Ultrasensitive blood test predicts head and neck cancer relapse months earlier
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A new study by investigators from Mass General Brigham Cancer Institute has found that an ultrasensitive blood test called HPV-DeepSeek could help identify which people with HPV-associated head and neck cancer still had cancer cells in their bodies after surgery and may benefit the most from additional treatments. The results are published in Science Translational Medicine.
"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 of treatment, while others receive less treatment than they should—and later have their cancer come back."
HPV-associated head and neck cancers are caused by human papillomavirus (HPV). The virus inserts its DNA into the person's cells, which helps drive them to grow into a tumor. As the tumor cells grow and die, they release small fragments of HPV DNA into the bloodstream. HPV-DeepSeek detects those tiny fragments of viral DNA in a person's blood.
Previous studies by the research team showed that HPV-DeepSeek could accurately detect HPV-associated head and neck cancers at diagnosis with much higher accuracy than existing approaches. They also found that it may have potential as a screening tool for identifying cancers years before symptoms develop.
How the study worked
The new study, called Clear-HPVca, studied whether the test could be used to tailor cancer care plans. They followed 103 people with newly diagnosed, untreated HPV-associated head and neck cancer, who were scheduled for surgery at Mass General Brigham Cancer Institute between August 2020 and March 2024. Researchers collected and analyzed 560 blood samples before surgery, after surgery and during surveillance, following the patients for more than two years. Of those patients, 73% had more treatments after surgery, including radiation or chemoradiation.
At diagnosis, HPV-DeepSeek found circulating tumor HPV DNA in 98.1% of patients. In the key testing window after surgery, 23% had detectable circulating tumor HPV DNA. Compared to an existing HPV blood test, HPV-DeepSeek was substantially more sensitive.
What the results showed
The study found that people who had positive HPV-DeepSeek results after surgery did significantly worse than those without detectable tumor HPV DNA. Only 60% of them were disease-free at two years, compared with 100% of patients with negative tests. Overall, only 73% of patients with detectable tumor HPV DNA were still alive at the end of the trial, compared with 98% of patients with negative HPV-DeepSeek tests after their surgery.
HPV DeepSeek could also detect cancer recurrence earlier than traditional methods and existing HPV DNA-based blood tests—about seven months before clinical detection, nearly double the lead time of existing HPV DNA blood tests, and extending up to 17.5 months.
"What excites me most about this approach is the possibility of moving beyond generalized risk estimates and toward truly personalized care," said Faden. "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."
Limits and next steps
One limitation of the study is that it was observational—investigators only collected the data; they didn't use it to make treatment decisions. The study was also done within a single health care system, with a small number of patients whose cancer came back or who died.
The team is now planning larger, multi-site clinical trials to choose treatment after surgery for patients with HPV-associated head and neck cancer.
Publication details
Shun Hirayama et al, Clinical validation of an HPV whole genome sequencing assay for MRD detection in patients with HPV+ head and neck cancer treated with surgery, Science Translational Medicine (2026). DOI: 10.1126/scitranslmed.aec1724
Journal information: Science Translational Medicine
Key medical concepts
Circulating Tumor DNAHuman papillomavirus
Clinical categories
OncologyLaboratory medicine Provided by Mass General Brigham Who's behind this story?
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