HPV Oropharyngeal Cancer Treatment

[Dr. Mihir Patel]
At that point, when we talk to them [patients] at their postoperative visit, I tell them, "I know you're going to be worried about this, but you just got to understand that we've likely removed it. Or there is a possibility that it transitioned into the neck when it spread." Either way, I don't have an answer as to where it is directly. What I can tell you is that for us, and the way we would treat this is we would just radiate your neck on. Typically because the primary in theory could be from the tongue base, both necks get radiated.

When you radiate patients with typical IMRT, they are going to receive about, let's say, 30, 50 gray to the oropharynx, somewhere in that range, even if you're only radiating the necks. I tell them, "We're only going to radiate the necks. The oropharynx will get some radiation dose.

…

[Dr. Ashley Agan]
Interesting. Okay. Then when do you recheck that ctDNA? Does that happen before they start their radiation or do you wait?

[Dr. Mihir Patel]
We do it before. We do. We now use that as a biomarker for looking at the degree or the intensity of radiation. We have now cut back. Dr. Bates is one of our lead radiation oncologists, and he is championing this trial where we actually lower the dose to 36 gray. Three weeks of radiation, 36 gray for any patient that has a non-detectable ctDNA after surgery.

As you can imagine, a number of these patients are these unknown primary patients. That's a far departure from the standard 60 grade that patients would get after surgery. The side effects are minimal. Again, this is on a clinical trial and this is where I was getting at, we are finding ways to lower doses meaningfully and studying it, but it takes a large randomized control trial to really understand the implications or change practice.

…

[Dr. Ashley Agan]
Okay. Do you have patients that say, "I've got undetectable levels. I don't want radiation. It's not there anymore. Can I just skip that?"

[Dr. Mihir Patel]
Yes, we have. I do caution them about that because we have seen recurrences. There's pretty good data to show that there is a worse hazard ratio in the event that you have no positive disease that likely warrants radiation. It's until we get a better understanding of the biomarkers to determine when we can back off radiation completely. I would never advocate that to a patient.

[Dr. Ashley Agan]
Yes. Right. Right now it's just trying to maybe de-intensify lower doses, like you mentioned, so that you can decrease the morbidity associated with radiation… Then I assume that the pathway, if we're talking about our patient where we did find the primary, it's a similar pathway, except they've got that additional information to be able to focus on where the primary was.

[Dr. Mihir Patel]
Yes. In fact, it still makes for some interesting discussion because in those situations, when you're talking about a very small primary, if we have two millimeter margins or greater at our institution, we won't even radiate the primary site. That's our standard workflow, but Penn has done it as a trial, in a clinical trial to show that you can avoid, it's called the avoid trial, you can avoid the primary site in situations that-- and so it's been studied in a meaningful way.

…

[Dr. Ashley Agan]
Yes. If you feel like you found the primary, you got two millimeter margins, the disease is not there anymore. It's not necessary to radiate that area. It's just going to add morbidity... For advanced disease, that's the conversation that you're having with people. If you want to do a combination of surgery with post-op radiation, it should be usually TORs followed by radiation or just chemoradiation from the start.

[Dr. Mihir Patel]
Yes. We tell patients, at least when I go talk to them, I say, look, you have a couple of options if they actually have a cancer that is resectable with surgery. A smaller T1, T2 primary, I'll tell them, you have two good options and it's really up to you in how you want to manage this. We will discuss the benefits and the side effects of each one. Thankfully, I'm able to do this with our medical and radiation oncologists in real time. We all work together and talk to the patient together to help them understand a little bit.

It can be overwhelming for patients. Some of them just say, "Look, tell me what you want us to do." We'll do that in that setting as well. It's a balance of understanding the patient and helping them understand what's going on with them, and letting them know what the reality is, is you have a stage one disease. What used to be called a stage four disease is actually now stage one disease. Now we're just trying to understand how we can minimize the morbidity for the next potentially 20 to 30 years of your life. That's usually what the discussion is centered around.

[Dr. Ashley Agan]
I wanted to just ask you a couple of things about talking to patients about HPV transmission in the patient who presents with cancer. Frequently for me, sometimes I'll have patients who maybe have a papilloma on their palate or something, but as we start talking about like, what is this? Then, oh, you say HPV and then they go, "Oh, I've heard of HPV. Isn't HPV an STD? Oh, wait, now are we allowed to kiss?" The conversation always devolves into that. I'm just curious how you counsel your patients about that.

[Dr. Mihir Patel]
Navigating that is a challenge. There's no doubt about it. The patients that get papillomas, I do worry about those patients because papillomas are, while they are considered the low-risk types, I worry about patients that, those patients in particular, if they get a high-risk HPV infection, then I do think they are at risk because for whatever reason, their immune system has not been able to take care of the infection. Those patients I would even consider for vaccination.

Now, getting back to transmission in partners, as we talked about earlier, this was likely an infection that happened years ago, chronic infection, something that may be there, may not be there, may not be in the saliva, but in the tonsil hiding. I tell patients that, look, the chance that you've already had an HPV infection is already very high, and the chance that you've cleared it is also pretty high.

…

[Dr. Mihir Patel]
Then there are studies to show that the ctDNA level, when it's elevated, actually finds or is an earlier way to detect a recurrence… We check it every six months, so based on their follow-up schedule.

[Dr. Ashley Agan]
Okay. If it looks like it went from undetectable to, "Oh, it bumped up a little bit," then you start imaging and PET scan, whatever?

[Dr. Mihir Patel]
I'll tell them that we're going to want to get a second test to confirm. Usually we'll do that. We'll do an early second test within six weeks to three months, and then we'll image early.

[Dr. Ashley Agan]
Okay. Is that because sometimes when you see that little bump, it's just too early to pull out all the testing because it might be negative too early?

[Dr. Mihir Patel]
You can get a false positive. Yes, you can get a false positive. The number's low, and I don't remember the exact number, but that can happen.

[Dr. Ashley Agan]
Okay. Interesting. Before I let you go, you mentioned the vaccine. How do you talk to your patients about the HPV vaccine? From an age standpoint, is there an age where it's like, oh, it's probably not worth getting it at this point? What are your thoughts?

[Dr. Mihir Patel]
Such an interesting question, only because I just think about the evolution of the vaccine. My wife was one of the first to get the vaccine when it was released around 2008, and she was right at the age limit. At that time it was only for females 26 and younger, so she was 26 at the time. Then it started to include boys and girls, maybe like six, seven years later, again at age 26. I remember thinking to myself, I was beyond that age and I was thinking, gosh, I really wouldn't mind getting this vaccine.

I feel like I'm exposed to it all the time. I just paid for it out of pocket, I guess when I was around 40 years old or so. Interestingly, now the age has bumped up to 45, 46 years old where it's covered. I just tell patients that story a little bit. I say, "I don't know what the answer is here. I would highly recommend, first and foremost, that you get your children vaccinated. This is not a vaccine that's associated with sexual promiscuity. This is a cancer vaccine. I would highly encourage you get your children and your family members that are younger vaccinated. For you, I don't know how much benefit it's going to provide.

It's something that you can do if you like to, you might have to pay for it out of pocket depending on their age." I tell them that and I say, "I just don't have any evidence to support doing it at this time. What's really important is to think about that next generation.