Bill Klaproth (host): This is OMS Voices, an AAOMS podcast. I’m Bill Klaproth and with me is Dr. Simon Young, who is here to discuss oral cancer and the future of treatment. Dr. Young, thanks for being here today. 

Dr. Simon Young: Thank you so much for having me, Bill. I really appreciate it. 

Bill Klaproth (host): Yeah, it’s great to talk with you. So, let’s start at the beginning. Can you explain to us what oral cancer is, how many people are affected, and what are the different types? 

Dr. Simon Young: Sure. So, a baseline for folks out there who want to, I guess, a definition of what cancer is, it’s really an unregulated proliferation of cells. So, essentially what happens is for your average person who may notice an oral cancer, it may start off almost as a lump or a strange-looking ulceration that’s red or white in their mouth. 

And sort of the biology of it is that these cancerous cells will continue to grow and grow and nothing stops them. And the other problem about cancer is that it can spread to other parts of the body, and that’s a process called metastasis. So, oral cancer specifically deals with these cancerous outgrowths that are occurring in the oral cavity.

 But just as a note for your listeners, oral cancer is part of a larger subset of cancers called head and neck cancers. And so head and neck cancers, as you can imagine, from the neck up, they can occur in various places and we sort of categorize them into the oral cavity and oropharyngeal cancers which I started off mentioning. 

And that’s sort of like the mouth, the tongue and the back of the throat. Then you have these laryngeal or hypopharyngeal cancers, and that’s the voice box. Other areas include the nasal cavity and the sinuses. There can be nasopharyngeal cancers. And of course, all of us make saliva. 

And even your salivary glands can get cancer as well. So those are all sort of the big soft-tissue areas where cancer can occur. Also, rarely you can get cancers in the bones of the jaws and so those can arise as well and cause issues. 

Bill Klaproth (host): Yeah, there’s a lot there, Dr. Young. So, let me ask you this. You said early symptoms would be lumps or sores or discolorations. You also mentioned this could be cancer of the larynx, if you will, or voice box, or up in the nasal passages. For areas that we can’t see, are there any symptoms or warning signs that we should be aware of? 

Dr. Simon Young: Yeah, oral cancers, they can be, unfortunately, caught late. And so, you know, almost as a public service announcement, I had this feeling that if everyone was diligent about looking in their oral cavity, becoming familiar with it, and what I mean by that is, if we’re all brushing our teeth twice a day and flossing and looking at our mouths, we should all be sort of familiar with what our mouths and tongues and gums look like on a daily basis. 

And so, you know, if something like a red or white ulceration starts showing up, and let’s say it’s there for days and days and days and weeks go by, a lot of us clinicians feel that if you have this strange-looking growth in your mouth that is not gone after two weeks, you know, it’s one thing if you burn your mouth with a slice of hot pizza and it’s gone after a couple of days, okay, but if you don’t have any sort of obvious traumatic events and this ulceration or this mass is sticking around for weeks on end, that’s definitely something that should be taken up with your oral healthcare provider. 

Whether you go to a dentist who refers you to an oral surgeon later or you go straight to the oral surgeon. But someone definitely has to look at that. And that’s oral cancers. At least those are accessible. You know, for harder to reach places like the throat, you know, so if you think about people who have laryngeal cancers or the voice box, they may not really know they have a problem, and so they start having, let’s say, hoarseness of their voice or difficulty swallowing or those kinds of things. 

Bill Klaproth (host): So, if you’re experiencing hoarseness of your voice or difficulty swallowing, pay attention to that. Don’t delay. If you think something is wrong, it’s lasting more than two weeks, be safe, not sorry. Go see your OMS. So, let me ask you about HPV, the human papillomavirus. So, what role does that have in the development of oral cancers and what are those symptoms? 

Dr. Simon Young: Yeah, absolutely. And so, human papillomavirus has already been implicated in other cancers. And so, one huge benefit of living in a society like ours is that we have many screening programs in place. And so one thing that females get, for example, are regular pap smears because their physicians are looking for signs of changes in the cervical mucosa, for potentially HPV-related disease. 

So while HPV, the high-risk human papillomavirus, which is also essentially known as genital warts, while those things are known to be linked with cervical cancer in females, it’s also known to be linked with oropharyngeal cancer. And essentially, it’s a sexually transmitted infection and so, for patients who we counsel, who have a diagnosis with HPV-associated head and neck cancers, sometimes they wonder how they got those, and essentially these cancers take a long time to develop. Usually the theory is that at the time where sexual intercourse was initiated, that patient may have had exposure to high-risk human papillomavirus. 

And there’s thankfully nowadays our children and adults now have access to vaccines. But for those who started their sexual activity before these vaccines came on the market and were exposed to the human papillomavirus, this virus can essentially invade the tissues sort of at the base of the tongue and the tonsil areas and it sort of sets up shop there. 

And if it gains sort of this low-level infection, the proteins that this virus makes, they inhibit the normal sort of cell machinery that our cells use to check for errors. And if our cells can’t check for errors, they may start to grow and form progeny that have errors in their DNA code. 

And given enough time, and I mean time as in years, these sort of genetic mutations can pile up and eventually can lead to things like HPV-related cancers. And so the hope is in the long term that our vaccination efforts in children and our young adults will maybe decades from now result in lower rates of HPV-related cancers. 

But for those of us who sort of became adults before these vaccines were available, these HPV-related cancers are quite prevalent. What I mean by that is a lot of these oropharyngeal cancers, these ones at sort of the base of the tongue and the tonsils, up to 70 percent of those cancers are actually caused by the human papillomavirus right now. 

Bill Klaproth (host): Wow. So that’s why vaccines are so important, especially for a younger person right now, but this is really important to know. And Dr. Young, when you say sexual relations, we’re basically talking about oral sex, right? That’s how this happens, right? 

Dr. Simon Young: Yes. And so, when we explain that to patients, at some point there was a lesion in the form of a genital wart that was spread into the throat area, the oral cavity of the person who now has the cancer. And to be clear, also, Bill, not all HPV viruses are the high-risk ones. 

So, the vaccines cover both the low-risk types and the high-risk types, but the so-called high-risk types of human papillomavirus. Those are the ones that are associated with cancer development decades later. And the vaccine covers both the lower risk and the high-risk types. 

Bill Klaproth (host): Got it. So can you have HPV and not have it turn into cancer? I mean, can you have this in you, but it’s not going to develop into cancer if you were exposed at an early age or whatever? 

Dr. Simon Young: That is right. And don’t I believe that scientists really have a perfect grip on who develops cancer from HPV and who doesn’t. So it is known that the high-risk HPV infections can cause cancer. But, I don’t think it’s known with any certainty, why some people clear the human papillomavirus and never get cancer and others do. 

And so the best we can do right now is that if someone walks through the door with one of these cancers, especially the oropharyngeal cancers, as part of their workup, we’ll see if they are HPV-related or not, and that sort of drives their treatment. 

Bill Klaproth (host): So, you said our body can clear these, and in most cases, they do clear them. What are the factors that may contribute then to oral cancer risk? Are there certain lifestyle things that put us at a higher risk for developing oral cancer? 

Dr. Simon Young: Yeah, absolutely. And I also want it to be clear, Bill, the head and neck region, it’s a fairly complex region, and the vast majority of HPV-related cancers are actually not oral cancers. They’re the oropharynx cancers. So those are the ones sort of like back of the throat, you know, like sort of really far back on the tongue area of the tonsils. 

Interestingly, if you look at the oral cavity cancers, sort of like the inside of your cheek, or your tongue or your lips. Those ones are actually not really as HPV-related, possibly because of the mechanism of transmission. Right, but as you noted, you’re completely correct. I mean, for many, many, many years, we have known that oral cancer, one of the main key factors driving it are the so-called carcinogens, you know, the things that can cause cancer. 

And of course, it’s not just viruses that can cause cancer, it’s our habits. And so for those people who have exposure to tobacco, whether that’s smoking cigarettes, cigars, pipes, smokeless tobacco products like chewing tobacco and actually interestingly in, countries outside the U.S. parts of Asia, where betel leaf is chewed a lot and put into the oral cavity, those countries have extremely high rates of oral cancer. So, the use of those tobacco products, the use of heavy alcohol consumption also contributes. And, for people who smoke and drink their risk is much higher as well. 

Bill Klaproth (host): Oh, man. Well, I could definitely see that. So, say you have HPV, but it’s dormant. But you’re a smoker, and you’re a drinker. Because of those lifestyle activities, you could be inhibiting the growth of this, where it actually turns into cancer. Is that correct? 

Dr. Simon Young: I would see them as separate issues. So, what we would tell our patients is that, if you’re smoking, that is a risk factor for, I mean, aside from all the pulmonary issues, of course, you know, your risk of getting cancer and especially oral cancer is higher. If you’re just drinking and you’re drinking heavily, your risk of oral cancer is higher. 

If you’re doing both, it’s also higher. And separately from that, if you have happened to have been exposed to high-risk human papillomavirus, then that puts you at a higher risk for oropharyngeal cancer, which is further back in the throat. And so, you could have all those multiple risk factors. 

So, whether the cancer ends up, I mean, of course, stochastically, you may just live your entire life never have cancer. There’s some people who smoke and drink and never get cancer, but of course, we do know at the population level that if you smoke and drink and have exposure to high-risk HPV, your risk of getting these sort of cancers is definitely increased. 

Bill Klaproth (host): So, then what is the latest understanding of how precancerous changes in the mouth, through lifestyle or whatever, then turn into oral cancer, especially for those cases not linked to HPV? What’s the progression there? 

Dr. Simon Young: Right. So the common thread between cancers that are HPV-related and those that are sort of drinking- and smoking-related is that it all boils down to genetic changes. Now interestingly, now that the human genome has been sequenced and all of our cancer patients can all sort of have access to the sort of mutations that their cancers have, we’ve found at the population level that while both HPV-related cancers and the non-HPV-related cancers, like the drinking and smoking cancers, they both are full of mutations. 

Interestingly the sets of mutations are different, but they’re still bad. So I have to say, the take-home message is that, cancer by definition essentially is a whole bunch of genetic mutations in a cell that allows it to escape. 

So, in the normal course of life, we are constantly, our bodies have, there are trillions of cells in our bodies and constantly little errors happen, but usually, a cell either corrects the mistake in the genetic code before it forms two sort of progeny cells, or the mistake is so bad that the cell just dies and it never has progeny and so, you know, it ends right there. 

But of course, in rare events, and since you have trillions of cells always reproducing, the chances of, even if, a mutation is a rare event, you have trillions of cells which are reproducing all the time. And so, when you have these, constant smoking and drinking and HPV, you’re upping your risk for one of these sort of genetic errors to propagate to the progeny. 

And how that happens, interestingly, is that certain genes are, as I mentioned, they’re important to sort of doing what you call genetic housekeeping. So you know, cell A is dividing, it notices a mistake, and the cell machinery fixes that mistake before the cell goes on. But if that machinery, the one that does all the double-checking, if that machinery has a mutation and it can’t double-check things, then that cell can sort of escape its correction, and now it becomes a mutated cell. 

And it may sort of form progeny, and those progenies have that mutation, and they form it down to their progeny in an exponential fashion over time. Again, the bottom line is that cancer is a genetic process and it can be really sort of promoted by the use of either viruses or carcinogens. But, Bill, sometimes you’re just unlucky and you never smoke, you never drink, and you never get exposed to HPV and you get cancer anyways. 

It’s rare, of course, but that can happen. 

Bill Klaproth (host): So as I hear you, Dr. Young, this is how I’m thinking about it. Healthier cells have a much better chance of correcting themselves on a regular basis, whereas if you partake in bad lifestyle decisions – smoking, drinking, other things – your chances of your cells regenerating and correcting themselves properly are a lot less. 

So the bottom line is, if you partake in these bad lifestyle choices, bad things are more likely to happen at that point, like oral cancer. Is that right? 

Dr. Simon Young: Absolutely. I think the easiest way to think about it is this. You and I can get on the highway tomorrow, and there’s a finite chance that’s well-defined, I guess, by statistics, that you and I could get killed in a car crash. But if we’re safe, and we don’t speed, and we’re not drinking and driving, then, you know, our chances are a certain level. 

If you go out and have, a 24-pack, and go on this bender, and then jump in your car and decide to go 100 miles an hour, your risks are really increased, right? 

Bill Klaproth (host): Right – that’s a great analogy that makes it easy to understand. So let’s turn to treatment. What are some of the ways that are being researched right now to treat oral cancer in the future? 

Dr. Simon Young: Right. And so just to let your audience know, I mean, the basics right now is that the vast majority of oral cancers all get some sort of surgery. So the traditional sort of pillars of cancer treatment were originally surgery because that’s all human beings knew how to do for hundreds of years, let’s say. 

And then sort of radiation therapy sort of came around, the late 1800s and then chemotherapy arrived sort of around World War II. So, for decades, sort of the armamentarium of what doctors have been able to treat people with cancer with is surgery, it’s a combination of surgery, chemotherapy and/or radiation therapy. 

And because we haven’t had enormous massive strides in those areas over the past few decades, the overall survival rate of five years for oral cancers hasn’t really risen much above, 55, 60 percent. We’re still, it’s not like their survival was a lot better despite surgeries maybe being a little safer and having better reconstructive techniques. 

And so one of the main breakthroughs that happened about a decade ago now is so-called immunotherapies. And that discovery was won by a pair of scientists around 2018 or so. Actually, it might have been 2015. But immunotherapy for cancer was one of the Nobel Prizes in medicine. 

And the reason it was such a breakthrough, because this was sort of one of the first times that you were administering a drug that was not treating the cancer, it was treating the immune system. And so, if you listen to the talks by one of those Nobel Prize winners, Dr. Jim Allison, who’s at MD Anderson right now, when he was working on this idea decades ago the pharmaceutical companies, it kind of messed with their thinking because they were like, wait, wait a second. 

You’re pitching an idea where you’re trying to treat the immune system and not the cancer. And so the breakthrough innovation there was that, with typical drugs, let’s say you may kill parts of a tumor, but remember, a tumor that’s growing in someone’s body, the cells aren’t exactly the same. 

They’re not all twins of each other, they’re not all clones. There’s sort of heterogeneity in that tumor. And so your targeted therapy may kill off 80 percent, 90 percent, 95 percent of that tumor. But if 5 percent of those cells are not killed off and they’re resistant to that drug, they can just kind of regrow and recur. 

And so one of the breakthroughs about immunotherapy is that because we have like this incredibly sort of diverse, like, billions of different kind of antigens can be recognized by your immune system, right? And so if your immune system is able to recognize all the different sort of parts of a cancer, even if one part escapes, there might be other parts of the cancer that don’t escape recognition from the immune cells. 

And not only that your immune system has memory. And so we take advantage of immune memory all the time, right? You know, if, someone catches a cold, or they catch the flu, or they get COVID and then, someone next to them gets COVID, that person who gave it to them in the first place, they’re not going to re-get it, right? 

Because your immune system recognizes that original pathogen, and you can apply that sort of concept to cancer, too. So the idea is that the results that we’re seeing for people on immunotherapies were breakthroughs at the time because they were getting so-called durable results. And what that means that at five years, not everyone responds to immunotherapy, mind you, maybe about one-fifth of people, 20 percent of people respond to immunotherapy. But if you were lucky enough to respond, you had a durable result, meaning that likely, your body was going to eliminate the recurrence. You know, the cancer would not come back. That was the idea behind it. 

But of course, I think on the research side, we want to do a lot better than helping just 20 percent of people on immunotherapy. And, I mean, aside from the very large cost and expense and toxicity with current immunotherapies, we’re trying to work on ways to deliver them more safely with less toxicity, but also increase the effectiveness of it. 

And when we were looking at that is that excited by the fact that for better or worse, oral cancer is an accessible cancer. It’s something that can be seen and physically manipulated, so it’s unlike if someone has a pancreatic cancer, deep inside your body, it’s not so easy to just like, see the pancreatic cancer and treat it with a needle. 

But oral cancer, I mean, dentists, oral surgeons, I mean, we’re in people’s oral cavities all the time. So if there’s an oral cancer that’s accessible to the clinician by someone just opening their mouth, there’s a way to potentially treat it by injecting it right there, chairside, with a potential immunotherapy drug. 

And, so what our lab works on are these new sort of injectable formulations of immunotherapies where we hope one day we can get into the clinic and the results are promising, you know, you could look at, you know, maybe it’s a little bit of a pipe dream to say we will eliminate cancer that way, but we would certainly hope that the kind of work that we’re doing would help become a solid part of the armamentarium of what an oral surgeon has, right? 

And so, to be clear, I’m not saying that we’re trying to find this silver bullet where you would inject in cancer and someone’s cured the next day or two weeks later and they just walk out the door. But certainly, in combination with surgery, potentially, maybe you would need a smaller surgery because the tumor shrinks, right? 

Or maybe you would need less radiation or less toxic chemotherapy in combination with what we’re proposing. And hopefully not only could we reduce the toxicity of treatment and the safety of treatment, but also increase the efficacy of, the treatments right now. 

Bill Klaproth (host): And as we’ve mentioned, it goes without saying that early detection is really important. 

Dr. Simon Young: Oh, absolutely, Bill. I like to harp on this a lot to our trainees, but I truly feel that if we had a very strong public awareness campaign about oral cancer, I really think that prevention would be a huge driver of bringing down rates. I mean, society’s done such a great job about raising awareness for things like breast cancer in women, colon cancer screenings, all these kind of things. 

And, you know, the oral cavity, it’s so accessible. We all hopefully see our own oral cavities every day when we brush our teeth. It’s not like a tumor, it’s like deep inside your body, you can’t see it. And so if people just were aware of what their oral cavities looked like, and when they saw something abnormal, go to seek help I think that would be extremely beneficial for all of us. 

Bill Klaproth (host): For sure. If you see something, a lump, a lesion, a rough patch, it doesn’t go away after a couple of weeks, it’s still there. Better safe than sorry. Go see your OMS. Have it checked out. So, Dr. Young, how would a patient find out more about oral cancer? The problems with smoking, the latest research, treatment options. 

Where could someone research and find that information out? 

Dr. Simon Young: Oh, yeah. there’s a lot of stuff out there I would encourage people not to just Wikipedia it because that’s not necessarily validated, but, certainly our organization, so AAOMS has a website and if you go to MyOMS.org, there’s a lot of resources on there. 

And so, folks who are interested, they can learn about not just oral cancer, but various oral health issues. They can look for personalized advice and treatment options on there to start them on their journey. And if there is something that interests them there and they want to learn more, whether they visit their general dentist and get referred to an oral surgeon or go visit their oral surgeons with their concerns I would highly recommend that. 

Bill Klaproth (host): Dr. Young, this has been fascinating. As we wrap up, anything else you want to add as we’re discussing oral cancer and the future of treatment? 

Dr. Simon Young: Bill, I just like to say we’re living at a very exciting time. If you look at the history of cancer treatment, the innovations were slow over decades and decades and decades. I like to think about it almost like heart disease, you know? So you could make the argument that in the forties and fifties this country made a concerted effort to just learn everything they could about heart disease and how to prevent it, and how to treat it and do all these sort of preventions. And, I’d say that, yes, heart disease is still one of the number one killers in this country. 

But, we’re pretty good on the treatment side of things, and of course there could be a lot more done on the prevention side, but treatments are pretty good now. And I’d like to think, I’m very hopeful that with all the effort and resources that are being thrown at all the various cancers, including oral cancers and head and neck cancers hopefully in my generation, we’ll really be able to put sort of a dent in that disease and get a lot better sort of survival outcomes than where we’re seeing right now. 

Bill Klaproth (host): Well, that would be great news for sure. Dr. Young, thank you so much for your time. We really appreciate it. 

Dr. Simon Young: Thanks Bill, appreciate it. 

Bill Klaproth (host): Absolutely. And once again, that is Dr. Simon Young. And for more information and the full podcast library, please visit MyOMS.org. And if you found this podcast interesting, please share it on your social media and don’t forget to subscribe. 

Thanks for listening.