Anal cancer: Causes, HPV, reducing your risk and new treatments  

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson Hi, I'm Dr. Emma Holliday. I'm a GI radiation oncologist at UT MD Anderson. And today I'm joined by my good friend, Dr. Van Morris, a GI medical oncologist also at UT MD Anderson. And this is the Cancerwise podcast. It's so great to see you and get to chat with you today, Van. 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson Yes, it's always good to see you in the clinic and it's good to you here too. So excited to talk about anal cancer today. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson Absolutely. My favorite topic. 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson Yes. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson Why don't we start with talking about how anal cancer is a rare malignancy, but a growing problem, both in the state of Texas and in the U.S.? 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson We treat a lot of patients with colorectal cancer. And when you look at just the numbers of anal cancer, far fewer people who are being diagnosed. But every year, more and more people are being diagnosis with this disease. And for us in medical oncology, there are more and people who are being diagnosed with metastatic disease at the time of initial presentation. The numbers are showing that this just is not a cancer that's heading in the right direction in terms of the number of diagnoses among Americans. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson You kind of mentioned this already, but I see in my clinic, a lot of people get confused about the diagnosis of anal cancer and how it might be different than colorectal cancer, which is a lot more common. Do you see that among your patients and how do you set the stage or set things straight? Why is it important to make the distinction? 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson It's important for a lot of reasons. They are treated entirely differently. When we're talking about rectal cancers, those are more, I mean, to get into the science or the medicine, you know, what we call adenocarcinomas. They kind of arise from the glandular parts of our GI tract. Anal cancers are very different, right? They arise from squamous cell epithelia. And I always describe this to patients as our body has squamous cells all over our body. The squamous cells in our body are there to kind of withstand the external forces of the outside environment. We have squamous cells on our skin, in our mouth, throat, in our lungs, our esophagus, anything that's kind of, you know, interfacing with the external environment. And so does the end of the GI tract, the anus. So, where they start from is very different. Where they come from is very different as well. Anal cancers arrive by far and large from the human papillomavirus, which probably accounts for 90, 95% of all of these cancers, and as we'll talk about, treated very, very differently. Patients with rectal cancer oftentimes are gonna have chemotherapy, radiation and surgery as the backbones of their therapy. With anal cancer, that's, that's very very different. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson Yes, we're trying to put the surgeons out of business for anal cancer, so we cure those with the radiation and chemotherapy going along with it. You brought up HPV, you know, I think it's no secret that that's the driving force for probably 90% of squamous cell anal cancers. And when a lot of patients come to our clinics, they ask, why do I have this cancer? Why did this happen to me? Is there anything I did? And I know when I'm sitting down chatting with somebody who's facing this new diagnosis, it's really important to me to just take away blame and stigma wherever I can. Cause the reality of it is 90% of us have probably had HPV at some point in our life, especially those of us who grew up and went through adolescence before the time of the HPV vaccine. And so, HPV doesn't just affect certain kinds of people. It really can happen to anybody. And although most of us can clear this virus and we never know we had it and it never does anything bad to us, an unlucky few folks will develop an anal cancer or a cancer in the throat or the genitalia. And it's really just bad luck. It's not a moral consequence of doing something wrong. 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson No, I always make this point when meeting with a patient for the first time about this, which is the patient is coming in with a diagnosis of anal cancer. So, they're already feeling, this is something I don't feel comfortable maybe necessarily telling my friends or family about. On top of that, my doctor is telling me that this came from human papillomavirus, from HPV, from sexual activity. And it's very understandable that they're gonna feel that stigma that you're talking about when they come through the door. And we really want to make an effort to make patients know that it's OK. It's OK to talk about this. We are here to fully help you and meet you at the point of your disease. There is zero judgment. I mirror exactly what you say, is that all of us have had HPV at some point. Like all of us have had it. And exactly like you said, the majority of us, we clear this like we would clear the common cold or some other virus, you know? And we go on and live our lives. But for other people, for reasons that aren't fully understood, it just lingers around. The average age of anal cancer in the United States is patients in their 60s. So, we also just, in addressing this issue of stigma, really just want to make the case that these cancers take decades to develop. So, you don't have this cancer because, you know, of something that happened, an exposure that happened one or two years ago. It's oftentimes, you when people are exposed perhaps to the virus that caused this, this is happening decades later. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson Yeah, I know I think it is an important point to make and anything we can do to make our patients feel more comfortable and just know that it's not their fault. There's nothing they did to cause this cancer and that's one less thing they have to carry with them through treatment. 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson We really just want to make the point that the HPV vaccine is a cancer-preventing vaccine, specifically for the cancers that are caused by HPV. These include head and neck cancers, cervical cancers, anal cancers, vaginal, vulvar and penile cancers. It doesn't prevent all of these cancers because each of these cancers can arise for reasons other than HPV, but for those cancers that could go on to be caused by HPV, it can help to prevent these cancers from developing. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson Yeah, it's certainly the number one step anyone can take to reduce their risk of developing anal cancer among the other cancers that you mentioned. 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson And I'll just say like on a personal note, I even got one right after I turned 40. You know, once these became available years back now, dating myself, for adults as well. This is important for me and, you know, I'm glad I did it. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson Certainly as a mom, all four of my kids are gonna get the vaccine as their pediatrician recommends when they become of age. So, maybe now we can pivot to talking about the treatment of anal cancer. So, we talked about how we might be able to prevent it. We talked about how patients kind of come to process their diagnosis. How is anal cancer treated? 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson I would just say that one of the really reasons I really love taking care of patients with this disease is that when a person comes through our door at MD Anderson, there's always naturally, and very understandably, anxiety that comes with a diagnosis of cancer. And with the treatment that our group gives, we get to see a lot of people go on and graduate from our clinics and live life after cancer. Many of these patients could be cured, but I do tell patients that we have a window to do this right. This is a rare cancer. And maybe your local oncologist, wherever a person lives, sees, you know, one case of this a year. This is not a rare cancer for us. So, best position your chance for cure, find and make sure your doctors have a lot of experience with this. Our approach in general is for chemoradiation, giving radiation at the same time of chemotherapy. How would you say within the landscape of radiation, why treatment at MD Anderson is different as a radiation oncologist? 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson I think it's a good question. And I have similar conversations with my patients who see me in clinic. Big picture: anal cancer has a high chance of cure with radiation and chemo alone. We mentioned earlier that's different than a lot of colorectal cancers that need the three big treatments. They need chemo. They need radiation, and then they need a big surgery. Importantly, a lot of our patients, most of our patients, with anal cancer will be cured without surgery. And that's good news for them, because the surgery that it takes is a really big one: removing the whole rectum, removing the anal canal and anus itself, and leaving the patient with a permanent colostomy bag. 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson Permanent, yeah. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson Permanent, yeah. So, since we look at radiation and chemo as the curative treatment for non-metastatic anal cancer, we've really got one chance to do it right. And while I think there's really great doctors practicing at a lot of great places across the country, I do think like a lot of rare cancers, experience matters. And from the radiation side, it's certainly not just me. I'm not necessarily anything special, but I have a whole team behind me, the top-of-the-line equipment and machinery and physicists to keep everything calibrated. Our teams are just so singularly focused on optimizing every variable under our control to get patients through treatment with as few side effects as possible and with the greatest chance of cure as possible. 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson Yeah, I mean, say for us from the medical oncology side and the chemotherapy, we always kind of explain to our patients that chemotherapy is just increasing the efficacy with the radiation. Historically, for, you know, what, over 50 years now, the kind of the classic treatment has been two drugs, 5-FU and mitomycin C. We're a little bit different in our approach to MD Anderson, and I think this kind of gets and touches, you know, on the point that you made earlier that it's not just getting a patient to cure but doing so with focus and prioritization of quality of life. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson Absolutely. 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson And our approach of using, in general, 5-FU and cisplatin, so kind of changing the two drugs we give from taking the mitomycin C out and replacing that with cisplatin, we've shown, and studies have also shown, that it is equally effective to 5-FU/mitomycin and far less toxic. We further break the chemo up into kind of smaller doses once a week. And what we've really found is that a lot of the chemo-related side effects that people worry about, very understandably, when, when they read about this or talk to their doctor, you know, low blood counts, infection, sepsis, very serious words, we don't see as much of that if at all in, you know, in research that you've led and published on, we've shown that, that our numbers in doing so with how we practice, are safer, I would say, for patients based on how we use chemotherapy. So, it's not. Of course it's the cure. It's getting patients a cure, but it's also making sure that patients are able to get through their treatment, feel as well as possible, like, through their treatments. And I think that's also where having doctors who treat this week in and out really makes sense and helps our patients because we see them on a weekly basis. You know, we're able to kind of tweak things, support them as they go through their treatment, just to make sure that they finish. So, it is different here, and I think our experience shows that. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson Yeah, and I mean, it really is one of the things I love most about this job. And I tell my patients this when I first meet them and we're talking about all these scary things and starting treatment. Um, but I always like to end with, you know, we are focusing on curing you, but we're focusing on curing you with life after cancer in mind. So, we want to get you to cure, but we also want to use all of our knowledge and the benefits of all of our research to, where we can, keep the side effects as manageable as possible. And I think it's really important when we're talking about radiation to the pelvis because it's a really expensive real estate, there's a lot of vital organs down there. Organs that dictate a lot of really important functions, right? Bowel function, bladder function, sexual function, and toxicity of radiation to the pelvis can really impact somebody's quality of life moving forward in the years and decades we hope that they live after they finish with their cancer. So, there's a couple things our group likes to do and that we're really proud of. For our female patients, we do recognize that radiation to the pelvis can cause narrowing and shortening of the vagina, which can lead to painful sexual intercourse and even difficult gynecologic exams. So, for a while now, we have done our radiation treatments with a vaginal dilator or spacer in place, really aiming to keep radiation dose away from the parts of the pelvis that don't need it. And just putting a simple cylinder in the vagina, we're able to keep the radiation dose away from the front side so that we get less of that scarring that can cause problems down the road. We're also looking at incorporating pelvic floor physical therapy earlier into treatment because we know radiation to the pelvic floor and the sphincter muscles can weaken them and cause problems. And so, in general, our group really takes a proactive rather than a reactive approach to radiation side effects, attacking them head on and really doing everything that we can in a proactive manner to optimize patients' life after cancer. 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson And that's such a good point because sometimes it's not uncommon, I would say, to hear a patient say something like, well, you know, I'm two years out from treatment. I'm just thankful that my cancer is gone and doesn't seem to be coming back. I can learn to live, you know, with whatever side effects come out of that. And then you talk to them and they're like, if I go out to eat, I always have to know where the bathroom is because I need to be able to run immediately, or if, and just not having that security. And you're exactly right. It's oftentimes as simple as let me refer you to our friends who are pelvic floor physical therapists. And again, it's not a one size fits all. They work with that patient. Where's your area of need? Is it bowel issues? Is it bladder issues? Is it sexual, you know, whatever, and to create and devise a personalized plan for them because we want our patients to survive and thrive. You know, after. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson Live and live well. 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson Yes, live well and I always just think, you know especially in the surveillance period, prioritization of quality of life is so key. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson Absolutely, and it's funny in the research; I feel like there are many decades where we kind of took all patients with anal cancer, put them in the same bucket, and the treatment was one-size-fits-all, right? People got between five and six weeks of radiation. They got a two-drug chemo regimen, mitomycin C and 5-FU at most places, and we kind of treated everybody the same. And in the last decade or so, the research in the anal cancer field at large has really been looking at patients as individuals, and we're recognizing that some people have really big, bulky, aggressive anal cancers with lots of lymph nodes. And for those people, our current standard of care may not be good enough, and we need to be looking at maybe adding immunotherapy, maybe turning up the dose of radiation, doing something to intensify treatment for them. On the other end of the spectrum, we have patients who maybe have smaller tumors, their cancer hasn't spread to lymph nodes in their pelvis and groin, and those folks may be able to have less intense treatment. Maybe a lower radiation dose. Maybe less chemotherapy. Maybe both. 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson Yeah, and certainly a lot of exciting trials, you know, which have been, you know, run in the United States and led the United States, which are looking exactly this question, you know. Can we decrease the amount of treatment that patients are getting if they have a kind of a lower stage of diagnosis? Alternatively, can we add something like kind of, you mentioned immunotherapy after chemoradiation to see if that helps. These trials, you know, I'm excited. I think we're a couple, hopefully a couple of years away, hopefully sooner from learning how we can hopefully incorporate this into the care we give our patients. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson I mean, I think it's, we're overdue, right? We're overdue to update those guidelines and the national standard of care. I know, right, 50 years is too long. 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson Of the same treatment. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson On the topic of, kind of, personalization of treatment and not treating patients with anal cancer in a one-size-fits-all approach, do you want to talk about the incorporation of the new diagnostic test we've been using in our clinic, the HPV ctDNA? 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson Yeah, historically what we do is the patients finish their, you know, five, six weeks of chemoradiation and then we say, we'll see you back in three months and we'll just kind of watch and wait and just kind, we're just gonna have to see what happens. You know, we look, we use CT scans. We use MRIs, PET scans. The surgeons will do endoscopy procedures, different ways to see if the cancer has or hasn't come back. One of the really exciting technologies that I think has really revolutionized oncology in general, you know, when you look at all of the cancer types has been the use of circulating tumor DNA. And kind of this idea that if there's any cancer which may be left in the body or present in the body, it will secrete its unique DNA into the bloodstream, and you can pick this up in a lab test. Our group has been very interested in this, you know, for over a decade now, and we had actually reached out to industry my first year of faculty, 2015, 2016, and said, we really think that as you guys are building your ctDNA platforms, incorporating HPV is a very simple and easy way to help patients with a lot of cancers. And they were interested, but I don't think at that time it was the top priority for, and that's understandable. So, what did we do? We went and found people at this institution who shared that vision and passion to bring more and better to our patients. And we created; and I really just want to acknowledge Dr. Maura Gillison, just such an amazing trailblazer, collaborator, mentor, friend, but really in that collaboration with Dr. Gillison we worked across disease types. This was very much a team science approach to create an HPV ctDNA assay and then show that it doesn't matter which HPV-associated cancer you're talking about, head and neck, cervical, anal, anogenital cancers, you can use this test to identify if a patient's cancer is likely to come back or not. And in the last year, we've validated this and it's gone live. So, if a patient comes to MD Anderson, we can test their blood starting three months after they finish their chemoradiation. And if we don't see any ctDNA present, we can use that as one additional very strong data point that likely we're not able to see even microscopic levels of cancer. Alternatively, if the ctDNA is present, that's gonna kind of raise our radars and our suspicions. We're gonna watch these patients much, much more closely to kind of figure out, is this cancer? Where is it coming back? And really try to intervene early. Because again, this kind of goes back to what you were saying earlier, like if it's gonna come back, we really want to address it. And in doing so, try to minimize the morbidity and complications and side effects that people could have from treatments like surgery or things like that. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson Yeah, I've been so excited to bring the HPV ctDNA test for our patients in clinic. I feel like it's been a long time coming. Lots of other cancers have a blood test, right? And a lot of times patients are in our clinic, they're like, OK, well, I'm glad the CT looks good. I'm glade the scope didn't show any cancer, but how do we know we got it all? How do we there's not microscopic disease lurking? And for many years, the answer was we don't. We just have to wait and see what declares itself. But this HPV ctDNA test really gives us more advanced warning. It allows us, again, to personalize treatment for patients, give some additional reassurance to folks where they have a negative test. You know, that's one more good check in the column that things are probably good. And on the other hand, folks who have a positive blood test, maybe we'll do their CT scans more frequently. Maybe we'll keep a closer eye on them. Maybe we'll be able to intervene on that recurrent tumor before it gets out of hand. So, yeah, it's been practice changing. It's been great. 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson Patients really like it. I think having that added layer of security and reassurance is important. And I think, again, this just like, it's a novel intervention and approach for patients with rare cancers. And this all arose from us taking care of these patients. Listening to them. Talking to them about what are the unmet needs. Learning from other cancer types and bringing that to the forefront of care in the patients with rare cancers. So, really, really excited about it. And again, I think it's been a great win for patients. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson And not to get into the weeds, but how is the in-house HPV ctDNA assay different from, say, the commercially available one you could just order? 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson That's a good question. We both treat a lot of patients with colon and rectal cancers. And a lot the tests that are out there that people hear about require tissue and oftentimes that's surgical tissue. So, you need a fairly large piece of tumor to be able to create a test for a patient and turn that into their own kind of ctDNA test. Because anal cancer is not treated with surgery in most cases, it's a smaller tumor. You don't have access to a large surgical specimen because the patients are being treated with chemoradiation. So, that represents like another opportunity for us. All we need, because we know that the majority of these are going to be derived from HPV, for these patients, and again, it's the majority patients, we can use just a single blood test. So, the limitations of needing surgical tissue or needing tissue, we don't necessarily need in this particular case. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson And we don't need the additional time it takes to create a person-specific assay for each patient. 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson Results come back in like a week. So, it's very good. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson Yeah, it's been fabulous. So, we talked about patients with non-metastatic anal cancer and how we treat them here at MD Anderson. What's going on in the space for patients with metastatic anal cancer? 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson Yeah, so it's been an exciting time, I think, in the past couple of years. I think the most important advance; we had our first positive Phase 3 trial for patients with untreated metastatic anal cancer. That was called the POD1UM-303 trial, and what it showed was that when you take immunotherapy, specifically with a drug called retifanlimab, and add that to chemotherapy, carboplatin and paclitaxel, which we've used for years for patients with metastasic disease. That that really kind of improves best the survival for patients with this disease. So, that's been, I think, a really big breakthrough. There's another trial looking at a similar combination, chemotherapy with or without nivolumab, so a similar drug. That trial will also probably report out in the coming years. So, a lot of research in looking at how we can combine therapies. The challenge we're facing though right now is very much kind of what I felt when I was a fellow here, which was, you know, back then it was, there was only chemo. So, a patient would come to MD Anderson. We would see and say, I have been diagnosed with stage 4 anal cancer. I've had chemo and my doctor told me there's no other treatment for me. What do I do? So, POD1UM-303 has been a huge success. And we're very excited about that, but there still continues to be a challenge and a very much of an unmet need for this rare population. When that treatment stops working, what do patients have? And, and there really isn't a good answer for that right now. So, our passion is bringing the best to patients with this rare cancer. And MD Anderson has been very supportive about rare cancer research. You know, oftentimes patients will come with a biomarker, what we call a next-generation sequencing panel, which says these are my mutations that are present in my cancer. This is very informative for patients with colon or rectal cancers but typically is not helpful at all for the management of patients with metastatic anal cancer. And the reason for that is we just don't have good drugs which can target and treat cancers based on those mutations. One of our fantastic fellows here has, you know, done some research where she looked at RNA and what she was able to show is that when DNA is not effective in helping us to direct our path, RNA could very well be effective. So, there's a new class of therapies coming out called antibody-drug conjugates and the RNA, kind of, patterns of how they're present in patients with metastatic anal cancer is really creating paths for us to bring antibody-drug conjugate trials to MD Anderson. And we're very excited because we'll launch the first of these in the world, you know, in the very near future, specifically as a trial here for anal cancer. So, that's just kind of one example. We're looking at other examples, other clinical trials here, which incorporate kind of novel immunotherapy approaches. Oftentimes when we think immunotherapy, we think about drugs that target PD-1/PD-L1, CTLA-4. But there's certainly other ways in oncology that are emerging where we can bring other immunotherapy modalities to our patients. So, we're really excited because we have a lot of other trials coming as well to look at these approaches really with a goal of bringing more and more therapies. And we always tell our patients, we will leave no stone unturned to find what the best treatment is and try to help in every way we can. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson Well, thanks, Van, for sitting down with me and chatting a little bit about our favorite topic. 

Van Morris, M.D., GI Medical Oncologist, UT MD Anderson Anal cancer. 

Emma Holliday, M.D., GI Radiation Oncologist, UT MD Anderson Yeah, absolutely. And thank you for tuning in today. If you enjoyed this episode, be sure to follow or subscribe on Apple Podcasts, Spotify, YouTube, or wherever you get your podcasts. And don't forget to comment or review. For more information or to request an appointment at UT MD Anderson, call 1-877-632-6789 or visit MDAnderson.org. Thanks for listening to the Cancerwise podcast.