Secondary Prevention of Cervical Cancer Resource-Stratified Guideline Update

An interview with Dr. Surendra Shastri from the University of Texas MD Anderson Cancer Center in Houston, TX, and Dr. Jose Jeronimo from the National Cancer Institute in Bethesda, MD, co-chairs on "Secondary Prevention of Cervical Cancer: ASCO Resource-Stratified Guideline Update." Dr. Shastri and Dr. Jeronimo review the updated recommendations in the guideline, covering screening, triage, management, follow-up, and considerations for special populations. Read the full guideline at www.asco.org/resource-stratified-guidelines.   TRANSCRIPT Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at: asco.org/podcasts.  My name is Brittany Harvey, and today I'm interviewing Dr. Surendra Shastri from the University of Texas MD Anderson Cancer Center in Houston, Texas, and Dr. José Jerónimo from the National Cancer Institute in Bethesda, Maryland; co-chairs on ‘Secondary Prevention of Cervical Cancer: ASCO Resource-Stratified Guideline Update’.   Thank you for being here, Dr. Shastri and Dr. Jerónimo.  Dr. José Jerónimo: My pleasure.  Dr. Surendra Shastri: Thank you very much.  Brittany Harvey: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest policy is followed for each guideline. The full Conflict of Interest information for this guideline panel is available online with a publication of the guideline in the JCO Global Oncology.   Dr. Shastri, do you have any relevant disclosures that are directly related to this guideline topic?  Dr. Surendra Shastri: No, I don't have any disclosures.  Brittany Harvey: Thank you. And Dr. Jerónimo, do you have any relevant disclosures that are directly related to this guideline topic?  Dr. José Jerónimo: No, I don't have any.  Brittany Harvey: Thank you both. So, to start us off, Dr. Jerónimo, what prompted this update to ASCO’s guideline on secondary prevention of cervical cancer, last published in 2016? And what is the scope of this guideline update?  Dr. José Jerónimo: That's a great question. Yes, it's natural for people to start wondering why the guidelines change or are updated so frequently. And I think there are several factors. The main one is that science on cervical cancer and other diseases is evolving very rapidly; there are new publications, there are new technologies, there is new information about different aspects of cervical cancer prevention specifically. The updates of those technologies is so fast that we need to periodically update the guidelines to accommodate these new options.  Now, I have to highlight that the ASCO guidelines in 2016 -- those guidelines were already very ahead of everyone else. What I mean is, in 2016, we were already recommending HPV testing for everyone all over the planet as a preferred option. It's something that other guidelines, other organizations were still wondering about, but we were really very upfront on that recommendation, considering that that’s the best technology we have. I think the updates of the guidelines is important because we need to keep with science, and we need to keep the doctors using the guidelines also updated on what exactly is out there, and what options could be usable for the different settings.  Brittany Harvey: Great, thank you for that background on the guideline update and for describing why the guideline needs to be updated over time. So then, Dr. Shastri, as this is a resource-stratified guideline, can you describe the four-tiered framework of the guideline? Specifically, what are the Basic, Limited, Enhanced and Maximal resource levels?  Dr. Surendra Shastri: Saying one size doesn't fit all would be a cruel example in health situations where it's really unfortunate that there are large disparities across the world, between countries, within countries, and that's the reason why we need resource-stratified guidelines. We can't just sit in ivory towers and preach to people who don't have anything. So that's the reason why we have the resource-stratified guidelines, and we have followed the same resource structure that the Breast Health Global Initiative is following.  So, we basically have four different resource levels. The most Basic one, or the core resources, is where you have just very basic public health services available. It's not services which are looking for outcomes and are just part of the social welfare that the country has to provide. Many times, those are also situations where the health priorities are very different.  For example, health priorities for some countries might still be infectious diseases, as it was amply displayed in the current pandemic. So, considering those situations, the expenditure that the country does or expenditure a local governing body does on a particular disease could be very different. So, at Basic, just available screening services at the lowest level.  Then you have the Limited; the Limited is slightly better than the Basics. They have maybe some of the newer technologies like Dr. Jerónimo just explained, not all of it. Some of those may not be able to provide in the same frequency or to everybody out there. But they are at this point of time looking at outcomes, looking at cost-effectiveness and those kinds of things.   Step up a little bit, and you have Enhanced level. That's the third tier of the resource level that we are talking about. In the Enhanced level, we have much better services available, we have organized services available. And those services have probably a system of tracking and recording clients or people who undergo screening and early detection.  And the final is the Maximal level. In the Maximal level, it is what we see across North America, or what we see in Europe, where you have the latest technologies, you have established systems, and you have systems to track and follow people. Again, I will caution here, even if I say North America or Europe, it's not across North America and across Europe. There are several places in North America, there are several places in Europe, which do not have the same resources. And that's why in this guideline, we're not talking about country guidelines, we're talking about resource-limited guidelines.  Brittany Harvey: Understood. I appreciate that description of the stepwise approach and how it isn't necessarily applicable just to one country, but there are differences in resource levels across countries and within countries.   So then, the guideline panel made recommendations across these four resource levels. Next, I'd like to review the key recommendations of this guideline update across those resource levels. So, Dr. Jerónimo, what are the recommended methods for cervical cancer screening?  Dr. José Jerónimo: That's a challenging situation on what to use in the different settings. Dr. Shastri already described very clearly the different scenarios we are facing; places with extremely limited resources where basically you have only maybe an evaluation table there, and places in the other extreme with all the resources and all the technologies available.  But even though we have very different areas with very different resources, the most recommended test for a screening for cervical cancer in all of them is HPV testing; the testing for the Human papillomavirus that is directly related to cervical cancer. The question could be, "Okay, why are you recommending that test for places where maybe now they are not going to be able to do it?" I think it's important to put that technology as a target, even though the sites are not prepared right now to do it, but they have to go towards that goal of implementing HPV testing.  Meanwhile, the guidelines also highlight that there are other options that could be used in the meantime to do some screening, one is visual inspection with acetic acid that is being already implemented in many places. And the reason why we are recommending HPV testing even in those places with extremely limited resources is because there are some advantages. First, with HPV testing, it's very highly sensitive, extremely highly sensitive. That means that you have a sensitivity over 90% with good validated tests. Second, because it's highly sensitive, you have the option to have a smaller number of screenings in the lifetime. Instead of -- some people remember, some years ago, the screening for cervical cancer with Pap smear was done every year.  But now we know that it's changing. With HPV testing, we are now recommending every five years or in these guidelines, depending on the resources, could be every 10 years, or could be once or two times in the lifetime of the woman. And with that, we are going to have a huge impact.  The other great advantage of HPV testing is that it can be self-collected by women. That means that basically, a woman takes the small brush, goes to a private place and introduce that in their vagina and collect the sample herself, without the need of specula, without the need of trained personnel, without the need of having all the infrastructure that is required for a pelvic evaluation.  And that's big because in that way, we can reach populations that are hard to reach. And also, we are dealing with some issues like cultural resistance to have a pelvic evaluation. I mean, that's the biggest advantage for HPV testing. And we have now examples showing that this is very well accepted in many, many studies around the world with different populations around the world showing that self-collection is very accepted. That means that the preferred test for cervical cancer prevention is HPV testing right now. There are options displayed in the guidelines for cities where it's not possible to do it now, but that’s the role.  Brittany Harvey: Understood. Thank you for explaining what testing is recommended; HPV testing, and then also the timing and collection strategies across settings. So, then following that, Dr. Shastri, what is recommended regarding triage for patients who have positive results or other abnormal results?  Dr. Surendra Shastri: So, let me briefly explain what triage is; right up following the primary screening when the woman has a positive result, a second technique or technology is used to determine whether this person needs to be treated, or this person needs to be tracked and followed up in a particular way. So, our recommendations for triage in the updated guidelines is that for the Basic settings, just like Dr. Jerónimo mentioned, if we have used HPV screening in the basic settings; that's the molecular test, and if that is positive, then we use another strategy which is known as, visual assessment for treatment. And this strategy is used to determine whether a woman should be treated with thermal ablation, or with LEEP, or she just needs to be followed. Whereas all the other three settings, HPV genotyping along with cytology, or cytology alone should be used for triage.  Brittany Harvey: Great. Thank you for explaining those triage recommendations. So then following triage, Dr. Jerónimo, what is recommended regarding management and follow-up strategies for patients with precursors of cervical cancer?  Dr. José Jerónimo: I think treatment also has evolved significantly in the last 20 or more years. And specifically, in the last five years or 10 years, there are new options that are becoming more popular because there is more evidence supporting the effectiveness of this technology, and ablation of that tissue is really one of the best options in most of the places.  I always try to compare the pre-cancer lesion like the paint on your wall, in your house. If one of the kids come with something and you start to scratch something in there, you don't need to turn the wall down in order to fix that problem. Basically, you just have to remove that area and put some new paint, and that's going to be corrected. In the same way, when you have a pre-cancer of the cervix, it's very, very superficial. It's not cancer, it's pre-cancer. You don't need to remove the whole cervix or the whole uterus to treat that. With ablation, basically what we are doing is destroying that tissue that is in the very surface, and new cells, healthy cells are going to come and are going to cover that area. That's the idea. The technologies that are more usable for areas with limited resources could be the thermal ablation or could be cryotherapy.  The other advantage of those technologies is basically there is no major complication; no bleeding, no major problems. Of course, as Dr. Shastri explained, there are more resources in other places. In other places, you have more resources, you can do a LEEP; that is, basically using an electrical device, removing part of the cervix and sending that to the pathologist. That's also one option that is acceptable and recommended in the guidelines. I think the main idea is, we need to remove that area with disease, with pre-cancer. We can remove it using ablation; just destroying the cells, or we can remove it using some excisional procedure. That all depends on the resources you have.  But how effective those technologies are, I could say there is very high cure rates using thermal ablation, for example, or LEEP. Very important to consider, doing the procedure, you can do it anywhere. Doing a LEEP, in theory, you can do it anywhere where you have electricity and you have the equipment. But remember, you have to be prepared not only for the treatment, you have to be prepared for the complication. If you have a LEEP, a very portable device and you have electricity, but if you are far from the next health facility, if you have a complication like you are bleeding in that setting, it's going to take hours, hours and hours just to evacuate that patient to the health facility. That's why you need to be very careful not only on the treatment, but also managing the complication.  Brittany Harvey: Understood. I appreciate you reviewing those technologies. So then, following those notes that Dr. Jerónimo just made, Dr. Shastri, are there any changes to the recommendations for special populations or highlights that you'd like to note that are identified in the guideline?  Dr. Surendra Shastri: This is a speciality of the ASCO guidelines really also to take a look and make recommendations for special populations. And by special populations here I mean the ones that we have looked at and recommended cervical cancer screening for are; women who are HIV positive or immunocompromised, immunosuppressed due to any other disease, or any other reasons, maybe because of medication, or cancer or other disease conditions which requires immunosuppressives.  For such women, we would say you start screening for cervical cancer as soon as the first diagnosis; the diagnosis of the disease which is causing immunosuppression is done. That's the first time. And then, through their lifetime, you screen them twice as frequently as you would do for other women who do not have an immunocompromised situation. So, you do it more frequently. As far as the management post-screening with positive results is concerned, for women with HIV as with all immunosuppressed women, it is the same. The triage is the same and the management will be the same as for all other women.  Then also pregnant women. For pregnant women, we recommend in the very Basic settings, pregnant women should be screened six weeks postpartum. And in all other settings, all other levels, we recommend that they should be screened six months postpartum. The very reason is, in many basic settings, you may not even get those women back for screening. That's the reason why we try to screen as early as possible. But on the safer side, the earliest possible is six weeks postpartum; that is, she is still probably following up for postpartum reasons of the pregnancy or immunization for the kid. That's the time we should go ahead and do it.  And finally, women who have undergone a hysterectomy but still have an intact cervix, need to get screened in the same way as other women. However, they could stop screening over a period of time, if they have more than three negative results.  A very interesting subject that we discussed in our committee, and we have put it up there as a statement to bring it up is that, we now come across several people who are transgender, who have an intact cervix. So, getting such people into screening, and screening them like all others, will be an important priority. We have put out a statement saying that, although we mentioned that this is for women, it is for all persons who have an intact cervix. So these screening guidelines apply to everyone.  Brittany Harvey: Yes, it's important that all persons with a cervix get screened for cervical cancer as it is something that can affect anyone with a cervix. And those are important considerations for clinicians that you noted across several different populations.   So then, in your view, Dr. Jerónimo, what is the importance of this guideline overall, and how does it impact clinicians?  Dr. José Jerónimo: That’s, I think the core of the guidelines is how this is going to affect the practice of clinicians. I think the main message here with the guidelines is: first, clearly acknowledging that the resources are different in different settings, and we need to accommodate to those settings to provide the best service. I think for clinicians, it is presenting options that could be suitable for their setting. As Dr. Shastri mentioned at the beginning, we are not talking specifically about countries. Because in one given country, you can have areas with Maximal resources, you can have areas with Limited resources, and you can have areas with Basic resources. If you try to apply that new, most modern, expensive technologies everywhere, you're going to be just doing the screening in very few places in the country because it's not possible.  With the guidelines, we are giving the option saying, "Okay, if you don't have access to those technologies, you can get started using this. For example, visual inspection. If the technology becomes available, for example, HPV testing, you can start to use HPV testing, because that's the goal. That's what you really need to look for. If you don't have the resources or the conditions to do excision procedure like a LEEP, you can do ablation, and that's okay. And basically presenting, you have different options to accommodate to your place. But the most important part is, do it well. Do it well, reach as many women as possible with your screening, and treat as many positive women as possible." I think that's the best message here. And I think that's the way these guidelines are going to help and impact the world of clinicians.  Brittany Harvey: Yeah, that's the core message of the resource-stratified guidelines; is using the resources you need to help and treat and screen the most people possible. So then finally, Dr. Shastri, how do these guideline recommendations affect patients?  Dr. Surendra Shastri: I will just add one line to the response that Dr. Jerónimo just gave you. We already have an existing country guideline, these are meant to complement those guidelines, and meant for the policymakers in those countries to open their eyes and realize that there are people at different resource levels, who may or may not have an insurance program, who may or may not have a socialized system which provides the same level of health care for everyone. So, use what we recommend because that's the current evidence for use.  Coming to how people are going to benefit, which was your question, these guidelines are going to make cervical cancer screening available and accessible to all women across the globe. We are talking about different options. We are not saying that, "if you don't have X, don't screen." We are saying, "if you don't have X, try Y. If you don't have Y, try Z." So, this opens up doors for all women across the globe to get screening. That is the ultimate goal, because if you want to reach the WHO goal of eradication of cervical cancer, then that's possible only through two means; one, is giving cervical cancer screening, preferably HPV, through whatever means or resources that the country has, and the vaccination, which is of course, being dealt by another committee over here.  So of course, all women across the globe will get benefit of newer technologies, simpler, cost-effective technologies, technologies that don't require them to -- for example, a self-collection, the woman doesn't really have to go anywhere. She doesn't have to go and wait in a clinic for hours to get a screen. She doesn't have to make repeat visits to get a screen. She doesn't have to lose her wages. These are things which are real. She doesn't have to lose her wages for the day, she doesn't have to arrange for child support to look after her children just to go and get herself screened. Those are some of the social determinants of health, which prevent women from going and getting themselves screened. So, by a simple technique like self-collection, we removed that entirely.  Going forward, we are going to see Artificial Intelligence, we are going to have deep machine learning, we are going to change the technology and the strategies, and we will come back with another update to this, maybe very soon, sooner than what we did this time.  Brittany Harvey: Absolutely. Those are excellent points. And we'll look forward to future updates as technologies continue to advance. So, I want to thank you both so much for your work on updating these resource-stratified guidelines for the secondary prevention of cervical cancer. And thank you for your time today, Dr. Shastri and Dr. Jerónimo.  Dr. José Jerónimo: My pleasure.  Dr. Surendra Shastri: Thank you for inviting us.  Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO guidelines podcast series. 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