Intro: Welcome to UAB MedCast, a continuing education podcast for medical professionals, providing knowledge that is moving medicine forward. Here's Melanie Cole.

Melanie Cole, MS (Host): Welcome to UAB MedCast. I'm Melanie Cole. And today, we have three UAB physicians in a thought leader panel conversation to highlight the intricate nature of head and neck cancer surgery. Joining me today is Dr. Harishanker Jeyarajan, he's a Head and Neck Surgeon in the Department of Otolaryngology and an Associate Professor; Dr. Carissa Thomas, she's a board-certified Otolaryngologist and fellowship-trained in Head and Neck Surgical Oncology and Microvascular Reconstruction, and she's an Assistant Professor; and Dr. Benjamin Greene, he's an Otolaryngologist and Associate Professor.

Doctors, thank you so much for joining us today. And Dr. Jeyarajan, I'd like to start with you. How have you seen the incidence in head and neck cancer change in recent years and where in the continuum of diagnostic criteria is HPV a factor in this trend?

Harishanker Jeyarajan, MD: So, you know, when we talk about head and neck cancers, we're largely talking about head and neck mucosal cancers and predominantly squamous cell cancer. So, squamous cell carcinomas form about 90% of all the head and neck cancers that we deal with at UAB. Now, head and neck cancer is in general the seventh most common cancer in the world. And, overall, historically, but still kind of to some degree, about three quarters of these cancers are due, or attributable to some degree, to smoking and drinking. And that's been historically the case for a number of years.

What we have noticed, however, is a combination of factors has changed that landscape. So, over the past couple of decades, there's been a significant improvement anf progress that's been made in tobacco control around the world. Not necessarily in every state, every country, but overall on a global scale, there's been a significant reduction in smoking, or in daily smoking, to the degree of about 30% reduction in men and women, roughly over the past 10 to 20 years. So, that's led to a significant reduction in the amount of cancers that we see attributed to smoking. And at the same time, we've seen the emergence of HPVs, or the human papilloma virus, and that is slowly becoming the predominant cause for head and neck cancer overall on a global scale. Now, the important thing to remember is this is significantly variable depending on where in the world you are. So, for example, here in the South, we still have a pretty high incidence of cigarette smoking and alcohol intake. So, that still plays a significant role for us overall.

The human papilloma virus at the moment is predominantly associated with oropharyngeal cancer. So, we can go into this later, but the human papilloma virus is a sexually transmitted virus, of which there are over 200 subtypes, of which 13 to 15, classically associated with cancer. And head and neck region HPV 16 is the most common subtype that's associated with cancer. Broadly speaking, we consider maybe three subsites in the head and neck aside from skin. Three mucosal subsites being oropharynx, oral cavity, and the larynx have some association with HPV with the oropharynx being the predominant subsite that has a direct correlation to HPV-related malignancies. At the moment, we would say that, in the U.S., 70% of oropharyngeal cancers are now attributable to HPV 16. And that's a significant shift from 10 to 20 years ago.

Benjamin Greene, MD: I think that was a really good summary, Hari. The thing that's unique about Alabama is that we are an outlier in terms of head and neck cancers compared to the rest of the country, where we have many more per 100,000 than many of the other states. And we're considered a high risk state from the Alabama Centers for Public Health for head and neck cancers. And while, you know, HPV is a huge, huge cause of this, the most common associated risk of head and neck cancer is still alcohol and tobacco use. And so, the number one thing you can do to avoid head and neck cancer really is quitting smoking.

Because we talk in terms of HPV and we speak in terms of HPV, but what we're finding is a lot of the HPV infections didn't come, you know, six months ago and then you get cancer. They came years and years and years ago, five to 20 years ago, the HPV infection happened or maybe even longer and has eventually came into cancer.

Carissa Thomas, MD, PhD: Yeah, and I guess I would just jump in with one more piece in that it kind of ties into the decreasing incidence of smoking, which has resulted in a decrease in the incidence of oral cavity cancer. But there's still actually a rise in oral cavity cancer in young patients who don't have any of the typical risk factors, so not smoking or alcohol related and not HPV-driven. So, that's a trend that we're seeing as well.

Host: And now, we're going to get into the HPV diagnostic criteria a little bit later. But Dr. Thomas, as we're getting into this topic, what makes head and neck cancer so challenging and unique? I'd like you to speak about some of the effects of these types of cancer and the treatment on patients themselves and for other providers that are counseling their patients on what to expect as they head into this journey of cancer treatment. I'd like you to speak about that for a minute.

Carissa Thomas, MD, PhD: I think there are a few reasons why head and neck cancer is so challenging, both for patients and providers. You know, one aspect is it's just an anatomically complex, dense area. It's a small region of the body that has really important structures related to function, nerve structures, vessels, those sorts of things. So, any sort of treatment that you do is going to have a lot of morbidity and a lot of side effects.

And those side effects affect functions that not only are essential for life, but also bring a lot of enjoyment to life. So, things like eating and swallowing. You know, so much of our lives centers around social gatherings with food, going out to eat at restaurants. So, any impact on the ability to do that really affects the person, both from a nutrition standpoint, and a social and psychological standpoint. There's also, of course, talking, speaking, and not just being able to produce voice, but also being able to articulate words so people can understand you. All of those things can be affected by our treatments. And then, finally, just appearance overall. We have come a long way in reconstruction, but we're still far from perfect. And so there are significant effects on appearance, which can make people feel socially isolated and lead to other psychological issues, depression. And we do know that head and neck cancer patients have a really high rate of suicide out of all cancer patients.

So, I think trying to balance aggressive treatment, because survival rates are still poor. So, trying to balance that aggressive treatment with minimizing long-term morbidity and functional outcomes makes head and neck cancer really, really difficult.

Host: Dr. Greene, due to the intricate nature of these cancers, tell us a little bit about how it's evolved in recent years, how medicine has changed to improve outcomes and help patients live longer, better lives. I'd like you to speak about some of the emergent technologies, improved imaging, advancements in screening techniques, intraoperative imaging, and how they are impacting early diagnosis.

Benjamin Greene, MD: One of the things that I really like about treating head and neck cancer is the amount of change that is going on within the field. And I think that at a place like UAB, what we don't want to be doing is looking at ourselves in 10 years and be doing the same thing that we're doing now. We want to be doing something better and having more to offer for the patients. And a lot of that has to do detecting tumors and how we detect them with advanced imaging, how we utilize ultrasound and point-of-care ultrasound within the clinics to be able to monitor people's necks and look using a high-definition ultrasound technology that we have in the clinic to examine people's necks and even biopsy things using the ultrasound guided technologies that we have.

But there's also things that we can do to just raise awareness of head and neck cancer. And so, just knowing that a neck mass in an adult is something that you have to be worried about all the time is something that we want to get out there and just improving the education, improving that about people, that people have will really help.

Now, in terms of advanced diagnostics, PET imaging, and being able to localize tumors more with the advanced MRIs and PET imaging that we have is obviously just slowly, gradually changing, but our monitoring techniques are even improving. And so, we're looking at circulating high-risk HPV DNA. And it's a new adjunct for cancer monitoring in HPV-positive cancers and looking at the circulating DNA in terms of is this cancer coming back. Even though it's not detectable by imaging, we can detect it in bloodstreams of patients who have had previous cancers that were HPV-related.

On the intraoperative side, you know, when you think of these things you think of preoperatively, how do we diagnose the patient? Intraoperatively, how do we do surgery to treat this patient? And then postoperatively, how do we monitor the patient for recurrence and healing? And so, our intraoperative improvements have really come in terms of access to the tumors like you had mentioned, Melanie. And the real change that has happened is through some of the robotic technology and some of the endoscopic technology. And I'd really like to hear Dr. Jeyarajan talk about that more, because he's really a national and international expert on robotic surgery, especially using a specific type of robot that is geared very much towards otolaryngology and head and neck cancers.

Harishanker Jeyarajan, MD: Just to add to what Ben said, I think, the only other thing I would say before I get into robotics, probably HPV vaccination has been a significant evolution and development over the past decade or so and the introduction of vaccination for boys as well as girls. We know that the 9-valent HPV vaccine covers over 80-90% of the viruses responsible for orophageal cancer. And we know that will significantly reduce the incidence, prevent cancer moving forward.

But leading onto robots, so like Dr. Greene said, you know, when we talk about the operative management of cancers, probably one of the more well-known, well-established advancements in the management of surgical robotics and advanced endoscopics has been incredibly useful in assisting us in the surgical management of head and neck mucosal cancers. Most tumors or cancers of the oropharynx, or the pharynx and the larynx, are very difficult to access traditionally because of difficulty in access. Surgery used to consist of having to split the face open to get access, to even start operating on the tumor. As you can imagine, this is a pretty significantly morbid approach to treating the cancers. And because of that, in the '80s and early '90s, that led to a big shift. Patients weren't getting surgery for these kind of cancers because their morbidity or the complications and the downsides of surgery was worse than what could be offered with non-surgical techniques.

The introduction of the surgical robot in the early 2000s really sort of changed the field. UAB was actually one of first three institutions involved in the FDA approval process for surgical robotics in head and neck mucosal cancers. And since then, there's been a significant evolution in the type of robots that we use. And like Dr. Greene alluded to, we've now got a new robot called the single-port robot, which was FDA approved for head and neck cancers in 2018 to 2019. And this allows us to enter the pharynx and get access to the pharynx and the larynx using a three-dimensional camera, and multi-jointed instruments with 720 degrees of instrument articulation, which allows fine articulation, fine dissecting ability, as well as magnified endoscopic assessment, which significantly improves our ability to operate within these tumors and bypass the morbidity of just the access part of the surgery.

And so with that introduction, particularly when we see people with HPV-related disease, there's been a shift backwards to now offering these patients surgery as a formal management protocol and avoiding the need for radiation altogether in some patients or sometimes reducing the radiation dose they get, which significantly improves their long-term function. Along with these advanced instrumentation, we have seen improvement in surgical optics to assess margins.

One of the biggest issues when you're trying to operate on a patient is you want to be able to get clear margins on a cancer. There's no point in offering surgery for a cancer patient if you don't get clear margins. That means if you don't get all the cancer out, leave no cancer behind. And sometimes it can be very difficult to do, because sometimes it's really hard to know microscopically where the end of the cancer is. We sort of use our eyes. And with magnified loops, it does help, but it doesn't always give us an exact answer. We traditionally have relied on what we call frozen section analysis, which means that we cut the tumor out, and then we send a margin, a sample tissue from the margin to the pathologist, and get them to look at it and tell us have we cut the cancer out or is there still cancer left behind in the tissue that I'm leaving behind?

The problem with that is while the pathologists are very good, it is a technique that's prone to sampling error, which can sometimes mean that it's not as accurate. And if we don't get a clear margin in the first cut, there's a significant risk that even if we cut back to a clear margin, we will leave microscopic residual bits of cancer behind. And again, that's due to a sampling error. But we have developed a lot of techniques over the past decade or so, particularly the past five years, using different modalities such as surgical fluorescence. We are one of the leading centers in the U.S. trialing intraoperative fluorescence to help us detect microscopic cancer with our eyes and with the camera systems that we use. So, that means that we can actually see the microscopic margin of the cancer rather than without having to rely on taking samples to send to the pathology lab. And other techniques such as confocal laser endomicroscopy, that is essentially using a tiny little camera that acts as a microscope in real time. We can put that probe on the tissue, and we can see when the cells start looking abnormal and starting to look like cancer. And so in real time, we can use that microscope in the operating room to guide our resection margins, to improve our ability to get what we call clear margins in the first instance. And that gives us the best chance of offering the patient a long-term cure.

Host: That's fascinating. Dr. Thomas expand a little bit and follow the thought line of Dr. Jeyarajan and speak about reconstruction. As he was talking about what the evolution of treatments has been, speak about reconstruction and how that has evolved over the years to really give a better quality of life and the technical considerations you'd like other providers to know as your expertise in this area.

Carissa Thomas, MD, PhD: Microvascular reconstruction has certainly evolved over the years. You know, the first microvascular cases probably really started in the 1970s. And these cases were historically 24 hours plus, patients spent weeks in the hospital, and doing a variety of different techniques to try to get to these, basically, what are tissue transplants to survive.

And over the course of the last 50 years, we've come a long way. First of all, the surgeries are significantly shorter. Techniques have improved. We know how to be more efficient in the OR. Reduced surgical times decreases postoperative complications. That's well established. So, being more efficient is key for these surgeries. We've learned a lot from our outcomes about appropriate medications to use, appropriate fluid management, things along those lines. So, we've gotten a lot more precise on how we manage patients postoperatively, to both improve our free flap survival as well as decrease complications from the medications and other interventions that we used to do.

So, I would say now our success rate at doing microvascular reconstruction's, you know, 95% or better. And the real key with these kinds of reconstructions is you can more precisely kind of replace like with like, and try to improve the functional outcomes more than we could in the past.

And I think I'd probably conclude with the biggest advance in reconstruction that's happened in the last 10 to 15 years is the use of virtual surgical planning, and essentially that's taking the preoperative imaging of the patient's tumor and the donor site that you're planning to use for reconstruction. And these are typically all bone reconstruction cases. And you work with an engineer and a planning software and very precisely plan out where you're going to make your tumor cuts, how you're going to cut your reconstruction, and you can get prefabricated cutting guides and plates so that everything fits together much better in the operating room, and this then leads to better outcomes. So, you have less complications with the reconstruction, less complications with the hardware that's used to put things together, and then also decreases the operative time. So, I think that's been a really exciting evolution in reconstruction and continues to evolve in that people are doing dental implants at the time of surgery so that they can have dental reconstruction, relatively quickly after surgery. And my hope is that we'll continue to try to push the envelope and try to get more functional outcomes with more innervated type of reconstructions that will hopefully long-term improve the speech and swallowing difficulties that we struggle with now.

Host: Dr. Greene, as the three of you are here together, tell us about the multidisciplinary approach at UAB Medicine, the importance of this comprehensive approach with many different subspecialties involved for these complex patients.

Benjamin Greene, MD: I think that what makes head and neck cancer so unique as this has been alluded to a little bit by Doctors Jeyarajan and Thomas, is just how important it is to the way that human beings function and interact with the world. And so if you think about the head and neck, not only is it cosmetically sensitive in that, you know, if you make an incision on somebody's face, it's very important to them, but also what we do affects how people speak. We remove people's voice boxes for cancer and have to rehabilitate not only how they speak because they have no voice box, but also how they swallow because we've changed the inside lining of their throat and sometimes move skin from their arm or thigh there to recreate the esophagus. So, you can imagine that now you're thinking in terms of not only is the cancer gone, but we have to have speech and swallowing therapists, and speech pathologists that are within our department to really meet with these people beforehand, during and after their time and work with them basically for their whole life. So, that's one aspect of it that we work closely with.

Another is dentistry and oral surgery in terms of whether or not patients have to have their teeth removed before radiation. If we have to make it cut through the bone near a tooth and is that tooth going to be healthy, and to doing an implants after surgery, if necessary or desired by the patient. So, that's another person. How we work with radiologists and the Radiation Oncology teams, because cancers can be treated with chemotherapy, radiation therapy, surgery, and a variety of other treatments. And so, we're working with medical oncologists for chemotherapy, radiation oncologists for radiation and proton therapies. And that is another aspect of the team. And the list goes on and on.

We have multidisciplinary tumor boards for squamous cell carcinoma, for skin cancers, for thyroid cancers, all of these that work within the head and neck and all of them have different folks that interact with us. And so usually, for head and neck cancer, as the surgeon, and this isn't always true, but usually we're the point of contact for the patients coming in first. And when they come in to see us, we coordinate the care for those patients in terms of where they're going, how they're doing and facilitate the followup.

And now that being said, we say that we coordinate the care, but what we really do is have nursing coordinators and specific patient care coordinators who also work with the patient. So, that is another aspect of this, where we talk about interdisciplinary teams. These can all of a sudden include speech pathologists, radiation oncologists, medical oncologists, surgeons, dentists, oral surgeons, radiologists, nurse coordinators, social workers. A lot of patients have difficulty coming to places to get care. And if they do need surgery, how are they going to care for the tracheostomy tube after this? How are they going to care for their feeding tube after this? And so, all of these resources go in to really making sure the patient has not only the best prognosis and cure, but also the best functional recovery afterwards and making sure they get to treatments on time, making sure that they're doing all this. So, it really is truly the definition of a team effort to get patients the care they need in a timely fashion and the rehabilitation that they need. And that's what makes head and neck cancer different from a lot of other elements that people can get because of how intricate and how important it is to people's lifestyle and function going forward.

Carissa Thomas, MD, PhD: Dr. Greene was saying, and I wanted to mention an aspect of UAB that I think is particularly unique, and that is our Sullivan Survivorship Clinic, which was started a few years ago basically to help patients navigate this kind of complex multidisciplinary team and identify at the time of diagnosis, what that particular patient needs, to have a successful treatment course. And they follow the patient through treatment and then in the surveillance phase and then finally in the survivorship phase. And I think that that's a real strength of UAB that we have this resource for the patients. And so, I didn't want to be remiss and not mention, that aspect.

Host: Such a robust care team and a comprehensive approach, and I thank you all for being with us. And Dr. Jeyarajan, last word to you, you were speaking about HPV, Gardasil, how that could change the landscape of what you're seeing as far as head and neck cancers. I'd like you to wrap it up for us. What excites you in the research world? Promising new therapies, any game changers? How do you feel that the field of head and neck cancer is evolving in the coming years and the conditions under which you believe patients would benefit most from your incredible experience and expertise.

Harishanker Jeyarajan, MD: As we sort of alluded to before the last question, I think that we look at it in with regards to surgical modalities and surgical techniques. If we look at it to surveillance and screening, I think each of those areas has promising developments that I'm really looking forward to seeing how they evolve over time.

When it comes to cancer prevention, the HPV vaccination I think is showing a lot of promise. We know that particularly with the introduction of the vaccination for boys, I think that that is going to help us a lot, because these cancers often affect patients that are young and otherwise fit and healthy and have no other risk factors. And as we've alluded to, all of us today, surgery or any kind of treatment in the head and neck, particularly in the oropharynx or the pharynx near the larynx, has significant morbidity that will stay with them. for the rest of their lives. And so if we can prevent that, that's amazing.

The use of HPV DNA for long-term surveillance is an amazing, very simple, but an amazing modality. It's cheap. It's easily obtainable. And as we're finding now, especially if the testing is done before treatment and they continue throughout the course of recovery and surveillance, it can even be more sensitive than our current standards of imaging. So, it's a very nice technique to screen patients. It's very convenient and it's very sensitive, which is excellent.

With regards to treating these cancers, obviously, I'm a little biased. I'm a robotics surgeon, and so I'm really excited about the developments in robotics, which UAB is really kind of at the forefront, both in the adjunctive measures that we can use with robotics, such as advanced optical imaging, the use in targeted interoperative fluorescence, but also with the expansion of what we can use robotics for.

Currently, the surgical robot, particularly the Intuitive system, is really FDA approved for cancers of the pharynx, particularly the oropharynx. But what we are finding is that with application of the technology and modification of some of the instrumentation that we use, we can use it for management of difficult-to-assess and difficult-to-examine laryngeal cancers. We can use it for management of hypopharyngeal and I've even used it for the management of early upper esophageal cancers. And so, it's offering patients a new form of treatment that avoids the morbidity of an open surgery. And what that does is it gives patients options and that's really what we want. We want patients to feel like they have options, in deciding their treatment course. It means that we can still look at radiation. But surgery is now an increasingly available option, it's increasingly viable option. And even if you have an advanced tumor that needs radiation, by using these kind of techniques, we can look at reducing the radiation, which will significantly affect the long-term morbidity and improve their long-term function, which again we've highlighted numerous times. The head and neck region is a very complicated region with numerous different functions that are important for the way that we interact and communicate with the world around us. And so, anything we can do to preserve those functions, particularly in these patients that are otherwise high-functioning and doing well and young, I think, is essential.

Host: Thank you all so much for joining us today. And this physician roundtable thought leader conversation was absolutely fascinating and really eye-opening. So, thank you so much. And for more information, please visit our website at uabmedicine.org/physician. That concludes this episode of UAB Medcast. I'm Melanie Cole. Thanks so much for joining us today.