A groundbreaking study by researchers at the University of Chicago Medicine Comprehensive Cancer Center has demonstrated promising results for treating advanced HPV-negative head and neck squamous cell carcinoma (HNSCC) using a novel immunotherapy-based approach. Published on March 6, 2025, in JAMA Oncology, the study highlights a potential treatment strategy that combines immunotherapy, chemotherapy, and radiation to improve survival rates while minimizing long-term side effects.
Challenges in Treating Advanced HPV-Negative HNSCC
HPV-negative HNSCC is an aggressive type of head and neck cancer that primarily affects older adults with a history of heavy smoking and alcohol consumption. Patients diagnosed with early-stage cancer (Stages 1 or 2) can often be treated successfully with surgery or radiation. However, many cases are detected in advanced stages (Stages 3 or 4), making treatment more complex and increasing the risk of mortality.
Current standard treatments, including chemotherapy, radiation therapy, and surgery, offer limited survival benefits and can significantly impact essential functions like swallowing and speaking, reducing patients’ quality of life. There is a strong need for better treatment options that can enhance survival while reducing harmful side effects.
Exploring Immunotherapy as an Early Treatment Option
In recent years, immunotherapy has revolutionized cancer treatment, especially for patients with recurrent or metastatic head and neck cancers. However, its use in curative treatment (rather than disease control) has not been widely explored.
This new study investigated the effectiveness of neoadjuvant therapy, where treatment is given before surgery or radiation to shrink tumors and improve patient outcomes. Researchers enrolled 36 patients with advanced HPV-negative HNSCC and administered: Three cycles of chemotherapy combined with the immunotherapy drug nivolumab
Followed by chemo-radiation therapy
Patients who showed significant tumor shrinkage (more than 50%) were placed on a reduced-dose treatment plan with lower levels of radiation and chemotherapy to minimize side effects. Patients who did not respond as well continued with the standard full-dose chemo-radiation regimen.
Encouraging Survival and Response Rates
The study aimed to determine how many patients experienced at least a 50% reduction in tumor size after the neoadjuvant chemo-immunotherapy. Results showed that 53% of patients achieved this level of tumor shrinkage, exceeding expectations based on previous chemotherapy-only treatments.
“This outcome surpassed what we typically see with chemotherapy alone,” said the study’s lead author, an Assistant Professor of Medicine at UChicago Medicine.
Researchers also evaluated treatment-related side effects, quality of life, and survival outcomes. Patients who responded well to the chemo-immunotherapy and received the reduced-dose treatment experienced fewer side effects while still maintaining high survival rates.
Another key finding was the correlation between PD-L1 protein levels and treatment response. Patients with higher PD-L1 expression showed better tumor responses, suggesting that PD-L1 could serve as a biomarker to identify individuals who would benefit most from immunotherapy.
A New Era for HPV-Negative Head and Neck Cancer Treatment
Dr. Rosenberg, one of the study’s leading researchers, emphasized that this is the first trial to assess neoadjuvant chemo-immunotherapy followed by personalized, response-based treatment adjustments in non-surgical HPV-negative HNSCC patients.
“These promising findings pave the way for new treatment strategies that not only improve survival rates but also help preserve patients’ quality of life,” Dr. Rosenberg stated.
The study was funded by Bristol Myers Squibb, Celgene, and the University of Chicago Medicine Comprehensive Cancer Center, with contributions from researchers at Rush University and the UChicago Medicine Head and Neck Cancer Program.
With these encouraging results, this research represents a major breakthrough in redefining treatment for advanced HPV-negative head and neck cancer, offering new hope for patients battling this aggressive disease.
