TY - JOUR
T1 - Prognostic gene expression signatures for HPV-negative head and neck squamous cell carcinoma
AU - Cavalieri, Stefano
AU - Brakenhoff, Ruud H
AU - Leemans, C René
AU - Hoebers, Frank J P
AU - Poli, Tito
AU - Scheckenbach, Kathrin
AU - Iacovelli, Nicola Alessandro
AU - Franceschini, Marzia
AU - Orlandi, Ester
AU - Licitra, Lisa
AU - De Cecco, Loris
PY - 2025/4/17
Y1 - 2025/4/17
N2 - BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer-related deaths worldwide, with HPV-negative cases being particularly aggressive. These cases often show poor prognosis and low responsiveness to radiotherapy. Improved prognostic tools and treatment strategies are needed to enhance outcomes. AIM: To evaluate the prognostic value of various gene expression signatures in predicting survival outcomes in HPV-negative HNSCC patients receiving radiotherapy and to compare their accuracy against the current TNM staging system. METHODS: This observational cohort study used data from the European BD2Decide project, systematically analyzing gene expression in loco-regionally advanced, non-metastatic HPV-negative HNSCC patients (stage III-IVa/b) treated with curative radiotherapy (post-operative or definitive) between 2008 and 2017. The primary outcome was overall survival (OS), with secondary outcomes including disease-free survival (DFS), distant metastasis-free survival (DMFS), and loco-regional recurrence-free survival (LRRFS). The prognostic performance of selected gene expression signatures was evaluated using receiver operating characteristic (ROC) curves and hazard ratios (HR) from Cox models. RESULTS: The study included 783 patients, with a median age of 63 years, mostly male (68 %), with significant tobacco (84 %) and alcohol (69 %) exposure. The 172-gene signature (172GS) showed the highest prognostic accuracy, outperforming the TNM system in predicting OS, DFS, DMFS, and LRRFS. Multivariable analysis confirmed its independent prognostic value. CONCLUSIONS: The 172GS gene signature offers superior prognostic information compared to TNM staging, supporting its potential use for better risk stratification and personalized treatment planning in HPV-negative HNSCC. Future trials should consider tumor biology and gene signatures for better patient selection. TRIAL REGISTRATION: NCT02832102.
AB - BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer-related deaths worldwide, with HPV-negative cases being particularly aggressive. These cases often show poor prognosis and low responsiveness to radiotherapy. Improved prognostic tools and treatment strategies are needed to enhance outcomes. AIM: To evaluate the prognostic value of various gene expression signatures in predicting survival outcomes in HPV-negative HNSCC patients receiving radiotherapy and to compare their accuracy against the current TNM staging system. METHODS: This observational cohort study used data from the European BD2Decide project, systematically analyzing gene expression in loco-regionally advanced, non-metastatic HPV-negative HNSCC patients (stage III-IVa/b) treated with curative radiotherapy (post-operative or definitive) between 2008 and 2017. The primary outcome was overall survival (OS), with secondary outcomes including disease-free survival (DFS), distant metastasis-free survival (DMFS), and loco-regional recurrence-free survival (LRRFS). The prognostic performance of selected gene expression signatures was evaluated using receiver operating characteristic (ROC) curves and hazard ratios (HR) from Cox models. RESULTS: The study included 783 patients, with a median age of 63 years, mostly male (68 %), with significant tobacco (84 %) and alcohol (69 %) exposure. The 172-gene signature (172GS) showed the highest prognostic accuracy, outperforming the TNM system in predicting OS, DFS, DMFS, and LRRFS. Multivariable analysis confirmed its independent prognostic value. CONCLUSIONS: The 172GS gene signature offers superior prognostic information compared to TNM staging, supporting its potential use for better risk stratification and personalized treatment planning in HPV-negative HNSCC. Future trials should consider tumor biology and gene signatures for better patient selection. TRIAL REGISTRATION: NCT02832102.
KW - HNSCC
KW - HPV-negative
KW - Prognostic factor
KW - Radiosensitivity
KW - Radiotherapy
KW - Transcriptomics
U2 - 10.1016/j.radonc.2025.110900
DO - 10.1016/j.radonc.2025.110900
M3 - Article
SN - 0167-8140
VL - 208
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
M1 - 110900
ER -