NEW YORK – A University of Michigan lab has developed a blood-based test to detect recurrence of human papilloma virus-positive head and neck cancer sooner than standard-of-care imaging and clinical examination and is preparing to offer the test nationally.
The Michigan Health system's MyHPVscore test uses Bio-Rad's Droplet Digital PCR (ddPCR) technology to detect HPV DNA fragments that are released by HPV-positive oropharyngeal squamous cell carcinoma. It has been available to p16-positive head and neck cancer patients of the University of Michigan Health system as an optional test to monitor treatment response and identify residual disease.
Chad Brenner, director of the Michigan Otolaryngology and Translational Oncology Laboratory, said that the test is used to detect biomarkers of six HPV strains that are responsible for 99 percent of HPV-related cancers. Brenner's lab created the test with support from the university's cancer center, among other departments on campus. He said that the lab has so far tested samples from about 500 patients using Bio-Rad's ddPCR instruments.
The test was performed every three months to monitor patients following head and neck cancer therapies, and unpublished study results so far show that it identified recurrence between 28 and 161 days earlier than could be detected through imaging. Brenner said that, in those studies, the assay has performed with 99 percent predictive value.
"There's been a really impressive lead time on diagnosis of recurrence for these head and neck [cancer] patients over what the current paradigm enables," he said.
Brenner said that DNA fragmentation patterns can help to identify sequences that are released by tumors and distinguish them from noncancerous HPV infections. He noted that HPV infection is also not believed to be present in the bloodstream and early data support that claim, although additional research would be needed for verification.
Niema Razavian, a radiation oncologist at Moffitt Cancer Center who specializes in head and neck cancers, said that doctors at the cancer center typically use a PET scan and physical examination to monitor patients for disease recurrence three months following radiation therapy or radiation with surgery. Follow-up monitoring typically involves periodic physical examination of a patient's mouth, palpating the head and neck, and, potentially, fiber laryngoscopy to further examine the back of the throat, base of the tongue, vocal cords, and larynx, he said.
"Use of a blood-based test is definitely something that people in head and neck cancer have been really interested in," he said.
Razavian is not connected with the development of the University of Michigan test. However, he said that blood tests could aid the detection of recurrence while tumors are still small.
Moffitt uses Naveris' NavDx test prior to treatment and during monitoring to identify tumor tissue-modified HPV DNA that is shed by dying tumor cells and provide a score of cancer recurrence or progression. That test can be performed in conjunction with the physical examinations every three months.
"It's nice to have another test on the market so, hopefully, patients will have better access to these kinds of tools," Razavian said.
Qiagen also has been collaborating with BioNTech since 2020 to develop a tissue-based companion diagnostic that would be used to identify patients who have HPV-associated squamous cell carcinoma of the head and neck and are eligible for treatment with BioNTech's investigational treatment BNT113. A Qiagen spokesperson said this week that the test is initially for investigational use only to enroll patients into clinical trials, but can detect multiple genotypes and will be developed for use in multiple types of HPV-driven cancers.
Brenner said that MyHPVscore targets the HPV E6 and E7 oncogenes that are commonly found in HPV-positive head and neck tumors as well as DNA fragments that provide additional information about the tumor. He said that the lab is initially focused on cancer detection, although future tests could be used to aid decisions on targeted treatments with emerging T-cell therapies.
The lab runs about 50 tests per week on samples from University of Michigan Health System patients, but it could perform upward of 400 tests per day, Brenner said. Meanwhile, the lab has been performing stress tests to ensure it could handle an increased workload ahead of a national launch of the assay, and leaders from the lab have been collaborating with the pathology department's marketing and collaboration services.
Brenner said, though, that licensing the test could help to make it available to more patients.
"Even though we can run 400 tests a day, that's still not very many in the grand scheme, and, so, licensing to a larger company that could handle a larger volume of samples is the most logical next step for this test," he said.
Brenner noted that the lab also plans to soon begin clinical trials of the test in patients with HPV-positive cervical, anal, and vulvar cancers, and the American Cancer Society and US Department of Defense are also funding clinical trials for the use of MyHPVscore as a screening test for the early detection of head and neck cancer. He said that a recent study on the use of the test to aid an initial diagnosis of cancer ended with promising results, and those results are under review ahead of publication.
His lab is trying to determine in an ongoing clinical trial the impact that MyHPVscore has on overall patient survival. Brenner said that the trial began in March 2024 and is expected to take between five and eight years.
Brenner said he is optimistic that the test is identifying patients when they have earlier-stage cancers and therapies are more likely to result in positive outcomes. For now, though, patients whose test results are positive for recurrence undergo additional monitoring but still require secondary confirmation through imaging and clinical surveillance to begin treatment.