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-conventional-vs-liquid-basedcytology-detection-cin-new-data-netherlands/7649/ ReachMD www.reachmd.com info@reachmd.com (866) 423-7849 Comparing Conventional vs. Liquid-Based Cytology in the Detection of CIN: New Data from the Netherlands 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. Welcome to a special edition of Advances in Women's Health. I am your host, Dr. Thomas C. Wright, Professor Emeritus of Pathology and Cell Biology at Columbia University. Joining me today is Kirsten Rozemeijer, a Ph.D. student at the Department of Public Health, Erasmus Medical Center in the Netherlands. 2018 ReachMD Page 1 of 7
Kirsten, welcome to the program. Thank you for inviting me to be part of the program. It is really an honor. I would like to thank you for giving the listeners of ReachMD a chance to hear about your recently published study that evaluates the impact of liquid-based cytology on the detection of CIN in the Netherlands. As you know, the comparative performance of liquid-based cytology compared to conventional cytology has been hotly debated over the last decade. Your study provides some of the best data that we now have on this topic. Can you describe the design of your study for our listeners? Well, of course. We performed a retrospective study using data of the Dutch National Pathology Database. This database contains, amongst other things, the records of all cervix, uteri, cytological and histological tests taken in the Netherlands inside and outside the population-based screening program. So, within our study we included more than 6 million primary cytological smears taken within the Dutch screening program from 2000 to 2011. We had a minimum follow-up of 15 months after a positive screening smear in order for a CIN lesion to be detected. Accordingly, we assessed whether a trend in increased CIN detection rate was present by performing Joinpoint analysis; and thereafter, we performed logistic regression analysis. This in the time period depicted by these Joinpoint analyses to assess the quantity of the increase, then corrected for confounding factors. And by correcting for the type of cytology test used, we could assess better increase, caused by the introduction of liquid-based cytology or not. The major finding of your study is that between 2003 and 2009, as liquid-based cytology was being implemented in the Netherlands, there was a fairly significant increase in the detection of CIN or cervical cancer precursors. What was the magnitude of the increase in detection rates, and was this 2018 ReachMD Page 2 of 7
true for all grades of CIN? Well, we found that a trend in increased CIN detection rates was present around 2003 to 2009 for all CIN grades. And when comparing CIN1, we found the detection rates were 2 times higher in 2009 as compared to 2003. For CIN2 and CIN3, the detection rates were 1.7 and 1.5 times higher in 2009 as compared to 2003, and then correcting for differences in demographic factors did not have much influence on these increases. In the discussion of your article, you describe a number of potential factors that could be responsible for this increase in the detection of CIN. What were they? Well, first of all, the introduction of liquid-based cytology, in addition to that, image-assisted reading of liquid-based cytology has been implemented in the Netherlands, although on a very small scale. And also, the underlying cervical cancer risk of the general population could have increased; although, we think it is unlikely that a strong increase could solely have been caused by an increased prevalence of risk factors. Higher attendance rates of women with a higher risk to develop CIN lesions is also a possibility, and last a small part of the increased CIN detection rates may have been a compensation for observed previous period of decrease in CIN detection, which we saw after 1998, and this decrease was probably the effect of a period of more frequent screening due to restructuring the program and thus a period with increased CIN detection rates. How did you actually determine that the increased detection rate was due, or at least partly due, to the introduction of liquid-based cytology? 2018 ReachMD Page 3 of 7
Well, we corrected for the type of cytology test used, this SurePath, ThinPrep or conventional cytology, and we assessed the impact on trends in the CIN detection rate. We found that the increase in CIN detection rate became smaller, so meaning that the introduction of liquid-based cytology contributed to the CIN increase. However, the majority of the increase in trend in CIN detection rate was still present. So, for CIN1 the detection rates were still 1.9 times higher in 2009 as compared to 2003, and for CIN2 and CIN 3, detection rates were 1.5 and 1.6 times higher. However, we have to mention that no data for laboratory were available, and liquid-based cytology was implemented over time between laboratories. So, if the effect of liquid-based cytology differs between the laboratories, this could mean that we underestimated the effect of implementing liquid-based cytology. And the presence of the interaction between screening region and the type of cytology test used seems to confirm this. That's fabulous. 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, and I am joined by Kirsten Rozemeijer, and we are talking about her recently published study that evaluates the impact of liquidbased cytology on the detection of CIN in the Netherlands. Kirsten, did you see a different impact depending on the type of liquid-based cytology used, in other words, the labs that introduced SurePath and those that introduced ThinPrep? Well, the goal of the study was to determine the increase in CIN detection rates over time and to assess whether it was caused by introduction of LBC testing, so our goal was not to assess the impact of SurePath versus ThinPrep. However, I can say that we are currently examining the impact of using SurePath or ThinPrep first as conventional cytology as primary test method, and we hope this paper will be accepted for publication in the coming weeks. So, because of this we cannot share all our results in public yet. However, as I already presented, these were showed in some conferences. I can reveal that the impact on CIN2 plus detection rate depends on the type of liquid-based cytology test used. 2018 ReachMD Page 4 of 7
We will look forward to seeing that paper when it comes out, Kirsten. I also find it fascinating that you saw a marked increase in the detection rate of BMD cytology. And for the American listeners, BMD is borderline mild dyskaryosis, which is very similar to our ASCUS diagnosis. Is that correct, Kirsten? Yes, yes, that's true. So, for those of you in America who are listening, we're really saying a marked increase in the detection of ASCUS cytology, and this occurred over the same time period as you saw the increased detection rates of CIN2 and CIN3, but the change in detection rates of higher-grade cytological abnormalities appears to be smaller, although still statistically significant. And in trying to interpret this, does this mean that most of the increased detection in CIN2 and CIN3 came from those women who had borderline mild dyskaryosis, what we would refer to as ASCUS in the U.S.? Well, this is a very interesting question. When restricting analysis to CIN detected via the (inaudible 8:41) the CIN detected via the BMD pathway or in the ASCUS pathway, we found that the probability of a CIN1, CIN2 or CIN3 diagnosis was 1.9, 1.6 or 1.8 times higher in 2009 as compared to 2003. And then restricting the analysis to CIN detected via direct referral pathway was via the worsened of BMD outcome, we found similar results. So, I will say that relatively seen, both BMD or ASCUS and worsened BMD equally contributed to the CIN2 and the CIN3 increase. However, from an absolute point of view, this is, of course, different, and approximately half of the CIN2 lesions are detected via the BMD pathway, but for CIN3 this is normally 25%. So, in that case I would say that approximately half of the (inaudible) detected CIN2 lesions came via women with a BMD outcome and the other half via women with a worsened BMD outcome. And for CIN 3, I would say that the majority of the (inaudible) detected lesions came via women with a worsened BMD outcome. 2018 ReachMD Page 5 of 7
Women with different degrees of cytologic abnormality are followed up very differently in different countries, and I would expect that this would have a significant impact on the detection rates of CIN. Can you explain how different levels of cytologic abnormalities are followed up in the Netherlands? Yes, of course. Women with BMD smear or ASCUS are invited to come back for another cytology test 6 months later. In case no cytological abnormalities are found, women will be invited for another cytology test in 18 months before being referred back to the routine screening program. If 1 of the 2 tests is positive, the women will be referred to a gynecologist for colposcopy. However, to make it more difficult, within the last decade cytology triaging could be combined with HPV testing, but it means that both cytology and HPV tests are performed at 6 months. In case both tests are negative, women are referred back to the routine screening program, which wasn't the case, and only cytology testing was performed. And in case a BMD smear at 6 months was combined with a negative HPV test, this results in another cytology test at 18 months instead of an immediate referral to a gynecologist. Women with primary a worsened MD outcome are immediately referred to the gynecologist. You found that beginning in 2003 there was a fairly dramatic increase in the detection rate of CIN3, and this continued to increase until about 2009 with a yearly rate of about 6.6% increase per year. Interestingly, you did not see a corresponding reduction in the detection rate of invasive cervical cancer during this time period. Can you give our audience your thoughts as to why this has not occurred, a reduction in cervical cancer, despite this dramatic increase in detection of high-grade precursors? Yes. The trend we can expect in the cervical cancer detection depends on the underlying cause of the increase, so in general, there are 2 explanations for the increase in CIN detection rates. The first explanation is increasedvariability of the program to detect cervical lesions, so for example, due to the increased (inaudible) of a test. And the other explanation is an increase in the prevalence of cervical abnormality in the screening population. So, in case of the first explanation, the first would expect an increase in detection of both CIN and invasive lesions; although, the latter was not confirmed by our data; or you would expect an increase in only CIN (inaudible) lesions. In that case you would expect a 2018 ReachMD Page 6 of 7
decrease in invasive cancer after one or multiple screening rounds. And since it takes quite a long period for cervical cancer to develop, so approximately 10 to 15 years, and it s possible that we're not able to see the decrease in cervical cancer yet. And assuming (inaudible) of CIN are progressive CIN lesions. And in case of the second explanation, we would expect an increase in the invasive cervical cancer rates; but also, in this case, as it is estimated for CIN3 detection rates to progress to cervical cancer within approximately 10 years, it could be that just not enough data is present yet. So, to conclude, closely monitor the screen-detected and general cervical cancer incidence and review more of the underlying cause, and more importantly, it seems that the screen-detected cervical cancer incidents already increased in the latest period of our study, although not significant. Kirsten, I would like to congratulate you on a fascinating study that I'm sure will affect the way policymakers and clinicians view the benefits of liquid-based cytology. Thanks so much for providing our ReachMD listeners with this new information. Thank you for inviting me. 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 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. 2018 ReachMD Page 7 of 7