[18F]FDG PET/CT multiomics identifies Hedgehog-driven HPV-negative head and neck squamous cell carcinoma
Year: 2026
Type: article
Study design: Observational Study
Abstract: Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous malignancy with limited predictive markers to guide personalized treatment, particularly in human papillomavirus (HPV)-negative cases, which exhibit poor outcomes. Identifying reliable biomarkers for prognosis and therapeutic response remains a critical challenge. In a retrospective cohort of 51 patients with primary HPV-negative HNSCC, we investigated the prognostic significance of the Hedgehog (HH) signaling pathway and its association with imaging biomarkers. Genomic and transcriptomic analysis revealed that HH pathway activation correlated with distinct [18F]FDG PET/CT radiomic features, notably the PET-derived “histogram:ih.max”, a surrogate for peak [18F]FDG uptake that was associated with inferior survival outcomes. Functionally, pharmacologic inhibition of HH signaling demonstrated anticancer efficacy across multiple models, including HNSCC cell lines, patient-derived tumoroids, and in vivo xenograft models. Importantly, HH pathway inhibition induced reproducible changes in imaging characteristics in xenografts, including a measurable reduction in [1⁸F]FDG uptake, closely mirroring patterns observed in patient tumors. Together these findings demonstrate that integration of multi-level molecular profiling with functional imaging captures HH-driven tumor biology in HPV-negative HNSCC. Our study underscores the value of [18F]FDG PET/CT multiomics in linking tumor biology with imaging features, providing a framework for biologically-informed patient stratification and hypothesis-driven evaluation of treatment response. These results support further translational validation of HH pathway inhibition in HPV-negative HNSCC within appropriately designed preclinical and clinical studies.
Source: Molecular Cancer
Authors: Stefan Stoiber, Daniel Pölöske, Clemens P. Spielvogel, Elisabeth Gurnhofer, Michaela Schlederer, David Haberl, Cécile Philippe, Dominik P. Elmer, Richard Morrigl, Heidi A. Neubauer, Vojtěch Bystrý, Karolína Trachtová, Hanne Verswyvel, Hannah Zaryouh, Abraham Lin, Christophe Deben, Gregor Heiduschka, Maik Dahlhoff, Fritz Aberger, Daniel Schramek, Marcus Hacker, Alexander R. Haug, Lukas Kenner
Institutions: Medical University of Vienna, University of Veterinary Medicine Vienna, University of Salzburg, Central European Institute of Technology, Masaryk University, Central European Institute of Technology – Masaryk University, University of Antwerp, Mount Sinai Hospital, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Center For Biomarker Research In Medicine
Language: English
Topic: Head and Neck Cancer Studies
Subfield: Otorhinolaryngology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,090
OpenAlex ID: W7142499365