Pub Date : 2026-01-20DOI: 10.1016/j.oraloncology.2026.107860
Xiao-Hu Wang , Lei-Ming Cao , Zhao-Qi Zhu , Yao Xiao , Han-Yue Luo , Guang-Rui Wang , Kan Zhou , Yi-Fu Yu , Jun Jia , Bing Liu , Lin-Lin Bu
Cervical lymph node metastasis (CLNM) is the most critical prognostic factor in oral squamous cell carcinoma (OSCC). To facilitate individualized risk assessment, this study aimed to develop and internally validate a novel prediction model. We retrospectively analyzed 3723 patients with OSCC from a single center (2012–2023), with 2792 eligible patients randomly allocated to a training (n = 1954) and a validation set (n = 838). A rigorous variable selection process was employed, where predictors significant in univariable analysis were entered into a multivariable logistic regression model that utilized a stepwise forward and backward elimination procedure to identify the final set of predictors. Six factors were ultimately incorporated into the nomogram: clinical T stage, clinical N stage, histological grade, perineural invasion, time from onset to treatment, and alcohol consumption. The model demonstrated good discrimination in both training (AUC = 0.780) and validation (AUC = 0.744), excellent calibration, and clinical utility. In conclusion, this internally validated nomogram accurately predicts CLNM risk and can aid in tailoring neck management, pending external validation.
{"title":"Cervical lymph node metastasis in oral squamous cell carcinoma: From metastatic patterns and risk factors to the development and validation of a predictive model","authors":"Xiao-Hu Wang , Lei-Ming Cao , Zhao-Qi Zhu , Yao Xiao , Han-Yue Luo , Guang-Rui Wang , Kan Zhou , Yi-Fu Yu , Jun Jia , Bing Liu , Lin-Lin Bu","doi":"10.1016/j.oraloncology.2026.107860","DOIUrl":"10.1016/j.oraloncology.2026.107860","url":null,"abstract":"<div><div>Cervical lymph node metastasis (CLNM) is the most critical prognostic factor in oral squamous cell carcinoma (OSCC). To facilitate individualized risk assessment, this study aimed to develop and internally validate a novel prediction model. We retrospectively analyzed 3723 patients with OSCC from a single center (2012–2023), with 2792 eligible patients randomly allocated to a training (n = 1954) and a validation set (n = 838). A rigorous variable selection process was employed, where predictors significant in univariable analysis were entered into a multivariable logistic regression model that utilized a stepwise forward and backward elimination procedure to identify the final set of predictors. Six factors were ultimately incorporated into the nomogram: clinical T stage, clinical N stage, histological grade, perineural invasion, time from onset to treatment, and alcohol consumption. The model demonstrated good discrimination in both training (AUC = 0.780) and validation (AUC = 0.744), excellent calibration, and clinical utility. In conclusion, this internally validated nomogram accurately predicts CLNM risk and can aid in tailoring neck management, pending external validation.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"174 ","pages":"Article 107860"},"PeriodicalIF":3.9,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019157","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 : 2026-01-19DOI: 10.1016/j.oraloncology.2026.107861
Sindhura Sridhar , Annie Moroco , Shravan Gowrishankar , Mitra Mehrad , Kim Ely , James S. Lewis , Madalina Tuluc , Stacey Gargano , Melanie Hicks , Kyle Mannion , Arielle G. Thal , Adam J. Luginbuhl , Joseph M. Curry , David M. Cognetti , Michael C. Topf
Introduction
Current guidelines for the management of metastatic squamous cell carcinoma of unknown primary (SCCUP) recommend submission of suspicious primary sites for frozen section analysis (FSA). This study aims to investigate the diagnostic accuracy of FSA for identification of HPV-associated SCCUP.
Methods
A retrospective cohort study of patients with biopsy-proven p16-positive SCCUP who underwent diagnostic operation at two tertiary care institutions was performed. Sensitivity, specificity, PPV, and NPV of diagnostic FSA were assessed.
Results
77 patients were included in analysis. 66 patients underwent definitive TORS (diagnostic TORS operation with subsequent neck dissection after identification of the occult primary tumor), 7 patients underwent diagnostic TORS (TORS to identify occult primary tumor, no neck dissection), and 4 patients underwent direct laryngoscopy and biopsy only. Primary tumors were identified in 63 patients (82%) with a mean tumor size of 1.1 cm. There was no significant difference in size between patients whose tumor was identified on FSA (mean 1.1 cm) and on permanent only (mean 0.9 cm) (p = 0.26). The sensitivity, specificity, PPV, and NPV of FSA for SCCUP was 86%, 100%, 100%, and 86%, respectively. Diagnostic frozen specimens included 52 direct laryngoscopy biopsies and 69 TORS excisions. In the biopsies, sensitivity was 100% and NPV was 100%, whereas in the TORS-excised specimens, sensitivity was 77% and NPV was 77%.
Conclusions
In this case series of 77 patients with SCCUP, the sensitivity and NPV of FSA for identification of the primary tumor was over 85%. FSA is valuable during diagnostic operation for SCCUP.
{"title":"Accuracy of frozen section for HPV-Associated squamous cell carcinoma of unknown primary","authors":"Sindhura Sridhar , Annie Moroco , Shravan Gowrishankar , Mitra Mehrad , Kim Ely , James S. Lewis , Madalina Tuluc , Stacey Gargano , Melanie Hicks , Kyle Mannion , Arielle G. Thal , Adam J. Luginbuhl , Joseph M. Curry , David M. Cognetti , Michael C. Topf","doi":"10.1016/j.oraloncology.2026.107861","DOIUrl":"10.1016/j.oraloncology.2026.107861","url":null,"abstract":"<div><h3>Introduction</h3><div>Current guidelines for the management of metastatic squamous cell carcinoma of unknown primary (SCCUP) recommend submission of suspicious primary sites for frozen section analysis (FSA). This study aims to investigate the diagnostic accuracy of FSA for identification of HPV-associated SCCUP.</div></div><div><h3>Methods</h3><div>A retrospective cohort study of patients with biopsy-proven p16-positive SCCUP who underwent diagnostic operation at two tertiary care institutions was performed. Sensitivity, specificity, PPV, and NPV of diagnostic FSA were assessed.</div></div><div><h3>Results</h3><div>77 patients were included in analysis. 66 patients underwent definitive TORS (diagnostic TORS operation with subsequent neck dissection after identification of the occult primary tumor), 7 patients underwent diagnostic TORS (TORS to identify occult primary tumor, no neck dissection), and 4 patients underwent direct laryngoscopy and biopsy only. Primary tumors were identified in 63 patients (82%) with a mean tumor size of 1.1 cm. There was no significant difference in size between patients whose tumor was identified on FSA (mean 1.1 cm) and on permanent only (mean 0.9 cm) (p = 0.26). The sensitivity, specificity, PPV, and NPV of FSA for SCCUP was 86%, 100%, 100%, and 86%, respectively. Diagnostic frozen specimens included 52 direct laryngoscopy biopsies and 69 TORS excisions. In the biopsies, sensitivity was 100% and NPV was 100%, whereas in the TORS-excised specimens, sensitivity was 77% and NPV was 77%.</div></div><div><h3>Conclusions</h3><div>In this case series of 77 patients with SCCUP, the sensitivity and NPV of FSA for identification of the primary tumor was over 85%. FSA is valuable during diagnostic operation for SCCUP.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"174 ","pages":"Article 107861"},"PeriodicalIF":3.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011604","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}
The management of the clinically negative neck (N0) in oral squamous cell carcinoma (OSCC) remains a challenging clinical dilemma. Although imaging techniques have advanced, occult metastases are present in approximately 20–30% of patients with early-stage oral cancer and clinically negative necks.
Objective
This review examines current evidence on optimal strategies for managing the N0 neck in oral cancer patients.
Methods
We discuss diagnostic modalities for detecting occult metastases, including clinical examination, conventional imaging (ultrasonography, computed tomography, magnetic resonance imaging), functional imaging (positron emission tomography), and sentinel lymph node biopsy. The review evaluates the main management approaches---elective neck dissection, watchful waiting, and sentinel lymph node biopsy---analyzing current evidence from randomized controlled trials and meta-analyses.
Results
We examine patient and tumor factors that influence decision-making, including tumor thickness, location, differentiation, and pattern of invasion. Special considerations for specific subsites and clinical scenarios are discussed.
Conclusions
Finally, we explore emerging technologies and future directions in the management of the N0 neck, including molecular biomarkers, liquid biopsy techniques, and personalized approaches to treatment. This review provides evidence-based recommendations to support clinical decision-making for managing patients with oral cancer and clinically negative necks.
{"title":"Contemporary management of the clinically N0 neck in oral squamous cell carcinoma","authors":"Makoto Adachi , Shinsuke Ohta , Ayaka Ishii , Masayuki Motohashi","doi":"10.1016/j.oraloncology.2025.107839","DOIUrl":"10.1016/j.oraloncology.2025.107839","url":null,"abstract":"<div><h3>Background</h3><div>The management of the clinically negative neck (N0) in oral squamous cell carcinoma (OSCC) remains a challenging clinical dilemma. Although imaging techniques have advanced, occult metastases are present in approximately 20–30% of patients with early-stage oral cancer and clinically negative necks.</div></div><div><h3>Objective</h3><div>This review examines current evidence on optimal strategies for managing the N0 neck in oral cancer patients.</div></div><div><h3>Methods</h3><div>We discuss diagnostic modalities for detecting occult metastases, including clinical examination, conventional imaging (ultrasonography, computed tomography, magnetic resonance imaging), functional imaging (positron emission tomography), and sentinel lymph node biopsy. The review evaluates the main management approaches---elective neck dissection, watchful waiting, and sentinel lymph node biopsy---analyzing current evidence from randomized controlled trials and <em>meta</em>-analyses.</div></div><div><h3>Results</h3><div>We examine patient and tumor factors that influence decision-making, including tumor thickness, location, differentiation, and pattern of invasion. Special considerations for specific subsites and clinical scenarios are discussed.</div></div><div><h3>Conclusions</h3><div>Finally, we explore emerging technologies and future directions in the management of the N0 neck, including molecular biomarkers, liquid biopsy techniques, and personalized approaches to treatment. This review provides evidence-based recommendations to support clinical decision-making for managing patients with oral cancer and clinically negative necks.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"174 ","pages":"Article 107839"},"PeriodicalIF":3.9,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003831","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 : 2026-01-16DOI: 10.1016/j.oraloncology.2026.107856
Suhani Ghai
{"title":"Mandibular canal invasion as a T4a criterion: a step forward with important caveats","authors":"Suhani Ghai","doi":"10.1016/j.oraloncology.2026.107856","DOIUrl":"10.1016/j.oraloncology.2026.107856","url":null,"abstract":"","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"174 ","pages":"Article 107856"},"PeriodicalIF":3.9,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145969259","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 : 2026-01-16DOI: 10.1016/j.oraloncology.2026.107855
Weiqun Wang, Yaling Lou
{"title":"Methodological and clinical considerations for a novel nomogram predicting central lymph node metastasis in papillary thyroid microcarcinoma","authors":"Weiqun Wang, Yaling Lou","doi":"10.1016/j.oraloncology.2026.107855","DOIUrl":"10.1016/j.oraloncology.2026.107855","url":null,"abstract":"","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"173 ","pages":"Article 107855"},"PeriodicalIF":3.9,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978464","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 : 2026-01-16DOI: 10.1016/j.oraloncology.2026.107857
Congcong Cheng, Juanjuan Zhang
{"title":"Advancing methodological rigor in exercise oncology trials for head and neck cancer","authors":"Congcong Cheng, Juanjuan Zhang","doi":"10.1016/j.oraloncology.2026.107857","DOIUrl":"10.1016/j.oraloncology.2026.107857","url":null,"abstract":"","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"173 ","pages":"Article 107857"},"PeriodicalIF":3.9,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978462","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 : 2026-01-15DOI: 10.1016/j.oraloncology.2026.107853
Francesca Carosi , Sara Demurtas , Antonio Ciarfella , Ester Orlandi , Laura D. Locati
{"title":"Perioperative immunotherapy for head and neck cancer: from early successes to clinical challenges in relapsed and/or metastatic disease","authors":"Francesca Carosi , Sara Demurtas , Antonio Ciarfella , Ester Orlandi , Laura D. Locati","doi":"10.1016/j.oraloncology.2026.107853","DOIUrl":"10.1016/j.oraloncology.2026.107853","url":null,"abstract":"","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"173 ","pages":"Article 107853"},"PeriodicalIF":3.9,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978463","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 : 2026-01-13DOI: 10.1016/j.oraloncology.2025.107847
Allen S. Ho , Michael Luu , Daniel Manzoor , Horacio Maluf , Cedric Bailey , Bonnie Balzer , Evan S. Walgama , Julie K. Jang , Kevin C. Scher , Justin T. Moyers , Jon Mallen-St. Clair , Joel B. Epstein , Zachary S. Zumsteg
Background
While numerous cancer staging systems have incorporated grade into stage, the impact of grade on oral cavity carcinoma (OCC) prognosis has been conflicting. We investigated grade as a prognostic determinant in OCC staging.
Methods
Multivariable Cox regression models of OCC patients identified via U.S. cancer registry data were constructed to determine associations between grade (G1 = low-grade, G2 = intermediate-grade, G3 = high-grade) and overall survival (OS). Recursive partitioning analysis (RPA) was used to derive staging schema.
Results
Overall, 46,789 OCC cases were identified across 1,222 institutions. On univariate analysis, higher grade was associated with worse 5-yr OS (G1: 73% [95% CI 72–74%], G2: 61% [95 CI 60–61%], G3: 49% [95% CI 48–51%] (p < 0.001). On multivariable analysis adjusting for other prognostic factors, these survival differences persisted. Compared to G1 tumors, both G2 (HR 1.25 [95% CI 1.19–1.30], p < 0.001) and G3 (HR 1.52 [95% CI 1.45–1.61], p < 0.001) tumors were associated with significantly worse OS. Similar results were seen when utilizing propensity score matching. RPA generated subgroups that mirrored AJCC8E, but with G3 cases performing worse for a given stage. A proposed TNM + G staging schema was created with AJCC8E G3 cases upstaged by one category. Overall, 11.5% (4,745/36,623) cases were upstaged. TNM + G performed better than AJCC8E by c-index (0.673 vs. 0.671) and Brier score (0.174 vs. 0.175).
Conclusion
Large-scale analysis supports grade as an influential predictive determinant in OCC outcomes, with hazard on par with conventional staging factors. Incorporation of grade into stage strengthens existing AJCC OCC schema and pragmatically improves its ability to convey prognosis.
虽然许多癌症分期系统都将分级纳入分期，但分级对口腔癌（OCC）预后的影响一直存在矛盾。我们研究了分级作为OCC分期的预后决定因素。方法构建通过美国癌症登记数据确定的OCC患者的多变量Cox回归模型，以确定分级（G1 =低分级，G2 =中分级，G3 =高分级）与总生存期（OS）之间的关系。采用递归分区分析（RPA）导出分级模式。结果在1222家机构共发现46789例OCC病例。在单因素分析中，较高的分级与较差的5年OS相关(G1: 73% [95% CI 72-74%], G2: 61% [95 CI 60-61%], G3: 49% [95% CI 48-51%] （p < 0.001）。在调整其他预后因素的多变量分析中，这些生存差异仍然存在。与G1肿瘤相比，G2肿瘤（HR 1.25 [95% CI 1.19-1.30], p < 0.001）和G3肿瘤（HR 1.52 [95% CI 1.45-1.61], p < 0.001）的OS均显著恶化。当使用倾向得分匹配时，可以看到类似的结果。RPA生成的子组反映了AJCC8E，但G3病例在给定阶段的表现更差。提出了一个TNM + G分期模式，其中AJCC8E G3病例被一个类别抢了上风。总体而言，11.5%（4745 / 36623）病例被抢镜。TNM + G的c指数（0.673比0.671）和Brier评分（0.174比0.175）优于AJCC8E。结论：大规模分析支持分级是OCC预后的重要预测因素，其危险性与传统分期因素相当。将分级纳入分期强化了现有的AJCC OCC图式，切实提高了其传达预后的能力。
{"title":"Incorporation of grade into stage in oral cavity squamous cell carcinoma: A novel staging schema","authors":"Allen S. Ho , Michael Luu , Daniel Manzoor , Horacio Maluf , Cedric Bailey , Bonnie Balzer , Evan S. Walgama , Julie K. Jang , Kevin C. Scher , Justin T. Moyers , Jon Mallen-St. Clair , Joel B. Epstein , Zachary S. Zumsteg","doi":"10.1016/j.oraloncology.2025.107847","DOIUrl":"10.1016/j.oraloncology.2025.107847","url":null,"abstract":"<div><h3>Background</h3><div>While numerous cancer staging systems have incorporated grade into stage, the impact of grade on oral cavity carcinoma (OCC) prognosis has been conflicting. We investigated grade as a prognostic determinant in OCC staging.</div></div><div><h3>Methods</h3><div>Multivariable Cox regression models of OCC patients identified via U.S. cancer registry data were constructed to determine associations between grade (G1 = low-grade, G2 = intermediate-grade, G3 = high-grade) and overall survival (OS). Recursive partitioning analysis (RPA) was used to derive staging schema.</div></div><div><h3>Results</h3><div>Overall, 46,789 OCC cases were identified across 1,222 institutions. On univariate analysis, higher grade was associated with worse 5-yr OS (G1: 73% [95% CI 72–74%], G2: 61% [95 CI 60–61%], G3: 49% [95% CI 48–51%] (p < 0.001). On multivariable analysis adjusting for other prognostic factors, these survival differences persisted. Compared to G1 tumors, both G2 (HR 1.25 [95% CI 1.19–1.30], p < 0.001) and G3 (HR 1.52 [95% CI 1.45–1.61], p < 0.001) tumors were associated with significantly worse OS. Similar results were seen when utilizing propensity score matching. RPA generated subgroups that mirrored AJCC8E, but with G3 cases performing worse for a given stage. A proposed TNM + G staging schema was created with AJCC8E G3 cases upstaged by one category. Overall, 11.5% (4,745/36,623) cases were upstaged. TNM + G performed better than AJCC8E by c-index (0.673 vs. 0.671) and Brier score (0.174 vs. 0.175).</div></div><div><h3>Conclusion</h3><div>Large-scale analysis supports grade as an influential predictive determinant in OCC outcomes, with hazard on par with conventional staging factors. Incorporation of grade into stage strengthens existing AJCC OCC schema and pragmatically improves its ability to convey prognosis.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"173 ","pages":"Article 107847"},"PeriodicalIF":3.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978460","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 : 2026-01-12DOI: 10.1016/j.oraloncology.2026.107849
Sebastian Søby , Danny Mortensen , Anita Gothelf , Niels Gyldenkerne , Christian Maare , Camilla K Lonkvist , Maria Andersen , Rasmus Kjeldsen , Kasper Toustrup , Trine Tramm , Jesper Grau Eriksen
PD-1 inhibition has become an established treatment option for recurrent/metastatic head and neck squamous cell carcinoma (rmHNSCC). However, there is a clear need for improved prognostic tools.
This study aimed to identify immune-related tissue biomarkers associated with overall survival (OS) or progression-free survival (PFS) in patients treated with PD-1 inhibition.
This national real-world phase IV multicenter retrospective cohort study included Danish patients treated between 2017 and 2023. Pre-treatment biopsies were collected for immunohistochemical analyses. All patients were PD-L1 positive with histologically confirmed rmHNSCC treated with pembrolizumab or nivolumab monotherapy.
Biomarker expression was assessed for CD4, CD8, FOXP3, CD20, CD66b, CD68, STING, cGAS, and tumor-infiltrating lymphocytes (TILs), using the median expression as the cut-off value.
Formalin-fixed, paraffin-embedded tumor tissue was obtained from 263 eligible patients. Concurrent above median levels of FOXP3 and CD68 were associated with a lower risk of progression (HRPFS: 0.47 [95 % CI: 0.33–0.67]). This interaction appeared to be driven by p16+ oropharyngeal cancers (OPC), where patients with concurrent above median levels of FOXP3 and CD68 showed a median 2-year PFS of 68 % [95 % CI: 42–86] in contrast to those with one or none of the two markers above the median level with a 2-year PFS of 3 % [95 % CI: 0–12] (p < 0.001).
In this real-world cohort, a subgroup with a promising prognosis was identified. This subgroup was characterized by p16+ OPC along with concurrent above median levels of FOXP3 and CD68. PD-L1 alone showed no significant association with outcomes.
{"title":"Prognostic significance of p16 and immune cell infiltration in recurrent/metastatic head and neck squamous cell carcinoma treated with PD-1 inhibition: a national DAHANCA cohort study","authors":"Sebastian Søby , Danny Mortensen , Anita Gothelf , Niels Gyldenkerne , Christian Maare , Camilla K Lonkvist , Maria Andersen , Rasmus Kjeldsen , Kasper Toustrup , Trine Tramm , Jesper Grau Eriksen","doi":"10.1016/j.oraloncology.2026.107849","DOIUrl":"10.1016/j.oraloncology.2026.107849","url":null,"abstract":"<div><div>PD-1 inhibition has become an established treatment option for recurrent/metastatic head and neck squamous cell carcinoma (rmHNSCC). However, there is a clear need for improved prognostic tools.</div><div>This study aimed to identify immune-related tissue biomarkers associated with overall survival (OS) or progression-free survival (PFS) in patients treated with PD-1 inhibition.</div><div>This national real-world phase IV multicenter retrospective cohort study included Danish patients treated between 2017 and 2023. Pre-treatment biopsies were collected for immunohistochemical analyses. All patients were PD-L1 positive with histologically confirmed rmHNSCC treated with pembrolizumab or nivolumab monotherapy.</div><div>Biomarker expression was assessed for CD4, CD8, FOXP3, CD20, CD66b, CD68, STING, cGAS, and tumor-infiltrating lymphocytes (TILs), using the median expression as the cut-off value.</div><div>Formalin-fixed, paraffin-embedded tumor tissue was obtained from 263 eligible patients. Concurrent above median levels of FOXP3 and CD68 were associated with a lower risk of progression (HR<sub>PFS</sub>: 0.47 [95 % CI: 0.33–0.67]). This interaction appeared to be driven by p16+ oropharyngeal cancers (OPC), where patients with concurrent above median levels of FOXP3 and CD68 showed a median 2-year PFS of 68 % [95 % CI: 42–86] in contrast to those with one or none of the two markers above the median level with a 2-year PFS of 3 % [95 % CI: 0–12] (p < 0.001).</div><div>In this real-world cohort, a subgroup with a promising prognosis was identified. This subgroup was characterized by p16+ OPC along with concurrent above median levels of FOXP3 and CD68. PD-L1 alone showed no significant association with outcomes.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"173 ","pages":"Article 107849"},"PeriodicalIF":3.9,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966683","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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