Mass General Brigham's HPV-DeepSeek test enables much earlier cancer detection through a blood sample, creating a new opportunity for screening HPV-related head and neck cancers.

Human papillomavirus (HPV) is responsible for about 70% of head and neck cancers in the United States, making it the most common type of cancer linked to the virus. Rates of these cancers continue to rise each year. Unlike HPV-related cervical cancers, which have established screening options, there is currently no test to detect HPV-associated head and neck cancers.

As a result, most cases are diagnosed only after tumors have already expanded to billions of cells, causing symptoms and often spreading to nearby lymph nodes. Developing screening tools that can identify these cancers much earlier would allow patients to begin treatment sooner and improve outcomes.

Detecting cancer years before symptoms

In a newly funded federal study published in the Journal of the National Cancer Institute, researchers at Mass General Brigham demonstrated that their liquid biopsy test, called HPV-DeepSeek, can detect HPV-related head and neck cancers as early as 10 years before symptoms develop. According to the study's authors, diagnosing these cancers earlier could increase treatment success rates and reduce the need for aggressive therapies.

"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, MD, FACS, a head and neck surgical oncologist and principal investigator in the Mike Toth Head and Neck Cancer Research Center at Mass Eye and Ear, a member of the Mass General Brigham healthcare system.

"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."

How HPV-DeepSeek works

HPV-DeepSeek relies on whole-genome sequencing to identify tiny fragments of HPV DNA that separate from tumors and circulate in the blood. Earlier studies by the same research group demonstrated that the test could reach 99% specificity and 99% sensitivity in diagnosing cancer at a patient's initial clinic visit, performing better than existing diagnostic approaches.

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 (NIH) using hundreds of samples collected as part of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) at the National Cancer Institute.

Reference: "Circulating tumor human papillomavirus DNA whole genome sequencing enables human papillomavirus-associated oropharynx cancer early detection" by Dipon Das, Shun Hirayama, Ling Aye, Michael E Bryan, Saskia Naegele, Brian Zhao, Vasileios Efthymiou, Julia Mendel, Adam S Fisch, Zoe Guan, Lea Kröller, Birgitta E Michels, Tim Waterboer, Jeremy D Richmon, Viktor Adalsteinsson, Michael S Lawrence, Matthew G Crowson, A John Iafrate and Daniel L Faden, 10 September 2025, JNCI: Journal of the National Cancer Institute.
DOI: 10.1093/jnci/djaf249

Funding for this work came from the National Institute of Dental and Craniofacial Research (NIDCR) of the National Institutes of Health (NIH), grant no. R03DE030550.

Faden receives salary support from NIH/NIDCR K23 DE029811, NIH/NIDCR R03 DE030550 and NIH/NCI R21 CA267152. He has also received research funding or in-kind funding from Bristol-Myers Squibb, Calico, Predicine, BostonGene, Neogenomics and Haystack (Quest), in addition to consulting fees from Merck, Noetic, Chrysalis Biomedical Advisors, Neogenomics, Arcadia, and Focus. None of these sources relate to the work in this manuscript. Waterboer serves on advisory boards for Merck (MSD) Sharp & Dohme. The remaining authors have declared no conflicts of interest.

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