Transcript:Ezra Cohen, MD: So, we talked a lot about HPV and its implications on prognosis. But, there are other factors that we consider. Let’s talk a little bit about those. Kevin, what other things come into play when you are discussing prognosis with a patient?

Kevin Harrington, MD, PhD: Well, the first thing that we will look at is we will stage the patient’s tumor. We know that patients with high T-stage, especially those patients with T3 and T4 tumors, have a worse prognosis. We know that patients with high end stage, and this includes both HPV-negative and HPV-positive disease—even though there’s a tendency for HPV-positive disease to present at stage N2 and above fairly commonly—we know that those higher end stages for both negative and HPV-positive disease will have a prognostic benefit. And then, we have to consider patient-associated factors, so, the patient’s age, the patient’s general performance status, and comorbid conditions. These are the sort of factors that we would routinely take into account when designing treatment plans for these patients and deciding whether or not they are fit for unimodality or multimodality therapy, whether or not they are candidates for surgical or nonsurgical management.

Ezra Cohen, MD: And Viktor, any other factors that you take into account?

Viktor Grünwald, MD: No. I think Kevin really summarized all those that are really essential, because something you really would like to avoid is that you challenge a patient with a multimodality approach, which he cannot basically handle. And, I think it is very important with these multimodal aggressive treatments to select the right patient to the right treatment. And, as Kevin said, these are the factors that we also use and they are important in a clinic.

Ezra Cohen, MD: A lot of things to consider when facing an individual patient. Tanguy, any other molecular markers that you use to think about prognosis?

Tanguy Y. Seiwert, MD: So, clinically, we do exactly what Kevin and Viktor pointed out. And I think that’s the standard of care. I do believe that there are factors that we’re investigating that are research assays that might help. There’s a lot of talk about the immune system, the immunoscore, and we actually don’t know what the impact is. But, the suggestion may be that patients who already have a preexisting immune response might do better. We actually don’t know the answer for head and neck cancer, so I think we don’t know that.

The other factors that have been described, they are actually heterogeneities regarding p53 status. Does presence or absence of a p53 mutation mean something? Then, there’s also the dignity of the p53 mutation specifically. And I think it’s a bit controversial. So, clinically, we don’t use either of those factors. Other things are being explored. But, I think it’s important for us to keep looking and further refine this. And just to comment on Kevin’s point a little bit more, I think for the HPV-positive tumors, there’s a general sense that even though somebody is “locoregionally advanced,” they actually behave so much more favorably. By prognosis, they actually mirror more intermediate stage HPV-negative tumors. So, they are very good outcomes.

Kevin Harrington, MD, PhD: Yes, I think that’s true. But, again, I think for those patients with T4, N2C, and especially N3 disease, we know that our local and locoregional therapies, including chemoradiation, may be particularly successful in controlling disease above the clavicles. That’s the group of patients where we have the concern about metastatic relapse, either in the early or in the later phases of their disease process.

Ezra Cohen, MD: And, in fact, Kevin, the new AGCC staging is going to take that exactly into account for HPV-positive disease.

Transcript Edited for Clarity