Researchers clinically validated a sensitive blood test as a whole-genome sequencing assay for detecting circulating tumor human papillomavirus (HPV) DNA in patients with HPV-associated head and neck cancer after surgery to search for residual disease as a sign of potential recurrence, according to findings published in Science Translational Medicine.
The study authors suggested that the assay, called HPV-DeepSeek, could be used as a tool to guide personalized adjuvant therapy in patients with HPV-associated head and neck cancer.
“After surgery for HPV-associated head and neck cancer, we currently rely on very general clinical risk factors to determine which patients need more treatment and which patients do not,” said senior author Daniel Faden, MD, Director of the Head and Neck Cancer Genomics and Liquid Biopsy Program at Mass General Brigham Cancer Institute. “That means some patients receive more treatment than they actually need, resulting in more side effects... while others receive less treatment than they should—and later have their cancer come back.”
Background and Study Methods
Researchers conducted the Clear-HPVca study to assess the prognostic value of the HPV-DeepSeek assay and in comparison with existing assays.
The study prospectively enrolled 103 patients with stage I to IV HPV-positive head and neck cancer who were treated with surgery. The research team collected blood samples before and after surgery as well as during surveillance. Samples were analyzed with both the HPV-DeepSeek assay and droplet digital polymerase chain reaction (PCR) assays.
Key Findings
Patients were followed for a median of 27 months, at which point those with residual circulating tumor HPV DNA found in their postsurgery blood samples had a worse disease-free and overall survival rate compared to those with residual disease. Residual disease found after completion of all treatment was also associated with worse outcomes.
Minimal residual disease was found to be a stronger predictor of disease recurrence than standard clinicopathologic factors. Researchers found molecular recurrence up to 17.5 months earlier than clinical recurrence and recurrence was identified almost twice as early with HPV-DeepSeek as with droplet digital PCR.
The findings could be used to stratify patients for postoperative risk of recurrence and to identify patients who may benefit from adjuvant therapy.
“What excites me most about this approach is the possibility of moving beyond generalized risk estimates and toward truly personalized care,” Dr. Faden said. “If we can accurately identify residual disease at the molecular level, we may eventually be able to make treatment decisions based on the biology of an individual patient’s cancer rather than broad clinical categories.”
DISCLOSURES: Dr. Faden disclosed receiving in the past 36 months, research, salary or in-kind funding from Calico, Predicine, BostonGene, NeoGenomics, PacBio, and Haystack (Quest); consulting fees from Merck, Noetic, Chrysalis Biomedical Advisors, NeoGenomics, Arcadia, Focus, GT Molecular, and Olympus. For full disclosures of the other study authors, visit science.org.
