Comparing Liquid-Based Cytology Methods in the Detection of Cervical Cancer: Perspectives from Dr. Edward Wilkinson

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1 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: ReachMD info@reachmd.com (866) Comparing Liquid-Based Cytology Methods in the Detection of Cervical Cancer: Perspectives from Dr. Edward Wilkinson 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. You host is Dr. Thomas C. Wright, Jr., Professor Emeritus of Pathology and Cell Biology at the Columbia University Medical Center. Dr. Wright welcomes Dr. Edward Wilkinson, professor and vice chairman in the University of Florida Department of Pathology, Immunology and Laboratory Medicine in the UF College of Medicine, where he also directs the Cytopathology Fellowship Program and is the medical director of the Department's Quantitative Pathology Laboratory. Drs. Wright and Wilkinson will discuss the performance of BD SurePath and ThinPrep liquid-based cytology methods in the detection of cervical disease based upon data from several large national 2018 ReachMD Page 1 of 7

2 organized cervical disease screening programs. These interviews will discuss these data within the context of impact to clinical practice. Welcome to a special edition of Advances in Women's Health, sponsored by BD Diagnostics. I'm your host, Dr. Thomas C. Wright, Jr., a Professor Emeritus of Pathology and Cell Biology at Columbia University. This expert panel discussion 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. Ed Wilkinson, Professor and Vice-Chairman at the University of Florida Department of Pathology in the University of Florida College of Medicine. There he also directs a cytopathology fellowship program and is a medical director of the department's Quantitative Pathology Laboratory. Welcome to the program. Thank you, Tom. The data showed a statistical difference between SurePath and the ThinPrep test in terms of HSIL detection as well as biopsy-confirmed CIN2 plus. Do you believe that these differences are clinically significant? Tom, they look like they're statistically significant, and how that will impact the clinical setting I think depends a bit on the setting of the patients and physicians involved. Certainly in our US situation where we have the HPV testing, that significance would probably not be of much importance. However, I think in a setting where you're totally dependent on cytology there would certainly be some cause for review. As you well know, from the ALTS and the ATHENA trials, there's a lot of variability in the pathologists' reading of cytology results, at least for ThinPrep slides, which are the ones that were used both in ALTS and in ATHENA. Is the inherent variability in cytology a confounding factor in the observed 2018 ReachMD Page 2 of 7

3 differences in these two new studies? And how do we account for this? It could be a confounding factor. These are the European cytopathologists, generally very expert and fairly centralized, but I think there is always observer variability even among experts as in the ATHENA trial. The accounting for it could be partially related to the sample preparation. It could also be partially related to the age of the population. We know that the Pap tests in younger women in their mid 20s or late 20s, those Paps are often very difficult to interpret and problems do occur in that setting. And, of course, the other group is the postmenopausal patient where you can have atrophic changes and such that may mimic abnormalities. We've seen data from the Netherlands cervical cancer screening program, and similar data has been reported out of the UK national screening program. What do you make of the fact that two completely separate national screening programs, one in the UK, one in the Netherlands, have both reported differences in the clinical performance between SurePath and ThinPrep? Is that going to make a change in your clinical practice at the University of Florida? Well, let me answer the last question first. It's not going to make a difference in our practice because we do have the HPV capability, and that gives us a great deal of power as far as the sensitivity of our testing; but if you're totally dependent on cytology, as apparently these two laboratory groups are, it could make a difference. I do know that in some parts of the UK there were serious problems with conventional cytology, and a lot of these problems seemed to be not so much in the collection but in the preparation of the slide itself. I think when you're looking, you're comparing SurePath to, say, ThinPrep, there is a significant clinical factor that we have to remember, and that is that with ThinPrep, the clinician is using a spatula and a brush, and they have to get that cytologic sample off those sampling devices into the transport media. Now, in my own experience working with a number of clinicians, I've found that this is often a difficulty for them. They have trouble getting the sample off or they put the spatula into the fixative; then the sample is fixed on to the spatula, and then they discard the spatula and the sample is not in the collection device. So, SurePath overcomes that problem by using the broom, and the broom is then detached from the handle, so the entire broom is in the transport media, so that this is a tremendous advantage. Now, the laboratory, when they get it, they can do whatever they need to do to completely clean that broom and get as many cells off as possible. So I think sampling errors and problems with that can be a significant issue. And certainly, we 2018 ReachMD Page 3 of 7

4 recognize from these data that have been shown, is that there is a higher unsatisfactory rate in the ThinPrep group, and I think that collection process is a major part of that problem. That's an interesting approach. I have not heard the collection process be addressed as the reason why there's such a difference in the unsat rates, but it makes total sense to me. The data from the Dutch screening program used a 5-year followup period as a timeframe to detect interval cervical cancers arising from undetected or missed clinically-relevant CIN2 plus lesions. How relevant is this time frame for the US using the newest cervical cancer screening guidelines? Well, I don t think that it is highly relevant in the US, in that the most current guidelines from the American Cancer Society and American Society of Cytopathology have addressed this question, and in the year age group, the evidence really supports this interval not be longer than 3 years. And the concern really circles about the fact that there is an increased risk of cancer actually is progressive risk but after 3 years the risk is considered excessively high. But let me say that in the states they were using human papillomavirus co-testing in that age population, and so, there is greater sensitivity of the test. So with the HPV supplement, the screening interval can go to 5 years recognizing that your front-end screening process is simply more sensitive and you are not going to miss cases as could occur with cytology. Also, there is cost-benefit in doing that, even though the HPV testing adds cost, because it permits greater interval time between screening, there is significant cost savings that s been shown. It is also possible with the new guidelines that a woman who is 65 years of age who has had all negative prior screening for the past 20 years and no evidence of prior CIN or severe cervical lesion, that her screening can be stopped and even if she has a new partner there is no reason to reinitiate screening. So there would be considerable cost savings with that approach. If you are just tuning in, you're listening to Advances in Women's Health sponsored by BD Diagnostics on ReachMD. I am your host, Dr. Thomas C. Wright, Jr., and I am joined by Dr. Edward Wilkinson, Professor and Vice-Chairman of Department of Pathology, Immunology and Laboratory Medicine at the University of Florida. Ed, the data from the Dutch screening program showed an increased detection of both CIN1 as well as CIN2+ lesions using SurePath. Can you comment on the issue of risk of overtreatment in younger 2018 ReachMD Page 4 of 7

5 women versus a detection of clinically-relevant disease? Well, I think screening too early in young women is a potential risk problem, and we certainly have seen this here in the States where early in the phase of finding CIN1 lesions we saw way too many young women being treated, sometimes being treated multiple times with electro loop excision and other approaches for lesions that we now know probably a fair number would have regressed on their own. So I think there are issues about that. Certainly, in detecting high-grade lesions like CIN2, we want to do the best we can to detect all of those and proceed accordingly; but certainly, in the younger women there is considerable risk in either overinterpreting or initiating screening too early or being too aggressive on the initial management. The data that was presented from the Dutch screening program reflects a performance of cytology alone. You addressed this a little earlier in this conversation about how the fact that doing cotesting may have an impact on the relative merits of the 2 screening tests. How do you think the inclusion of HPV testing would impact these observations? I think both ThinPrep and SurePath are excellent cytology preparation systems, but they both are limited by the very fact that the diagnostic cells have to get on to the glass slide and have to be interpreted appropriately. And we know that there's probably a false negative rate just intrinsic in the system; that in spite of the best abilities, we know it's somewhere around 30% or so. The advantage of HPV is that it's highly sensitive. It's not as specific by any means as cytopathology, but it is very sensitive, and that sensitivity gives us power to identify early lesions, especially when we can stratify the numerous HPV types that are oncogenic and identify the very high-risk ones; for example, HPV 16 and 18. So there is some real power in that sensitivity and also in being able to identify those very high-risk HPV-related lesions. Speaking in terms of high-risk HPV and the detection of it, do you think these data argue for the limitations of cytology and strengthen the argument for the use of HPV for primary screening? Primary screening is a bit of a subject, but I think if it started late enough, that's a reasonable strategy ReachMD Page 5 of 7

6 And I know that Jack Cuzick from the UK had proposed that years ago, and I think it is a reasonable way to come forward first with your most sensitive test and especially to be testing women that are at an age where we would be expecting them to clear HPV, and if they have persistent HPV, we would expect they might have a lesion detected, so it definitely makes a difference. And there's no question in the hands of these expert cytopathologists that cytology is strong, very strong, but it's not as sensitive as we might like. You mentioned Jack Cuzick as a supporter of HPV primary screening. One of the concepts that they are looking at in England and actually much of Europe is to use liquid-based cytology as a reflex test to determine which HPV+ women need colposcopy when they're using HPV primary screening. Do you think the data that you've seen from these two new studies would influence the choice of which form of the liquid-based cytology you would use as that reflex cytology test? There's a real advantage in the 1-visit approach. In other words, you use a transport media for the HPV testing that also contains your cell population that you can do cytology on, so with the current ThinPrep system, that's possible. So the clinician can collect the HPV testing using the ThinPrep solution, and the laboratory can test for HPV, and then if oncogenic types are identified, can reflex that HPV test to cytology. The SurePath group right now, at least in the States here, our FDA has not judged that as yet FDA-approved, so most laboratories are not using the SurePath system for this purpose. But I know that SurePath is working on this issue and exploring ways to make this happen. I know there are some good scientists trying to find the answer to how to make that HPV testing highly reliable, whether it be SurePath or ThinPrep. But right now in the States, only ThinPrep is the one that's FDA approved. Well, I very much want to thank our faculty, Dr. Ed Wilkinson from the University of Florida. He has been discussing new data that's recently become available comparing the performance of the ThinPrep and the SurePath liquid-based cytologies in European screening programs. Again, I'd like to thank Dr. Wilkinson for his insights. Well, thank you, Dr. Wright. I appreciate your questions and comments. Narrator: 2018 ReachMD Page 6 of 7

7 You ve been listening to ReachMD. The preceding program was sponsored by BD Diagnostics, committed to helping all people live healthy lives. If you have missed any part of this discussion and to listen to others in this special series of Advances in Women s Health, visit ReachMD.com/womenshealth. Thank you for listening ReachMD Page 7 of 7