HPV-DeepSeek, a liquid biopsy test combining whole genome sequencing and machine learning technology, has been reported to accurately identify head and neck cancers caused by the human papilloma virus (HPV) up to 10 years before symptoms appear. Results published in the Journal of the National Cancer Institute showcase the potential of this test to enable earlier detection and treatment of a form of cancer that is often diagnosed years after onset.
“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, head and neck surgical oncologist at Harvard Medical School and principal investigator in the Mike Toth Head and Neck Cancer Research Center of Mass General Brigham.
In the United States, HPV is estimated to cause 70% of head and neck cancers. It can take years for cancer to develop after being infected with the virus, and these tumors can grow undetected for over a decade before symptoms appear. Unlike cervical cancers caused by HPV, there are currently no early detection tests available for HPV-associated head and neck cancers. At the time of diagnosis, the cancer has typically grown and spread to the lymph nodes.
“By the time patients enter our clinics with symptoms from the cancer, they require treatments that cause significant, life-long side effects,” said Faden. “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 relies on whole-genome sequencing to detect DNA fragments from HPV that have broken off from a tumor and are circulating in the bloodstream. In a previous study, the test showed significantly higher accuracy than other diagnostic methods currently in use, including PCR, antibody detection, and tissue biopsy techniques.
While circulating tumor HPV DNA is known to be a sensitive and specific biomarker for HPV-associated head and neck cancers, it was unknown until now whether this marker is also detectable before the time of diagnosis. Faden and colleagues tested this hypothesis by running the test in 56 plasma samples obtained from the Mass General Brigham Biobank. These included 28 samples from patients that later went on to develop HPV-associated head and neck cancers, and 28 age- and sex-matched healthy controls.
The test results were positive in 79% of patients who later developed cancer, with the earliest positive result obtained for a sample obtained nearly eight years before diagnosis. Diagnostic accuracy was highest within four years of the patient receiving a cancer diagnosis, much earlier than what was achieved with HPV antibody detection methods.
Using a machine learning algorithm trained and tested on an independent cohort of over 300 samples, the sensitivity of the test results was increased to 96%, with the earliest positive result found in a sample that was obtained more than 10 years before diagnosis.
A validation study is already underway to test the performance of HPV-DeepSeek in hundreds of samples from the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial sponsored by the National Cancer Institute. The team is also conducting clinical trials to study whether this blood test could help detect residual disease after surgery, helping doctors determine whether additional treatments are needed to prevent recurrence after the tumor has been removed.
