N, M, and overall stage, respectively. Average annual concordance (SD) between expert review and Cancer Center Coders were 65.6 %(5.0), 67.0 %(5.4), 90.7 %(4.9), 65.8 %(11.9) for T, N, M and overall stage, respectively. Concordance (SD) between expert review and EHR stage were 65.6%(8.6), 58.5 %(7.8), 9.3 %(3.8) and 13.6 %(7.5) for T, N, M and overall stage, respectively. In a sub-cohort of patients with only chart-documented staging, concordance (SD) rates were 80.9 %(5.4), 74.1 %(5.6), 58.0 %(16.3) and 78.2 %(15.0) for T, N, M and overall cancer stages.</div></div><div><h3>Conclusion</h3><div>EHR stage documentation rates were good for T and N stages, however poor for M and overall cancer stages. Staging accuracy was moderate-to-good when comparing staging from expert reviews to staging by Cancer Center Coders and clinicians. Quality improvement interventions may improve accuracy and frequency of HNC staging, thus improving patient outcomes.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"171 ","pages":"Article 107795"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614997","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 : 2025-12-01DOI: 10.1016/j.oraloncology.2025.107741
Gnanaprakash Jeyaraj
{"title":"Commentary on “Uncovering chromatin factor landscapes in head and neck squamous cell carcinoma”","authors":"Gnanaprakash Jeyaraj","doi":"10.1016/j.oraloncology.2025.107741","DOIUrl":"10.1016/j.oraloncology.2025.107741","url":null,"abstract":"","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"171 ","pages":"Article 107741"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275453","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 : 2025-11-29DOI: 10.1016/j.oraloncology.2025.107799
Mei Zhao , Zhiyi Liu , Mutsuki Kawabe , Abdullah A Osman , Mitchell J. Frederick , Jeffrey N Myers
Head and neck squamous cell carcinoma (HNSCC) is characterized by frequent TP53 mutations, which include gain-of-function (GOF) variants that drive tumor progression and chemoresistance. While genomic evidence across multiple specimens ranging from oral pre-malignant lesions (OPL) through invasive and metastatic HNSCC indicates that TP53 loss or mutation occurs relatively early in HNSCC carcinogenesis, it has been difficult to discern how mutation of this tumor suppressor drives further tumor cell evolution and influences the tumor microenvironment to drive tumor progression. To address this question, we generated an immortalized human oral keratinocyte (iHOK) cell line expressing wt TP53 as well as TP53 mutant forms to determine how mutations impact functional and genomic characteristics of HOKs that can in turn drive their evolution to neoplastic cells.
We established a novel panel of iHOK cell lines harboring distinct TP53 mutations, including the high-risk C238F variant. Key results revealed significant phenotypic and molecular divergence: high-risk lines exhibited enhanced invasiveness and chemoresistance compared to low-risk counterparts. Weighted gene co-expression network analysis (WGCNA) linked high-risk mutations to pro-metastatic pathways and stress-response signatures, with the C238F line uniquely enriched for p53-related GOF mechanisms. Conversely, low-risk lines remained chemosensitive.
These findings underscore the clinical relevance of mutation-specific iHOK models in determining the transcriptomic events that drive invasiveness and drug resistance and identify ways to intercept these phenotypes. By mirroring the TP53 diversity observed in patient tumors, this cell line panel bridges a critical gap in head and neck carcinogenesis research, enabling mechanistic dissection of GOF phenotypes and preclinical evaluation of therapies in an array of TP53 mutant cell models. Its significance lies in providing a validated, annotated resource that accelerates drug discovery and clarifies the role of TP53 mutational subtypes in HNSCC development and progression, offering a framework for future translational studies in genetically complex malignancies.
{"title":"Establishment and characterization of a new immortalized human oral keratinocyte (HOK) cell line harboring various TP53 mutations","authors":"Mei Zhao , Zhiyi Liu , Mutsuki Kawabe , Abdullah A Osman , Mitchell J. Frederick , Jeffrey N Myers","doi":"10.1016/j.oraloncology.2025.107799","DOIUrl":"10.1016/j.oraloncology.2025.107799","url":null,"abstract":"<div><div>Head and neck squamous cell carcinoma (HNSCC) is characterized by frequent<!--> <em>TP53</em> <!-->mutations, which include gain-of-function (GOF) variants that drive tumor progression and chemoresistance. While genomic evidence across multiple specimens ranging from oral pre-malignant lesions (OPL) through invasive and metastatic HNSCC indicates that <em>TP53</em> loss or mutation occurs relatively early in HNSCC carcinogenesis, it has been difficult to discern how mutation of this tumor suppressor drives further tumor cell evolution and influences the tumor microenvironment to drive tumor progression. To address this question, we generated an immortalized human oral keratinocyte (iHOK) cell line expressing wt <em>TP53</em> as well as <em>TP53</em> mutant forms to determine how mutations impact functional and genomic characteristics of HOKs that can in turn drive their evolution to neoplastic cells.</div><div>We established a novel panel of iHOK cell lines harboring distinct<!--> <em>TP53</em> <!-->mutations, including the high-risk C238F variant. Key results revealed significant phenotypic and molecular divergence: high-risk lines exhibited enhanced invasiveness and chemoresistance compared to low-risk counterparts. Weighted gene co-expression network analysis (WGCNA) linked high-risk mutations to pro-metastatic pathways and stress-response signatures, with the C238F line uniquely enriched for p53-related GOF mechanisms. Conversely, low-risk lines remained chemosensitive.</div><div>These findings underscore the clinical relevance of mutation-specific iHOK models in determining the transcriptomic events that drive invasiveness and drug resistance and identify ways to intercept these phenotypes. By mirroring the<!--> <em>TP53</em> <!-->diversity observed in patient tumors, this cell line panel bridges a critical gap in head and neck carcinogenesis research, enabling mechanistic dissection of GOF phenotypes and preclinical evaluation of therapies in an array of <em>TP53</em> <!-->mutant cell models. Its significance lies in providing a validated, annotated resource that accelerates drug discovery and clarifies the role of<!--> <em>TP53</em> <!-->mutational subtypes in HNSCC development and progression, offering a framework for future translational studies in genetically complex malignancies.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"172 ","pages":"Article 107799"},"PeriodicalIF":3.9,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617263","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 : 2025-11-27DOI: 10.1016/j.oraloncology.2025.107789
Ying Li , Qianzi Kou , Chongyang Zheng , Pengkhun Nov, Changqian Wang, Peizan Ni, Lilin Li, Yangfeng Zhang, Duanyu Wang, Arzoo Prasai, Wen Fu, Jiqiang Li , Kunpeng Du
Purpose
Human papillomavirus (HPV) status is a key prognostic factor in head and neck squamous cell carcinoma (HNSCC), yet the precise immunological mechanisms and robust biomarkers for guiding personalized therapy remain elusive. This study aims to comprehensively delineate how HPV infection reprograms the tumor immune microenvironment (TIME) and to develop a novel prognostic model for stratifying patient outcomes and therapeutic responses.
Methods
Multi-omics data from TCGA and GEO databases were integrated. The immune landscape was compared between HPV+ and HPV- HNSCC using bulk transcriptomic deconvolution and single-cell RNA sequencing (scRNA-seq) profiling. A prognostic risk signature was constructed from HPV-associated genes via LASSO-COX regression and validated in independent cohorts. The model was evaluated for its association with immune infiltration, tumor mutational burden, and drug sensitivity. Cellular communication networks were deciphered using CellChat. Hub genes expression was confirmed by immunohistochemistry (IHC).
Results
Single-cell profiling revealed that HPV+ tumors were characterized by an immunologically active microenvironment with increased infiltration and enhanced crosstalk of cytotoxic CD8+ T cells, helper CD4+ T cells, and B cells. In contrast, HPV- tumors exhibited a stromal-rich, immunosuppressive niche. We developed and validated a prognostic model based on seven HPV-related genes (IER3, FHL2, MBOAT2, DSC3, IRAK3, RGMA, BARD1). This risk score robustly stratified patients into high- and low-risk groups with distinct overall survival (low-risk vs. high-risk, P < 0.0001) and was an independent prognostic factor. The low-risk group, mirroring the HPV+ phenotype, demonstrated an activated immune milieu, higher expression of immune checkpoints (e.g., PD-1, CTLA-4), and was predicted to be more responsive to both chemotherapy and immunotherapy. Conversely, the high-risk group displayed a barren immune landscape, enriched in stromal and pro-tumorigenic pathways (e.g., MIF, COLLAGEN), and heightened sensitivity to specific targeted agents (e.g., Dasatinib). IHC validation confirmed the tumor-promotive role of hub genes (IER3, FHL2).
Conclusion
Our study leverages single-cell profiling to elucidate HPV-driven immunological remodeling in HNSCC. The derived prognostic signature effectively captures the essence of the TIME, serving as a reliable biomarker for predicting patient survival and informing precision therapy, potentially bridging the gap between HPV status and clinical decision-making.
{"title":"Hpv-driven rewiring of the tumor immune microenvironment through single-cell profiling informs prognosis and therapy in HNSCC","authors":"Ying Li , Qianzi Kou , Chongyang Zheng , Pengkhun Nov, Changqian Wang, Peizan Ni, Lilin Li, Yangfeng Zhang, Duanyu Wang, Arzoo Prasai, Wen Fu, Jiqiang Li , Kunpeng Du","doi":"10.1016/j.oraloncology.2025.107789","DOIUrl":"10.1016/j.oraloncology.2025.107789","url":null,"abstract":"<div><h3>Purpose</h3><div>Human papillomavirus (HPV) status is a key prognostic factor in head and neck squamous cell carcinoma (HNSCC), yet the precise immunological mechanisms and robust biomarkers for guiding personalized therapy remain elusive. This study aims to comprehensively delineate how HPV infection reprograms the tumor immune microenvironment (TIME) and to develop a novel prognostic model for stratifying patient outcomes and therapeutic responses.</div></div><div><h3>Methods</h3><div>Multi-omics data from TCGA and GEO databases were integrated. The immune landscape was compared between HPV<sup>+</sup> and HPV<sup>-</sup> HNSCC using bulk transcriptomic deconvolution and single-cell RNA sequencing (scRNA-seq) profiling. A prognostic risk signature was constructed from HPV-associated genes via LASSO-COX regression and validated in independent cohorts. The model was evaluated for its association with immune infiltration, tumor mutational burden, and drug sensitivity. Cellular communication networks were deciphered using CellChat. Hub genes expression was confirmed by immunohistochemistry (IHC).</div></div><div><h3>Results</h3><div>Single-cell profiling revealed that HPV<sup>+</sup> tumors were characterized by an immunologically active microenvironment with increased infiltration and enhanced crosstalk of cytotoxic CD8<sup>+</sup> T cells, helper CD4<sup>+</sup> T cells, and B cells. In contrast, HPV<sup>-</sup> tumors exhibited a stromal-rich, immunosuppressive niche. We developed and validated a prognostic model based on seven HPV-related genes (IER3, FHL2, MBOAT2, DSC3, IRAK3, RGMA, BARD1). This risk score robustly stratified patients into high- and low-risk groups with distinct overall survival (low-risk vs. high-risk, P < 0.0001) and was an independent prognostic factor. The low-risk group, mirroring the HPV<sup>+</sup> phenotype, demonstrated an activated immune milieu, higher expression of immune checkpoints (e.g., PD-1, CTLA-4), and was predicted to be more responsive to both chemotherapy and immunotherapy. Conversely, the high-risk group displayed a barren immune landscape, enriched in stromal and pro-tumorigenic pathways (e.g., MIF, COLLAGEN), and heightened sensitivity to specific targeted agents (e.g., Dasatinib). IHC validation confirmed the tumor-promotive role of hub genes (IER3, FHL2).</div></div><div><h3>Conclusion</h3><div>Our study leverages single-cell profiling to elucidate HPV-driven immunological remodeling in HNSCC. The derived prognostic signature effectively captures the essence of the TIME, serving as a reliable biomarker for predicting patient survival and informing precision therapy, potentially bridging the gap between HPV status and clinical decision-making.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"172 ","pages":"Article 107789"},"PeriodicalIF":3.9,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145600471","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 : 2025-11-22DOI: 10.1016/j.oraloncology.2025.107791
Kevin J. Harrington , Ari J. Rosenberg , Muh-Hwa Yang , Jessica L. Geiger , Marc Oliva , Myung-Ju Ahn , Sun Min Lim , William Ince , Aarti Bhatia , Siddharth Sheth , Bhumsuk Keam , Robert Metcalf , Joshua C. Curtin , Kiichiro Toyoizumi , Mark Wade , Emrullah Yilmaz , Priya Kim , Remy B. Verheijen , Sujay Shah , Mahadi Baig , Paul L. Swiecicki
Overexpression of EGFR and MET occurs in a high proportion of recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Amivantamab, an EGFR-MET bispecific antibody with immune-cell directing activity, is approved in EGFR-mutated advanced non-small cell lung cancer and is being evaluated in phase 3 trials for other solid tumors. Cohort 1 of OrigAMI-4 (NCT06385080) enrolled adult participants with human papillomavirus–unrelated R/M HNSCC with disease progression on/after prior checkpoint inhibitor and platinum-based chemotherapy. Subcutaneous amivantamab was administered at 1600 mg (2240 mg for ≥ 80 kg body weight) on Cycle 1 Day 1 and 2400 mg (3360 mg for ≥ 80 kg body weight) thereafter. Primary end point was investigator-assessed objective response rate (ORR). As of July 1, 2025 (median follow-up, 3.5 months [range, 0–13.4]), 86 participants (median age, 63.5 years; 45 % Asian; 43 % White) received ≥ 1 dose of subcutaneous amivantamab. Subcutaneous amivantamab was well tolerated. Administration-related reactions were reported in 7 % (n = 6/86) of participants; no new safety signals were observed. In the efficacy population (n = 38; median follow-up, 8.3 months [range, 1.1–13.4]), confirmed ORR was 45 % (95 % CI, 29 %–62 %), median time to first response was 6.4 weeks (range, 5.7–18.3), and median duration of response was 7.2 months (95 % CI, 5.3–NE). The clinical benefit rate (responder or durable stable disease) was 76 % (95 % CI, 60 %–89 %). Median progression-free survival was 6.8 months (95 % CI, 4.2–9.0). Subcutaneous amivantamab as second-/third-line treatment among participants with R/M HNSCC demonstrated rapid and durable antitumor activity. The safety profile of subcutaneous amivantamab was consistent with previous studies.
{"title":"Subcutaneous amivantamab in recurrent/metastatic head and neck squamous cell cancer after disease progression on checkpoint inhibitor and chemotherapy: Preliminary results from the phase 1b/2 OrigAMI-4 study","authors":"Kevin J. Harrington , Ari J. Rosenberg , Muh-Hwa Yang , Jessica L. Geiger , Marc Oliva , Myung-Ju Ahn , Sun Min Lim , William Ince , Aarti Bhatia , Siddharth Sheth , Bhumsuk Keam , Robert Metcalf , Joshua C. Curtin , Kiichiro Toyoizumi , Mark Wade , Emrullah Yilmaz , Priya Kim , Remy B. Verheijen , Sujay Shah , Mahadi Baig , Paul L. Swiecicki","doi":"10.1016/j.oraloncology.2025.107791","DOIUrl":"10.1016/j.oraloncology.2025.107791","url":null,"abstract":"<div><div>Overexpression of EGFR and MET occurs in a high proportion of recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Amivantamab, an EGFR-MET bispecific antibody with immune-cell directing activity, is approved in <em>EGFR</em>-mutated advanced non-small cell lung cancer and is being evaluated in phase 3 trials for other solid tumors. Cohort 1 of OrigAMI-4 (NCT06385080) enrolled adult participants with human papillomavirus–unrelated R/M HNSCC with disease progression on/after prior checkpoint inhibitor and platinum-based chemotherapy. Subcutaneous amivantamab was administered at 1600 mg (2240 mg for ≥ 80 kg body weight) on Cycle 1 Day 1 and 2400 mg (3360 mg for ≥ 80 kg body weight) thereafter. Primary end point was investigator-assessed objective response rate (ORR). As of July 1, 2025 (median follow-up, 3.5 months [range, 0–13.4]), 86 participants (median age, 63.5 years; 45 % Asian; 43 % White) received ≥ 1 dose of subcutaneous amivantamab. Subcutaneous amivantamab was well tolerated. Administration-related reactions were reported in 7 % (n = 6/86) of participants; no new safety signals were observed. In the efficacy population (n = 38; median follow-up, 8.3 months [range, 1.1–13.4]), confirmed ORR was 45 % (95 % CI, 29 %–62 %), median time to first response was 6.4 weeks (range, 5.7–18.3), and median duration of response was 7.2 months (95 % CI, 5.3–NE). The clinical benefit rate (responder or durable stable disease) was 76 % (95 % CI, 60 %–89 %). Median progression-free survival was 6.8 months (95 % CI, 4.2–9.0). Subcutaneous amivantamab as second-/third-line treatment among participants with R/M HNSCC demonstrated rapid and durable antitumor activity. The safety profile of subcutaneous amivantamab was consistent with previous studies.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"171 ","pages":"Article 107791"},"PeriodicalIF":3.9,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569493","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 : 2025-11-22DOI: 10.1016/j.oraloncology.2025.107794
Revadhi C Chelvarajah , Shao Hui Huang , Jie Su , Maru Gete , Jolie Ringash , Ian Witterick , John de Almeida , Eric Monteiro , Ralph Gilbert , Anna Spreafico , John Waldron , Brian O’Sullivan , Ali Hosni , Scott Bratman , B.C.John Cho , Andrew Hope , John Kim , Andrew McPartlin , C.Jillian Tsai , Li Tong , Ezra Hahn
Purpose
We report our experience with resectable sinonasal squamous cell carcinoma (SNSCC) treated with pre-operative (preop-RT) or postoperative radiotherapy (postop-RT), focusing on oncologic outcomes and patient selection.
Material
All SNSCC treated with preop-RT or postop-RT from 2005 to 2021 were included. Clinical characteristics and outcomes were compared between cohorts. Actuarial rates of overall survival (OS), locoregional control (LRC), distant control (DC), and late toxicity were estimated.
Results
Among 71 eligible patients, 25 received preop-RT and 46 postop-RT. Preop-RT cohort comprised more ethmoid primary (32 % vs 0 %, p < 0.001) and T3-T4 diseases (versus T1-2) (96 % vs 65 %, p < 0.04), with larger tumors (mean 62 vs 49 cm3, p = 0.02). Reasons for preop-RT included reduced dose and volume of critical organs (n = 16, 64 %), avoidance of orbital exenteration (n = 2, 8 %), maximizing likelihood of achieving clear resection margins (n = 5, 20 %) and other (n = 2, 8 %). Eight (32 %) preop-RT patients had a pathological complete response. Positive resection margin was identified less frequently in the preop-RT (n = 2) vs postop-RT (n = 23) cohorts (8 % vs 50 %, p < 0.001). Five (20 %) patients in the preop-RT cohort had local recurrence (1 residual, 4 recurrence) vs 16 (35 %) in the postop-RT cohort. Five-year actuarial rates of LRC (78 % vs 64 %, p = 0.107), DC (92 % vs 81 %, p = 0.524), OS (76 % vs 65 %, p = 0.912), and grade 3–4 late toxicity (18 % vs 12 %, p = 0.394) were similar between preop-RT and postop-RT cohorts, respectively.
Conclusion
Preop-RT achieved similar oncologic outcomes to postop-RT despite higher T-categories, and is a reasonable option for select patients with locally advanced SNSCC in a collaborative multidisciplinary, high-volume setting.
目的报告可切除鼻窦鳞状细胞癌（SNSCC）术前（preop-RT）或术后放疗（post - rt）治疗的经验，重点讨论肿瘤预后和患者选择。材料纳入2005 - 2021年所有接受术前或术后放疗的SNSCC。比较两组患者的临床特征和结局。估计总生存（OS）、局部区域控制（LRC）、远处控制（DC）和晚期毒性的精算率。结果71例符合条件的患者中，25例接受术前放疗，46例接受术后放疗。术前放疗队列包括更多的筛原发疾病（32% vs 0%, p < 0.001）和T3-T4疾病（T1-2） （96% vs 65%, p < 0.04），肿瘤较大（平均62 vs 49 cm3， p = 0.02）。术前放疗的原因包括减少了关键器官的剂量和体积（n = 16, 64%），避免了眼眶切除（n = 2.8 %），最大限度地实现了切除边缘的可能性（n = 5, 20%）和其他（n = 2.8 %）。8例（32%）放疗前患者病理完全缓解。在术前rt组（n = 2）和术后rt组（n = 23）中，阳性切除边缘的识别频率较低（8%对50%，p < 0.001）。放疗前队列中有5例（20%）患者局部复发（1例残留，4例复发），而放疗后队列中有16例（35%）。LRC （78% vs 64%, p = 0.107）、DC （92% vs 81%, p = 0.524）、OS （76% vs 65%, p = 0.912）和3-4级晚期毒性（18% vs 12%, p = 0.394）的5年精算率分别在放疗前和放疗后队列中相似。尽管t分类更高，但preop - rt与stop- rt的肿瘤预后相似，对于局部晚期SNSCC患者来说，在多学科合作、高容量的环境下，preop - rt是一种合理的选择。
{"title":"Outcomes and characteristics of patients receiving pre-operative versus post-operative radiotherapy for sinonasal squamous cell carcinoma","authors":"Revadhi C Chelvarajah , Shao Hui Huang , Jie Su , Maru Gete , Jolie Ringash , Ian Witterick , John de Almeida , Eric Monteiro , Ralph Gilbert , Anna Spreafico , John Waldron , Brian O’Sullivan , Ali Hosni , Scott Bratman , B.C.John Cho , Andrew Hope , John Kim , Andrew McPartlin , C.Jillian Tsai , Li Tong , Ezra Hahn","doi":"10.1016/j.oraloncology.2025.107794","DOIUrl":"10.1016/j.oraloncology.2025.107794","url":null,"abstract":"<div><h3>Purpose</h3><div>We report our experience with resectable sinonasal squamous cell carcinoma (SNSCC) treated with pre-operative (preop-RT) or postoperative radiotherapy (postop-RT), focusing on oncologic outcomes and patient selection.</div></div><div><h3>Material</h3><div>All SNSCC treated with preop-RT or postop-RT from 2005 to 2021 were included. Clinical characteristics and outcomes were compared between cohorts. Actuarial rates of overall survival (OS), locoregional control (LRC), distant control (DC), and late toxicity were estimated.</div></div><div><h3>Results</h3><div>Among 71 eligible patients, 25 received preop-RT and 46 postop-RT. Preop-RT cohort comprised more ethmoid primary (32 % vs 0 %, p < 0.001) and T3-T4 diseases (versus T1-2) (96 % vs 65 %, p < 0.04), with larger tumors (mean 62 vs 49 cm<sup>3</sup>, p = 0.02). Reasons for preop-RT included reduced dose and volume of critical organs (n = 16, 64 %), avoidance of orbital exenteration (n = 2, 8 %), maximizing likelihood of achieving clear resection margins (n = 5, 20 %) and other (n = 2, 8 %). Eight (32 %) preop-RT patients had a pathological complete response. Positive resection margin was identified less frequently in the preop-RT (n = 2) vs postop-RT (n = 23) cohorts (8 % vs 50 %, p < 0.001). Five (20 %) patients in the preop-RT cohort had local recurrence (1 residual, 4 recurrence) vs 16 (35 %) in the postop-RT cohort. Five-year actuarial rates of LRC (78 % vs 64 %, p = 0.107), DC (92 % vs 81 %, p = 0.524), OS (76 % vs 65 %, p = 0.912), and grade 3–4 late toxicity (18 % vs 12 %, p = 0.394) were similar between preop-RT and postop-RT cohorts, respectively.</div></div><div><h3>Conclusion</h3><div>Preop-RT achieved similar oncologic outcomes to postop-RT despite higher T-categories, and is a reasonable option for select patients with locally advanced SNSCC in a collaborative multidisciplinary, high-volume setting.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"171 ","pages":"Article 107794"},"PeriodicalIF":3.9,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569571","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}
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