Novel Biomarker May Predict Recurrence in HPV+ Oropharyngeal Cancer

Matthew E. Spector, MD

In the current treatment landscape of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), there is a significant lack of biomarkers to predict recurrence. Additionally, as Matthew E. Spector, MD, notes, the incidence of OPSCC continues to rise.

“Due to HPV, people are getting more and more of these types of cancers, and hopefully that will go down once more people get vaccinated, but right now, we’re on this big upswing that’s probably going to keep going up,” said Spector, who is the lead author of a new biomarker study published in Clinical Cancer Research.

In the study, researchers found that patients whose oropharyngeal cancer recurred had higher levels of antibodies for 2 proteins, E6 and E7, which are found in HPV-driven cancers. These findings highlight the potential for a novel, blood-based marker that could predict when cancer is likely to return.

OncLive: Please discuss the lack of biomarkers in head and neck cancer, and how that affects the treatment landscape.

In an interview with OncLive, Spector, an assistant professor specializing in otolaryngology at the University of Michigan Medical School, discussed the results of this study as well as the pressing need for biomarkers in this patient population.Spector: Oropharynx cancer is one of the only types of cancer that is really increasing in incidence, especially in head and neck cancer. Due to HPV, people are getting more and more of these types of cancers, and hopefully, that will go down once more people get vaccinated, but right now, we’re on this big upswing that’s probably going to keep going up. These patients are usually younger, they’re healthier, and they have less smoking and drinking history. When we saw this, we needed a way to try to predict which patients would fail therapy, because most patients do pretty well.

Biomarkers in cancer are always a little tricky. There are some really good ones out there. Prostate cancer has a really good blood-based biomarker, as does thyroid cancer. But for head and neck cancer, we’ve tried a lot of different things, but we haven’t been able to detect it.

How was your study conducted, and what were the most significant findings?

What’s unique about this cancer is that there are actually viral oncoproteins that are circulating in the blood at some point, so we used that premise to develop this test. The test basically looks at antibodies against those viral oncoproteins, and they’re called E6 and E7, and we’re able to detect those in patients who are developing recurrence where their antibody levels are actually going up.The patients that we used for this trial were before my time here at the University of Michigan, but 1 thing we’ve done really well as a group is to collect samples on everybody. We collect blood samples every couple of months, we collect tumor samples when patients initially develop cancer, and then we store these to do studies like this.

We looked back at patients, who were treated from approximately 2000 to 2010, and we looked at their blood samples, and then we divided them into 2 groups: patients who recurred and patients who didn’t. Then we used their blood samples to measure these antibody levels.

So this is measured more on a patient-by-patient basis, rather than a one-size-fits-all approach?

Are there any next steps planned following these results?

Are there any other related trials looking for biomarkers in this particular cancer type that you’d like to discuss?

It was very interesting that, before anyone received any treatment at all for their cancer, everyone had high antibody levels—which is expected. Everyone has these proteins in their blood, so after treatment, or when you were treated, everyone all saw those levels go down. But the interesting thing was that, for patients who developed recurrence, their antibody levels went back up again—especially the E7 antibody. So if you take a patient at baseline, and you track their antibody levels, they go down and then up, and that uptick is a chance for us to detect recurrence before we’re actually finding it in the patient.Yes, this is definitely patient-specific. My antibody levels might be different than yours, and yours might be different than someone else’s. But if you track them over time within a patient, the levels should definitely go down and never go back up. And everyone kind of starts at a different level, too, so it’s a very personalized way to watch for cancer recurrence.We wrote a phase II clinical trial that we’re currently conducting, and we’re also in collaboration with other groups to look at bigger sets of patients with this type of cancer to see if we can develop other markers.This one is specific for HPV-positive cancer, but we have a second trial that’s looking at all head and neck cancers, and it’s called MiOTOSeq. That trial is looking at genomic markers, meaning patients who have a gene mutated in their type of cancer, and it’s something we can follow or find a treatment for that may not be specific to head and neck cancer.

What would you like to see in the next 5 to 10 years in the development of biomarkers in this space?

Are there any major challenges standing in the way of that kind of revolution?

Like right now, there are maybe a dozen drugs approved for head and neck cancer, but there are thousands of drugs out there that could potentially be used in one of our patients, we just don’t know it yet. So the premise of MiOTOSeq is to sequence patients’ cancer genome, find out where the mutations are, and see if there are any druggable targets against this particular cancer—and maybe it’s not even a drug used for head and neck cancer, maybe it’s traditionally used for something else.I would like to see blood-based biomarkers used almost in conjunction with a physical exam to follow cancer patients. If you look at the NCCN guidelines, patients are supposed to be checked every 2 to 3 months in the first year. But if they live far away, maybe they could, instead, send a vial of blood every 2 or 3 months, and then we can test their blood and see if it’s clear, and we can possibly change how often we see them, or maybe we detect something and bring them in sooner for a scan. A blood test could revolutionize the way we follow patients after treatment and how we scan them, or how we decide which imaging studies to use, based just on a small test.I think that getting large numbers of patients together to do research is always hard. Head and neck cancer doesn’t have as many patients as maybe breast cancer or colon cancer, and so some of these other cancers have already paved the way for this type of research.

Spector ME, Sacco AG, Bellile EL, et al. E6 and E7 antibody levels are potential biomarkers of recurrence in patients with advanced stage human papillomavirus positive oropharyngeal squamous cell carcinoma [published online November 21, 2016]. Clinical Cancer Research. doi: 10.1158/1078-0432.CCR-16-1617.