A new federally funded study published in the Journal of the National Cancer Institute by researchers at Mass General Brigham introduces a promising advance. The team developed a liquid biopsy test called HPV-DeepSeek, which can identify HPV-linked head and neck cancers up to 10 years before symptoms begin. Detecting the disease this early could increase the chances of successful treatment and reduce the need for aggressive therapies, the researchers report.

"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."

HPV-DeepSeek works by using whole-genome sequencing to identify trace fragments of HPV DNA that have separated from a tumor and entered the bloodstream. Earlier research from this team showed that the test could reach 99% specificity and 99% sensitivity in detecting cancer during its initial clinical presentation, outperforming all existing diagnostic methods.

To explore whether HPV-DeepSeek could identify these cancers long before symptoms appear, the researchers analyzed 56 blood samples from the Mass General Brigham Biobank. The samples included 28 from people who later developed HPV-associated head and neck cancer and 28 from healthy individuals who served as 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.