BackTable / ENT / Podcast / Transcript #23

Podcast Transcript: Human Papillomavirus and Head and Neck Cancers

with Dr. Andrew Day

We talk with Dr. Andrew Day about the Human Papillomavirus (HPV) and Oropharyngeal Cancers. You can read the full transcript below and listen to this episode here on BackTable.com.

Table of Contents

(1) Definition of HPV-Positive Oropharyngeal Cancer

(2) HPV Transmission, Infection, and Immune Response

(3) Treatments for HPV-Positive Cancers: Surgery, Radiation, and Chemotherapy

(4) Long-Term Prognoses of HPV-Positive and HPV-Negative Cancers

(5) HPV and Cancer Screening Methods: Oral Rinse, Flexible Scope Exam, and Imaging

(6) History of HPV Vaccines and Gardasil 9

(7) Current CDC Guidelines for HPV Vaccination

(8) Spreading Vaccine Awareness

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Human Papillomavirus and Head and Neck Cancers with Dr. Andrew Day on the BackTable ENT Podcast)
Ep 23 Human Papillomavirus and Head and Neck Cancers with Dr. Andrew Day
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[Dr. Gopi Shah]
Hello everyone and welcome. This is the BackTable ENT Podcast. Here we bring you conversations with the best and brightest minds in the field of otolaryngology with the hope that you can take this information and apply it to your practice. I am Gopi Shah and I'm a pediatric otolaryngologist practicing at Children's Medical Center in Dallas at UT Southwestern. And I'm here with my partner in crime.

[Dr. Ashley Agan]
I'm Ashley Agan. I'm a general otolaryngologist practicing in an academic setting at UT Southwestern in Dallas, Texas, and we are your hosts. We are so glad that you stopped by to check out the podcast today.
I'm so excited about our guest. I'll go ahead and roll into the introduction because there's a lot to say about Dr. Andrew Day.

Andrew Day is an assistant professor in Otolaryngology- Head and Neck Surgery at UT Southwestern Medical Center in Dallas, Texas. He is a Eugene P. Frenkel, M.D. Scholar in Clinical Medicine and a member of the Population Science and Cancer Control Program at the Harold C. Simmons Comprehensive Cancer Center. Following his residency in otolaryngology at Washington University in St. Louis School of Medicine, he received advanced training in head and neck oncologic surgery and microvascular reconstruction at Johns Hopkins University School of Medicine. As a head and neck surgical oncologist, he performs transoral robotic and transoral laser microsurgery for patients with throat cancer.

He has also obtained funding to study whether we can detect HPV-mediated throat cancer before patients have symptoms or clinical signs of the disease. This could be similar to the widely accepted practices of screening for breast, cervical, lung and colon cancer. He is about to open a study which will screen 500 middle-aged men in Dallas for HPV-mediated cancers using oral and blood-based biomarkers. Andrew is also a great friend and a wonderful colleague, and I'm so happy to have him on the show today. Welcome Andrew.

[Dr. Andrew Day]
Thank you, Gopi and Ashley.

[Dr. Gopi Shah]
It's so nice to have you. We have a pretty important and heavy topic today. I'm going to talk about HPV cancers in the head and neck. First, tell us a little bit about your practice and then go into what it means to say that a cancer is HPV-positive.

[Dr. Andrew Day]
Sure. I'm 50/50. I spend 50% of my time caring for patients and 50% of my time doing clinical research. A portion of my practice is dedicated to caring for patients with HPV-positive oropharyngeal cancer. I do perform transoral laser microsurgery and transoral robotic surgery for those patients, more often the latter. It's really exciting to be able to merge my clinical practice with my research interests in a very tangible way.

(1) Definition of HPV-Positive Oropharyngeal Cancer

[Dr. Ashley Agan]
When you say “HPV-positive oropharyngeal cancer,” tell us and our listeners, what does that mean? What's the difference between that and someone saying “throat cancer”?

[Dr. Andrew Day]
I'll start this answer by defining some terms, specifically head and neck cancer and human papillomavirus, or “HPV.” To the lay public, head and neck cancer is just any cancer that involves the head and neck, which could be thyroid cancer, skin cancer, sarcomas, anything. But to those of us in the field, head and neck cancer really specifically refers to cancers of the mucosa or skin that's lining the upper digestive tract. So those would be cancers of the mouth, throat or voice box. And HPV, which I'll talk about in a second, is known to specifically cause at high rates of cancers of the throat or oropharynx. And oropharynx is the part of the pharynx that is behind the oral cavity or the mouth. So that's why it's called the oropharynx.

The other term that I'd like to define is HPV. HPV stands for Human Papillomavirus. There are over 200 types or strains of HPV and some of these cause warts or cancers. But 13 high-risk types have been defined and identified and are known to cause cancer. We think that these are transmitted primarily through sex, and then there's debate about non-sexual transmission, which we'll discuss later. So to back into your question again, at the risk of oversimplifying things, to say something is an “HPV-positive cancer” is to distinguish it from what has been traditionally categorized as “head and neck cancer” for decades, honestly until 2007.

We always thought that the skin cancers that were lining the throat were caused by smoking tobacco, or maybe trauma like a sharp tooth that's irritating the tongue constantly, or constantly biting your cheek. But in the later 1990s and early 2000s, we started identifying cancers that were behaving really differently than those traditional chemical carcinogen-induced cancers. And in 2007, ultimately the International Agency for Research on Cancer determined that HPV does cause throat cancer. And so now there are these two buckets. There are the HPV-mediated throat cancers, throat cancers that are caused by HPV (we also call those “HPV-positive cancers”). And then there are “HPV-negative cancers,” so those that are not caused by HPV, which are caused by those other etiologies that I mentioned earlier.

[Dr. Gopi Shah]
Yeah, that's a great way to distinguish it. In terms of the oropharynx, just to get into specifics, so tonsils and tongue base are the two primary locations when I think of HPV-positive oropharynx cancers.

[Dr. Andrew Day]
Yeah, that's true. And a much smaller proportion might involve the soft palate (which is also part of the oropharynx) or the back of the throat (which is called the posterior oropharynx). But basically, Gopi, you're right. Those are the two dominant locations for these cancers.

[Dr. Gopi Shah]
When we say “HPV-positive,” I always also think of cervical cancer, anal cancer, penile cancer. Is it the same HPV strains? Are these all sort of similar in terms of the relation with HPV?

[Dr. Andrew Day]
Yeah. So these 13 high-risk types are responsible for all the cancers of these different anatomic sites: cervical, anal, penile, vaginal, vulva and oropharynx cancers. The thing that's different about them is that the distribution of which type causes cancer at which location varies. So for instance, HPV 16 is actually the dominant cause of cancer in the oropharynx and anus, whereas the other types are responsible for a greater proportion of cervical cancers.

[Dr. Ashley Agan]
For patients who present to our practices with new cancers, can you talk about how a patient with an HPV-positive squamous cell carcinoma might present differently? Is it different? Is it the same? Do they look just like your patients who come in, or is the clue that maybe they don't have that history of smoking and drinking?

[Dr. Andrew Day]
Yeah, they have a very unique presentation, which immediately clues you in to the fact that they likely have HPV-mediated disease. I would say at least 50%, if not more, patients will present with neck mass and oftentimes they'll be totally asymptomatic otherwise. They might not even have pain. Some other patients will present with issues with swallowing, maybe voice changes, maybe a sensation of their lump in their throat or minor discomfort. That's in pretty stark contrast to our HPV-negative patients whose dominant symptom is fairly severe pain associated with weight loss and everything else.

(2) HPV Transmission, Infection, and Immune Response

[Dr. Ashley Agan]
Can you go briefly into how the virus can lead to cancer?

[Dr. Andrew Day]
Yeah. This will be a big oversimplification as well. I'm not a molecular biologist and I imagine that they might take me to task for oversimplifying this much. But if I think about how HPV causes cancer, I simplify it down to three steps. The first is that the high-risk human papillomavirus has to infect a cell. Once it infects a cell, this second step is centered on our immune systems and whether or not our immune systems can recognize the infection and clear it. When an average person has an oral cavity or a throat infection, they clear it within six to seven months and almost everyone, probably 99% of people, clear it within two years.

But, there's a small fraction of patients, that for some reason, the immune system doesn't detect the infection, doesn't clear the infection and it just hangs around. And in those patients in whom the infection hangs around, this third step is that the virus starts to make these two proteins called E6 and E7. These two proteins inactivate tumor suppressor proteins. Our cells normally have these proteins that prevent the cells from going rogue and becoming cancerous. The proteins are called p53 and retinoblastoma. Those are active in us all the time right now. But when HPV infects a cell, E6 and E7 proteins inactivate those tumor suppressor proteins and then the cell can go rogue and essentially become a cancer. So that's the mechanism by which HPV causes cancer.

[Dr. Gopi Shah]
Do we know the numbers for the prevalence of the virus in the community? What percentage of people have been exposed?

[Dr. Ashley Agan]
We're saying it's sexual transmission. So on one hand, I think that the prevalence should be high, but on the other hand, in terms of the HPV causing cancer, we said it's a small percentage. So how do you explain that to patients and families? Is it just bad luck?

[Dr. Andrew Day]
Yeah, that's a great question. And honestly, we don't fully understand why. I mean, there's so much we still don't know about this. We only recognized that it definitively caused cancer in the throat 14 years ago, which is just a blip in time. In terms of community prevalence, specific to oral cavity and throat infections: I think that if you take 100 middle-aged men, aged 45 to 65 right now, and you tested them, 15 of them would have evidence of an oral or throat infection, and 7 would have evidence of a high-risk oral HPV infection.

Now, that's in stark contrast to females. If you took the same group of females, we think that only 1 of 100 might have a high-risk oral HPV infection. So the community prevalence of this virus really varies significantly according to age and sex. I bypassed this when I was talking about this earlier, but there's a bi-modal distribution. There's this peak in prevalence of HPV in individuals in their 20s, and then another peak in individuals in their 50s and 60s. We think that this can provide clues to what's going on and why patients are getting cancers in their 50s-60s, but we don't fully understand exactly why that's happening. Again, the highest prevalence is in this middle-aged men group.

[Dr. Ashley Agan]
Do we know why men specifically?

[Dr. Andrew Day]
We really don't. We think that maybe for women they may have been exposed to HPV in the cervix and the cervix may potentially be more immunogenic and may elicit more of an immune response than the throat does. And maybe when women get an oral HPV infection, the body's already seen it before, recognizes it, and clears it. This is in contrast to men who don’t have a cervix, so if they get an oral infection, their body might just be poor at recognizing it potentially. But we just really don't understand.

[Dr. Ashley Agan]
Just as I clarify, I want to go back to those 100 middle-aged men that you were talking about. When you say that a certain number of them would have an infection, are we talking about active infections or dormant infections? Could you clarify that?

[Dr. Andrew Day]
Yeah, that's a great question, Ashley. Infection, according to the best studies that are available, is just defined by what happens when someone swishes their mouth and gargles with something like a salient solution or a mouthwash. And if HPV is detected in that, then we consider that an infection. But what does it mean that someone has HPV? Is it active, or not? Is it just colonizing cells or is it infecting cells? Is it about to become a tumor or not? Is it already a tumor? There are so many things that we don't fully understand.

[Dr. Gopi Shah]
Okay. I feel like when the vaccine was coming out, the rationale for the age distribution of who would get it, if I remember correctly, was based on, "Oh, well, a significant portion of older people will have already been exposed and should already have immunity." So it makes it seem like that the virus is kind of everywhere and everyone is going to be exposed at some point and develop immunity and I guess some people will continue to have infection.

[Dr. Andrew Day]
One of the things that we don't really understand is what's happening from age 50 to 60. Some people are surmising that maybe our immune systems are just not as strong. And so maybe there was some latent infection, some dormant virus, that was just hanging out and for some reason got reactivated because the immune system just gets weaker as we age. So again, there's so much we don't know, which is why this is a pretty fascinating field to study.

[Dr. Gopi Shah]
And before I move on, in regards to transmission, patients ask a lot about kissing when we talk about sexual transmission. Do we mean that it might be passed through kissing, or are we strictly talking about oral sex?

[Dr. Andrew Day]
The really well-defined risk factor for transmission, particularly for oropharygeal cancer, is oral sex. Giving oral sex is the most dominant exposure associated with getting an oral HPV infection. But vaginal sex and anal sex are associated with it as welll. The discussion about kissing is much less defined and I think there's a lot less evidence around it. I think that it is probably a mechanism by which people could get the virus, but it's just so poorly defined. Some people wonder if patients who engage in deep kissing or French kissing are more likely to get it. Again, I think that the risk of transmission by that means is certainly lower and less concerning to us than giving oral sex.

[Dr. Gopi Shah]
I can only imagine how difficult it is to have this conversation with patients if they are active or have a spouse or partner. As a patient, there’s this whole other person that they have to think about.

(3) Treatments for HPV-Positive Cancers: Surgery, Radiation, and Chemotherapy

[Dr. Gopi Shah]
In terms of treatment, I liked how you put the two buckets. You have HPV-positive oropharyngeal cancer, and HPV-negative cancer. I always think about cancer options. You have surgery, radiation, and chemo. When you first see the patient, do you think of transoral robotic surgery more often for HPV-positive than HPV-negative?

[Dr. Andrew Day]
I'll define treatment terms in general principles. Although these are biologically-distinct cancers, the overarching treatment principles that we apply to patients with chemical carcinogen-induced and the HPV-mediated cancers are actually largely the same. Depending on the stage, clinical, radiographic, and pathologic risk factors, patients are usually eligible for one of two curative approaches to treat HPV-positive oropharynx cancer.

The first is a primary surgery approach, and that could be followed by radiation with or without chemotherapy. These days, surgery is probably most commonly performed via transoral robotic surgery, less commonly by transoral laser microsurgery or other approaches. If radiation is needed, we usually give it about six weeks after surgery, with or without chemo. And the radiation is usually given at a lower dose. It's often by about a week. So five less treatments when surgery is performed, and the proponents of a primary surgery approach argue that this exponentially reduces the side effects of radiation.

The second curative approach is radiation with or without chemotherapy. And in this circumstance, radiation usually lasts seven weeks. The chemo drug of choice is cisplatin. And that's the most effective drug that we know of against this cancer, but it's also the most toxic. Now, to answer your question more correctly, to the best of our knowledge, patients are equally as likely to be cured by a primary surgical approach as a primary non-surgical approach.

[Dr. Gopi Shah]
That’s great. With HPV-positive versus HPV-negative cancers, is one more responsive to radiation or surgery? Is one a cleaner surgery? Do you feel like you get a better resection when it is HPV-positive? Does that kind of stuff matter on the micro level?

[Dr. Andrew Day]
We've recognized that patients with HPV-positive throat cancers have really good outcomes in general. And so because of that, we've been exploring whether or not we can reduce the toxicity of treatment. So with regard to your question about surgery, we haven't developed the definitive evidence for this yet, but we're leaning towards thinking that a smaller, closer margin, like a 2 mm margin, is going to be acceptable. Whereas for an HPV-negative cancer, we think that only a 5 mm or greater margin would be acceptable.

We're exploring a bunch of other ways in which we might reduce treatment toxicities, like seeing if we can decrease the amount of radiation we give after surgery. There’s less evidence on this, but we are seeing if we can maybe reduce or eliminate the amount of chemotherapy we give patients who might have lymph nodes that are involved with just a little bit of tumor spilling out of those lymph nodes. So we are really actively exploring what we call “treatment de-intensification” in this patient population.

[Dr. Ashley Agan]
Can you talk about why that's important just for people who may not be familiar with the long term side effects of having chemotherapy and radiation? What does that mean for outcomes as far as swallowing and things like that? Why is it important to think about de-intensifying the treatment?

[Dr. Andrew Day]
That's a really great question, Ashley. I would say the most common side effect that our patients deal with after treatment is dry mouth. Backing up just a little bit more, it's pretty common for most of our patients to require more than one therapy. Only a small percentage, maybe 15% or so, will get away with just a radiation-only approach or a surgery-only approach. Because a lot of our patients will need surgery and radiation or radiation and chemo, there is some real treatment toxicity. Because radiation is commonly a common denominator, the side effects of radiation are very real things that are experienced by our patients. That would include dry mouth and sometimes difficulty swallowing from either surgery or the radiation. I would say those are our two most common ones, but those can really profoundly affect patients. Decreasing these treatment toxicities is something that's really desirable for us and our patients. There are unfortunately a lot of other risks of therapy that we are trying to avoid, but I won’t get into that.

[Dr. Gopi Shah]
Andrew, if you have the same T2 tonsil in a 22-year-old and a 62-year-old, let’s consider side effects and potential. When I think of the 20-year-old, they have another hopefully 40 to 60 years left. But with the 62-year-old, I'm thinking, okay, in terms of life span, maybe they have 10 to 20 years left. How does age play a role in different treatment side effects, what do you recommend initially, in terms of surgery or radiation? And I'm sure other medical comorbidities come into play.

[Dr. Andrew Day]
Another great question, Gopi. The younger the patient is, the less inclined we are to give radiation for a variety of reasons, including the risk of radiation-induced cancer, which is very, very low risk, probably less than 1%, but it does happen in some of our patients. Late effects of radiation can be significant side effects. Sometimes, 5 to 10 years later, patients can develop strictures in their throat or in their swallow tube. So if we can, all things considered, we ideally want to avoid radiation, especially in younger patients. Now, our radiation techniques have evolved substantially. So the kind of toxicities that we were seeing even 10 years ago are so different than what we're seeing today. So the amount of dose that's given to nontumor structures is so much better today. Now, I'm only seeing an occasional patient with minimal, if any, side effects after treatment.

(4) Long-Term Prognoses of HPV-Positive and HPV-Negative Cancers

[Dr. Ashley Agan]
That's great. When I see that a patient is HPV-positive, I tend to be more hopeful because my sense is that the long-term prognosis is better. Is that accurate? Can you talk about prognosis for patients with HPV-positive squamous cell carcinoma versus HPV-negative?

[Dr. Andrew Day]
Thankfully, it [HPV-positive cancer] is a definitely more favorable cancer. It is by far more favorable cancer than conventional head and neck cancer caused by alcohol or smoking. When I think about this, most patients present with stage I disease, probably 60% to 65%. And we think that somewhere around 90% or more of these patients will be cured. In patients who present with very early stage I disease with favorable other risk factors, the likelihood of cure is over 95%. Even in patients with stage II and III disease, we still think the likelihood of cure is way higher than it is for patients with conventional squamous cell carcinoma.

(5) HPV and Cancer Screening Methods: Oral Rinse, Flexible Scope Exam, and Imaging

[Dr. Ashley Agan]
As a general ENT, when I have patients presenting to my practice with new neck masses, what are things that I need to be doing to make sure that we're getting these patients teed up and expedite sending them over to you guys to get treated?

[Dr. Andrew Day]
If you identify someone with a neck mass, especially in middle age, and there's no clear other explanation, with no obvious recent tonsillitis or infection, then going straight to a biopsy with an ultrasound guided FNA really helps accelerate our management. Also get a neck CT, and some imaging. If a patient comes to me with a neck CT and an ultrasound guided FNA, especially if it identifies that there's a cancer there, that helps me initiate treatment more quickly.

[Dr. Gopi Shah]
In terms of screening, when I think of cervical cancers in women, I think of pap smears. For oral cavity, sometimes when I go to the dentist, there's like a black light they’ve started to use. Is there a swish and spit, brush, or some other screening method for oropharyngeal HPV cancers?

[Dr. Andrew Day]
The best way that I can describe this is to contrast cervical cancer with oropharynx cancer, in terms of the anatomy. The cervix is smooth and if you put a brush in the cervix and you twist it around, you're likely to capture all representative cells in that area. Whereas if you were to brush the oropharynx (and people have used the term “oropharyngeal pap smear”), you are missing the tonsillar crypts. And we actually think that this cancer is arising in the tonsillar crypts.

So if you brush, you're just getting the surface of the tonsils, missing the crypts. Because of that, there's really no enthusiasm for a brush to detect these cancers, especially early on. If you brush someone who has an obvious cancer, then you'll detect it. But that, again, it's sort of irrelevant since we're trying to detect these early and it's not uncommon for patients to present with tiny, tiny little cancers (sometimes that are nearly undetectable) and a neck mass. So we know that these things can cause cancer when they're super, super small.

Now, to more directly answer your question in terms of oral rinse, unfortunately, all that tells us right now is that someone might have an oral HPV infection, which we know is super common. If we tried to do additional screening for the 7 out of 100 men that have a high-risk HPV infection, most of those people are going to clear that infection anyway, and we'll use way too many resources to further investigate that since only a fraction of those 7 out of 100 will end up developing cancer. So the study that we’re opening, we are exploring the use of oral rinse and some blood-based biomarkers to test for antibodies against those E6 and E7 proteins and evidence of circulating HPV DNA.

Evidence of HPV DNA in the blood really signals to us that a patient might have a cancer. We think that if patients have either of those two things, the risk of them having a cancer may be somewhere between 100 to 500 times higher than someone who doesn't have them. So if you were to triangulate someone like this, if they have a positive blood test and a positive oral rinse test, or even just a positive blood test, especially the people with positive blood tests, they should get screening, or at least in our study that's how we're evaluating it.

[Dr. Gopi Shah]
Let's say the blood test is positive. How are you going to screen? Where do you go looking? Is that just in your office, you're looking at the oral cavity, you put a glove finger, you're feeling stuff? Or are they getting an ultrasound to look for something?

[Dr. Andrew Day]
I guess it's probably really important for me to mention that I'm doing this not independently, I'm doing this with other key collaborators at MD Anderson and at Baylor College of Medicine. This is a multi-institutional study that I'm doing, with Erich Sturgis at Baylor and Kristina Dahlstrom at MD Anderson. So if someone has a positive blood test, all that tells us is that they're at higher likelihood for having an HPV-associated cancer somewhere. We have no idea where. It could be the throat, it could be the penis. It could be the anus for in a man and the vagina, vulva, cervix in a woman.

In our study, we're evaluating the feasibility of screening these people and sending them to an otolaryngologist to evaluate their throat and mouth with a flexible scope exam, sending them to a colorectal surgeon to do anoscopy and look at the anal mucosa, sending them to a urologist to test the urethra and penis, and also to sending them to a radiologist to look for lymph nodes that might be enlarged but still smaller than what we can detect clinically. And the radiologist is also using the ultrasound to look at the back of the tongue. I have great collaborators here: Brittny Tillmann, David Fetzer, Aditya Bagrodia, Craig Olson, Dwight Oliver, and pathology, who are helping me execute this study.

[Dr. Ashley Agan]
Wow. That's so cool, Andrew. You mentioned that the cancer is maybe developing in the crypts of the tonsils. Does that mean if you've had a tonsillectomy for whatever reasons in the past, this would be protective against getting an HPV-associated cancer?

[Dr. Andrew Day]
There are a handful of studies on this. I don't think that there is a significant drop in risk because in those patients, the cancer could just arise in the base of the tongue. Honestly, I would have to look back at those studies to answer that question definitively. And that's another question that people ask, like say I had an oral HPV infection and it didn't go away. What would I do? Like should I get my tonsils and my base of tongue (lingual tonsils) removed? That's really, really toxic therapy and patients are not going to swallow well after that. They may recover to something close to baseline, but it will be incredibly painful and there are other risks like narrowing of the throat with that kind of procedure. You'd probably have to do it staged. So there's not a lot of enthusiasm for that. Basically, this is still very investigational. I want to emphasize, if someone has an oral HPV infection with no clinical signs of anything, we're not currently recommending any kind of clinical action.

[Dr. Ashley Agan]
Right. In my practice, I see anxious spouses who feel like they've seen their loved one just go through this and now they feel like they have a tickle in their throat or something. They’re saying, "Take a look at my tonsils. I think there might be something there. We've been sexually active together. I probably have it too." There's just so much stress and anxiety around all of it. It can be a difficult conversation.

[Dr. Andrew Day]
Yeah. I agree. I have those often too.

(6) History of HPV Vaccines and Gardasil 9

[Dr. Gopi Shah]
This actually is a good segue to get into the HPV vaccine. Do we think, or do we know, if it is protective against certain cancers? I'm sure patients ask you about it, especially your younger ones or even the older ones and maybe their spouses. Can you tell us a little bit about the vaccine and its role for these patients?

[Dr. Andrew Day]
Right now, Gardasil 9 is the only HPV vaccine that's available in the US. Understanding its predecessors a little bit better can help patients and other clinicians understand what it does. So Cervarix was a bivalent vaccine, which meant it was designed to help the body develop immunity to two types of HPV, HPV 16 and 18. Those are the two high-risk strains of HPV that are most likely to cause cancer. It's a very strategic vaccine. Then, Merck developed Gardasil 4, which is a quadrivalent vaccine. So it targets four types of HPV, and they added HPV 6 and 11 to the mix. And those are the types that cause warts.

That was sort of a standard for a while, and then Merck developed Gardasil 9. So that's a nonavalent vaccine, which means it targets nine types of HPV. And so in addition to 6, 11, 16, and 18, it also targets HPV 31, 33, 45, 52, and 58. To more directly answer your question, we know that vaccination reduces the rates of high-risk HPV infections in the mouth. We think maybe by somewhere around 90%. So, we presume that it also protects against head and neck cancer. Because it hasn't been around long enough, so we don't know that definitively, but it's pretty much universally accepted that it does offer protection.

[Dr. Gopi Shah]
Has there been enough time to see a decrease in the incidence or prevalence of HPV-positive oropharynx cancers? Like for recurrent respiratory papillomas in children, I would say in the last five, seven years, those numbers have gone down because of the HPV vaccine. And I just don’t know if there had been enough time to see some of those numbers go down in your oropharyngeal patients.

[Dr. Andrew Day]
That's really interesting. I didn't know that about our RP. Actually, it's interesting because it's the opposite. Despite the fact that we developed and implemented the vaccine in 2006, in the US, HPV-positive throat cancer is actually almost an epidemic. It's expected to be 1.5 to 2 times more common in 2030 than it was in 2020. And if you don't mind, I'll give your audience some background information to better understand why we think this is the case. Most people get HPV-positive oropharynx cancer in middle-age, usually in their late 50s. And as I've already mentioned, we don't understand when these people got the HPV infection that caused their cancer.
What we do know is that there's evidence that some of them got their infection decades ago. I think the longest known case is someone who had HPV antibodies in their blood 28 years before they got their cancer. So we think that that person was exposed many decades ago. What we don't know is what percentage of people were exposed decades ago and got their cancer from an infection that might have hung around, versus patients that may have gotten it from more recent sexual activity. I think that's one of the holy grail questions in our field.

The way that I like to think about this and explain this to patients (which probably will be disproven in a few years) is the analogy that uses the concept of chicken pox and the varicella-zoster virus: They get the virus when they're young. In a portion of patients, it stays inactive and for some reason, reactivates as shingles when they're older, later in life. At least for some of our patients, that is what we think is going on. They got it decades ago, it hung around, and it didn't cause any problems. Then all of a sudden, it got reactivated and became cancerous.

Ultimately, because we think that many of today’s older patients were exposed decades ago. The cohort of people that have been vaccinated today is only in their 20s because the earliest people were vaccinated in 2006. If most cancers are popping up in your 50s, and we still have three decades of patients that have already been exposed, but won't get a benefit from the vaccine because we don't think the vaccine treats active infections. It only prevents infections from occurring. Those people in their late 20s, 30s, 40s, are all at risk still for developing this cancer. That's why we think that it [prevalence] is going to continue to rise, unfortunately.

[Dr. Gopi Shah]
So it's safe to assume that your patients who are presenting with HPV-positive squamous cell carcinoma did not receive the vaccination?

[Dr. Andrew Day]
No, they did not receive the vaccination. To additionally emphasize this point, we don't think that the vaccine benefits patients who have HPV-positive oropharynx cancer because again, we don't think that it treats active infections. It's just preventative. There are therapeutic HPV vaccines that are being studied that we think may treat active infections, but those are still in clinical trials.

(7) Current CDC Guidelines for HPV Vaccination

[Dr. Gopi Shah]
For your patients, who do you recommend to get the vaccine?

[Dr. Andrew Day]
Since patients that have HPV-positive oropharynx cancer probably again aren't going to benefit from it, their partners probably won't benefit from it either, particularly if they're in long-term monogamous relationships. Whatever the patient has, the partner's probably already been exposed to it for a long time. The partner has probably cleared the infection and developed an immune response to it. We think that partners might have a 1-2% likelihood of having an oral HPV infection. So partners and patients are less likely to benefit.

Setting aside the head and neck cancer patient, the CDC (Centers for Disease Control) has this advisory committee on immunization practices, and they're the group that makes recommendations for who should get the vaccine and who should consider getting the vaccine. This committee recommends that all children get two vaccine doses between the ages of 11 and 12. There are some circumstances in which they might need three doses, particularly if their immune system isn't working as well. They say that patients can get vaccinated between ages 9-26, but 11-12 is their ideal.

More recently, they expanded eligibility for the vaccine to people that were 27-45 years old. It’s a process called “shared decision-making'' where patients and their doctors come together, have a discussion about the risks and benefits of getting vaccinated, and then make a decision together. The thought is that most patients in this age range have already been exposed to HPV and maybe even a variety of different high-risk HPV types. They're less likely to benefit from vaccination, and we don't actually know how effective and how much vaccinating this group of people will actually benefit patients and serve the population. There are a certain group of patients that may be more likely to benefit. We know, for instance, that men who have sex with men are more likely to have higher rates of HPV infections. And so that might be a group in which doctors and patients might have a stronger preference for getting vaccinated. In my mind, if I were to identify the perfect person to get vaccinated in the 27-45 year age range, it would be the person who has had very few, if any, sexual partners before age 26, but who intends to have new sexual partners after vaccination. This person would have had a low likelihood of exposure in the past, but is more likely to be exposed in the future.

[Dr. Ashley Agan]
Thank you for clearing that up. That's very helpful.

(8) Spreading Vaccine Awareness

[Dr. Ashley Agan]
The last piece I wanted to ask you about is our role regarding vaccinations in general. As otolaryngologists, patients will ask us, what do you think about the COVID vaccine? Should we be reminding patients to get their flu shot every year? I always ask, "Are your immunizations up to date?" But I may not always specifically say, "Did y'all get the flu vaccine?" That discussion I think can be a little controversial just because I have people that don't believe in vaccines. I was just curious, what are your thoughts on the role of the otolaryngologist in vaccination? Should this be more of a discussion for the primary care doctor?

[Dr. Andrew Day]
I think that particularly with regard to HPV, we have this unique opportunity to discuss how vaccination could prevent throat cancer, which is something that we treat down the line. We know exactly how significant the treatment toxicities are for these patients. We could be helping patients avoid this or substantially reduce the likelihood of getting it. I think that all of us have a responsibility, and we should all be really encouraged to recommend and remind our patients to do this, again, because we see the substantial side effects that cancer patients end up incurring.

I would strongly encourage pediatric ENTs to encourage families to remain up-to-date on vaccines. Unfortunately, Gopi, this is a big issue. Barely 50% of children or adolescents who are eligible for their vaccines are up-to-date on their vaccinations. In Australia,where vaccine uptake has been much higher, there's evidence that HPV might be eliminated there. There's discussion about that becoming a reality. Whereas here in the US, unfortunately it's not, because our uptake rates are low.

[Dr. Gopi Shah]
I wish that the HPV vaccination age was younger, before 9 and 11, because when my kids are 9, we're not going to the pediatrician except for maybe once a year. If there's an immunization at 9, you might accidentally skip that visit. It would be easier to remember the HPV vaccination if your kids were young, and they were going to the pediatrician all the time, especially that first year.

[Dr. Andrew Day]
Exactly, they're getting vaccinated all the time during that first year.

[Dr. Gopi Shah]
I wonder if sometimes this HPV vaccination might get lost. Because it is sexually transmitted, I think that social stigma can play a role in vaccination. And so that counseling has to be tough as well.

[Dr. Andrew Day]
One thing that I don't think that we've mentioned in this talk, that’s really important for families and parents to know, is that HPV is almost ubiquitous. The CDC and a reasonable number of researchers think that somewhere between 80% to 90% of people will get an HPV infection at some point in their life, somewhere in their body. It's so common and prevalent I think the stigma of this needs to be substantially reduced because again, almost 9 out of 10 people will get this at some point. If we're vaccinated, we have the chance to make a real mark on reducing that.

[Dr. Ashley Agan]
Well, this was a great talk. We really appreciate it, Andrew. Do you have any last thoughts that you might want to leave listeners with, any big take home points or things that we might've forgotten to touch on?

[Dr. Andrew Day]
We're still making tons of progress. Gardasil 9 still only covers 7 of the 13 high-risk types. Those are minor causes of cancer. Hopefully, we'll continue to make progress. The vaccine may not prevent every cancer that can be caused by HPV, but has real significant potential. I would implore our listeners to emphasize that to their patients, and if they're patients, to make moves on getting their kids vaccinated.

[Dr. Ashley Agan]
That's awesome. Thanks for being here today, Andrew.

Podcast Contributors

Dr. Andrew Day discusses Human Papillomavirus and Head and Neck Cancers on the BackTable 23 Podcast

Dr. Andrew Day

Dr. Andrew Day is an an Assistant Professor of Otolaryngology Head and Neck Surgery at UT Southwestern Medical Center.

Dr. Gopi Shah discusses Human Papillomavirus and Head and Neck Cancers on the BackTable 23 Podcast

Dr. Gopi Shah

Dr. Gopi Shah is a practicing ENT at UT Southwestern Medical Center in Dallas, TX.

Dr. Ashley Agan discusses Human Papillomavirus and Head and Neck Cancers on the BackTable 23 Podcast

Dr. Ashley Agan

Dr. Ashley Agan is a practicing ENT and assistant professor at UT Southwestern Medical Center in Dallas, TX.

Cite This Podcast

BackTable, LLC (Producer). (2021, May 25). Ep. 23 – Human Papillomavirus and Head and Neck Cancers [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.

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Head and Neck Cancer Condition Overview