New blood assay identifies HPV-related head and neck malignancies a decade earlier

Human papillomavirus (HPV) leads to an estimated 70 percent of head and neck cancers in the U.S., rendering it the most prevalent malignancy triggered by the virus. However, unlike cervical cancers induced by HPV, there currently exists no screening method for HPV-related head and neck tumors.

In a recent federally supported investigation, researchers from the Harvard-affiliated Mass General Brigham have demonstrated that an innovative liquid biopsy instrument they created, known as HPV-DeepSeek, is capable of detecting HPV-associated head and neck cancer up to 10 years prior to symptom onset. By diagnosing cancers earlier with this groundbreaking assay, patients might experience improved treatment success and necessitate less intensive regimens, according to the authors.

Results from the research were disclosed in the Journal of the National Cancer Institute.

“Our study reveals for the first time that we can reliably identify HPV-related cancers in asymptomatic individuals many years prior to their cancer diagnosis,” stated lead investigator Daniel L. Faden, principal investigator at the Mike Toth Head and Neck Cancer Research Center at Mass Eye and Ear and assistant professor in otolaryngology–head and neck surgery at Harvard Medical School. “By the moment patients arrive at our clinics presenting symptoms from the cancer, they require treatments that incur considerable, lifelong side effects. We anticipate that tools like HPV-DeepSeek will enable us to catch these cancers at their earliest stages, which can enhance patient outcomes and quality of life.”

HPV-DeepSeek leverages whole-genome sequencing to locate minuscule fragments of HPV DNA that have detached from a tumor and entered the bloodstream. Prior studies from this group indicated that the assay could achieve 99 percent specificity and 99 percent sensitivity for diagnosing cancer at the initial patient presentation to a clinic, surpassing existing testing methods.

To ascertain whether HPV-DeepSeek could identify HPV-associated head and neck cancer long before the formal diagnosis, investigators examined 56 samples from the Mass General Brigham Biobank: 28 from individuals who subsequently developed HPV-associated head and neck cancer years later, and 28 from healthy participants.

HPV-DeepSeek found HPV tumor DNA in 22 out of 28 blood samples from patients who later developed the malignancy, whereas all 28 control samples yielded negative results, suggesting the test’s elevated specificity. The test was more effective at identifying HPV DNA in blood samples collected closer to the time of patients’ diagnoses, and the earliest positive result came from a sample taken 7.8 years prior to diagnosis.

Employing machine learning, the researchers enhanced the test’s accuracy to correctly identify 27 out of 28 cancer instances, including samples obtained up to 10 years before diagnosis.

The authors are in the process of validating these discoveries in a subsequent blinded study financed by the National Institutes of Health, utilizing hundreds of samples gathered as part of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial at the National Cancer Institute.

Funding for this research was provided by the National Institute of Dental and Craniofacial Research of the National Institutes of Health.