A new blood test can identify cancers of the head and neck caused by the human papillomavirus (HPV) up to 10 years before symptoms appear.
This is the discovery of Mass General Brigham researchers who have shown how liquid biopsy—blood tests that detect circulating tumor DNA—could improve cancer care and outcomes.
HPV causes around 70 percent of oropharyngeal cancers in the U.S., making it one of the most common cancers caused by the virus, with rates increasing faster than all other head and neck cancers.
However, unlike cervical cancers caused by HPV, the lack of a screening test for HPV-associated head and neck cancers means patients are usually diagnosed after a tumor has grown large enough to cause symptoms and spread to lymph nodes.
Screening methods that can detect these cancers much earlier could lead to earlier treatment interventions for patients, higher treatment success rates and require a less intense regimen, say the researchers who developed the tool, dubbed “HPV-DeepSeek.”
“This is the first study to show that sensitive and specific blood-based detection of HPV-positive head and neck cancer is feasible, years before symptoms develop,” study author Dr. Daniel L. Faden, a head and neck surgical oncologist at Mass Eye and Ear and a member of the Mass General Brigham healthcare system, told Newsweek.
“Blood-based cancer screening using circulating tumor DNA is an exciting field, and our study demonstrates likely the longest reported lead times for detection of any cancer using this approach.”
In the federally funded study, all cases were HPV-positive oropharyngeal cancers, which are the most common type of HPV-related head and neck cancer.
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 by the same 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. This included 28 from individuals who went on to develop HPV-associated head and neck cancer years later and 28 from healthy controls.
They discovered the liquid biopsy tool 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. 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 before diagnosis.
“Early detection could be transformative. If cancers are found years earlier, treatment could be less invasive, with fewer side effects, lower costs and—most importantly—hopefully, better survival,” Faden emphasized.
“Right now, we are completing blinded validation studies with the NIH and building models to determine who should be screened, how often and what the potential benefits and risks would be.”
Explaining why screening is already possible for cervical cancer, Faden said this is because they can directly sample cells with a Pap smear and track well-defined steps from HPV infection through precancer to cancer.
“For HPV-related oropharynx cancer, it’s different. The high-risk area—the base of the tongue and tonsils—is hard to see or swab in clinic,” he said.
“We also don’t yet know the exact steps from HPV infection to cancer. Most infections clear naturally, but in a small fraction of people, the virus persists silently for decades before cancer develops. Because no precancer stages have been clearly defined, a Pap smear–like test is not possible in the throat.”
Having developed the new blood test, the study authors are now validating the findings in a second blinded study using hundreds of samples collected as part of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO).
“Right now, we don’t know for certain whether we’re detecting cancer itself or a precancerous state. Answering this is a key focus of our ongoing research,” Faden added.
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Reference
Bryan, M. E., Aye, L., Das, D., Hirayama, S., Al-Inaya, Y., Mendel, J., Naegele, S., Efthymiou, V., Alzumaili, B., Faquin, W. C., Sadow, P. M., Lin, D., Varvares, M. A., Feng, A. L., Deschler, D. G., Chan, A. W., Paly, J., Park, J. C., Roberts, T., … Faden, D. L. (2025). Direct Comparison of Alternative Blood-Based Approaches for Early Detection and Diagnosis of HPV-Associated Head and Neck Cancers. Clinical Cancer Research, 31(16), 3483–3493. https://doi.org/10.1158/1078-0432.CCR-24-2525
Das, D., Hirayama, S., Aye, L., Bryan, M. E., Naegele, S., Zhao, B., Efthymiou, V., Mendel, J., Fisch, A. S., Guan, Z., Kröller, L., Michels, B. E., Waterboer, T., Richmon, J. D., Adalsteinsson, V., Lawrence, M. S., Crowson, M. G., Iafrate, A. J., & Faden, D. L. (2025). Circulating tumor HPV DNA whole genome sequencing enables HPV-associated oropharynx cancer early detection. JNCI: Journal of the National Cancer Institute. https://doi.org/10.1093/jnci/djaf038
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