A new study by researchers at Massachusetts General Brigham Cancer Institute has found that an ultra-sensitive blood test called HPV-DeepSeek can help identify which patients with HPV-related head and neck cancer still have cancer cells in their bodies after surgery and may benefit most from additional treatment. their results are scientific translational medicine.
“After surgery for HPV-associated head and neck cancer, we currently rely on very common clinical risk factors to determine which patients require further treatment and which do not,” said lead author Daniel Faden, MD, director of the Head and Neck Cancer Genomics and Liquid Biopsy Program at Massachusetts General Brigham Cancer Institute. “This means that some patients receive more treatment than they actually need, resulting in greater treatment side effects, while others receive less treatment than they need, and their cancer later returns.”
HPV-related head and neck cancers are caused by the human papillomavirus (HPV). The virus inserts its DNA into a person’s cells and helps the cells grow into a tumor. As tumor cells grow and die, small pieces of HPV DNA are released into the bloodstream. HPV-DeepSeek detects small pieces of viral DNA in a person’s blood.
Previous studies by the research team have shown that HPV-DeepSeek can accurately detect HPV-related head and neck cancers at the time of diagnosis with much higher accuracy than existing approaches. They also discovered that it may have potential as a screening tool to identify cancer years before symptoms develop.
The new study, called Clear-HPVca, investigated whether the test could be used to adjust cancer treatment plans. The research team followed 103 newly diagnosed, previously untreated HPV-related head and neck cancer patients who were scheduled for surgery at Massachusetts General Brigham Cancer Institute from August 2020 to March 2024. The researchers followed the patients for more than two years, collecting and analyzing 560 blood samples before, after, and during surveillance. Of these patients, 73% received additional treatments such as radiation or chemoradiotherapy after surgery.
At diagnosis, HPV-DeepSeek detected circulating tumor HPV DNA in 98.1% of patients. Circulating tumor HPV DNA was detectable in 23% during the main testing period after surgery. Compared to existing HPV blood tests, HPV-DeepSeek’s sensitivity has been significantly improved.
The study found that those who had a positive HPV-DeepSeek result after surgery had significantly worse outcomes than those whose tumor HPV DNA was undetectable. After two years, only 60% of patients were disease-free, compared to 100% of patients who tested negative. Overall, only 73% of patients with detectable tumor HPV DNA were alive at the end of the study, compared with 98% of patients who had a negative HPV-DeepSeek test after surgery.
HPV DeepSeek may also be able to detect cancer recurrence earlier than traditional methods or existing HPV DNA-based blood tests. This is approximately 7 months before clinical detection, nearly double the lead time of existing HPV DNA blood tests and extending it by up to 17.5 months.
What excites me most about this approach is the potential to move beyond generalized risk estimates to truly individualized care. Precise identification of residual disease at the molecular level may ultimately allow treatment decisions to be made based on the biology of an individual patient’s cancer rather than broad clinical categories. ”
Daniel Faden, President, Brigham Cancer Institute, Massachusetts
One of the limitations of this study is that the observational researchers only collected the data and did not use the data to make treatment decisions. The study was also conducted within a single health system in a small number of patients whose cancer returned or died.
The team is currently planning a large, multicenter clinical trial to select postoperative treatments for patients with HPV-related head and neck cancer.
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Reference magazines:
Hirayama, S., others. (2026) Clinical validation of an HPV whole genome sequencing assay for MRD detection in surgically operated HPV+ head and neck cancer patients. Science translational medicine. DOI: 10.1126/scitranslmed.aec1724. https://www.nature.com/articles/s41467-026-72359-y.
