Transcribed by Anam KhalidFriday, June 18th, 2014

[Diagnosis and Treatment of Oral Diseases[ [Lecture #11 and 12] [Dx and Tx of Oral Cancer and Precancerous Lesions] by [Dr. Kerr]

[1] [D2 Diagnosis and Management of Oral Cancer][Dr. Kerr] Good afternoon. Did you guys get the posting? Fantastic. Is this it? The class? Seems like a smaller group than usual but anyway. Okay. Lets just turn some of the lights down. Thats better, right? Okay. Okay, so in the second year, you obviously learn a little bit more than we gave you in this area than last year but youve still got a lot to come in third year. In the famous OMPR course which Im sure youve all heard is the most enjoyable course in the college which I think it is. So, but I hope youre enjoying this course and I know youve had some good lectures with Dr. Shah

[2] [N/A][Dr. Kerr] I cant remember whether I showed you this case but its sort of a nice case to get this lecture going. So here was approximately 40 year old Hispanic male who presented to the College of Dentistry, can you imagine what his chief complaint was? Right. So hes got a toothache. And thats what brought him in unfortunately. And so, you know, this is an opportunistic examination. In other words, you take the opportunity and when we took the opportunity, the student, who was actually a D3 student, spotted something in the floor of the mouth. It didnt look quite right and so if you compare one side to the other, it looks different. So can anyone see or comment on what they see?

[3] [N/A][Dr. Kerr] so what you see is a little white change and that white change has a little bit of a redness around it and when you look at that white change and you can see a little bit of granularity. Maybe a couple of little fissures on the surface. And thats not supposed to be there, is it? I mean, the normal epithelium doesnt look like that. And so then you ask yourself the question, at least you should be asking yourself the question, well, you know, what is this? You know? Its not normal. You can sort of wipe it, and it doesnt wipe off. And youre asking yourself well how would someone traumatize the underside of their tongue? And of course you take a history and this gentleman is a heavy smoker, hes a heavy alcohol user. He has some medical issues and so you put all that into the equation and you cant quite work out still why its there, hes not sticking an aspirin on the surface there because of his toothache. Some people do that, they can cause aspirin burns in their mouth. And theres nothing else really going on other than, of course, hes a smoker and a heavy alcohol user so that tips it off and you go through that sort of algorithm, that thought process that we went over when I lectured to you last year. And then youre left sort of in your own mind, scratching the top of your head thinking well what do I do now? And as you may recall, if you come across an epithelial lesion that you cant explain why its there, you start thinking about some sort of pathology and you start thinking well, is this potentially malignant oral disorder? And so the right thing to be thinking is its abnormal, we have to rule out that it isnt malignant or doesnt have the potential to become malignant and so the next step would be to what? Take a sample. Yeah. Procure a tissue sample. So we did that.

[4] [N/A][Dr. Kerr] And this is what the histopathology shows. Now, you know, you havent really gone into, you know, histopathology in a big way yet but this is a superficially infiltrating squamous cell carcinoma. So this is actually a cancer. And I think this is probably the earliest cancer, well, one of the earliest handful of cancers that Ive seen that are that small. That, first of all, you have to ask yourself the question, well would I have actually detected that? Would I have visualized that? Of course when its projected about a thousand times the size on the screen or more, you know, its pretty obvious. But believe me, if you were to, you know, have a hundred dentists come in and examine the patient and none of them, you know, were biased to what the other ones were seeing, I guarantee you wouldnt have all 100 of those, you know, looking for it or seeing that little lesion. Particularly if theyre coming in to the emergency clinic because most dentists when someone comes in for an emergency, just really focuses in on that emergency. But when youre looking at that tooth right next to it you see this little area. So, the question is, how many people would really be looking for it? And even if they were looking in the area, how many would sort of go, hang on, theres a lesion there? So, if you can do that part, youre doing really well. And then, the decision is well what do I do with it? And thats another decision-making sort of process. So by the time you graduate, hopefully youll have a good solid decision strategy, you know, for these types of things. But its all contingent upon being able to detect this in the first place.

[5] [N/A][Dr. Kerr] So what happens to a patient like this? Well this is quite a few years ago and here is the patient in the operating room. The small circle circles the area that we biopsied. We actually removed most of it just taking a little punch biopsy. And then around that is another circle and thats the margin. So generally when you have a malignancy, an oral malignancy, you take the malignant tissue and the margin just to be safe. And that margin depends on whos doing the surgery but its usually anywhere from a centimeter to a centimeter and a half. And so thats what happened.

[6] [N/A][Dr. Kerr] And so it was surgically removed. These little probes or lacrimal probes to reposition the submandibular, sublingual ducts, the Whartons duct. Because the lesion was right in that area.

[7] [D2 Diagnosis and Management of Oral Cancer][Dr. Kerr] And then he had a split thickness skin graft taken from his lateral thigh with a little dermatome and then its sutured into place. And Ive been following this guy for the last six or seven years now and Im happy to report hes had no recurrence of this disease. Hes had some issues related to tobacco use. We got him to quit, then he started smoking again, we got him to quit, and then he started smoking again and so hes been back and forth trying to deal with his tobacco habit. But he didnt develop any further disease.

[8] [N/A][Dr. Kerr] So, compare and contrast that patient to a patient that presents, and by the way when that first patient presented, he had no idea he had this little lesion in the floor of the mouth. It didnt cause him any discomfort. He was just in for that toothache. On the other hand, this gentleman who is in his 60s, and African American male, also very long history of over a pack a day of smoking for at least, you know, 40 years. Heavy alcohol intake, you know, in the range of greater than 10 units a day. Poor nutrition. He presents with a severe pain in his mouth. And his pain is from the problem that you see here. So this is at the other end of the spectrum. Youve seen the very very early squamous cell carcinoma. Well, here, were seeing an advanced carcinoma. And when you look in his mouth, you know, it just doesnt look right. And it doesnt take a lot of experience to be able to go, wow. I mean, youre looking at something that is, you know, a hundred times the size of the first one you saw. So its impossible to overlook this. Absolutely impossible. So he opens his mouth and you have to restrain yourself from going, OH MY GOD. And, obviously, when you palpate the area, you put your finger into the floor of mouth, thats his tongue and its all into the floor of mouth. Stretching over onto that edentulous alveolar ridge, pushing back posteriorly and infiltrating deeply into the floor of the mouth, such that when you do a bimanual palpation and you compare the normal side to the affected side, its indurated. That tissue is rock hard. Its infiltrated into all of the normal floor of mouth tissue which is normally soft and spongy. You are feeling that induration. So thats a malignancy that has spread deep into the tissues and is exquisitely tender to push on it. And the patient is having difficulty swallowing because every time he moves his tongue, it bothers him. And hes really in a lot of pain. when you examine his neck, hes already got a rock hard lymph node in his anterior neck and you can see this lump in his neck and you put your finger on it and hes got this hard, enlarged, fixed lymph node. And its totally different from what you feel on the other side. So youre already thinking well, hes got a malignancy and its already metastasized into his regional lymph nodes. So what are you going to do now? Well, obviously, youre going to refer him to the same person.

[9] [N/A][Dr. Kerr] And this is what the head and neck surgeon removed. So on top is the better part of his mandible because the lesion stretched across the midline all the way back into the oropharynx. And then on the bottom are all of the lymph nodes that they dissected including the metastatic lymph node. And that was a massive operation.

[10] [N/A][Dr. Kerr] And so here he is, having had the cancer removed. So, he doesnt have much of his tongue left. He doesnt have much of his mandible left. And thats his carotid sitting there with a little piece of string just above it with the carotid bulb. And now you ask yourself well what do we do now?

[11] [N/A][Dr. Kerr] Well, he has to have a grafting procedure done to replace all of that missing tissue. So, nowadays the surgical reconstruction is very sophisticated. I mean, for, you know, over at NYU theyre doing face transplants now. So, you know, this is relatively an easy procedure in comparison. So theyre taking the fibula and theyre using the fibula bone, which you can manage without. And they fracture it into the shape of the mandible. It comes with a skin paddle. It comes with its own blood supply. This is a free flap, a vascular free flap and they reanastamose that blood vessel to the local blood vessels and sow him up.

[12] [N/A][Dr. Kerr] and so here is the free flap and its been shaped into the shape of his mandible. Theyve already worked out what that shape needs to be, preoperatively.

[13] [N/A][Dr. Kerr] They bolt it all into place and sow that piece of skin. Thats going to be the rest of his tongue and then the floor of his mouth.

[14] [N/A][Dr. Kerr] and then sow him up. And thats just the first step to his therapy. So, hes going to have to wait for another six weeks and then hell need to undergo head and neck radiation and chemotherapy because he has advanced disease that has already metastasized into the regional lymph nodes. So, no matter how good a surgeon you are, you cant be assured that youve removed all of that disease and quite often, the pathology will show something at the margins. So he goes in and he has head and neck radiation and chemotherapy. And unfortunately, he had some problems tolerating he had a lot of side effects from the radiation and chemotherapy, had very very . mucositis he wasnt able to do the full regimen. Had a couple of breaks in treatment. And he ended up getting through and within six months he developed a recurrence in his neck and he died. So he went through all of this and the morbidity associated with all of this and really went through its an awful thing to go through all of the treatment and then died. So this is the problem with advanced disease versus early disease. So one guy is alive and well, 7 years later. This fellow didnt make it that long. And you ask yourself the question well how is it that we couldnt intercept him at that early stage? I mean, what happened? Did he never go to the dentist? And it turns out; he had been going to the dentist. I mean, maybe he wasnt completely reliable but there probably had been an opportunity to intercept this disease. So the question of delay in diagnosis is something that a number of researchers are investigating because, you know, there are a lot of different reasons for delay in diagnosis.

[15] [N/A][Dr. Kerr] So this was an email that I received from Jerry Yu, one of your former classmates from several years ago, class of 2009. I doubt youd remember me as I was rather unremarkable student wise and I dont think we had much personal interaction. I hope you are well and thank you for taking the time to read my email. So I entered private practice in 2010 after my residency, a very break-n-butter dentistry practice and actually had a patient with a lesion on the right lateral border of the tongue. I recommended a biopsy and of course he hemmed and hawed but after a while, finally convinced to do so and it came back as a squamous cell carcinoma. He ended up having that section of the tongue resected, and though his speech is more difficult to understand, hes overall fine and in good spirits. I hadnt really seen that many oral pathology cases and I really dont have much of an interest. But I did have to say that I noticed it because of your repetitive insistence from the school days. So both I and him owe you a personal gratitude. I was wondering da ra da da da and you dont need to worry about the rest. So of course, you know, I showed that around to Dr. Phelan, to Dr. Shah, to other people in the department and we were all really, you know, thats we live for this because, you know, were happy this may never happen to this dentist again, I mean, if you think about what the incidence is of oral cancer, its a rare disease. But you want to be there and you want to detect it because if nothing else, you can save one life, potentially. And it feels very good to do the right thing. Did you have a question?

[Student]So with like the most recent example you gave, would you even biopsy it or send straight to the surgeon?

[Dr. Kerr}Right. So, in a situation where you have something that is absolutely obvious and are you talking from the perspective of a general dentist? Yeah. So if you have something that you think is obviously a malignancy, dont touch it. Just send them right off. Because youre not really helping them along unless because youre basically delaying it by getting a biopsy. I mean, theyll get a biopsy anyway. But, sometimes when you do get a biopsy, in certain situations, it can actually cause some of the nodes to light up in an inflammatory way that when they get a CT scan, it can, you know, suggest that theres more disease in the nceck than there probably is. So thats one of the justifications for not getting a biopsy and probably sending them for a scan and then getting a biopsy. Yeah?

[Student]-- How long does it take for the disease to get to that point, to such an advanced stage?

[Dr. Kerr]Very good question. And Ill get to that in a minute. Generally speaking, this disease, overall, is relatively slowly growing but there are always examples of patients who have highly aggressive disease that literally, between one week to the next, its growing visibly each time you see them. So, its a good question. And unfortunately we dont always have, you know, when you see someone in a cross-point in time you dont really get that sense, other than by asking them questions. But many of these patients, theyve had this disease. I bet you anything that second guy had had that disease for at least a year and it just got slowly slowly worse. Now, it may have been in a precancerous state for quite a long time then suddenly transformed and then it really took off in terms of sort of a growth spurt. But, you know, again its hard to say because were not always following these things over time.

[16] [N/A][Dr. Kerr] So just some stats, I know youve had a bunch of this but this is the latest data from American Cancer Society, about 40,000 8,000 will die in the U.S., 2014.

[17] [N/A][Dr. Kerr] Most of these are squamous cell carcinomas. Im not going to get into all the other types. I might have a couple of slides later on but its mostly squamous cell carcinoma when it comes to the oral cavity and pharynx.

[18] [N/A][Dr. Kerr] Its about a 2.7 ratio, men to women.

[19] [Demographics of Oral Cancer-Age][Dr. Kerr] it tends to be in an older age group and thats probably related to longer exposure to potential risk factors, coupled with changes in the immune system, the immune surveillance, things like that. But, median age is 62 in the U.S.

[20] [Race/Ethnicity in USA][Dr. Kerr] its mainly in white males. Thats the biggest incidence, about 16.7 in white males. You know, it used to be that it was higher in, you know, in African American males but thats not true now. But what we do know is that African American males have a much higher mortality rate and thats probably related to the size of the tumor at the time of diagnosis and access to care issues. And so, thats probably whats going on.

[21] [N/a][Dr. Kerr] there are a lot of famous people whove developed oral or pharyngeal malignancies. Youve probably recognized quite a few of them. Sigmund Freud, Babe Ruth, Grover Cleveland who actually had his cancer removed in the East River on a boat. Colleen Zenk Pinter is a soap opera star. Aldous Huxley, one of my favorite authors. Sammy Davis, Jr. And most recently, of course, Michael Douglas. Ill get to that in a moment

[22] [N/A][Dr. Kerr] Unfortunately, you know by the time these patients have presented to us, theyve already got a lot of them have got spread in their cancer. So, over 50% of oral cancers are diagnosed after theyve already metastasized into the regional lymph nodes or to distant organs.

[23] [N/A][Dr. Kerr] Like this patient. And again, you ask yourself, you know, how is it that it took so long for her to come in and this thing didnt grow overnight.

[24] [N/A][Dr. Kerr] Sometimes they metastasize to the lungs or to other organ systems. So we generally will take a chest x-ray of our patients at baseline just to be sure that theres no cancer in the lungs.

[25] [N/A][Dr. Kerr] again, an overall 5-year survival rate, around 62%. So its a lot worse than many of the other cancers that are plaguing our population. Certainly a lot lower than breast cancer, colon cancer, prostate cancer. And its shocking really when you think about it, this is an accessible part of the body. I mean all you have to do is open your mouth. Its not like the pancreas. You can understand why pancreatic cancer is detected so often in late stage because you know theres no way of really screening for it. You cant look for it. You cant examine the pancreas very easily. Whereas with the mouth and pharynx, these are accessible parts of the body.

[26] [N/A][Dr. Kerr] And Ive mentioned to you about the mortality between African Americans and whites and its usually related to the staging at the time of diagnosing they usually have more advanced disease.

[27] [N/A][Dr. Kerr] This is a little study that we did with Dr. Morse.

[28] [N/A][Dr. Kerr] Whats interesting and if you read the American Cancer Society cancer facts and figures for 2014, were seeing an increase in tongue and tonsil cancers in the United States. So, oral tongue, not quite sure whats going on there and tonsil. Now what is tonsil? Well the tonsils, some of you may have had your tonsils removed. I had mine removed when I was five years old. Not only did I have my palatine tonsils removed, which are the ones at the back of the tongue or the ones at the back of the mouth in the oropharynx but I also had my adenoids removed, which are my nasopharyngeal tonsils. And then there are lingual tonsils, which are on the base of the tongue, thats what Michael Douglas had, is a base of tongue or lingual tonsil cancer. So, were seeing an increase in these oropharyngeal cancers and in tongue cancers. Again, Im not sure whats going on with the tongue cancer but the oropharyngeal cancers are on the rise. Does anyone know what the cause is for that? Right, you guys had a lot of information about HPV. So weve seen this emerging epidemic of HPV associated oropharyngeal cancers.

[29] [N/A][Dr. Kerr] So youve already been through the risk factors. You know, cigarette smoking, any form of tobacco is risky.

[30] [Its not just about cigarettes ][Dr. Kerr] So its not just about cigarettes. But there are lots of other habits that people use tobacco. And it depends; there are many sort of cultural factors. So in South Asia, theyre using tobacco with the areca nut. Thats an independent risk factor. And there are various chew tobaccos. Im not going to get into too much detail.

[31] [The Risk of Oral &Pharyngeal Cancer by Smoking & Drinking Status, USA, Males][Dr. Kerr] and we know that tobacco added to alcohol, theres a multiplicative effect such that it, you know, multiples the risk so in patients that are smoking and drinking heavily, they really have a really high risk. Some patients are, you know, between thirty to forty times the risk compared to the general population.

[32] [How any fruits and vegetables do you need?][Dr. Kerr] We also know that diet can play a protective role. A number of case control studies have shown this and patients who have poor diets are potentially at higher risk for developing cancer.

[33] [Human Papillomavirus 16][Dr. Kerr] And then weve got HPV 16. So I was rather shocked to see, it was probably a year ago now, on the New York Post that Sex Gave Me Cancer. Im actually going to be at the largest ever head and neck cancer meeting, 2,800 attendees here in New York in 10 days from now. And Michael Douglas is actually giving the keynote address. So Im sort of quite interested to see what he has to say. And so Ill be going to listen to him. Its principally HPV 16. There are other oncogenic subtypes of HPV but thats the predominant one. And we know that patients are more at risk for developing persistent HPV infection if they engage in multiple sexual encounters, both oral sex and otherwise and so we know that is a risk factor. We dont understand the natural history of this disease sufficiently to be able to pinpoint whos going to be at risk but, you know, its one of those things where we do know its the sexual habits. And it seems to be occurring in a more affluent population and potentially these are the patients more likely to come to the dentist so you may be encountering patients who present with the signs and symptoms of oropharyngeal cancer, which is usually lymphadenopathy because it tends to metastasize quite quickly from the oropharynx into the neck. The good news is that they seem to be very amenable to treatment, particularly radiation and/or chemotherapy. They seem to do pretty well. Having said that, you know, receiving radiation treatment is no walk in the park, in the short term, nor the long term. And these patients have a lot of problems for the rest of their lives as a result of being exposed to such high levels of radiation.

[34] [N/A][Dr. Kerr] So patient comes in and, you know, you do your exam and at some point youll see something. Were not quite sophisticated enough to be able to detect, you know, the changes, the early genetic changes, so generally, its contingent upon us performing an exam and visualizing something. And so if we visualize a lesion that we cant work out why its there and we think that there may be the possibility that this could be what we call a potentially malignant lesion or potentially malignant disorder, then we have to ask ourselves, well whats the nature of that? And is it cancer now? Is it potentially going to turn into cancer? Is it never going to turn into anything? What is going on? And so generally what we do is we take a biopsy and then we look at it under the microscope and it could be depending on the microscopic features, it could be a malignancy at that point or it could be a precancerous lesion and histopathologically we call that epithelial dysplasia. There are abnormal features that we see when we look at the cells of that epithelium that is in that sample. But all of those abnormal changes are confined to that epithelium. Its only when those abnormal cells break through the basement membrane into the underlying connective tissue that we have an actual malignancy. So until then there may be nasty cells. Those cells may harbor genetic mutations that are bad and it could drive that lesion to undergo malignant transformation down the road. We dont know because we dont have sophisticated tests to be able to assess those genetic mutations, at least not yet. In the research domain, may be, but its very expensive and its certainly isnt the standard of care. And so we rely on, you know, histopathology to guide many of the decisions that we make as clinicians. If its a malignancy, no question they need to be as per the standard of care. But if theyre a precancerous lesion, dysplasia, theres a little debate about what we should do.

[35] [N/A][Dr. Kerr] So, it used to be thought that, you know, this whole process took quite a long time and it would go through this sort of series of events, accumulation of genetic mutations over time that would lead from an innocuous lesion into something that looked a little more suspicious and that would be associated with a commensurate change in histopathology that was worsening from a mild dysplasia to a moderate dysplasia to a severe dysplasia to a carcinoma in situ, eventually to a malignancy. What we know is that this is not always linear, this process, carcinogenesis, and not always predictable. So sometimes Ive seen patients, they just jump right into a cancer. They dont go through all of the precancerous stages. And then Ive seen others who go through, you know, these precancerous stages and then become a malignancy and sometimes it takes 10 years. And sometimes it goes from a mild dysplasia and rapidly goes into a cancer. We dont know whats going to happen. Its very difficult to predict. Every patient is a little bit different.

[36] [4 Major Driver Pathways][Dr. Kerr] and there are a number of different pathways but the cell biologists, the experts on this have really whittled it down really to four major driver pathways. And this is related to, you know, defects in the genes that control the cell cycle of the keratinocytes as they start as a basal cell and they slowly divide and mature and then they get to the surface. Theyre the grandparents. They fall off. And then the other ones come through from the basal cells, which are the baby cells, ride their way up and it keeps going through that process. Well that whole process, that cell cycle, that differentiation of those cells from basal cells to the superficial cells, that can go wrong. Its, you know, its controlled by various genes that produce various proteins. And when you get genetic mutations in these different pathways, things go wrong. Cells dont divide properly. They divide in a way that they shouldnt. So thats one thing. The ability to suppress a cell that has gone wrong, we have systems, tumor suppressor genes that we produce in our cells that tell a cell, we dont like you and we shut them down and then we put them into apoptosis. Thats our way of dealing with it. But sometimes the ability to produce those normal tumor suppressor proteins is lost because of mutations in that tumor suppressor gene. And, you know, differentiation, you know, the way that the cell differentiates can sometimes go wrong. And then there are various other pathways. Again, Im not going to get into it but I want you to understand that there are lots of different ways that this carcinogenesis can lead to an immortal, you know, cell line.

[37] [N/A][Dr. Kerr] And it can be that certain mutations and certain genes, we get increases or losses in genetic material. We can get epigenetic changes where we get methylation in the promoter regions, which has an impact on how those genes are transcribed. So, lots of different things going on and these are some of the different genes in the differentiation, proliferation, cell cycle pathways, where we can find these genetic mutations and many of these cancers, you know, there are multiple genetic defects. And the primary cancer can have a different blend of those mutations than the metastatic cancer. So the cancers evolving constantly to be able to kill the host.

[38] [Progression vs. Regression? Aggressive vs. indolent?][Dr. Kerr] So this is why early detection is very important. So the question is, does this lesion that I see, that I encounter in clinic, will it progress? Will it regress? Will it be aggressive and move quickly or will it be fairly indolent? We know some cancers, breast cancers, prostate cancers can be youve all heard of patients whove had fairly indolent cancers. And then you hear of these other patients who have an early breast cancer and its very aggressive. And so, the same thing probably holds true for squamous cell carcinomas.

[39] [N/A][Dr. Kerr] And to answer your question again, I mean, youre not the fly on the roof of the mouth. I mean, if you were the fly on the roof of the mouth, looking down on that, on, you know, all of the oral structures youd be able to see how that lesion truly is evolving. But we dont have the luxury of being the fly on the roof of the mouth, do we? So we detect patients opportunistically, whenever we can, when patients come in for a new patient exam or a recall exam or an emergency exam.

[40] [Mild dysplasia: No progression][Dr. Kerr] So heres an example of a patient who has a white lesion involving the right buccal mucosa. We cant explain why its there. Theyre not rubbing it in any way. Theres nothing in the history that makes us, well thats the reason for that. So because we dont have a reason for it, we biopsy it to work out whats going out at baseline. It turns out to be a mild, precancerous change, a mild epithelial dysplasia. Nothing has happened. Ive seen this patient in 2014, still nothing going on, really should update the slide because its just looking just the same. So heres someone in five years, absolutely no change.

[41] [Moderate dysplasia: Progression to SCCA][Dr. Kerr] And yet we have patients who, you know, over a period of a year can go from a moderate epithelial dysplasia through to a squamous cell carcinoma. And that can happen quite quickly. The good news is we discovered it very early on and it was treated and shes still coming to see me. Shes in good health.

[42] [Severe dysplasia: Progression to SCCA & 2 Recurrences][Dr. Kerr] and then we have patients who, at baseline, had a severe epithelial dysplasia. They had an operation to remove it. They continued to smoke. They got a recurrence. They go to new cancer. Then they were treated for that cancer and then they got another recurrence. And then they got treated even more aggressively. This guys still alive.

[43] [N/A][Dr. Kerr] we have a staging system. And generally speaking, the staging system, the more advanced the stage, the more likely that patient is going to die. So if you pick up someone with very early stage disease, stage I, stage II, you can see weve got a T, N, M staging system. T is the size of the primary tumor. N is the nodal metastasis, the lymph node metastasis in the regional area. And then M is distant metastasis, below the clavicle. So, if you have someone whos stage I or stage II, you can see that the five-year survival rate is pretty good. When you get into advanced stage disease, the five-year survival rate is much poorer.

[44] [Other Non-Epithelial Oral Cancers][Dr. Kerr] And there are other types of cancers. Im not going to get into this.

[45] [N/A][Dr. Kerr] This was a Hodgkins lymphoma.

[46] [N/A][Dr. Kerr] Kaposis sarcoma

[48] [N/A][Dr. Kerr] This is a salivary gland malignancy.

[49] [An ideal screening test][Dr. Kerr] Well talk more about it next year. So, lets get back to what youre going to do as dentists. So, how do you screen for cancer? Well, we dont actually have, you know, a screening test per se, but if we did, we want it to be highly sensitive. In other words, it captures every cancer that you would want it to test. Its non-invasive, its fast, its easy to perform, its low cost. That would be the ideal screening test.

[50] [N/A][Dr. Kerr] So what is the evidence for screening for cancer? Well this actually just came out very recently back in November November 2013. And this is really designed; this U.S. preventive task force is really looking at, you know, primary health care providers. It doesnt really include dentists and people who are expert at looking at the mouth. And it concludes the current evidence is insufficient to assess the balance of benefits and harms of screening for oral cancer in asymptomatic adults. Now when they first put it out, the results of this, they put it out for a test period where you could send in a letter to comment. And I actually sent in a letter to them because, initially, this is what they were putting out. But they didnt consider what the dentist was doing and the way that the wording was that, you know, even for dentists there was no reason for them to be doing that. And I thought that was absolutely wrong and so, on behalf of the American Academy of Oral Medicine and a couple of other organizations, we wrote some strong letters. And they actually changed the wording as a result of our efforts, which was great.

[51] [N/A][Dr. Kerr] So, this recommendation applies to asymptomatic adults aged 18 years or older who are seen by primary care providers. That wasnt in the wording before. This recommendation focuses on screening (visual inspection and palpation) of the oral cavity performed by primary care providers and not dental providers or otolaryngologists. That was added in based on our commentary. This recommendation is intended for primary care providers and does not pertain to dental providers. Dental care providers and otolaryngologists may conduct a comprehensive examination of the oral cavity and pharynx during the clinical encounter. This is what we do! Right?! This is what we do. We look in the mouth. Okay? You can understand that a physician isnt going to be spending the time looking in the mouth. So for them to add that to what they do, you can understand that that would add an extra bonus to what they do, given that there isnt any evidence for or against doing it. Some of them will do that, but for us, we need to be doing this.

[52] [N/A][Dr. Kerr] And then theres the Cochran Collaboration. This is a recent systematic review that also just came out in 2013 and I was very fortunate to be on this.

[53] [N/A][Dr. Kerr] And we looked at all of the data to support whether or not we should be performing screening using, you know, the conventional exam versus other adjunctive techniques to help us screen. And so, the results were that index tests at a prevalence reported in the population were better at correctly classifying the absence of any lesions in disease-free individuals than classifying the presence in diseased individuals. So were very good pretty good at looking at someone and if they have nothing going on saying, youve got nothing going on. Were not so good at finding the disease but when there isnt any disease, were pretty good at saying there is no disease. Unfortunate, but thats the result. General dental practitioners and dental care professionals should remain vigilant for signs of potentially malignant disorders and oral cancer whilst performing routine oral exams in practice. And if you want to look at that and read more about it, youve got the citation.

[54] [N/A][Dr. Kerr] So the only really good study, and again, its questionable and theres a lack of generalizability to the United States and to industrialized countries, really comes from this big study in India, where they actually showed that oral visual screening can reduce mortality in patients who are high-risk: smoking, drinking, using tobacco products, and that in those individuals we really should be performing a screening exam.

[55] [N/A][Dr. Kerr] So what do we do? Well? We look and we palpate. Okay? I dont think thats swearing in any particular population. Youve got to watch out which finger you stick up there but

[56] [N/A][Dr. Kerr] And we know that dental offices are much better at picking up early disease. Because early disease is generally asymptomatic and when we do our opportunistic screening, were more likely to pick it up. Physicians actually pick up more cancer but thats because more cancer is advanced and so a patient comes in, they go, hey, doc, Ive got this pain, Ive got this lump. You know, and then they go stick out your tongue and well, there it is. Of course. Its standing there as obvious as can be.

[57] [N/A][Dr. Kerr] So, our motto here at the college is if your dentist doesnt do an oral cancer exam, change dentists. Very important. Youve got to promote what you do. Yank. Were the tongue-yankers. We look at the tongue. We pull out the tongue. This is what defines us.

[58] [N/A][Dr. Kerr] And Im not going to go through the exam today. Youve seen it before.

[59] [N/A][Dr. Kerr] But we do a careful head and neck extraoral and intraoral exam.

[60] [N/A][Dr. Kerr] And Ill post those videos if you want to have another look. So regardless of your ability, the clinician has an obligation to inform the patient in terms they will understand about the nature of something that they find thats abnormal. And what the plan is to reach a definitive diagnosis and/or rule-out serious pathology. Well any persistent and progressive epithelial lesion for which a clinican can determine no clear cause should raise suspicion and must be evaluated to rule out premalignant or malignant changes. Now, the issue is, what is persistent, what is progressive? Say, if youre finding a patient at a time point, then youve got to decide, well should I let it go on a little bit longer so that I can assess that progressiveness or the persistence. So sometimes youll have the patient, youll go, okay, well lets just send you off but youve got to come back in three weeks if its still there. Then that really confirms that it is persistent. And it may be progressive in terms of it may look a little bit worse. But at least its not going away so we need to do something. Other times, you dont really need to prove that its persistent and progressive because the patient will tell you its been there for a while. Thats good enough. Or it just looks highly suspicious at baseline and therefore you know youve got to just get going on that diagnostic testing.

[61] [N/A][Dr. Kerr] So, I call this an across-the-room diagnosis. Patient looks at you, sticks their tongue out if they can and theyve got this nasty, deeply infiltrative cancer. You dont need to win an award. I hope that your patient who youve been seeing for twenty years doesnt come into your office showing you this. Youre not going to feel too good, but it happens.

[62] [N/A][Dr. Kerr] And look at it. It has all these characteristic features. You put your finger on it. Its rock hard. Its not spongy like a normal tongue. Its rock hard. And theres ulceration. Its very, very painful.

[63] [N/A][Dr. Kerr] Some patients will present with a lump in the neck. And you palpate their lymph nodes in the neck and theyre hard. And you know that theres probably a primary, either in the oral cavity or the oropharynx. In this case it was the oropharyngeal disease. This may be the only finding in that patient. You may examine their oral cavity, their oropharynx and not detect anything.

[64] [N/A][Dr. Kerr] Heres another guy. You already saw this picture.

[65] [N/A][Dr. Kerr] These lesions are friable. These cells dont behave normally. They fall apart. Theres a release of angiogenic factors that cause these lesions to bleed profusely.

[66] [N/A][Dr. Kerr] Sometimes theyll get advanced. Theyll just railroad right through the alveolus form the floor of the mouth. I had just pulled out this patients tooth. I was worried they were going to aspirate it. Theyre in a nest of cancer coming through the alveolar bone

[67] [N/A][Dr. Kerr] Sometimes patients will present with a gingival lesion that isnt healing and they have bone loss.

[68] [N/A][Dr. Kerr] And you go ahead and you think well maybe thats a periodontal problem so you scale them and root planing. Nothings getting better. Its getting worse. Well, what are you going to do? Youre going to biopsy and this was a patient that had a delay in diagnosis because they went through three rounds of periodontal treatment in this local area, nothing else going on elsewhere in the mouth until it was biopsied.

[69] [N/A][Dr. Kerr] sometimes the cancers are deeply invasive and dont have much on the surface. It may be just this rolled border that we see.

[70] [N/A][Dr. Kerr] Heres another one; an ulcer with a rolled border. Ulceration can sometimes be the solitary sign of the malignancy.

[72] [N/A][Dr. Kerr] Heres another one. Very firm, patients in a lot of pain. Seeing a periodontist for, you know, lots of periodontal therapy. But the periodontist never put two and two together that this was a malignancy.

[74, 75, 76] [N/A][Dr. Kerr] These are all advanced cancers. Sometimes theyre very granular, nodular, exophitic. And they can occur on any surface. Sometimes they are very white, sometimes theyre red.

[77] [N/A][Dr. Kerr] And again, you can see. If you palpate the tongue, its firm. Theres a deep ulceration in the centre.

[78] [N/A][Dr. Kerr] I know we have some Canadians in the room. And you guys automatically get five points just for being Canadian.

[79] [N/A][Dr. Kerr] So, red and white. So these are all advanced cancers. You dont have to see too many of them in your career. The ones that you may see that really pays off is when you see the earlier lesions where the features arent always as ominous and as obvious. Theres no lymphadenopathy associated with them. Theyre often not causing any pain. They may cause pain. Early cancers can cause pain. But the red and white feature is quite often something that we look for so thats why I call it the Canadian-flag type lesion. So, we use terms like erythroleukoplakia or leukoplakia. Erythroleukoplakia is a red and white lesion that you cant explain why its there. And erythroleukoplakia is a term that we use when weve ruled out everything else. Its a clinical diagnosis and it means that we have to rule out precancer or cancer. So we have to take a biopsy. So its a clinical diagnosis, not a histopathologic diagnosis. And so youll see here, the clinical diagnosis, and then next to it, the histopathologic diagnosis. So this is an erythroleukoplakia and it turns out, when its biopsied, to be a squamous cell carcinoma. And its very friable. You can see a little area where I just rubbed it with my periodontal probe and it bled quite easily.

[80] [N/A][Dr. Kerr] So you can see the mixed red and white change.

[81] [N/A][Dr. Kerr] Heres another erythroleukoplakia with ulceration. Also, a squamous cell carcinoma.

[82] [N/A][Dr. Kerr] But these are early. This was a patient who had a denture and the dentist thought, well, you know, its a denture sore. And they kept whittling down the denture and it just didnt go away. And finally, they referred it to have a biopsy and it was a squamous cell carcinoma. But look at it! It has all of the high-risk features. Its red and white and it has ulceration in it. But its not an advanced cancer; its an early cancer.

[83] [N/A][Dr. Kerr] Heres another example where we just have ulceration but it is a malignancy. So no red and white features but its ulcerated. It just has a slight rolled border to it. Very easy to mix.

[84] [N/A][Dr. Kerr] And theres a little bit of bone loss in the area too.

[85] [N/A][Dr. Kerr] And there it is.

[86] [N/A][Dr. Kerr] Another example of an erythroleukoplakia. Turns out to be a malignancy. It was thought to be a little cheek bite. But when you look at it carefully

[87] [N/A][Dr. Kerr] it has a heterogeneous surface topography. Its a little bit friable to palpation. Its small but thats an early malignancy.

[88] [N/A][Dr. Kerr] Heres another one, seen by an EMT and two other physicians was thought to be a candidiasis or something like that, put on antifungals. Eventually got to me, I take one look at it; its an erythroleukoplakia with ulceration. Turned out to be a squamous cell carcinoma.

[89] [N/A][Dr. Kerr] Look at it. Its quite bumpy and granular in appearance. The orange area is ulceration. Non-homogenous lesions. Its got white and red changes and ulcerations. Squamous cell carcinoma.

[90] [N/A][Dr. Kerr] Heres another one. Way posterior in the mouth. Little ulceration, slight rolled border. Squamous cell carcinoma.

[91] [N/A][Dr. Kerr] Again, look at it. Its not obvious.

[92] [N/A][Dr. Kerr] Heres another one. Right on the gingival tissues. Erythroleukoplakia. Squamous cell carcinoma.

[93] [N/A][Dr. Kerr] Look at it.

[94] [N/A][Dr. Kerr] Floor of mouth. You ask yourself well where is that? Its a little erythroleukoplakia on the left floor of mouth.

[95] [N/A][Dr. Kerr] Look at it. Its got a little bit of a roll to it. Its a little bit firm. Squamous cell carcinoma.

[96] [N/A][Dr. Kerr] This patient has a leukoplakia with ulceration. We dried it off.

[97] [N/A][Dr. Kerr] Got a really good look at it. Squamous cell carcinoma.

[98] [N/A][Dr. Kerr] Again, erythroleukoplakia. This time, a severe epithelial dysplasia. Look at the surface topography.

[99] [N/A][Dr. Kerr] Very granular, and so when you get this abnormal surface topography, thats quite often what it is.

[100] [N/A][Dr. Kerr] Again, another leukoplakia with abnormal surface topography. It has grooves and bumps. It shouldnt be there.

[101] [N/A][Dr. Kerr] Severe dysplasia.

[102] [N/A][Dr. Kerr] Sometimes the lesions are quite heterogenous and it makes it quite difficult because if you take a sample from one area of the lesion, its different histopathological than in another area. So you can get variability of the histopathology. So it means that if you are going to take a sample, you better make sure you get the worst area. So where would you go, what area would you biopsy? What dictates that thought process? Well I always go to an area where it feels a little bit firm because that tells me that there may be some submucosal spread that could be where the cancer is. Otherwise, a red area or an ulcerated area. Generally the white areas arent as ominous as the red or the ulcerated areas.

[103] [N/A][Dr. Kerr] Yes?

[Student]So when you find severe dysplasia or moderate dysplasia, what do you do? Do you just watch it and tell the patient to come back?

[Dr. Kerr]Well get to that in a minute, okay? So, thats a very, very good question. And it really depends on the individual. So, you know, I have some patients who have high-grade dysplasia and Im watching them. But you know, if you were to ask ten experts what to do in those situations, theyll go well you must remove that. But in some situations, theyve had them removed and many times it keeps coming back. Ive had severe dysplasias that have regressed. Very rarely, but it occurs. So in general, surgical excision is the treatment of choice for high-grade dysplasia. And, of course, cancer. When you get below high-grade dysplasia, when youre in the moderate to mild category, its a little debate about what to do and what should guide your decision and I wish we had better evidence to support what we should do. Some people feel we should still remove them, some people feel we shouldnt. So, theres sometimes a little bit of creativity that goes into this. And the evidence doesnt support removal of every time of lesion. Okay?

[104] [N/A][Dr. Kerr] So, again, this was thought to be a little canker sore on the soft palate, on the oropharynx and you can see that ulceration when you look at it. Theres white changes but the cancer is in that ulcerated area.

[105] [N/A][Dr. Kerr] Again, a little ulcer in the floor of mouth.

[106] [N/A][Dr. Kerr] Little red area. Its only red. Squamous cell carcinoma.

[107] [N/A][Dr. Kerr] Slight rolled border posteriorly.

[108] [N/A][Dr. Kerr] Again, gingival lesion was just red. That was it. Turned out to be a squamous cell carcinoma

[109] [N/A][Dr. Kerr] right in that gingivae. Very subtle.

[110] [N/A][Dr. Kerr] Youve got to know how to pick that up. Again, leukoplakia with a little bit of ulceration, was carcinoma in situ.

[112] [N/A][Dr. Kerr] Moderate dysplasia and erythroleukoplakia with moderate dysplasia.

[114] [N/A][Dr. Kerr] Erythroplakia that was carcinoma in situ.

[115] [N/A][Dr. Kerr] Sometimes we have patients with multifocal disease. And these patients we call this proliferative verruca leukoplakia. And these generally are older, female individuals that have a high propensity for malignant transformation. So when you see patients with multifocal precancerous changes or have a propensity for malignancies and have had their first malignancy already, these patients, they should be followed in a surveillance clinic by experts.

[116] [N/A][Dr. Kerr] Lip cancers.

[117] [Oral submucous fibrosis][Dr. Kerr] Oral submucous fibrosis which is a disease, a precancerous disease that occurs in patients who chew the areca nut which is a nut that grows on palm trees in South Asia. This will cause this fibrosis but it also puts the patient at a high risk for developing malignancy.

[118] [Erythroleukoplakis in field of OSMF][Dr. Kerr] And here is an erythroleukoplakia in the field of oral submucous fibrosis that turned out to be a malignancy.

[119] [Leukoplakia in field of oral lichen planus: severe epithelial dysplasia][Dr. Kerr] Here is a leukoplakia in the field of oral lichen planus, turns out to be severe epithelial dysplasia. So oral lichen planus also itself confers a slight increase risk for developing the disease.

[120] [Leukoplakia: Mild dysplasia][Dr. Kerr] Now as you get earlier on in the disease or when you only have a white component in the disease, it usually is not high-grade dysplasia or carcinoma. Although, having said that, I have had patients with a leukoplakia, which is just a white change, a white patch that doesnt wipe off. You cant explain why its there and therefore you have to rule out precancer or cancer. Very rarely would it be cancer. Very rarely. Its usually going to be a precancerous change.

[121] [Leukoplakis: Mild dysplasia][Dr. Kerr] And so all of these leukoplakia, mild dysplasia

[123] [N/A][Dr. Kerr] mild dysplasia.

[125] [N/A][Dr. Kerr] Mild dysplasia.

[127] [Leukoplakia: Mild dysplasia][Dr. Kerr] Mild dysplasia.

[128] [Leukoplakia: Moderate dysplasia with candid ][Dr. Kerr] Moderate dysplasia.

[130] [Leukoplakia: Epithelial][Dr. Kerr] Mild dysplasia. Actually this was epithelial hyperkeratosis. But we couldnt explain why it was there.

[132] [Leukoplakia: Epithelial ][Dr. Kerr] Epithelial hyperkeratosis hyperplasia but still, couldnt explain why it was there. There were no sharp or anything like that.

[137] [Leukoplakia: moderate epithelial dysplasia][Dr. Kerr] So these all tend to be low-grade epithelial dysplasias or benign diagnosis.

[139] [Leukoplakia: mild epithelial dysplasia][Dr. Kerr] But we cant explain why theyre there. But these are the things that we need to pick up on.

[141] [Leukoplakia: carcinoma in situ][Dr. Kerr] This one turned out to be a carcinoma in situ. It has a little bit of pigmented changes. I was surprised about that.

[142] [Leukoplakia: mild epithelial dysplasia actinic cheilitis][Dr. Kerr] And here is a mild epithelial dysplasia of the lip.

[143] [N/A][Dr. Kerr] So. In general, those higher risk features having ulceration, red and white changes, theyre ususally commensary with higher-grade disease than just the white changes on their own, but not always. So, youve all heard of these adjunctive techniques. Theyre all in the marketplace being marketed to dentists left, right, and center. And so the question is, can these add value in how you perform as a clinican? So can you use any of these adjunctive techniques to help you decide and differentiate out which of those lesions truly are the ominous ones? And so the answer is that were also doing a very big Cochrane review on this at the moment. Itll be published hopefully in the next three or four months. So I cant present that data to you today but maybe next year. So there are a number of different devices that are available in the marketplace and techniqes in the marketplace. And one of the groups of devices is called visualization adjuncts. Theyre basically fancy lights that you shine on a lesion and it gives you a little bit more information about whats going on. And the ones that I like are the auto-fluorescence devices. These are the devices that work on the premise that if you shine a certain wavelength of light on the mucosa, there are naturally occurring molecules in the mucosa and submucosa that differentially fluoresce and so you can then look at a lesion and go well, is that a normal fluorescence pattern for epithelium or is there a loss of fluorescence or an increase in fluorescence.

[144] [N/A][Dr. Kerr] the other group of adjuncts that we use are what are known as vital stains or vital dyes. So we use a dye called toluidine blue and that can sometimes help us determine areas of a lesion that are harboring the worst histopathology. Because this works extremely well in cancers and high-grade dysplasias to stain those particular areas.

[145] [N/A][Dr. Kerr] And then theres a commercially available kit that we use and this is the toluidine blue stain. Youll learn more about this next year.

[146] [N/A][Dr. Kerr] So heres an example of a patient who develops an erythroleukoplakia in the floor of the mouth and when we do the toluidine blue staining, it really shows very nicely the area of the worst disease and thats all carcinoma in situ. So this helps sometimes in where you should select your biopsy site and/or for a surgeon working out, well where are the worst areas of disease, I need to get around all of these areas. I dont want to miss that little tiny speck, you know, that I see right here and here because those harbor bad disease and yet I might have missed that looking at this area alone. Question from someone? No.

[147] [N/A][Dr. Kerr] Heres an example of a cancer. The cancer stains beautifully with toluidine blue but the normal tissue around it doesnt because its normal tissue. So that shows how it can be very specific for high-grade disease.

[148] [N/A][Dr. Kerr] But yet none of these adjunctive techniques are perfect. They dont always work. So not every case of dysplasia will show a positive toluidine blue staining. Ive had cancers that dont stain with toluidine blue. Ive had a lot of other lesions that are not precancerous that do stain with toluidine blue and the same is true for the visualization adjuncts. So, these are not perfect but used collectively, they add nuances to the entire examination that guides you in making decisions. So when I say you, it could be you or me, it depends on the level of expertise how you use these adjuncts.

[149] [N/A][Dr. Kerr] So here is the auto-fluorecense device that I use. Its known as Velscope.

[151] [N/A][Dr. Kerr] And you can see very clearly in this advanced cancer that it really helps to delineate the margins of that cancer very nicely.

[152] [N/A][Dr. Kerr] and in this cancer in the floor of mouth, if you happen to be using it as a dentist, you might have missed that little tiny lesion in the floor of the mouth on a normal white-light exam but pick it up when you use the Velscope. Now, should you be charging patients in using this? We dont have enough data. But there is an example where you might, it might be of benefit.

[153] [N/A][Dr. Kerr] And heres another example of where we get a loss of fluorescence and so the apple green color that you see on the lateral border of the tongue, thats the normal fluorescence pattern of the tongue. But where you get this dark area and you can see the real interface between the normal and the abnormal, you can see that that area of loss of fluorescence which correlates with this actually is quite a bit bigger than the lesion. So that suggests that that neoplasia thats going on actually is quite a bit bigger than what you see visibly and there are some studies showing that when you take these margins of tissue auto-fluorescence loss, youre more likely to capture all of the bad cells that harbor those genetic mutations. But again, we need more research in this area.

[154] [N/A][Dr. Kerr] And heres some other examples of loss of fluorescence.

[155] [N/A][Dr. Kerr] Here are some confounding lesions. So, just like toluidine blue, this tissue auto-fluorescence has a high degree of sensitivity but not great specificity in the hands of front-line clinicians. So you may encounter a patient in the bottom who has an erythematous candidiasis from an asthma inhaler. Theres a red patch on the roof of the mouth but thats candidiasis. You put them on anti-fungals and it completely goes away. Its not a precancerous change. Its not an erythroplakia. If you take a careful history and you have a good education in mucosal diseases, youll know whats going on there and yet you get this loss of fluorescence and so any red lesion in the mouth, any inflammatory lesion will show a loss of fluorescence because the blue light of that auto-fluorescence scope is absorbed by the hemoglobin in that inflammatory lesion. So youve got to be able to tease out this other one as a hematoma. So there are going to be false positives, we call them confound lesions. So this is why using it in the hands of someone who doesnt have the experience of diagnosing mucosal diseases can sometimes be problematic because it means that more patients are going to be sent or a biopsy than should be.

[156] [N/A][Dr. Kerr] So, again we need to have more training in this area and well give you lots of training next year.

[157] [Other single light autofluorescence devices][Dr. Kerr] Heres another system thats just come out in the marketplace, which is just another auto-fluorescence device.

[158] [N/A][Dr. Kerr] There are cytopathologic devices where we can collect cells from a lesion. So instead of performing a tissue biopsy, you as dentists may not feel comfortable procuring a tissue biopsy. You may not want to give an injection to the patient. You may not want to take a scalpel blade and remove a piece of tissue and submit it for histopathology. Well, this system can help you because its based on a sampling. Its rather like a pap smear for the oral cavity, although its different. A pap smear is a screening test where we do a blind sweep of the cervix but when it goes to the lab they look at those cells. This is when you encounter a lesion; you can take a little brush, sample the cells from that lesion and then send it off for an analysis. Now, if youve got a lesion that you have an index of suspicion that you think this might be something concerning, then youre going do a scalpel biopsy. Youre going to refer to a patient to do a scalpel biopsy because in the end of the day, a scalpel biopsy will yield a piece of tissue where the histopathologist can see that architecture, how those abnormal cells organize in the epithelium. They can differentiate between the different levels of dysplasia or a carcinoma. This cant do that. Youre just taking the cells. It cant tell whether those cells came from, you know, a squamous cell or a mild epithelial dysplasia. So, we generally reserve these cytopathologic techniques for lesions that we have a low index of suspicion that they are something serious, where we dont feel the urgency to send that patient to the expert right away. And this way, without doing an expensive and uncomfortable procedure we can rule out with very good accuracy that there isnt a precancerous change in that lesion or even a cancerous change in that lesion. The problem is that if you get a lesion and you do use one of these cytopathologic techniques, you want to make sure that it is a small lesion, its very homogenous in its presentation. Because if you sample one area of a lesion and theres another area over here, that could be the area with the malignancy. So you dont want to use on a larger lesion that is heterogeneous unless youre willing to map out the entire lesion with ten different brushes and go this is brush number one from here, brush number 10 is from down here. I dont think youre willing to do that. So, this is available but it has to be used in the appropriate way.

[159] [N/A][Dr. Kerr] One of these techniques is looking at abnormal DNA content within the nuclei of cells. This is known as ploidy or quantitative DNA cytology. This isnt here in the US yet but its mainstream in Europe and Canada. And this will pick up cells that have abnormal changes in their DNA content which you know to be true because of those mutations, we can have increases, gains and losses in genetic material. This will help you find that.

[160] [N/A][Dr. Kerr] And then the other one which is known as the brush biopsy and there are other cytopathologic techniques and platforms out there but this is probably the most common one. Its based on cytopathology on its own. It looks for abnormal looking cells. And we know that the abnormal looking cells have properties like an abnormal nuclear to cytoplasmic ratio, you know, thats a sort of a classic one. And there are other things that they look for. Abnormitotic figures. Things like this.

[161] [N/A][Dr. Kerr] And so you can look at these cells and go wow or those cells dont look like your healthy, keratinocyte which is a small, nucleus and a large cytoplasm. So, the cytopathologist will give you this diagnosis.

[163] [N/A][Dr. Kerr] Again, the quandary related to getting a sample that represents the worst disease within that field of lesions. Some lesions are large and heterogeneous. Where would you take the biopsy? Anyone? Youd go with C, right? Because its the red area. Youre more likely to get the high-grade disease in C and remember, palpate. If you feel any firmness or induration, thats the area you go with. Sometimes Ill take multiple biopsies and sometimes Ill use these adjuncts, particularly the toluidine blue to guide me because when we stain with toluidine blue, well get possibly, it will show where the high-grade disease is.

[164] [N/A][Dr. Kerr] We use these little dermatologic punches to sample our tissue.

[165] [N/A][Dr. Kerr] And here is a patient where Ive stained it with toluidine blue and Im going with one of the areas

[166] [N/A][Dr. Kerr] And we just basically pick it up, pop it into the bottle and send it off to the lab.

[168] [N/A][Dr. Kerr] No sutures, generally, are needed.

[169] [N/A][Dr. Kerr] And we get the histopathology, in this case, a severe epithelial dysplasia.

[170] [Molecular markers for early cancer][Dr. Kerr] While there are some molecular markers that people are looking for now in these lesions, but again, its not mainstream. And weve talked a little bit about this, Im not going to get into too much detail. But there are a number of different molecular markers that we can look for but thats for next year.

[171] [N/A][Dr. Kerr] So if your patient had a lesion diagnosed as an oral cancer or precancer

[172] [1. Would you treat the oral lesion(s)?][Dr. Kerr] The questions you need to be asking are, what is the diagnosis? Do you have a diagnosis? Do you need to know the definitive diagnosis? Given the diagnosis, do you know how to treat the patient? Okay, you may not be the one whos going to treat the patient but its very important to have a definitive diagnosis.

[173] [2. If you dont know how to treat the patient, what do you do?][Dr. Kerr] If you dont know how to treat the patient, what do you do? Well, you know, either youve got to train yourself so that you can treat the patient, get an advanced training, become an oral medicine expert, oral pathologist, oral surgeon, whatever you want. Or would you prefer to refer to an expert? And if youve got an expert, you know, down the hall, thats great. Sometimes that expert isnt always the expert and, you know, academic centers, in general, you know, theyre the people who have the greatest expertise. You know, comprehensive cancer centers, these are the people that you should be referring to.

[174] [3. If you have a definitive or presumptive diagnosis, what are your treatment goals?][Dr. Kerr] If you have a definitive or presumptive diagnosis, what are your treatment goals? Do you treat with an intent to cure? Do you treat to palliate a condition which would resolve on its own? Do you treat to reduce or prevent the chances for recurrence? Do you counsel patients about risks for contagion? Well, this is a general question for oral mucosal diseases. Obviously in the area of cancer, we treat with an intent in most cases to cure. Sometimes they have such advanced disease that we dont. we treat to palliate these patients, to give them some quality of life at the end of their lives. Certainly if theyve had a history of cancer, theyre at a high risk for getting a recurrence and therefore, you know, we need to follow these patients very closely.

[175] [4. What are your treatment options?][Dr. Kerr] And what are the different treatment options?

[176] [Whats the role of the dentist in the management of patients with oral cancer or precancer?][Dr. Kerr] So whats the role of the dentist in the management of patients with oral cancer or precancer?

[177] [N/A][Dr. Kerr] First of all, cessation of risk activites. Alcohol, rather tobacco, heavy alcohol use, ultraviolet light for lip cancers, areca nut use. Promotion of good health, diet, nutrition, good oral health, safe sexual practices, possibly the HPV vaccine for the younger, nave patients.

[178] [Appropriate/timely referral][Dr. Kerr] Few dentists are qualified to actually treat oral cancer or precancer but they can and should play a role in the multidisciplinary approach to treatment. Timely referral. Other providers that you would work with in that multidisciplinary team could be head and neck surgeons. Most of them are otolaryngologists but the surgeons that I work closely with like Dr. Schmidt is not an otolaryngologist. He is a head and neck cancer surgeon. He has had an advanced training in head and neck cancer surgery but he came through the oral surgery track. There are very few surgeons like him in the country and I think that they do a really top-notch job at managing people with oral disease. He already knows the oral cavity. Its not to say that there arent fantastic otolaryngologist head and neck surgeons, there are. I work closely with them as well. Radiation oncologists. Medical oncologists to provide the chemotherapy. We work with speech and swallowing therapists. Nutritionists, psychiatrists, psychologists, social workers. So, we play a very important role.

[179] [Management of Oral Dysplasia][Dr. Kerr] How do we manage, going back to your question, how do we manage patients with oral precancerous changes or oral epithelial dysplasia? And so there are lots of different its quite controversial how we would manage. In some cases, we will do a surgical excision. And theres controversy over which type of surgical procedure that would be warranted. And there are investigators in some parts of the world that advocate the use of ablation with a CO2 or other type of laser. Others like cold steel and stripping a lesion in the mouth and thats what I advocate and thats what we do in our cancer center. So scalpel removal is the way that we usually will remove. And it depends again on is it a lesion that is amenable to surgical excision. Sometimes we have patients with multifocal disease. You cant surgically remove all of their mucosa. So, clearly, thats a group where we have to think of other options. And so in some cases we dont even remove the lesions, we really wait until they develop a malignancy. And then when they do we treat that malignancy and that area very aggressively. Avoidable risk factor modification, you know, again, this is very important and there are some studies that suggest that if you can get patients to quit smoking and heavy alcohol use that they actually can get regression of some of those precancerous changes. So, risk factor modification cannot be taken lightly. And so, we strongly advocate getting patients to quit. Performing a self-examination, very important. The mouth is amenable to self-examination. Nowadays, you know, with all these smart cameras Im asking patients to do selfies of their I train them how to take cellphone pictures of their lesions and they send them to me. Its great. Why not? You know? So, a little selfie of your tongue lesion and off it goes. I train the spouse to, you know, take the picture. And theyve got it down to a fine art. So self-examination is important. Knowing what are the features of worsening disease, if you decide not to excise. Sometimes you excise and these lesions come back. Very close surveillance. I use adjunctive techniques to give me a sense of where the areas are when we get a new area, particularly in patients who have had a history of radiation treatment. Its often very difficult to tease out, is this radiation damage versus a new lesion? Theres really very little data to support the use of chemoprevention or chemopreventive or chemotherapeutic agents that reverse precancer. And theres been a lot of study looking at things like vitamin A analogs, beta keratin, vitamin E, you know, extracts of certain berries and other antioxidants. None of these really seem to work. And the vitamin A studies suggest that when you take them off the vitamin A analogs, if theyve had some type of remission, that it tends to bounce right back. So we dont have anything good to say there. And how the diet really plays a role here is largely unknown because when you pull out the micronutrients that you think are protective, you know, its usually a collection of all these micronutrients working in tandem thats probably doing it and thats why a healthy diet is important.

[180] [Case A][Dr. Kerr] So well go through a couple of cases. Heres a patient who had an actinic cheilitis.

[181] [N/A][Dr. Kerr] Youve already seen his picture. So, what would you do for him? How would you manage this guy? Whwat would be your thought process? Lets talk about diagnosis first. Hes got actinic cheilitis. So how did we arrive at that diagnosis? Right, we took a biopsy and it showed that he had this sun damage. And the other thing is we want to know whether theres any epithelial dysplasia in there so in this patient, he had some mild epithelial dysplasia, some actinic, you know, cheilitis, which is sun damage. This is a precancerous change, its not a malignancy and the question is what are you going to do now? Any advice about health promotion? What do you thinks causing this? Right, sun exposure. So what would you tell him to do? Right. Apply sunscreen from now on. And so the question is would you surgically remove that? And generally in these situations, lip cancers, because of sun damage tend not to be, they tend to be more likely basal cell carcinomas. But they can also have squamous cell carcinomas and, you know, the skin rather is more likely to be basal cell carcinoma. The lips are more likely to be squamous cell carcinoma but they tend not to be aggressive diseases. So in this situation, there are things that can be done. We can apply certain chemotherapy agents to the lip but generally Im not going to do a lip shave for something that has mild epithelial dysplasia.

[182] [Case B][Dr. Kerr] Case B. 35 year old female. Tends the bar. 40 pack year history. 5 servings of fruits and vegetables. Drinks approximately 10 drinks a week. Diagnosis of a mild dysplasia.

[183] [Case B][Dr. Kerr] And here we have a mild dysplasia on the inside of the cheek. So what would you do for her? Okay. So certainly you would discuss with her risk factor modification, particularly the cigarette smoking. Now shes got a mild epithelial dysplasia. The likelihood of mild epithelial dysplasia transforming into a malignancy is probably in the order of 5 to 10% over a ten year period. Its not very common. So what would you do? What would be your options here? Okay, so you could put her into surveillance. Any other options potentially? You could present to her, look youve got a precancerous lesion in your mouth and heres the data on this. Now we can try first if youd like, you know, quitting smoking. Lets see what happens. And you can offer her, well, we can follow this or what else could we offer her? We could offer her surgical excision.

[185] [N/A][Dr. Kerr] And in this case, you know, she had surgical excision with a CO2 laser. Now, this was before, you know, I sort of changed my mind about CO2 lasers but I just want you to be aware that this is one of the modalities for removing a precancerous lesion.

[186] [Case C][Dr. Kerr] Case C. Hairdresser. 20 pack year history of smoking. Quit a year ago. Heavy alcohol use. Has a diagnosis of AIDS. Currently an undetectable load. Severe epithelial dysplasia.

[187] [Case C][Dr. Kerr] What would you do in this situation? Again, you would really focus on the risk factor modification and optimize that. But would you be more prone to refer this patient for a surgical excision? Yes, in this situation we would. Now the difficulty in this situation is mapping out the disease so what will happen is usually this will be done in an operating room environment because in an operating room, we can remove the lesion and we can sample the margins. And we can send those marginal tissues samples for a frozen evaluation so we can flash freeze the tissue, send it off to the pathologist while youre sitting in the operating room with the patient asleep and the pathologist can say, yea youve got disease at that margin so you can go a little bit further. Now what was interesting about this patient is hes recurred a couple of times with dysplasia. Hes never developed a malignancy. I still follow this patient. And he had to go back and have a couple of revisions because they kept finding more disease and he kept smoking or he kept, yes, he quit and then he started smoking again. So occasionally hell get back into cigarettes.

[189] [N/A][Dr. Kerr] And so here was the initial surgical incision. Now, because its severe epithelial dysplasia or carcinoma in situ, when you take those initial biopsies you cant be sure that there isnt one little area where there might be an early carcinoma. So its very important, once youve done that surgical excision, to submit that entire sample oriented in such a way that the pathologist knows whats superior, inferior anterior, posterior, orient that and then they can look at all of the margins and work out whether theres any carcinoma in there. If they find an area of carcinoma then theres a possibility you may have to go back and do a revision. But anyway, this is the type of surgical procedure that would be done.

[190] [N/A][Dr. Kerr] And then sometimes theyll put, you know, an artificial graft on there or a split thickness skin graft.

[191] [N/A][Dr. Kerr] And sometimes theyll bolster it, sometimes they wont.

[192] [Management of Oral Cancer][Dr. Kerr] So there are lots of different ways of doing this and we do a lot of surgical excisions, you know, in the oral cancer center here on the second floor in Bluestone. What about oral cancer? What are the, you know, the modalities that we use to manage patients with a malignancy? Well surgery its still a surgical disease, principally. Unless youve got a cancer in an area that is not amenable to surgery. And so the tonsilar cancers are very difficult to surgically operate in that location. So quite often, radiation will be the principal, the primary, modality. But in most cases, surgery is the primary modality. Nowadays these oropharyngeal cancers on the base of the tongue, theyre now looking at robotic surgery. And at this head and neck meeting itll be interesting to see what the latest advances are on this robotic surgery. So, in terms of radiotherapy there are different ways of delivering the radiation treatment. Most patients undergo whats called external beam radiation therapy where they go every single day except for the weekends for five to six weeks and they get delivered the radiation and they have a special helmet that they wear thats custom designed for them so that when they sit in the radiation machine, theyre locked in and their head and neck is oriented at exactly the same position every time. And then they get delivered packets of radiation from outside so as the machine will move around anywhere around the head and neck and theyll deliver a little packet there, a little packet from here, a little packet from there and that maximizes the dose to the tumor and minimizes the dose to all of the normal vital structures that are around. Because as you can imagine, in the head and neck, there are a lot of vital structures such as the eyes, the brain, the salivary glands, other important nerves and other structures. So we want to minimize the damage to those structures and maximize the damage to the tumor. Chemotherapy is sometimes added as an adjunct. Its never used as a primary modality in head and neck cancer. Not yet. One of these days we may be able to look at the genetics of that particular cancer, do a genomic analysis of the cancer and then lo and behold put it into a computer and work out a therapeutic, chemotherapy that is targeted just to that patients cancer, taken into consideration all of the different mutations that are driving that cancer. Thats sort of for the 21st century but were not there yet. Obviously, risk factor modification, self-exam, very close surveillance after theyve had their cancer treatment.

[193] [N/A][Dr. Kerr] And there is actually a more recent version than 2012 but you dont need to worry about this but there are clinical practice guidelines for the management for oral cavity cancers. So depending on, you know, the various features, the staging, the location of that cancer, there are algorithms that help head and neck oncologic surgeons and cancer experts how to manage these patients. So we actually go to a tumor board every Wednesday morning at NYU Medical Center where we sit down and we discuss each of these cancer patients and how theyre going to be managed and then we have this whole multidisciplinary team that all chime in their expertise to help work out whats the best way to manage this patient.

[194] [N/A][Dr. Kerr] And here is an example of, you know, how you would manage someone with cancer of the oral cavity.

[195] [Case D][Dr. Kerr] So we have case D. Social drinker, 85 year old, rinses 3 times a day with alcohol mouth rinse, stage II squamous cell carcinoma.

[196] [Case D: before][Dr. Kerr] And here we see this cancer on the lateral/ventral border of the tongue. And this is stage II so how do you think we would manage this patient? Surgery alone? Okay, so hes got lets say a pathologic staging of a T2, N0, M0 so its just in the tongue. Hes probably had a CT scan of the neck or an MRI that shows no nodal involvement. Hes probably had a chest x-ray that shows no chest disease so we stage him as a primary cancer greater than 2 cm in diameter. Between 2 and 4 cm in diameter. Surgical disease. So he will go in and they will do a margin thats about a centimeter to a centimeter and a half around it. They will surgically excise that and

[197] [Case D: after][Dr. Kerr] Here he is, having had that part of his tongue removed. Now, do you thin hes going to be able to speak normally? Not too bad, youd be amazed how much tongue you can have removed and with speech therapy you can get back on track. The secret is keeping your tip. So we always try and maintain the tip of the tongue. And so this patient can do remarkably well, you know, and function and have a pretty normal life after having had this tongue cancer removed.

[198] [Case E][Dr. Kerr] And then finally we have a patient with a much more advanced cancerous stage, stage IV cancer. Weve already seen a similar type patient. [199] [Case E: before][Dr. Kerr] This is before.

[200] [Case E: after][Dr. Kerr] and this is after. So hes had his tongue cancer removed and he needed to have a free flap so he actually had a flap that replaced the piece of his tongue thats missing. Sometimes they will take that flap. It can either be a free flap or they can actually move in tissue from other areas like pectoralis major flap and theyll stick it up there. Nowadays they pretty much do mostly free flaps. And so they may take something from his wrist or if they need a little bit more bulk, theyll take it from other parts of the body and theyll pop it in there. And then hell get head and neck radiation treatment.

[201] [Role of the dentist][Dr. Kerr] And possibly chemotherapy. So the role of the dentist, pre-treatment, early detection, prevention. Thats your role as a dentist. Oral assessment, routine oral care, oral hygiene and dietary counseling before treatment. When these patients are going in to have cancer treatment you want their oral cavity to be as in good of health as is possible. So if patients have got existing caries, theyve got existing periodontal disease and theyre going to be getting radiation therapy down the road, we dont want them to have complications long term. So sometimes the dentist role is to clean them up and get them ready for that cancer therapy ASAP. So I have patients that are referred to me to have an oral evaluation beforehand and then during treatment, some dentist play a role, we have a study at the moment where were doing oral care on patients who are going through radiation treatment and develop some of the key complications of radiation and chemotherapy. Thats particularly radiation therapy and they get terrible mucositis and youll learn more about that next year as well. And then after treatment, once theyre through and its successful then we play a role because there are a lot of long term complications in these patient populations. And there are about a quarter of a million cancer survivors that need dental care and its not just for oral cavity cancer, it could be for any head and neck radiation patients or whove had other operations for laryngeal cancer or other sub sites of pharynx or nasopharynx or, you know, other types of cancers that have received head and neck radiation. And so these long term complications, dry mouth because of irreversible damage to the salivary glands, difficulty opening their mouths because of damage to the muscles. And as a result, a propensity for lots of different complications, dental caries, periodontal disease, taste problems, you name it. These patients have a lot of oral complications. And theyre difficult to restore. We have maxillofacial prosthodontists who can restore patients whove had parts of their jaw removed and they can do that with implants and there are lots of really clever things. Imagine losing, you know, your maxilla and having that opening. Well they can create obturators that will block off the opening into the nasopharynx. Surveillance, again, very important. You, as a dentist, can play that role.

[202] [N/A][Dr. Kerr] Alright. And then in the bigger picture, you know, how many of you came out to the oral cancer walk this year? Fantastic, fantastic. Well, next year, we also give you the opportunity. Some of the students feel like I mandate it and of course I dont, you know, in our own MPR course we have a community service component. And so one of it is coming out to the oral cancer walk. You can, there are other alternatives. You can take an online course but you know, its more fun and easier to come out to the oral cancer walks. We love that you can come and join in and as a result of this, the funds that we raise go towards cancer research and so did you know that the funds that have been raised by the last nine years of the oral cancer walk are the funds that allowed professor MoreyGillison(?) to identify the relationship between HPV and oropharyngeal cancer. Now youre all hearing about it now but it isnt that old, this break through in the field. And the early money that was given to the oral cancer foundation funded some of her earlier research. So now youre hearing about it but its your fellow students that their devotion to the course led to a ground breaking, you know, opening in the research that is now affecting, you know, thousands of people in the United States. So I want you to see what can happen when you have a dream and you start a walk. And its not me; its you guys who started the walk. Im merely the glue to make sure that everything sort of comes together. But its the dedication of the students whove made this walk a success. So, feel good about it.

[203] [N/A][Dr. Kerr] Weve got an Oral Cancer Center at NYU. Many of you didnt know that. The NYU Oral Cancer Center. Dr. Brian Schmidt is the director. Were in the Bluestone Center and we conduct research. We see patients and any of you want to come by on a Wednesday morning to see us, delighted to have you.

[204] [N/A][Dr. Kerr] The Oral Cancer Foundation, a wonderful organization, non-for-profit organization that has changed the lives for many cancer survivors and also contributed to groundbreaking research.

[205] [N/A][Dr. Kerr] And finally, a little pitch to the American Academy of Oral Medicine. Im an oral medicine expert and there arent many of us in the United States but our dedication is to, you know, mucosal diseases. If any of you are interested in learning more about what is an oral medicine specialist or oral medicine expert, please come and speak to me. Im really interested in hearing from you. Its a great field and a great group of individuals. Alright, cheers. 1