Data from Development of a Clinical Assay to Guide Patient Therapy in HPV-Associated Head and Neck Cancer
Year: 2026
Type: other
Abstract: Purpose: Patients with human papillomavirus–associated head and neck squamous cell carcinoma (HPV+ HNSCC) have relatively favorable outcomes, but standard treatments like radiation or chemoradiation frequently result in long-term toxic side effects. Appropriate patient selection has been a barrier to effectively de-escalate therapy for HPV+ HNSCC, and the absence of accurate biomarkers likely contributed to failure of recent promising de-escalation trials that rely on histologic tumor characteristics, history of tobacco use, or tumor response to chemotherapy; This deficiency underlines the need to develop and validate an assay to accurately detect two subtypes of HPV+ HNSCC—one with good prognosis and one with poor prognosis. Experimental Design: These two subtypes are distinguished by the activity of NF-κB in tumors. We first developed a DNA-based marker panel consisting of genes that when mutated would lead to NF-κB activation. Additionally, we developed a custom NanoString assay to determine the expression of NF-κB target genes. These assays were tested to determine their accuracy in detecting tumor subtype. Results: We demonstrate that the NF-κB gene signature score, as determined using the NanoString assay, could more accurately classify HPV+ HNSCC as compared with the DNA-based marker panel. Patients with a high NF-κB gene signature score demonstrated significantly increased overall survival, indicating more sensitivity to (chemo)radiation treatment. Conclusions: The NF-κB gene signature score can accurately predict response to standard (chemo)radiation in HPV+ HNSCC. This molecular biomarker holds promise for clinical use in identifying patients who are likely to benefit from treatment de-escalation strategies, potentially reducing long-term side effects without compromising therapeutic efficacy.
Authors: Sri Vemulamanda, Aditi Kothari, Loris De Cecco, Sulgi Kim, Aditi Kulkarni, Pragati Upadhyay, Stefano Cavalieri, Christophe Courtine, Yasine Mirmozaffari, Jane Brown, Andrew Sewell, Yael Flamand, Yue Xie, Lili Zheng, Shanthi Marur, Trevor Hackman, Bart Singer, John Ayman Hakim, Lori Ramkissoon, Yan Li, Hina Rehmani, Xue Li, Siddharth Sheth, Xuguang Chen, Jennifer Dorth, Quintin Pan, Evan Graboyes, Bhishamjit Chera, Barbara Burtness, Robert L. Ferris, Rene Leemans, Ruud H. Brakenhoff, Frank Hoebers, Kathrin Scheckenbach, Tito Poli, Lisa Licitra, Wendell G. Yarbrough, Natalia Issaeva, Travis P. Schrank
Language: English
Topic: Head and Neck Cancer Studies
Subfield: Otorhinolaryngology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W7166866558