NEW YORK – Investigators from the University of North Carolina at Chapel Hill have reached a new milestone for their virus-associated oropharyngeal cancer detection assay, publishing validation data for the test, while a startup has begun to provide the test to early adopters.
Appearing last month in the Journal of Clinical Oncology, the group's study confirmed that the liquid biopsy assay could accurately detect recurrences of human papillomavirus-linked head and neck cancers, often at earlier timepoints than imaging. The data also helped confirm that when the method marks patients as cancer-free and unlikely to relapse, it does so very reliably.
The test was developed to allow doctors to more accurately and easily identify which patients with these tumors are free from cancer after radiation treatment, and which might be poised to relapse.
The UNC team announced previously that it had licensed IP related to the test to a startup called Naveris, which this quarter begun providing the test, dubbed NavDx, through its CLIA laboratory to "leading head and neck oncology treatment centers."
Unlike liquid biopsy methods that search for mutations in circulating tumor DNA, NavDx picks up sequences of the HPV genome. The test is also specific to HPV circulating tumor DNA and not to virus material that would be present from an active papillomavirus infection.
UNC radiation oncologist Bhisham Chera, the study's first author and now a consultant/advisory board member for Naveris, said that the main value proposition for the test is that it can help make the process of surveilling patients with these cancers both more effective and more efficient.
A big issue for the field, he said, is that surveillance practices are currently very variable. "Some places don’t do any imaging and other places image a lot [at great expense]," he said.
"With blood-based surveillance, you can better select patients for that expensive PET scan or for fiberoptic scopes," he explained.
In their recent study, Chera and colleagues reported on their prospective use of what is now the NavDx test in a 115-patient cohort who underwent chemotherapy and radiation treatment for oropharyngeal squamous cell carcinoma linked to HPV16 at UNC.
Patients were screened for recurrence using PET/CT body scans, chest imaging, and physician evaluations. They received a blood draw every six to nine months, and the group analyzed over 1,000 blood samples overall.
According to the investigators, the HPV ctDNA test was 99 percent accurate in identifying patients who were, and would remain, cancer-free through the time period of the study. None of the 87 patients who had negative HPV blood tests in all their screening sessions developed recurrence.
In addition, as long as a positive result was confirmed with a follow-on test, the researchers could identify patients with emerging recurrences with 94 percent sensitivity, and for the most part at significantly earlier timepoints than imaging.
Initially, 28 patients had a positive HPV blood test, 15 of whom went on to be diagnosed with recurrence. This represented a positive predictive value of only 54 percent. But after undergoing a second blood test, the researchers could see that only 16 of the 28 patients continued to show HPV ctDNA in their samples. Calculating according to this two-timepoint positivity, the PPV rose to 94 percent.
For 91 percent of those in the cohort who tested positive, their result preceded the detection of recurrence by imaging, with a median lead time of 3.9 months.
"When we presented [previously] at ASTRO and other meetings … we had less follow-up, and with just the one timepoint, one positive test, the positive predictive value was not very good," Chera said. "But the negative predictive value was good, so our main initial finding was that if you have a negative result, we are pretty strongly confident that you are without disease."
"As we continued the study, we followed individuals with a single positive test very closely – and noticed that some of them clear [their blood of HPV DNA], and it's those other patients with a second positive test who are the ones who have cancer recurrence. So just by observing this longitudinally, we saw that two positive tests [offers] a better predictor," he added.
Shoring up this finding is the fact that it reflects what has been seen with similar methods for noninvasive virus-associated cancer detection, for example the Epstein Barr virus head and neck cancer test being developed by Hong Kong University investigator Dennis Lo.
But while Lo has said that for the screening application he and his team are pursuing for their test, only a single timepoint model will be necessary, the surveillance use that Chera and colleagues have targeted finds repeat testing is not only acceptable, but desirable.
An important unanswered question that still remains for the HPV-oropharyngeal cancer space, Chera and colleagues wrote, is whether there will be clinical value in predicting recurrence early.
However, Chera said, the most immediate utility for the test is its high negative predictive value. This offers the field a way to more accurately and cheaply monitor patients, saving expensive imaging for follow-up in cases that test positive.
"Whether early detection improves outcomes is a very important question, but even if it doesn’t improve salvage, there is still value in the blood test in improving efficiency and efficacy of detection," he argued.
That said, the group is interested in continuing to work to try to establish clear utility evidence for the test as a predictor of recurrence, as well.
"I have, in my practice, with the blood test, detected cancer recurrences sooner in [an incipient] metastatic state, and we have put them in long-term remission — not just radiographic but molecular," Chera said. "They get radiosurgery, chemotherapy, and two years out, their imaging and blood is negative."
"But I know that there are folks wanting to partner now to do [more comprehensive] studies, to look at outcome benefit, and we should do them," he said.
Chera also said that there is talk within Naveris about establishing a registry study with incoming cases that can help to both further validate the PPV and NPV values that the UNC team reported in their smaller cohort and to begin to collect more data on early intervention and outcomes.
For widespread adoption, Naveris will be facing hurdles in seeing the NavDx approach recognized by both practice guidelines and insurance payors, but Chera said there are already some reasons for optimism on those fronts.
"Adoption looks like it's happening pretty quickly just based on numbers being seen by the company," and the group is seeing positive recognition from opinion leaders, some of whom sit on national committees that are involved in the creation of clinical practice guidelines.
In an email, Naveris Cofounder and CEO Piyush Gupta said that NavDx testing is currently available through Naveris' Waltham, Massachusetts CLIA lab "to all physicians throughout the US," adding that since the company's launch, it has "received samples from 10 states" and expects this to grow significantly over the next several months.
"We are just beginning to engage insurance companies and will have more detail on reimbursement in the upcoming months," he wrote. "That being said, we will work to make sure no patient has [undue] financial hardship from our test which would prevent use from providers."