DR COHEN: When we talk about head and neck cancer, we talk about a disease that has several different subsites. And we have to realize that the clinical manifestations, the behavior and the therapy for different subsites is going to be a little bit different. So for instance, a nasal cavity cancer is going to present and be treated much differently than a larynx cancer.

We know that historically these have been primarily tobacco-related cancers, so oral cavity, hypopharynx/larynx and even the oropharynx were primarily due to tobacco, with alcohol having a synergistic role, especially with oropharynx cancers. But what we’ve realized over the last 20 to 30 years is that HPV plays a very important etiologic role in oropharynx cancers and, in fact, in this country and some other countries around the world, now HPV-related oropharynx cancer is overtaking in terms of numbers, the tobacco-related head and neck cancers.

So this is almost, in the United States, a 50-50 disease between HPV-related oropharynx versus tobacco-related head and neck cancer.

DR LOVE: Do you consider HPV testing standard in this situation?

DR COHEN: We do do it standardly for oropharynx cancers. And there are a few things that we need to keep in mind about HPV testing. And there’s some controversy about this as well. First of all that HPV is really almost exclusively an oropharynx disease. And the most commonly used test for HPV, which is P16 immunohistochemistry — and it’s most commonly used because it’s the easiest. Every pathology department in the country can do a P16 IHC. But the caveat is that it really is only reliable for HPV in the oropharynx. We should not be doing P16 testing in patients with oral cavity, hypopharynx, nasopharynx or larynx cancers. It should be restricted to the oropharynx. If you suspect an HPV-positive cancer outside the oropharynx, there are more sophisticated genetic tests that one can do, but for P16, that should be restricted to the oropharynx.

Getting back to your question, we now do it on all patients with oropharynx cancers, not because it’s going to change our management but because it’s going to inform prognosis. The one thing that we have learned about HPV-positive cancers is that they do significantly better than their HPV-negative counterparts even after controlling for all the other things like comorbidities, age, smoking status. HPV-positive prognostically is a better disease.

DR LOVE: So if we were to take 100 people who present as you describe, nonsmoker, location of lesion, et cetera, what fraction would be HPV-positive?

DR COHEN: Oropharynx, nonsmokers, now probably 80% of them, 90% of them would be HPV-positive.

In terms of the biology of this disease, we know that it’s a virus that becomes integrated with DNA and can reside there for a very long time. In fact, we think it takes about 20 years to manifest as cancer. We know that the virus turns off important tumor suppressor genes, p53 and RB, specifically. And that is likely how the carcinogenic process starts. We know it’s also a virus that’s exceedingly well at evading the immune system. And that has a lot to do with the fact that it doesn’t send off the immune signals that some other viral infections do. So it’s often not cleared by our immune system, which is really interesting.