New blood test detects HPV-associated head and neck cancer 10 years early

Daniel Faden in his lab at Mass Eye and Ear. Mass Eye and Ear

Health

New blood test detects HPV-associated head and neck cancer 10 years early

Tool identifies disease before symptoms appear

Mass General Brigham Communications

September 10, 2025

3 min read

Human papillomavirus (HPV) causes an estimated 70 percent of head and neck cancers in the U.S., making it the most common cancer caused by the virus. Yet unlike cervical cancers caused by HPV, there is no screening test for HPV-associated head and neck cancers.

In a new federally funded study, Harvard-affiliated Mass General Brigham researchers show that a novel liquid biopsy tool they developed, called HPV-DeepSeek, can identify HPV-associated head and neck cancer up to 10 years before symptoms appear. By catching cancers earlier with this novel test, patients may experience higher treatment success and require a less intense regimen, according to the authors.

Findings from the study were published in the Journal of the National Cancer Institute.

“Our study shows for the first time that we can accurately detect HPV-associated cancers in asymptomatic individuals many years before they are ever diagnosed with cancer,” said lead study author Daniel L. Faden, principal investigator in the Mike Toth Head and Neck Cancer Research Center at Mass Eye and Ear and assistant professor of otolaryngology–head and neck surgery at Harvard Medical School. “By the time patients enter our clinics with symptoms from the cancer, they require treatments that cause significant, life-long side effects. We hope tools like HPV-DeepSeek will allow us to catch these cancers at their very earliest stages, which ultimately can improve patient outcomes and quality of life.”

HPV-DeepSeek uses whole-genome sequencing to detect microscopic fragments of HPV DNA that have broken off from a tumor and entered the bloodstream. Previous research from this team showed the test could achieve 99 percent specificity and 99 percent sensitivity for diagnosing cancer at the first time of presentation to a clinic, outperforming current testing methods.

To determine whether HPV-DeepSeek could detect HPV-associated head and neck cancer long before diagnosis, researchers tested 56 samples from the Mass General Brigham Biobank: 28 from individuals who went on to develop HPV-associated head and neck cancer years later, and 28 from healthy controls.

HPV-DeepSeek detected HPV tumor DNA in 22 out of 28 blood samples from patients who later developed the cancer, whereas all 28 control samples tested negative, indicating that the test is highly specific. The test was better able to detect HPV DNA in blood samples that were collected closer to the time of the patients’ diagnosis, and the earliest positive result was for a blood sample collected 7.8 years prior to diagnosis.

Using machine learning, the researchers were able to improve the test’s power so that it accurately identified 27 out of 28 cancer cases, including samples collected up to 10 years prior to diagnosis.

The authors are now validating these findings in a second blinded study funded by the National Institutes of Health using hundreds of samples collected as part of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial at the National Cancer Institute.

Funding for this work came from the National Institute of Dental and Craniofacial Research of the National Institutes of Health.