Viktor Grünwald, MD: We actually don’t. Because, we would do so in a research scenario, of course. For our day-to-day practice, this does not have the implications that we would change and alter our treatment approach. And so, therefore, we do not test on a routine basis. We do it in certain patients, but these are individual patients.

Ezra Cohen, MD: So, Viktor, in a research setting, you’ll test for it, but because it doesn’t change your management on a routine clinical setting, you won’t.

Viktor Grünwald, MD: Yes.

Ezra Cohen, MD: Kevin?

Kevin Harrington, MD, PhD: No, we will routinely test all patients with oropharyngeal carcinoma, and most departments in the United Kingdom would use p16 immunohistochemistry. And if those data were inconclusive, then we will often resort either to PCR analysis or FISH analysis, depending upon which department’s doing the test. And, at the moment, although it doesn’t necessarily lead to a change in management—because patients will still receive chemotherapy and radiation often in the locally advanced setting—what we think it adds to the equation is it does bring something that you can tell the patient about prognosis.

It tells you something about, perhaps, the way you need to follow these patients up because there are suggestions that patients with HPV-associated cancers are more likely to have later relapse in their course of disease. And so, you may need to remain more vigilant for a longer period of time in these patients. So, we do the test, we need the results, and we hope in the future that what we will have is stratified treatment approaches for those patients with HPV-positive disease. And breaking that down into different segments of the disease may undergo different treatment approaches, including de-escalation of therapy with the primary goal of reducing the toxicity we subject patients to.

Ezra Cohen, MD: And let me just clarify when you’re talking about testing for HPV, especially using p16 immunohistochemistry, are you talking exclusively about the oropharynx cancer patients or other sites of disease?

Kevin Harrington, MD, PhD: So, we discourage our pathologists from testing for HPV with p16 immunohistochemistry in sites outside of the oropharynx, largely because we have no clear evidence at the moment that it’s a driver of a different biological process within head and neck cancers. Although, occasionally, we will get a situation where they will present us with some data where, for instance, a young patient with a p16 positive hypopharyngeal cancer is presented in our meeting, it doesn’t necessarily lead to any change in management because we’ve got no data to suggest that we should treat those patients any differently from the p16 negative subgroup.

Tanguy Y. Seiwert, MD: And maybe I can add a little bit to that. I think for oropharyngeal tumors, most centers in the United States will routinely test by p16. And since the baseline incidence is so high, p16 is actually a very good test in the oropharynx. However, there are some cancers that are HPV driven that occur outside the oropharynx. And, there, however, the problem is p16 is about 50%, 60% of the time a false-positive. They are clearly 5% of HPV-negative tumors that are p16-positive. So, p16 is a surrogate of HPV. Some centers like our center, Johns Hopkins, and I think a number of other centers, have started to do actually do dual testing routinely where we add the PCR on. And so, that way, you can identify those false-positive p16. Even in the oropharynx when you have a positive p16, it doesn’t always mean that it’s HPV-positive. And, I think, Kevin is exactly right, it’s helpful prognostically, and we can talk about p16 separately, but likely it’s driven by HPV. But, especially for de-escalation approaches, this is very, very important.

The other point that I would like to make is recent data indicated that a few tumors, even though most HPV-positive tumors are associated with HPV-16, are driven by other HPV types. And those tend to have a worse prognosis. So, it might actually in the future help us to identify which subtype of HPV it is. And that’s largely the reason why we’ve started to test for the specific subtype like PCR, because they tend to have a worse prognosis as they’re non HPV-16.

Ezra Cohen, MD: And do you have an algorithm that you go through, Tanguy? Tell us a little about that.

Tanguy Y. Seiwert, MD: So, for oropharyngeal tumors, we test everybody with dual testing using p16 and PCR, and that’s an automatic process. The p16 comes, obviously, right away, and the PCR comes a week later. Outside the oropharynx, we usually trigger based on patients who are nonsmokers or have smoked little. Or sometimes, based on the histology, these tend to be less differentiated, undifferentiated tumors. And if there’s any suspicion, we will test in addition. I think the impact of HPV on non-oropharynx tumors is less clear. I think there are some data suggesting that it might make a role, but it’s still an area of active research.

Transcript Edited for Clarity