IBD Drive Time: Detecting and Managing Anorectal Cancer

Andrea Bafford, MD, and Jessica Korman, MD, join Drs Raymond Cross and Millie Long to review the challenges of detecting, diagnosing, and managing anorectal cancer among patients with inflammatory bowel disease.

Raymond Cross, MD, is director of the IBD Center at Mercy Medical Center in Baltimore, Maryland, and professor of medicine at the University of Maryland. Millie Long, MD, is a professor of medicine, Division Chief, and director of the Gastroenterology and Hepatology Fellowship at the University of North Carolina at Chapel Hill. Andrea Bafford, MD, is a colorectal surgeon with Johns Hopkins Medical Center in Baltimore, Maryland. Jessica Korman, MD, is a gastroenterologist with Capital Digestive Care in Washington, DC.

TRANSCRIPT:

Any views and opinions expressed are those of the authors and or participants and do not necessarily reflect the views, policies, or positions of the A IBD network or HMP Global its employees and affiliates.

Dr Long:

Hi, this is Millie Long from University of North Carolina and I'm here with my cohost Ray Cross from Mercy, and we are proud to introduce Dr. Jessica Korman and Dr. Andrea Bafford. Jessica is at Capital Digestive, and Andrea is a colorectal surgeon at Hopkins. And so we are pleased to have them here to share their expertise with us on a topic that is of great importance and I think probably not investigated enough, which is anal cancer. And so with that, I'm going to go ahead and start us off. So I'm going to start actually with you, Andrea, if you don't mind. Would you tell us a little bit about anal cancer and how common this is?

Dr Bafford:

Sure. Well, first of all, thanks for having me. Anal cancer is actually fairly rare. There's about 10,000 new cases per year in the US and if you compare this to colorectal cancer, there's about 150,000 or more new colorectal cancer cases per year. So 15 times more common is colorectal cancer compared to anal cancer. However, the incidence is increasing, and this has been happening since the 1970s with the increasing incidents. There's a little bit of a delineation of who is getting this disease. More two thirds of cases are in women and white women and black men seem to have a higher propensity of getting anal cancer. The average age of patients with anal cancers is the early sixties.

Dr Long:

So I think this is, it's really interesting, isn't it epidemiology wise that we're seeing more in women. What do you think, Andrea, do you think that is the HPV vaccine making any headway or how are we going to help to change this process?

Dr Bafford:

I certainly think HPV vaccination is making a difference, but we have a lag because the HPV vaccine and the identification of HPV 16 and 18 being associated with anal cancers is relatively newer. So the incidents going up from the seventies, the vaccination I think will lead to this disease being less common in the future.

Dr Long:

Gosh, I certainly hope so, because we obviously have a lot of morbidity associated with anal cancer. Let me bring Jessica into this. Jessica, you have a huge expertise in this area and I hope you can teach many more gastroenterologists a lot about what we do and help us with screening and surveillance. But talk us through first the symptoms that one should be on the lookout for, which would be something that you would then want to pursue diagnostic testing for?

Dr Korman:

Sure, absolutely. And thanks also for having me. I appreciate the opportunity to be here. So I would say that the most common presenting complaint is anal pain, but also rectal bleeding, anal itching, feeling an irregularity in the area that patients may notice on their own. And often they'll go to their provider and the provider either doesn't examine them, doesn't do a rectal exam or a good anal rectal exam. So really with attention to the perianal skin, the anal canal, not just an in and out in the rectum or they'll misdiagnose as hemorrhoids or a fissure sometimes. And so that's kind of a problem. So the recognition is really important to know what you're feeling, but those are usually the most common symptoms. So pain, bleeding, itching, that kind of thing,

Dr Long:

Which really correlates with hemorrhoids, right?

Dr Korman:

Which are much more common. And that's of other things, rectal cancer. And also some people will have leakage, so one might think fistula as well. So I think the take home point is you have to actually examine the patient.

Dr Cross:

I've only seen this twice in my career, so it is pretty rare. But one of the patients had symptoms that sounded a lot like bronchitis and calprotectin was normal and the symptoms persisted, and I did a sigmoidoscopy and I obviously felt it and then saw it on the sigmoidoscopy. So just add that to your list of potential symptoms. And the other thing we talk about frequently, I don't know if ever diagnosed this during an exam under anesthesia, but that stubborn perianal fistula that won't stop draining, that's really refractory. One of the things that we're supposed to think about is could there be a squamous cell cancer within the tract? And I don't know if that's technically considered anal cancer, but it's just another group to consider as having a potential complication.

Dr Korman:

There's actually the largest, I mean it was first reported by Dale in 1975 about the risk of perianal fistula transforming to cancer. But interestingly, in the largest case series, the majority of cancers arising from a fistula are actually adenocarcinomas, not squamous cell carcinomas. And that's because most of them are arising, the fistulas arising from the rectum, not the anal canal. So there's a big difference.

Management is different, treatment is different, and I know we'll get into it, but I wanted to go back to something about incidence. I think it's important to note that the highest risk group for anal cancer are in men who have sex with men living with HIV, in which if you look at cases per 100,000 people, so there's 2 per 100,000 persons per year in the United States who get anal cancer. So that makes it rare. But in men who have sex with men over 35 living with HIV, it's about 160.

So that is very high, higher than colon cancer, higher than prostate, breast, all of them. And the other thing to note is anyone living with HIV over the age of 45 is also an increased risk. Men who have sex with men who are not living with HIV, but maybe immunocompromised, I mean just in general, but also who may be immunocompromised in other ways, if they have Crohn's, ulcerative colitis, and they're on immunomodulators. And if you look through the literature about the incidences of anal cancer and IBD, it's not so easy to find because there's not a lot of research. But in 2018, the CSM group published their data on anal squamous cell carcinomas, and they found a rate in patients with Crohn's disease who had perianal or anal fistula or any anal or perianal pathology, the rate was 26 per 100,000. So that's quite significant, but not in patients with ulcerative colitis, not in patients with Crohn's that didn't involve the anus at all.

So I think we can probably include Crohn's patients with perianal, any history of perianal disease. And in their cohort, they found that they had a mean duration of disease of 10 years, and it was irrespective of advanced exposure to advanced therapies. When they did, it was a nested case control study. So I thought that was really interesting that it's really probably something about the inflammatory process itself, not necessarily the medication, although the medication may play a role, we don't have any data on that, and it's very hard to do this kind of epidemiologic study. So it's going to come from big databases like the Danish and the French databases, but they're starting to look at it, which is important. It would be nice to know how much correlated with sexual orientation, with history of vaginal or cervical HPV in women, that whole, if we could explore that, that would be helpful.

Dr Long:

Yeah, I think that's really interesting. And I think important in my practice, one of the things I do is we see a lot of those patients with Crohn's that have the very stricturing anal canal disease, and we do a lot of dilation. I personally do a lot of Hegar dilation and balloon dilation in those areas. And I really think it's important for us to intermittently biopsy those strictures because you don't want to miss this. I mean, I don't think you need to do it every time you dilate, but I think all of us should have on our radar that we do need over time to get serial tissue samples to make sure this haven't transformed into a malignancy. So I think it's a great point.

Dr Korman:

I mean, we have techniques to actually identify the high-grade dysplasia in the form of high-resolution endoscopies, so you don't have to do random biopsies, but it would be the actual stricture itself. That is true too, but I think it would also be useful to look with someone who does high resolution anoscopy to see if they can identify any HPV-related lesions or perhaps in that scenario, even swab for high-risk HPV, which is not yet FDA approved for the anal canal the way it is in the cervix, but most insurances, at least in the Washington, DC area, will cover it. So all you do is basically a swab in the anal canal and that way if there's the addition to randomly biopsying just the stricture to make sure, but on top of that, to determine whether there's high-risk HPV present in anal canal might help sort of give you a level of risk stratification that might help you follow these patients appropriately or not.

Dr Long:

Yeah, no, absolutely. But I think there are probably 2 processes. There's the HPV medicated process and also the inflammatory mitigated process of increased risk. I mean, you agree the ongoing inflammation and the stricture in the anal canal.

Dr Korman:

Well, for squamous cell carcinoma, it's over 90% of squamous cell carcinomas of the anus are HPV-related. So it's the combination of the oncogenic HPV and the inflammation. I don't think just the inflammation alone is a risk factor for anal cancer, not as much. I mean, for example, there are some people that it's extremely rare that will transform from chronic hyperkeratotic, chronically inflamed perianal tissue has nothing to do with IBD who will transform the squamous cell carcinoma, but it's very rare. The vast majority are HPV-related, and over 90% of people have been exposed to HPV. So it's more common than not that one would have anal HPV even if you don't have penetrated anal sex.

Dr Long:

So definitely important. As we're moving into some of the next questions, which we've talked about this, which is the risk factors which we addressed in terms of particularly HPV and potentially the inflammatory response of perianal disease and anal canal and IBD. With that, what I may do is turn this over to Ray because I know he had another series of questions for you.

Dr Cross:

Great. I just want to remind the listeners that we are sponsored by Advances in IBD and we have a series of AIBD regionals coming again in 2025. And Christina Ha and myself are cochairing those. And the first AIBD regional will be April 5th and April 6th in Nashville. We have a new format, a lot more emphasis on local regional faculty, and I think it's going to be a really great education series. So we hope to see you there.

Before I go to the next question, I wanted to follow up with Andrea because I think this is a blanket statement, which is not completely true of all gastroenterologists, but I generally think colorectal surgery does a much better job of doing a careful perianal exam than we do as gastroenterologists. So what are some clues for the gastroenterologist to look for on perianal exam other than an obvious mass, something that maybe should prompt them to refer to you for an exam under anesthesia?

Dr Bafford:

As far as a perianal exam, it does get tricky. And kind of going back to Millie's point about patients with perianal Crohn's disease, the way the changes I've seen with perianal Crohn's disease and anal cancers could really mimic each other with the strictures and firm tissue, fibrotic tissue. I think as far as an office exam, a digital rectal examination definitely gives a lot of information. So a lot of times when we're talking about doing HRA and endoscopies, the findings are more subtle, but you could feel firmness. This is anal cancer, not dysplasia, but anal cancer. The digital rectal examination I think is always important. You could feel if the tissues feel firm or fixed, which is much more concerning than more of a kind of rubbery circumferential narrowing. For example, perianal exam in the office, like good lighting is important. I usually have patients in left lateral position and really you could see a lot, you could see any fissuring by just spreading the buttocks open.

So you want to be inspecting all of the perianal skin and right at the anal verge by spreading. And what I would be looking for is any ulcerated mass, especially if the edges look really heaped up, any irregularity of the discoloration. So like pink and white discoloration. As far as perineal lesions like nodularity firmness, I think fissures usually look in Crohn's disease. I think if fissures persist. So hopefully some longitudinal exams I think is important in these patients because if things just look, if they might change over time, and that might be your clue as to there being something there. But really I think it's looking at the perianal skin with good lighting and spreading the buttocks open. And then a digital exam.

Dr Cross:

That's a really perfect segue to talk about screening. So I'll let you know why this has become important to me. I have two long-term patients, they're both still alive, thankfully, who I diagnosed anal cancer within a span of probably about 6 to 9 months. And it just really, really just shocked me and I thought, well, what could I have done that would've maybe picked up sooner? And both of them required systemic treatment, so it wasn't sort of an anal, it wasn't just a local treatment. And so that actually was a stimulus. Andrea and I wrote— this is a plug for the American Journal of Gastro—we wrote a review article on what can the gastroenterologist do to identify this? And that's where I'm getting at, sort of what can we do to get gastroenterologist to the basement floor or the first floor of the house as far as screening and then maybe getting up to the ceiling where Jessica is. So what we do at Mercy is every patient with a history of HPV, HPV-related complications, perianal fistula, anal complication of Crohn's, men having sex with men, men, people living with HIV, they get an annual perianal exam and digital rectal exam. And obviously if they have new complaints that would be increased in frequency. And then if they're getting an endoscopy, you're obviously doing it during that time as well. So to me, that's the first floor, Jessica. So what else can we do? I mean, every gastroenterologist can do that.

Dr Korman:

So we actually have guidelines that were published within the last year in the International Journal of Cancer. They're free, everyone can access them, which relates to all populations. So they do have specific recommendations, and I generally agree with them, which are that for anyone at risk, and I would probably in these guidelines, they use some epidemiologic data for IBD and immune-suppressed patients. But I think their data's a little bit off that probably the incidences in Crohn's patients with perianal disease is high enough that screening them is probably a good idea. So again, the floor would be, as you said, a good exam, a good digital rectal exam. And I always like to say in gastroenterology we learn the DRE, the digital rectal exam, but really it should be the DARE, the digital anal rectal exam, because most of us gloss over the anus and think we're just trying to get into the rectum, but we really need to pay close attention to the anal canal.

So that's one. I think it's also what is recommended is an anal pap smear annually in certain groups over a certain age, they're at high risk. So we really start to see the incidence go up at least in immune-suppressed patients, people who have had a solid organ transplant who are more than 10 years out, starting once they're 10 years out from solid organ transplant. But we don't really know how long the immune suppression of IBD would affect the risk for anal cancer. So it's hard to know at what age to start, but I would probably say age 40 is it, or 40 to 45 is a good starting point with shared decision making with the patient to start doing anal pap smears and an anal rectal exam.

And I also recommend if your local insurers will pay for it to do high-risk HPV testing that unfortunately the anal pap smear is very, it can be quite sensitive if you use atypical squamous cells of uncertain significance as a cutoff. But pretty much everybody has that, so it's not very specific. And then if the pap smear and the high-risk HPV tests come back abnormal, then the recommendation is to refer for high resolution. And now more and more people are becoming certified in high resolution anoscopy. I'll make the plug as the co-course director of the course given by the International Anal Neoplasia Society, we'd love to have more colorectal surgeons and more gastroenterologists involved in this technique. It's not hard, but so hopefully there's someone in your community you can refer to for an abnormal pap smear, and then they can enter into a program where they're being followed and surveyed. So that would be the next step. But if you're doing a colonoscopy or a flex sig, it's not ideal to find anal dysplasia because we do use dyes in a high resolution endoscopy and we have a very high magnification higher than with a colonoscope or flex sig, but you can probably still see something.

So my next suggestion is if you see something that doesn't look normal, don't be afraid to biopsy it, right? If it's proximal to the dentate line, the patient is not going to feel it. That's not sensate tissue. So they may have bleeding afterwards, but that's okay, to not be afraid and to take a biopsy because that's really useful to whomever you're going to refer to, whether it's somebody proficient in high resolution endoscopy and management of anal dysplasia or a colorectal surgeon. Either way, a tissue diagnosis is helpful. If you are still don't feel comfortable biopsying, then refer to someone who can get a good exam and get a tissue biopsy.

Dr Cross:

I got a couple of follow-up questions and just something practical. So I think for the gastroenterologist, she's doing a procedure and you're doing retroflex and you should really try to see 360 all the way around the anal canal. Sometimes it's not possible. I can tell you that Jessica and I have biopsied the anal canal during pouchoscopies on more than one occasion. In fact, if I don't see squamous tissue, I wonder did I really get the cuff because sometimes the cuff that Andrea creates is so short that you can barely see it. So you're not going to do harm in biopsying anal tissue, particularly if under propofol. And if we still haven't convinced you, if you see something abnormal, just send them the colorectal surgery for an exam under anesthesia. So you don't have to biopsy. You can just say, this looks funny and I want someone else to look at it pragmatically. Jessica, when you're doing the DARE and the pap, do you do the perianal inspection? Do you do the pap and then the DRE or do you do the DRE and then the pap?

Dr Korman:

So the way that that works, so first, usually I inspect again, as Andrea said, with good lighting is very important, inspect the perianal skin and then I'll usually palpate with my finger without any lubricant around the perianal skin. So a lot of times it's not just what you see, but it's what you palpate, exactly what Andrea said that you want to feel for firmness, tenderness, anything that feels unusual. Then you do your pap smear. That is a dacron swab, so a polyester swab that's dipped in water. This is really easy. You should be able to get these tools. And then you wet it with water and you spin it around an anal canal. You want to insert it as far as you can till you hit the rectal vault. And then you're sort of coming back while sort of using firm pressure around in a circular motion and an in and out fashion.

So you're basically trying to sample the whole, you want to imagine you're sampling the whole anal canal as best as you can. And then you take that out and you shake it off in like a thin prep or a sure prep for 30 seconds. You sort of bash it against the wall like you're mixing a martini and you're shaking, imagine you're shaking the cells off, and then you throw away the swab and send that off to cytology. And then you do your exam with your finger, with your lubricant. If you use lubricant beforehand, before the anal pap smear, the cells don't clinging to the dacron or polyester swab and you can't use a cotton swab because the cells will get stuck to the cotton swab. So you do your exam with your finger afterwards. And I usually use, I like to be nice and use some lidocaine jelly. It's always a nice touch.

Dr Cross:

So thanks for ruining my martini this evening. That was clearly awesome of you. Andrea, what percentage of colorectal surgeons do high resolution endoscopy? Is it the minority, the majority?

Dr Bafford:

That's a good question. I am in the Baltimore area and similar to the DC area, it seems like most colorectal surgeons in this area do high-resolution endoscopy. Most of us are doing it without formal certification, more trained to do it and then continue the practice. But I would say a good proportion, but I do think it probably varies depending on where you are.

Dr Cross:

And you'll need, the listeners will need to know which colorectal strategies in their areas see this and importantly have interest in it.

Dr Korman:

I would also say that if you look on, you can look up who is certified in high resolution anoscopy or who also reports that they do it on the UCSF anal cancer website. They keep a list of who performs high resolution endoscopy. The vast majority of people who are formally trained, and we're actually coming out with competency criteria. We're really trying to advance the field. Just like in most subspecialties we have competency requirements. You can find people in your area, but the vast majority of people are infectious disease providers or primary care or HIV providers. And there are some gastroenterologists. There are a lot of advanced practice providers. A lot of APPs do this. It's a great technique for APPs to learn. And then there are also surgeons and colorectal surgeons, but I would actually say the vast majority are just internists or infectious disease specialists because they come in through the lens of guidelines for people living with HIV who are really the highest risk group of people. But you can find out in your area, usually you can look up on the UCSF website and find them.

Dr Cross:

Andrea, last question before the fun fact. What's the treatment for anal cancer?

Dr Bafford:

Well, I wanted to just go back and say one thing. We haven't mentioned it, but vaccination I think is, or we mentioned in the beginning just as…

Dr Cross:

Vaccines are not controversial at all these days.

Dr Bafford:

Oh, right, exactly. But the FDA approved the vaccination up to the age 45. So I think everyone up to 26 is getting vaccinated with I think the 2-dose. And then after that, 27 to 45 is a 3-dose vaccine. But I do think it's important with a lot of these IBD patients being younger, maybe choosing based on risk factors, sexual activity, maybe some of the medications people are on. But it is a vaccine that's approved to the age of 45. And so I think that's an important part of prevention.

Dr Cross:

Completely agree.

Dr Bafford:

Treatment wise, anal cancers are treated with definitive chemotherapy and radiation. So this is squamous cell, squamous cell carcinoma, which is the vast majority. But in Crohn's patients, there's more adenocarcinomas, but squamous cell carcinomas are treated with chemoradiation with surgery kind of being considered salvage for persistent disease after treatment, the minority of anal cancers are able to be treated with wide excision, because especially in the anal canal, you just don't have enough tissue to get wide margin. So some of the perianal cancers can be, but most anal canal tumors are going to require chemoradiation.

And then anal adenocarcinomas really are treated the same way as rectal adenocarcinoma. So that has been evolving for rectal cancer. There's not too many programs that I'm aware of that would do nonoperative management of anal adenocarcinomas, but those would be chemoradiation with surgery. And then as far as patients with IBD with anal cancers, more patients do end up having surgery because I think that's two things is one. With chemoradiation, there's a lot of concern about the functional outcome after, if you have pre-existing perianal Crohn's, you could kind of expect for defecatory function, maybe leakage and things like that after treatment. And also surveillance after treatment would be much more challenging in patients with perianal Crohn's. So more people with IBD with anal cancers do end up having surgery, which would be an abdominal perineal resection. So a proctectomy with a permanent colostomy.

Dr Cross:

This has been really awesome. Jessica, tell the listeners your fun facts. So what fun thing about Jessica Korman should the listeners know?

Dr Korman:

I have seen every Cohen brothers movie ever made.

Dr Cross:

Alright.

Dr Korman:

All I got.

Dr Cross:

That's good. And any of them disappoint you in particular?

Dr Korman:

Disappoint me. Not that I can think of off the bat.

Dr Cross:

And Andrea, what's your fun fact? Hopefully I'm not going to have to pull anything out for my knowledge of working with you at University of Maryland,

Dr Bafford:

Honestly, cannot think of a kind of eccentric or odd fact.

Dr Cross:

I've got a good one. So Andrea is probably the worst hedge clipper in the history of the universe. So she cut the tip of her finger off —colorectal surgeon doing her own yard work, that shows you how dedicated Andrea is. And she took off the tip of her finger, which is sewed on, but has no feeling. So she and I share a numb appendage, although I am missing part of my pinky from a mandolin accident. So we share that common, the numb finger. How's that? For one?

Dr Bafford:

I had forgotten about that. That is true. And the setting of that was especially not smart as I had the hedge trimmer on a ladder to be able to reach the high ones.

Dr Cross:

So listen, listener, you know what? Use the hedge clipper without good vision, just like your perianal exam. And never for god's sake, never use a mandolin ever, because it's the most dangerous instrument ever. Alright, this has been great. Thank both of you for joining us. This is going to be really, we're going to have a lot of listeners. This is an important topic, and we hope to have you both back again on IBD drive time.

Dr Bafford:

Thank you.