Transcript Details This is a transcript of an educational program accessible on the ReachMD network. Details about the program and additional media formats for the program are accessible by visiting: https://reachmd.com/programs/advances-in-womens-health/comparing-liquid-based-cytology-methodsdetection-cervical-cancer-perspectives-dr-daniel-ferrante/7592/ ReachMD www.reachmd.com info@reachmd.com (866) 423-7849 Comparing Liquid-Based Cytology Methods in the Detection of Cervical Cancer: Perspectives from Dr. Daniel Ferrante Narrator: Welcome to ReachMD. You're listening to a special edition of Advances in Women's Health, sponsored by BD Diagnostics, committed to helping all people live healthy lives. This program is brought to you through an educational grant from BD Diagnostics. Host Dr. Matt Birnholz welcomes Dr. Daniel Ferrante, who is an OB/GYN with Lifeline Medical Associates, group practice with Women's Care Source. Doctors Birnholz and Ferrante will discuss the performance of SurePath and ThinPrep liquid-based cytology methods in the detection of cervical disease and how these results impact clinical practice. Welcome to a special edition of Advances in Women's Health, sponsored by BD Diagnostics. I'm your 2018 ReachMD Page 1 of 9
host, Dr. Matt Birnholz. This expert interview will discuss data results from the Erasmus Medical Center discussing the performance of SurePath and ThinPrep liquid-based cytology methods in the detection of cervical disease and how these results impact clinical practice. Joining me today is Dr. Daniel Ferrante, a physician with Lifeline Medical Associates, group practice with Women's Care Source. Dr. Ferrante, welcome to the program. Thank you, happy to be here. Great to have you. So, Dr. Ferrante, the data showed a statistical difference between SurePath and ThinPrep in terms of HSIL detection and biopsy-confirmed CIN2 plus, but the grander question here is: Does any of that for a practicing OB/GYN translate into relevancy for clinical practice? What's your perspective on that? Yes, it's of great clinical importance to us because being able to rely on results of our high-grade lesions and knowing that the accuracy of our Paps for our high grade is very important to us because they are really the only reasons that we're treating currently. The low-grade lesions we're able to watch almost indefinitely except in very few cases, but we really want to be sure about our high-grade lesions because they're the ones that we're going to treat and we're treating fairly aggressively. It's also going to allow us to triage our patients more effectively. Knowing that we have more accuracy in our high grades and fewer false positive low grades, we ll be, first of all, using less resources; we'll be following up on fewer false positive low-grade Paps; and, in addition, we'll be treating more appropriately patients who really need to be treated. 2018 ReachMD Page 2 of 9
That does seem like the big message here is treating the patients who really need to be treated. Do you think that this impact that you talk about could be an immediate one or a progressive one over time as this data becomes more aptly used in clinical practices around the country? Well, it will certainly show a cost benefit over time. The longer period of time that we're using a more effective test the more cost effective it becomes because we're using our resources and applying our resources only to where they re needed. When we're seeing more low-grade lesions, more false positives in our low-grade lesions, that means more colposcopies; it means more biopsies; it means more follow-up visits. More accuracy in our low grades and our high grades, in other words, not reporting false positive low grades, will allow patients to go back to an every 3-year schedule; and knowing that our high grades are truly accurate will allow us, again, to be treating only those patients that need to be treated. So from a cost effective standpoint, it certainly will, I think, build pretty exponentially over time. Now, speaking of time, that's a nice opening that you provided, because we know that the data from the Dutch screening program it used a 5-year follow-up period as the timeframe to detect interval cervical cancer arising from undetected or missed clinically-relevant CIN2 lesions, but is that timeframe relevant for you in an OB/GYN practice in the US using cervical cancer screening guidelines today? Yes, it's actually great news for us because we know that we're well within the safety zone using a 3- year interval here in the US. The data really clearly showed that a 5-year interval was safe and that the progression to cancer was very, very low. Using a 3-year interval, which we are in the US, puts us well within our margin of error, so to speak, about progressing lesions. So, at a 3-year interval as opposed to 5, we are very unlikely to miss a carcinoma. 2018 ReachMD Page 3 of 9
That's excellent. And you had also mentioned the idea of being able to rely on the results and things that help validate that. It seemed like they are, in the wake of having data from the Netherlands Cervical Cancer Program as well as data reported out of the UK National Screening Program, that there was a form of validation going on in which they both reported differences in this clinical performance between SurePath and ThinPrep. Having that sourcing from 2 international studies, does that provide more reliability for you, as a practitioner, in the United States? Well, it gives you an enormous level of comfort with the data. I mean, when you have 2 large independent studies that haven't coordinated any of their data or their methods show exactly the same thing, it's an almost incredible validation one study to the other and vice-a-versa. So, yeah, it gave me a great level of comfort knowing that this was independently found in 2 separate large, large studies that, by the way, were very accurate based on the fact that they're national databases in both cases and followed very, very closely. I thought the data was impressive. You know, as somebody who's practicing every day, really in the trenches of utilizing this liquid-based cytology, that element of comfort seems to be very important, and I imagine that comfort level is applicative to practitioners all over the place. Yes, and as a practicing OB/GYN, and anyone who does this for a living as well, is really aware of how often we see data change, how often we see people reporting one test being more accurate than the other, representatives that are in our office selling one technique versus the other. To have 2 large independent studies, this doesn't require any guesswork for me. The data was so compelling, I didn't need to hear anything else. Well, for those who are just tuning in, you're listening to Advances in Women's Health sponsored by BD Diagnostics on ReachMD. I'm your host, Dr. Matt Birnholz, and I'm joined by Dr. Daniel Ferrante, and we're discussing the performance of SurePath and ThinPrep liquid-based cytology methods in the 2018 ReachMD Page 4 of 9
detection of cervical disease and how these results impact clinical practice.. So, in returning to the data, we know that the data from the Dutch Screening Program, in particular, showed an increased detection of both CIN1 as well as CIN2 lesions using SurePath, but tell us a little bit about the potential issue of risk of overtreatment in younger women versus the detection of clinically-relevant disease. Is that an issue for you? Yes, it is an issue, because we're currently managing our low-grade lesions expectantly, so low-grade SIL even with a positive HPV -- and this may, granted, this may change depending on genotyping that we're doing on HPV and cells in the future -- but currently we're managing the overwhelming majority of low-grade lesions expectantly. So accuracy, especially in our high-grade lesions, isof critical importance. And true positives in our low grades is of critical importance as well, because we're not necessarily going to be overtreating, but it may end up requiring too much -- more surveillance -- than is necessary. So, a false positive in low grades is going to require colposcopic evaluation and repeat Pap smears, and potentially, many biopsies. Knowing that our true negatives are truly negative and that our true positives are truly positive allows usto use our resources adequately, and I'm not sure if that's the question you wanted to address. It's very similar to the one we talked about before. Yes, it's actually a good point to reiterate because specifically when you talked about colposcopy examinations, it seems like that's going to be influenced as well in the healthcare community given this data and the potential practice changes that come with it. How do you think colposcopy examinations will be influenced? Well, that's a great point because, you know, often you'll hear discussions about us going just to HPV as a screening test once we get -- really, fine tune our HPV testing and say, Hey, we don t really need cytology anymore; we can screen everybody on HPV and colposcope them based on that. But I think it s really important to keep in mind I think that even subconsciously, the colposcopy that we perform, 2018 ReachMD Page 5 of 9
knowing that somebody has a high grade using a reliable method of liquid-based cytology, that I'm really confident that a high grade on the cytology is a high grade, I'm performing the colposcopy very differently than if I didn't do that. I don't think it's necessarily on a conscious level, but I'm very surveillant, and I may take a little longer, in a patient I know is a true high grade If we go to just HPV testing and we say every positive HPV test gets colposcoped, my level of alertness and awareness -- and I tend to say probably many of us will do this -- is I don't know that our level of surveillance is going to be high. We may not do quite as good a job. We might not look quite as carefully just having a general positive HPV test versus knowing that, hey, there's a high-grade lesion here and I really need to find it. I think it's of critical importance as we move away from, as people are talking at any rate about moving away from cytology and just the HPV testing, kind of made me think, my gosh, do you know what, when I colposcope someone, I really do feel it a little bit differently when I have a low-grade lesion and a high-grade lesion on Pap. So, I think that's a great point that you brought up. I think it's going to impact our accuracy quite a bit, whether we want it to or not. That's fascinating. And it's sort of getting around that question that asks whether the limitations of cytology strengthen that argument for the use of HPV as the primary screen. Well, I think it weakens the argument. I think, you know, as we said, I think relying solely on HPV may be doing a disservice to our patients. Unless we all, you know, get in the mindset of just saying, you know, every HPV is a high grade and we've got to treat it as such, which is really what we ought to be doing, I just don't know that it's that simple. I think on a subconscious level we're going to be performing our colposcopies just a little more carefully knowing, having cytology as a crutch, so to speak, as to say, Hey, this one's a little more serious and take a little longer to look here, and, you know, if you don't see anything, we know those cells are there, where are they? I'm not sure that going to HPV screening alone is going to necessarily pan out. 2018 ReachMD Page 6 of 9
And, on that, let's say that you have followed an HPV primary screen; you get a positive result. Are the data compelling enough to say that, Hey, liquid-based cytology should become reflexive at that point? Well, that's a good question. You know, as we become more precise in our HPV testing, and we really hone in on the subtypes that are, are of concern, and we really know these high-risk types are, let's say, 80% likely to give us a lesion, if we start to get down to that level, I think that HPV testing alone may end up performing the same function as knowing that your cytology is also highly abnormal. So far we're not there, so HPV alone without the cytology, I don't know that this point is of benefit. So, reflexing HPV just based on the cytology means that you have to have a great, a really high level of, a really high level of confidence in your cytology; and certainly cytology that's going to give us false negatives, low grade and high grade, are not, isn't a test that we're going to want to rely on to reflex. So, if we're going to rely on the cytology before we do an HPV, we've got to be sure that our cytology is accurate. Certainly, you know, in low-risk populations I think that may be acceptable. I don't know that it necessarily is in a higher-risk population. This is where cytology really has to shine, right? Because we're missing high-grade lesions and we're missing low-grade lesions; then we don't reflex them at all; we don't know if anybody has a positive HPV -- high-risk positive HPV -- at all, and so, I'm concerned that just going purely to reflex we may be missing quite a bit, unless we're using a very, very effective method of cytology. And it looks like SurePath may be there based on these 2 large trials that demonstrated that it was certainly more accurate. Again, we'll have to know how many false negatives even SurePath is producing before I think we make that decision of going purely to reflexing. Right, so one of the morals here for you, as a practicing OB/GYN, is that the clinical decision-making process, the triaging, the careful evaluation shouldn't be abandoned here under the auspice of potential reflexive cytology, but cytology that gives you better results, that gives you more confidence, is something that you can potentially rely upon much better. 2018 ReachMD Page 7 of 9
Exactly. So, Dr. Ferrante, before we wrap up, are there any other thoughts, takeaways, insights or points that you want to reiterate for our audience regarding what you've seen, what you've observed, and how you think it might translate into your practice? To sum up our discussion here, we've talked about how important it is for us to be using reliable cytology and kind of what we're trying to do to come up with the optimum screening method for cervical cancer screening, which now is kind of muddy. Right now we're looking at cytology; we're looking at HPV; and we're trying to figure out how to combine the 2 to really accurately and cost effectively screen large populations of people and prevent disease, prevent cancer, cervical cancer in this case. We're still not there. We're still trying, again, to decide whether HPV alone, a combination of HPV and cytology and what kind of combination of those 2 is going to give us the best and most cost-effective result. Certainly we know that the more accurate the liquid-based cytology we use, the better it's going to be. Certainly we know the more accurate HPV testing, the finer tuned testing, the more accurate testing and the more we learn about genotyping and about high-risk HPV lesions and viruses, the better we're going to get at it. But I think it's still unclear how it's all going to shake out. Will we be using only HPV, will we be using a combination or will we be reflexing? Or will a new test come on the scene, which I know that there's some research going on now in genotyping cells that are abnormal, that will potentially change, change the whole picture? I think for right now we certainly know that we need the most accurate tests possible in our currentclinical practice. Andfewer false negatives, fewer false positives, fewer inadequate Paps, more accurate, especially high grades, are very important, and more accurate low grades in order to not overtreat people, not over evaluate people, not over biopsy people and use our resources in an effective manner certainly will be really important in the future. It will be 2018 ReachMD Page 8 of 9
interesting to see how this, how this turns out, but as of right now I think we need to be using the most accurate HPV screening we can and the most accurate cytology that we can. With that, I very much want to thank our guest, Dr. Daniel Ferrante, for helping us understand more fully and completely the impacts on clinical practice, specifically OB/GYN practice in the US and perhaps globally, in discussing this performance of SurePath and ThinPrep liquid-based cytology methods in the detection of cervical disease. Again, Dr. Ferrante, thanks so much for your time today. Narrator: You've been listening to ReachMD. The preceding program was sponsored by BD Diagnostics, committed to helping all people live healthy lives. If you've missed any part of this discussion, and to listen to others in this special series in Advances in Women's Health, visit ReachMD.com/Women's Health. Thank you for listening. 2018 ReachMD Page 9 of 9