An experimental assay detected residual HPV-related cancer DNA after surgery and was associated with poorer outcomes in an observational study.
Investigators from Mass General Brigham Cancer Institute have developed an ultrasensitive blood test that identifies patients with human papillomavirus (HPV)-associated head and neck cancer who may still harbor cancer cells after surgery.
The study, published in Science Translational Medicine, suggests the test could help clinicians determine which patients would benefit most from additional treatments like radiation or chemoradiation. Currently, clinicians rely on general risk factors to make these decisions, which can lead to some patients receiving more treatment than necessary and others receiving too little.
“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,” says Daniel Faden, MD, director of the head and neck cancer genomics and liquid biopsy program at Mass General Brigham Cancer Institute, in a release. “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.”
Detecting Viral DNA
HPV-associated head and neck cancers occur when the virus inserts its DNA into human cells, driving tumor growth. As tumor cells die, they release small fragments of HPV DNA into the bloodstream. The new test, called HPV-DeepSeek, is designed to detect these tiny fragments.
The research team followed 103 people with newly diagnosed, untreated HPV-associated head and neck cancer scheduled for surgery between August 2020 and March 2024. Investigators analyzed 560 blood samples taken before surgery, after surgery, and during surveillance over a period of more than two years.
At the time of diagnosis, HPV-DeepSeek identified circulating tumor HPV DNA in 98.1% of patients. In the testing window following surgery, 23% of patients had detectable viral DNA.
Predicting Survival and Recurrence
The study found that patients with positive test results after surgery had significantly worse outcomes than those with negative results. Only 60% of patients with detectable tumor DNA were disease-free at two years, compared with 100% of patients who tested negative. Additionally, only 73% of patients with detectable tumor DNA were still alive at the end of the trial, compared with 98% of patients with negative tests.
HPV-DeepSeek also detected cancer recurrence earlier than traditional clinical methods, providing a lead time of approximately seven months.
“What excites me most about this approach is the possibility of moving beyond generalized risk estimates and toward truly personalized care,” says Faden, in a release. “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.”
The researchers noted that the study was observational and conducted within a single healthcare system. The team is now planning larger, multi-site clinical trials to evaluate using the test to guide treatment selection after surgery for patients with HPV-associated head and neck cancer.
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