Researchers at the Mass General Brigham Cancer Institute have demonstrated that a new ultra-sensitive blood test, HPV-DeepSeek, can detect residual tumor DNA after surgery in patients with HPV-associated head and neck cancers and help identify those who may require additional treatment. The findings were published in the journal Science Translational Medicine.

HPV-associated head and neck cancers are caused by infection with the human papillomavirus (HPV). The virus integrates its genetic material into host cells, contributing to their transformation into cancer cells. As tumors grow and shed cells, tiny fragments of viral DNA enter the bloodstream. The HPV-DeepSeek test is designed to detect these fragments with exceptionally high sensitivity.

The study, known as Clear-HPVca, enrolled 103 patients with newly diagnosed HPV-associated head and neck cancer who underwent surgery between 2020 and 2024. Researchers analyzed 560 blood samples collected before surgery, after surgery, and throughout a follow-up period that extended beyond two years.

Following surgery, 23% of patients continued to show detectable levels of tumor-derived HPV DNA in their blood. This group experienced significantly poorer outcomes than patients whose tests were negative. Two years after treatment, only 60% of patients with detectable tumor DNA remained disease-free, compared with 100% of those with negative test results.

Overall survival also differed markedly between the groups. Patients with detectable circulating tumor DNA had a survival rate of 73%, whereas survival reached 98% among those without detectable residual tumor DNA.

One of the most important findings was the test’s ability to identify cancer recurrence substantially earlier than conventional monitoring methods. On average, HPV-DeepSeek detected relapse seven months before standard surveillance approaches, and in some cases nearly 18 months earlier.

According to the researchers, the technology’s greatest potential lies in enabling a more personalized approach to cancer care. Rather than relying solely on traditional risk categories and providing similarly intensive treatment to all patients, clinicians may eventually be able to tailor therapy based on molecular evidence of residual disease detected after surgery.

The authors suggest that such an approach could help identify high-risk patients earlier, guide decisions about additional treatment, and improve long-term outcomes for individuals with HPV-associated head and neck cancers.