Update on the Management of Skin Cancer of the Head and Neck

Additional Info

• Audio File:uab/ua196.mp3
• Doctors:Jeyarajan, Harishanker;Carroll, William
• Featured Speaker:Harishanker Jeyarajan, MD | William Carroll, MD
• CME Series:Clinical Skill
• Post Test URL:https://cmecourses.som.uab.edu/mod/quiz/view.php?id=4757
• Guest Bio:Harishanker Jeyarajan, MD Specialties include Head and Neck Surgery, Head and Neck Surgical Oncology, Microvascular Plastic Surgery, Otolaryngology and Surgical Oncology. 
  
  
  Learn more about Harishanker Jeyarajan, MD 
  
  William R. Carroll, M.D., the George W. Barber Jr. Endowed Professor and widely-recognized leader in the field of head and neck oncology, has been named the chair of the Department of Otolaryngology in the UAB School of Medicine. 
  
  Learn more about William R. Carroll, MD 
  
  Release Date: March 31, 2021
  Expiration Date: March 31, 2024
  
  Disclosure Information:
  
  Planners:
  Ronan O’Beirne, EdD, MBA
  Director, UAB Continuing Medical Education
  
  Katelyn Hiden
  Physician Marketing Manager, UAB Health System
  
  The planners have no relevant financial relationships with ineligible companies to disclose.
  
  Speakers:
  William R. Carroll, MD
  Professor and John S. Odess Endowed Chair; Director, Head and Neck Oncology
  
  Harishanker Jeyarajan, MD
  Assistant Professor, Head and Neck Surgery
  
  Drs. Carroll and Jeyarajan have no relevant financial relationships with ineligible companies to disclose.
  
  There is no commercial support for this activity.
• Transcription:Melanie Cole (Host):  Welcome to UAB Med Cast. I'm Melanie Cole, and I invite you to listen as we give an update on the management of skin cancer of the head and neck. Joining me in this panel are Dr. William Carroll. He's the Department Chair of Otolaryngology at UAB Medicine and Dr. Hari Jeyarajan. He's an Assistant Professor and Head and Neck Surgeon in the Department of Otolaryngology at UAB Medicine. Gentlemen, I'm so glad to have you join us today. Dr. Carroll, I'd like to start with you. Tell us a little bit about what's happening with the demographics and rates of skin cancer. What have you been seeing in the trends?
  
  William Carroll, MD (Guest): Well, thanks, Melanie. All of the types of skin cancer are increasing in frequency. There are increases in basal cell carcinomas, squamous cell carcinoma, melanoma and Merkel cell cancer. And by some evidence, they're up, almost double, over the last 20 years or so. Today we're going to be mainly talking about non-melanoma types of skin cancer and primarily squamous cell carcinoma. By some accounts, that one is actually gone up almost 200%, since the year 2000. So, it's really on the uprise and a big concern.
  
  Host: Well, thank you for that. So, Dr. Jeyarajan, tell us the hallmarks of these types of skin cancers that we're discussing today and predictors of high risk lesions. So, while you're telling us the hallmarks and characteristics, speak a little bit about the risk factors.
  
  Harishanker Jeyarajan, MD (Guest): Sure. Thanks, Melanie. So, squamous cell carcinoma is as Dr. Carroll said is the most common non-melanoma skin cancer there is, particularly in the head and neck region. So, generally we say that that 80 to 90% of cutaneous squamous cell carcinomas occur in head and neck. They can occur quite variably, but generally they'll present as a red or ulcerated indurated lesion, rising from the epidermal part of the skin, so the superficial part of the skin. Like classically in sun exposed areas, which is why the head and neck is one of the most prominent sites for them to arise in.
  
  And they can grow at variable rates. They can grow quite fast. And we know that particularly in the head and neck, they do have also a proclivity to spread to the regional lymph nodes. Some of the more common areas that we see in the head and neck, we see them quite commonly around the ears and the back of the ears, the back of the neck. We quite commonly see them around the forehead, around the eyes, the bridge of the nose and the tip of the nose as well. Again, all areas that are prone to sun exposure. Exposure to sunlight is the most common cause of cutaneous SCCs, particular UVA and some UVB light as well. Around the world, I'm from Australia. Australia is quite notorious for having a high rate of skin cancers, but that is almost rivaled by the South of the US as well. We know that in general, the southern part of the US are five times more likely to get cutaneous SCCs in the head and neck than the Northern part. There are a number of risk factors. So, there are number of features that predict lesions posssessing what we call a higher risk feature. And these are the ones we particularly worry about in the head and neck cause a lot of cancers that arise in the head and neck do tend to portend to having high risk features, position, location of the cancer.
  
  So, locations around the periauricular areas, so that's around the ear, around the eyelids and the bridge of the nose, all carry significantly higher risk of both local and regional recurrence. So, that's means that cancer coming back, but also carries a significant risk of metastasis to the lymph nodes.
  
  Some other features that we find out on once we take the cancer out, the most worrying one is something called perineural invasion. With areas around the head and neck, particularly around the ears, the eyes and the bridge of the nose, the skin is relatively thin and the cancers often arise in very close proximity to big nerves.
  
  And once they get to those nerves, they can travel pretty quickly along those nerves to deeper parts of the head and neck and even towards the brain. And so perineural invasion, which is a feature that we see when we examine the cancer under the microscope, is a significantly high risk feature.
  
  Other significant risk features include size, particularly one's greater than two centimeters, invasion into the deep planes, into the subcutaneous fat, and any cancer in an immunocompromised individual or any cancer that has come back, carries a significantly higher risk of both coming back again but also of having metastatic spread to the lymph nodes. Dr. Carroll, would you agree with that?
  
  Dr. Carroll: I do agree with that. And the factors that make squamous cell cancer of the skin high risk, you can kind of think of them in terms of patient factors. So, patients who are immunocompromised, patients who have recurrent lesions. Lesions that are large and in those locations that Dr. Jeyarajan mentioned, those are at higher risk. And then, there are tumor related factors or factors that are seen more on microscopic examination, such as poor differentiation or a deep invasion. In the current staging system, if tumors are greater than six millimeters in depth, they're thought to be, much higher risk.
  
  So there are patient-related factors and then there's specific tumor related factors that make them, more at risk. Immunocompromised patients, probably a hundred times risk of developing a squamous cell carcinoma of the skin than a non immunocompromised patients. As, Dr. Jeyarajan mentioned, those that invade more deeply and invade nerves and all are particularly prone to recur and spread to lymph nodes.
  
  Host: What a fascinating aspect of these types of cancers doctors. So, Dr. Carroll, as we're speaking about, and I've learned so much on these shows over the years about the really amazing advances in radiologic imaging that have augmented therapeutic capabilities and diagnostic capabilities. What imaging techniques are commonly used for this? Are there any that have changed the landscape for you?
  
  Dr. Carroll: I would back up and say that, you know, most skin cancers that we deal with in the US are fortunately early stage. And they're taken care of lot of them in a dermatologist's office and they're very effectively managed. They don't tend to spread, that sort of thing. But the ones that are higher risk are the ones that we end up seeing at the university setting more commonly, and those are ones that we end up relying on the imaging for more commonly. And we go back to those lesions that are higher risk that we were talking about before. Those are the ones that we use the imaging modalities for most commonly. There's not a single modality that's kind of turned into the Holy Grail for imaging this type of skin cancer. But we make use of several different modalities sort of, depending on the situation that we're in. The most common imaging modality that we use is CT scans.
  
  And we're looking at overall depth and extent of the lesion on those scans. We're looking at the lymph nodes in the area. And we're looking at things like bone invasion and things like that. So, that's probably the most common imaging agent we use. As Dr. Jeyarajan mentioned before with nerve involvement and things like that, we more commonly will use MRIs to see the cancer progressing along nerve pathways more effectively or invading centrally. There are lots of physicians that rely on ultrasound for looking particularly at nodal basins. It's a very effective, fairly inexpensive way of looking at lymph node disease. And in some people's minds, it's more effective at seeing the superficial lymph nodes and then advanced imaging, things like PET scans and things like that are usually done when we're quite concerned that there might be distant disease, less likely used simply to analyze the local and regional extended disease.
  
  Host: Dr. Jeyarajan why is elective management of salivary glands important? And while you're talking about glands, speak about lymph nodes and how those are most effectively managed, if you would combine that for us.
  
  Dr. Jeyarajan: Yeah, sure. No worries. So, when we talk about the head and neck salivary glands and its relationship to skin cancers, we're really talking about the parotid gland, which is one of the four major salivary glands that we have in the head and neck. The reason it's important is unlike the submandibular gland and the sublingual glands, the parotid gland actually develops and encapsulates after the development of the lymphatic structures in the head and neck do. And so it actually, the gland itself contains a number of draining lymph nodes and lymphatic channels within the substance and the capsule of the gland itself. And so it actually drains lymphatics from the rest of the head and neck before it reaches the lymph nodes in the neck. And I quote, prior Fellow of UAB and prominent Head and Neck Surgeon in Australia, Christa Bion used to talk about the parotid gland being what we call a metastatic basin for cutaneous head and neck cancer, in that is often the first area that cancer drains to before it moves onto the neck. And so that's the main reason to at least to be conscious of the parotid gland when you're managing a skin cancer, because if it's going to spread to the lymph nodes, the first area that will most likely spread to is the lymph nodes within the parotid gland.
  
  We know that even in some of the larger series today, particularly in the South and in Australia, metastatic deposits from cutaneous squamous cell carcinomas make up around 30 to 40% of parotid cancers that we deal with. So, that really kind of blends into the next topic, which is how we manage the lymph nodes in head and neck skin cancers. And so in particularly in the head and neck where we know that cancers around the ear, the nose, and the eyes, have a higher risk for metastasizing relatively early to the lymph nodes, we will often clinically assess them, when we even dealing with a small tumor, so a tumor that's within two centimeters around the periauricular region, I'll often clinically examine both the parotid gland and the head and neck region for clinical evidence of nodal disease.
  
  If we see nodal disease, within the parotid or within the neck, we know from a range of studies, both in cutaneous head and neck cancers but also in mucosal squamous cell carcinomas, that these are best managed in a multimodal fashion. What that means is they're best managed by surgical resection of the involved lymph nodes followed by adjuvant therapy. So, if we have clinical evidence that the cancer has spread to the lymph nodes, they're best managed with surgical resection, which would involve as superficial parotidectomy at least and resection of the upper lymph nodes in the neck. Dr. Carroll, would you like to talk about sentinel lymph node biopsies and elective management of the neck when you don't have obvious disease in the neck lymph nodes?
  
  Dr. Carroll: So for, uncomplicated, non-melanoma skin cancers, we don't typically do elective node dissections. So, if there's no clinical or radiographic evidence of lymph node involvement, we don't typically do elective dissections. For the higher risk lesions, the question arises, should we be treating the lymph nodes in those draining basins that Dr. Jeyarajan mentioned? And one of the ways to determine if the cancer has metastasized to regional lymph nodes is using sentinel lymph node biopsies, and everyone's familiar with sentinel node biopsies for melanoma, and also for breast cancer and other things. It's used less commonly for cutaneous squamous cell carcinoma.
  
  There've been a number of studies looking at the efficacy of sentinel lymph node biopsy, and I think the short answer is kind of the jury's out, whether that is something that should be routinely done. There's not clear evidence that it should routinely be recommended at this point, but a number of investigators have shown that it's feasible to do. And that usually you can identify the draining nodal basin when that's done and in the series that they've done that if they find that the sentinel nodes are negative, most of the time, the patient's neck remains negative. So, the negative predictive value of a negative sentinel node biopsy is quite high.
  
  Host: Dr. Jeyarajan, tell us what is the role, if any of immunotherapy in skin cancer. What's exciting in the field right now?
  
  Harishanker Jeyarajan, MD (Guest): So, with skin cancer, we know that the cancer itself due to the UV light induced carcinogenicity, the tumors themselves tend to have what we call it high tumor mutational burden, which is particularly unique to cutaneous SCCs, even when you compare them to other mucosal SCCs and to melanomas. And so that along with the fact that we see in people that have immune deficiencies or immunosuppression, these people tend to have a high rate of cutaneous SCCs. We know that cutaneous squamous cell carcinomas do tend to have an intimate relationship with the immune system.
  
  We also know that, through numerous studies over the past decade or so that we don't have any great systemic options for management of cutaneous SCCs. We have surgery and radiation, but a number of retrospective studies looking at both platinum type chemotherapies and a phase three study from the trial group in Australia has shown that platinum type chemotherapy really makes no difference to overall survival in cutaneous SCC. And so the arenas can kind of ripe for some form of systemic treatment to treat distal disease, but also to try and improve overall survival on local regional control. And so knowing that cutaneous SCCs have a relationship to the immune system, people have started looking into the possibility or the applicability of immunomodulation, in the management of cutaneous SCCs. And recently there has been some really great work looking at a drug called cemiplimab. So, cemiplimab is an IGG 4 monoclonal antibody, that targets PD-1. So, PD-1 is a receptor on our T-cells that its signals program death in the cell cycle.
  
  And by blocking the interaction of that receptor PD-1 with PD-L1 or PD-1 PD-L1, which is a program death cell leg on the tumor, it actually enhances the antitumor activity of your own immune system by directing T lymphocytes to kill the tumor cells itself. And so, the use of immune therapy has been relatively promising in other forms of skin cancer, but in cutaneous SCCs, it really shows a lot of promise and we know that in the past five to six years, there've been an international collaboration among multiple institutions around the world, Australia included and the US included, looking at the use of cemiplimab in the management of widely metastatic and surgically unresectable cutaneous SCCs and the results of both phase one and phase two studies have shown a significant tumor response in both of those categories.
  
  So, tumors that have metastasized and tumors that are considered unresectable. So, that's really shown some promise. We know that the, the data hasn't shown that it's a, it's a magic pill. It certainly doesn't replace standard of care, which is surgery and adjuvant radiation. But we do know that there is incredible promise. Overall cells are responding to the immunotherapy, which has both been demonstrated under the microscope where you can see real changes in the tumor micro environment, but also clinically when you can actually see a response by reduction in the size of either the tumor metastases or the primary tumor itself. We still don't know exactly which cancers will respond best.
  
  We do feel that it's probably going to be better in cancers that have a particular high tumor mutational burden. And it stands to reason that tumors that have a high expression of PD-L1 are going to be more likely to respond to this type of treatment, although it hasn't been exactly born out of the study so far, that's kind of what we're expecting to see.
  
  I think in the future, one thing that this will promise is an extra arm of treatment or an additional arm of treatment to supplement or compliment primary surgery and radiation therapy. And that's something that Dr. Carroll and I have been looking into, is whether we can use cemiplimab in what we call a neoadjuvant setting. The current phase two studies have been used as an alternative in patients that have already had treatment or can't receive surgery. But one thing that will be interesting to see, is whether or not patients that present with local, regionally advanced disease or patients that have a bit particular higher risk of local recurrence, so people that have already had multiple recurrent cancers, whether we can give them cemiplimab in a neoadjuvant setting, so before we operate and allow the immune system to identify the cancer and start recognizing it as the enemy of the body and start attacking it before we even start surgery or radiation, and whether that will improve our long-term regional control and overall survival. So, I think that's kind of where the promise of immunotherapy lies with regards to cutaneous SCCs.
  
  Dr. Carroll: I would agree with that. And, and we don't know yet how we're going to use immunotherapy in the future, all the way. But I think, it's clear that it's helpful in multiply recurrent or metastatic disease, that's otherwise untreatable, and these newer roles of using it in a neoadjuvant setting or using it as adjuvant therapy for high-risk lesions that have been removed along with radiation, for instance, those are where some of the clinical trials are really headed right now.
  
  Host: Well, it's certainly a fascinating increase in your armamentarium of therapies for these patients. I'd love you each to have a final thought if you want to. So, Dr. Carroll, do you have any final thoughts you'd like to leave other providers with?
  
  Dr. Carroll: You know, you think of skin cancer is just some small thing on the skin that is easily dealt with and most of the time that's correct. But in a high-risk situation or when the cancer has been neglected or has become quite large or in an immunocompromised patient, these cancers can be just as deadly as any other type of cancer. They need to be treated aggressively and often in a multi-modal fashion. And it's great to involve the entire team, the surgeons, the radiation oncologist, the medical oncologist, the pathologist, everyone, to provide the patient with the best chance of treatment.
  
  Host: Dr. Jeyarajan, last word to you. What would you like other providers to know about skin cancers of the head and neck?
  
  Dr. Jeyarajan: I would very much that to mirror Dr. Carroll's statement. These cutaneous SCCs, while 80 to 90% of them are very simply managed and in the head and neck region in particular, they can become quite deadly and often people that have a current squamous cell carcinomas, particularly in high-risk areas in immunosuppressed patients. The scary thing is they can spread without any obvious sign to the eyes. They can spread surreptitiously through tissue planes, into the parotid gland and into the lymph nodes. And from there very quickly migrate the skull base. These are best managed at a level where we have a multidisciplinary team that is really top-notch and has a lot of experience in managing these.
  
  And this is a particular interest of mine and I very much appreciate seeing these kinds of cases and helping manage them because they can be quite difficult. But if managed appropriately, we can really make a significant difference and effect their overall survival.
  
  Host: Thank you both so much. What a very informative episode this was. Thank you again. And a community physician can refer a patient to UAB Medicine by calling the MISTline at 1-800-UAB-MIST. That concludes this episode of UAB Med Cast. For more information on resources available at UAB Medicine, you can always visit our website at uabmedicine.org/physician. Please also remember to download, subscribe, rate, and review this podcast and all the other UAB Medicine podcasts. I'm Melanie Cole.
  
  
• Hosts:Melanie Cole, MS