And there's this wonderful audience today who's a lot of gynecology oncologists who know a lot more than I do about this, but it's fun and challenging. Okay, next slide. No disclosures. Next. This is a wonderful woman and her baby in Kigali, and she wants you to keep her mom healthy. So, okay, let's move on a little bit. So what we're gonna do today, we're gonna talk about the indications and the particular challenges of looking at the cervix in a pregnant woman. And we're gonna look at what the changes are, what the pregnancy does to the cervix, and indeed sometimes the whole lower genital tract. And we're gonna talk about techniques of colposcopy because it can be very challenging in pregnancy. And talk about the management of abnormal screening tests, as well as trying to translate that to low and middle income countries, because a lot of the information that's out there is really for a European or an American audience. And I try to think in terms of what different countries might be looking at as opposed to the States. Okay, next slide. So what I thought about is a quick word. So I think when a woman is pregnant, it's a unique moment for her because she's at that point more likely to have contact with a medical establishment of some sorts, either a healthcare worker or a midwife, a nurse, a physician, somebody, whereas in the rest of her life, she's either for lack of funds or for lack of... She might stay away from the medical environment at any of the other time, but there's an interaction there. And that gives the healthcare workers this opportunity to educate her about her risks of cervical cancer and pre-cancer. So this is really a medical community issue, not just the colposcopist or the specialist. And at that point, the healthcare workers can and should actually offer her, if she's age appropriate, for screening at these encounters and to assure her that any other further steps that are done in the screening and even the investigation are safe. So it's safe to do, it's safe to pursue these things. It will not hurt the pregnancy, which is a very important thing. Okay, next one. So what happens in the pregnant cervix? There's an increased diameter, becomes larger. I always used to tell my patients with skin lesions or anything, everything is on growth mode in pregnancy. Everything grows. Your hair grows, your moles grow, everything grows. And the cervix grows as well. There's tissue hyperplasia. There's a phenomenon which we're gonna talk about and look at some pictures of stromal decidualization. There's cyanosis, there's softening of the cervix, there's increased vascularity, which makes it challenging. And there's also edema of the cervix. So lots of things are happening. Okay, next one. We will look at some pictures. So here's some, we'll look at some per trimester changes. So these are some normal changes. You can see here, let me see if, I don't know if you can see my arrow, but lots of changes, metaplastic changes with all these gland openings there. There's a increase in the ectropion. You might see nothing before she's pregnant, then bang, when she's pregnant, you get this ectropion. Next slide, let's look at the second trimester. There are, there's some cyanosis, there's the Chadwick sign. There's again, lots of ectropion. And here you see hypertrophy of the columnar cells inside the cervix. You can see they're more, definitely more prominent, more visible, more vascular, redder than they were in earlier pregnancy. Okay, let's go to third trimester. And here, the third trimester is challenging. Even in a nulliparous patient, it dilated gland openings, lots of mucus. Visualization, because of the mucus, can be very challenging. In here, you can indeed see that someone is using a ring forceps to move aside the mucus to improve the visualization. Their cuff glands is an increase because of the increase in the visualization of the metaplasia. You'll see lots of Nabothean cysts, which are a hallmark of all of this. Okay, next one. And okay, these are just some other nice pictures of the increased changes. What you see here is lots of endocervical tissues with acetyl whiting. This is a vinegar-exposed cervix. And the tips of the endocervical cells appear white on visualization. And these are just three examples of about the same thing. On the left, there's increased magnification, so you can see along with the abundant mucus. So, deciduous. I had to wrap my brain around this a little bit to figure it out, but it's a normal change in about a third of pregnancies, late first and second and third trimester. You can see this, again, unless you're looking, you wouldn't know it. It's a benign growth that's stimulated by progesterone. So it's a progesterone phenomenon in the cervix, and we know there's more of progesterone around. And what you see is there's a nodularity and there's increased vasculature. And that, to naked eye, we're going to look at some pictures, but you'll see it can be confused for cancer because these vessels suddenly don't look what we would consider normal. So there is, especially if you're looking at the cervix because of some positive screening tests, here you might be required to biopsy to rule out a cancer. It can look like a polyp, atypical formation, irregular exophytic projections. Let's look at a picture in the next slide of this. So here, these vessels don't look normal. We are educated to look for atypical vessels. And sure enough, here, these vessels do not have the normal tree-like formation. They look hairpins. They look like they're coming out of nowhere, going nowhere. They don't look normal. And you can see the exophytic tissue and the nodularity of it. There's the, on the picture to the right-hand side of your screen, there's the os down in the lower with the mucus. And then going up in that, you can also see that nodularity and those formations. So this, if I'm seeing this and she already has an abnormal screening test, I'd say I would have to get the biopsy of this. OK, next slide. So here's the microscopic view on the bottom left. That's the normal. And then you can see these in the stromal cytoplasm. You can see these very plumped, which makes sense because the whole appearance of it is so exophytic, plump, polygonal stromal cytoplasm. It looks a lot different than the normal. But it doesn't look dysplastic. It just looks abolute. It looks like a lot's happening and very stimulated by the progesterone. OK, so that's decidualization. So what happens to CIN during pregnancy? So in pregnant women, the prevalence of abnormal findings on a screening test on the cervical cytology is about 2% to 7%, which is totally off the wall from non-pregnant population. The majority of this is CIN, which makes a lot of sense. But about 0.1% to 1.8% of those will turn out on biopsy to be CIN3. There's an interesting article. You have the citation here, which I read. They really took a lot of review of lesions during pregnancy, the impact on delivery mode. But they looked at, they had a whole report on the articles that showed regression. And the range is very high of regression of pregnant women with high grade that, in the postpartum period, there's spontaneous regression. There's just under 20% to almost 70%, depending on the literature that you read. But there is a significant amount of regression. So that's sort of the natural history of CIN. You see it in pregnancy. For some reason, when you do the postpartum COBO, a lot of it has regressed. Next one. So cervical cancer, the incidence, again, in the States, it's very low, 0.01. This is a young population, 0.01% to 0.09%. I did some research to find specific data from Africa. And it was really difficult to obtain. There were more conjectures. And it was difficult to find the specific, that pregnancy was sorted out. In other words, you could find data of cervical cancer. But the estimate that it's higher, it's about 1% to 3%. So it's not a non-issue in Africa to have cervical cancer seen in pregnancy, with the highest incidence being in East Africa. These numbers are probably because this is a less screened population than in higher income populations in countries. And there are higher numbers of women living with HIV. And that probably accounts for the higher numbers of cervical cancer. But it impacts a lot, because the decision around what to do if you have a cervical cancer and you're pregnant is a very difficult one. And we're going to get to that a little bit later, too. So next slide. OK. So again, most cancers found in pregnancy are mercifully early stage disease. And this is something I learned preparing for this talk, that the course of the cancer isn't really accelerated. The cancer, the five-year and 30-year survival, if you're diagnosed when you're pregnant or not pregnant, there's no difference in the survival rate. So it's not that the, you know, I thought the immune system and changes in the immunity would accelerate the cancer. But that's actually not the case. So you can picture that the cancer is going to behave exactly the same way in pregnancy. But any management of cervical cancer in pregnancy is way out of my field. And again, a general gynecologist will want to refer to oncology for this. Next slide. So if you have an opportunity or the need to do a colposcopic exam for a positive screening test, there are tricks. Because the biopsy is indeed preferred if higher-grade disease is suspected. It's acceptable any time, but a biopsy is preferred, not necessary if you really think it's all low-grade. So what you want to do is you want to limit the number of biopsies. You want to really have a good colposcopic exam of the cervix and target the areas where you know there's going to be higher-grade. The thicker white, the more central lesions, the straighter edges, abnormal mosaicism or punctation, those are the ones that you're really going to want a biopsy. And you have to anticipate that the cervix is going to bleed. It's vascular. Everything's growing. The biopsies do bleed. And be prepared, and we'll talk about some little tricks and techniques. And we always harass everybody. Why don't you do an ECC? In the pregnant woman, you do not do an ECC. You do everything external. You're not going to go inside the cervix. The fact that you know that they're going to bleed might limit your number, but it shouldn't deter the biopsies if that's needed for diagnosis. The risk of hemorrhage is real significant. Hemorrhage is very, very, very low. And remember that this bleeding is coming from the cervix. It's not coming from the placenta. It's not coming from higher up. And so prematurity or risk of losing the pregnancy is not an issue there. And you have to reassure the woman. We're so educated that any bleeding in pregnancy is abnormal, has to be investigated. This is cervical bleeding, and it's not going to impact the course of the pregnancy. You want to have lots and lots of swabs ready. And if you have moncells, it's a great tool. It's safe, safe, safe in pregnancy, and it's very effective. So you wanna have everything prepared for the fact that if you're doing a biopsy, you're also gonna have to control a little bit of bleeding that you're gonna see on the biopsy. Okay, next one. So we call this a two-handed technique. So I'm right-handed. So I have my biopsy forceps in my right hand. In my left hand, I already have a swab that has moncells on it. If you don't have moncells, just any swab will do. So you do, bang, you do the biopsy with your right hand, and immediately, you don't wait to look if there's going to be bleeding. You immediately tampon out the biopsy site and then hold it there for at least two to three minutes for you to peek, and then you repeat this as needed. So again, you might have to even put a little more tamponade on the cervix to prevent the bleeding. It will. Bleeding stops. It'll stop eventually if she's got good coagulation. But this two-handed technique is the best way to be prepared for the probable biopsy in, probable bleeding from the biopsy site more than in a non-pregnant woman. Okay, on the next one. So this is another challenge, the vaginal walls collapse. And visualization is a real challenge. Here, you can't see the whole cervix because the vaginal walls have collapsed in on your view, and the further she's advanced in the pregnancy, the less visualization is going to be possible. So on the next slide, there's some little tips of how to deal with the visualization. Can I have the next slide, please? So here, so what you'll want to do to be able to see the cervix, because you do have to see it, is use the largest speculum that she can tolerate. She might not be able to, maybe a null-up can't tolerate a big speculum, but you try to use the larger one. And then condoms or a cut-exam glove can be put over the, over the blades of the speculum with the end cut out. In this case, I know there's a big move not to have as much latex material around, but the latex gloves really, really work better than the non-latex glove. The elasticity is better, and you can just roll it up, cut the edges off, and then the rubber from the condom or the exam glove will bring those vaginal walls aside. My best friend is the lateral wall retractor. If you have one, that'll get nicely in there and retract the vaginal walls for you. We use that for the leaps a lot, the lateral wall retractor. And you might need, if you really can't see things very well, if you're in late trimester or in late second trimester or in third trimester, you might just have to move the speculum around and see each quadrant in succession and say, okay, doing this one. And sometimes you take the biopsy from one and then vaginal walls collapse and you can't see where the bleeding is. So you just might have to move your speculum around to do the best that you can to be able to see the whole cervix and to do a complete exam. It's possible, just takes more time. All right, moving along. So let's talk a little bit about the ASCCP guidelines. And again, this is a model where cytology and HPV is used. If she's young, if she's under 25, colposcopy is not recommended for low grade disease. You repeat the testing in the year. This is the recommendation. If they're pregnant or not, the cervical cancer risk is low. Five-year CIN three plus risk is 3%. So we know that a lot of these changes in this age group are very transient, 80 plus percent will never see it again and they'll just go away. So you say, when you're not pregnant, next year we're going to repeat this testing. Next slide for the little bit of the older woman. So 25 plus, so the newest guidelines from ASCCP take prior HPV testing. And again, this is pregnant or non-pregnant, but just to remind you, if the HPV test, if she's had an HPV test prior, this is not her first one. Her CIN risk, and it was negative, her CIN three risk falls below that colposcopy threshold. And you do, again, HPV-based testing, either HPV test alone or co-testing in a year after this test. If you have HPV positive or no prior testing, then colposcopy is recommended in this 25 plus age group. Again, in Africa, in the World Health Organization recommendations, you might not be testing until age 30. So this 25 to 30 population might not be screened. However, with all these low grade screening tests, it's acceptable not to do colposcopy during pregnancy and you can wait because the risk is low and you have to tell her, we do have to look after you're not pregnant. And say, please come back, we're gonna book you to come back six weeks to four months afterwards, depending on what the cervix is doing. Sometimes with nursing, you can't see very well, but it's acceptable in these low grade screening tests to wait until six weeks postpartum. And this is from the lower genital tract disease, Rebecca Perkins' very good article in the backup. To see that. Okay, next one. So high grade HSIL, ASC-H, or atypical glandular cells, colposcopy is definitely recommended. So, and here you biopsy lesions suspicious of 2, 3 or cancer. Again, no ECC, but if you have a biopsy proven high grade lesion, excisional or ablative treatment is not recommended in pregnancy. Her risk, remember the whole thing is preventing cervical cancer. Her risk of this evolving into cervical cancer is very, very low. So you don't want to treat these people. And there's a high rate of regression. So you can defer the treatment and relook at the cervix after she's had the baby and then make a treatment recommendation. But during the pregnancy, it's not. No treatment is recommended. If there's a suspicion of cancer, then again, referral to an oncologist to see if there's any treatment that's needed. That's a different beast. And then you want to repeat the colposcopy and cytology if you can, and the HPV test if they're greater than 30 years old, every 12 to 24 weeks. So if you're sort of at 20 weeks of gestation the first time you do the colposcopy, you're going to go early third trimester, look at it again. And this is where photography or good description, if you don't have the ability to do photography, having a very good description of where the lesions are and what they're like, so that the second time you look at them and when you look at them postpartum, you can say, aha, yes, it's still there. It's unchanged. We can wait. If anything has changed, you re-biopsy, but re-biopsy is not recommended if there's no suspicion of cancer. So you biopsy that first time, and only if there were really your eyes saying, wow, this looks a lot worse. It could be cancer. Then you would do the biopsy. If you have a biopsy that says AIS, there you again, you're not going to change anything, but you would, in this case, I would refer to oncology. And I've had a few patients that I've had to, just to know that they're a watch and wait with a possible hysterectomy. Then AIS is a totally different conversation, but those people you would refer to oncology to co-manage those and co-manage the pregnancies. Okay, let's go. So moving on. So here's where my thinking was, is that cytology screening is a luxury in a lot of countries and a lot of parts of the world. So where HPV is the sole screening method, I'm using that rather than visual inspection with acetic acid, because that, again, that model, again, if you see something that's significant, you would go to colposcopy and biopsy. But in the HPV, if HPV is the sole screening method, World Health Organization does recommend colposcopy as the next test when the high-risk HPV screen is positive. Again, recommended 30 plus for women without HIV, for women living with HIV, the HPV testing is recommended as a primary screening for 25 plus. And pregnancy does not alter these recommendations. So this is from Lancet Global Health. It's a good article about the management using World Health Organization guidelines. So in the next one, next slide. So one of the things that we thought about, we sort of played with, and I don't have, the HPV World Newsletter had this as a discussion about this. But in pregnancy, it might be okay to use colposcopy, not for everybody who's HPV positive, but to use it as your branch point for doing colposcopy using those who have the most oncogenic or most carcinogenic types, 16, 18, 45, or other combinations. And then with this approach, it has been shown that that's at least as sensitive as cytology. So you don't need cytology, but it might not account for other lesions associated with other HPV types. So a combination in your setting, you have to go with your setting, and it's very difficult because different countries do have different methods of screening. Combination of genotyping, cytology shows promises in some setting, not realistic, however, financially, in a lot of other setting. But using the HPV testing and the genotyping might be able to give a branch point when you do colposcopy in pregnancy for those women you've identified to be at the higher risk. Always keeping in mind, we're trying to prevent cervical cancer. That's the light at the end of the tunnel is we don't want any of these women to get cervical cancer. So, all right, next slide here. So there's a lovely mom and baby. That's a nice furry six to nine-month-old baby, colobus monkey. And the baby's saying, mommy, will you let me go? The scariest part was when she jumped and treated a tree holding this baby in one arm. It was terrifying. So next slide. So, in conclusion, so pregnancy's an ideal time to have that interface, introduce screening, do the HPV screening. If you can, if you have the method, if it's just visual, that's do some screening, but educate your population. Positive results are common and can be pursued during pregnancy. Pregnancy does not accelerate CIN or cancer progression. It's challenging, the colposcopy exam, due to physiologic changes, but it's appropriate. And again, the education of women saying this isn't scary. You are not going to lose your baby. Treatment is deferred and treatment discussions are very difficult if a cancer's been found. What trimester she is, if you find it in late pregnancy, find the cancer, then you can defer treatment. If you find the cancer in early pregnancy, then it's a big discussion with the family, with the woman. What are you going to do? You're going to save your life, baby's life. It's a very difficult cultural decision where a lot of information has to be transmitted. So I think next slide, I think just says, thank you. So thanks for your attention. There's a lot to think about with this. And so it's a fun subject to think about. So I will take questions from anybody or comments or experience in your different countries and scenarios about this. Thank you so much, Dr. Fry. It was a beautiful presentation.

cervical health

pregnancy

cervical cancer

screening strategies

gynecology oncologists

low- and middle-income countries