Okay, good afternoon here, good night over there. Most of the people are in a different time zone, I think. This presentation basically is just my personal opinion. It doesn't represent the position of the National Cancer Institute. And it's basically sharing some experience from the last 30 years I've been working on cervical cancer globally. I think the idea of the WHO initiative of elimination of cervical cancer is something that we were trying to do for many, many years, testing different approaches, testing different things. It's great that now the WHO came with this initiative. It's a global initiative with three very important parts, increasing the HPV vaccination, increasing the coverage of screening and treatment of those with cancer, and increasing the coverage of diagnosis and treatment of those with cancer, also palliative care. It's three components there, but they really involve a lot of work and considering especially that have to be done very rapidly. Otherwise, we are going to be just discussing all these things for the next 100 years. We know that if we don't do anything different in our approach for cervical cancer control, it's going to take more than 100 years and maybe we're going to be in the same position we are now. That's why intensive vaccination was proposed as one of the options. And that you can see because vaccination has been proven to be very effective, we can have a huge impact. In some countries, it's going to have a much earlier impact. In some other countries, it's going to take longer to do the implementation. But still, we are talking about many years of war until we see a significant impact in cervical cancer. That's why intensive screening and vaccination was being proposed because if we put together the population-based screening and vaccination also at the population-based program, the impact is going to be much bigger and sooner. But some months ago, I was in a small conference. The title of the conference was basically to think wisely. And I love the title of that conference because it's not only to discuss about what option we have, but also how to choose the best option for the setting where we are, considering that poverty is very prevalent. In this picture here, I put four different pictures, some of them from Africa, Asia, and Latin America. And just looking at the picture, you don't know exactly where these are coming from but poverty is quite similar in many places. And we need to do the prevention in those settings with very limited resources. That's why vaccination is one of the options we have. And we need to be clear that vaccination has proven to be effective. Here, I'm just showing the different HPV types that are linked to cervical cancer. HPV16 and HPV18 are two more important here. And just to give a graphic representation of the impact of the vaccines, if we have the bivalent or the tetravalent vaccines, where both of them have HPV16 and HPV18 in there, in the composition of those vaccines, and we see how much impact it's going to have in this other graph, we see that HPV18 and HPV16 are the two HPV types that are responsible. They are linked to most of the cervical cancers around the world. And this is the contribution of each one of these genotypes on cervical cancer burden. If we implement HPV vaccination using just the one that targets HPV16 and HPV18, we see that we're going to eliminate a significant part of the disease. We are going to eliminate the two biggest viruses responsible for cervical cancer. Now, we have another vaccine that is a 9-valent vaccine, where you have seven oncogenic types in there, plus two types that are related to condyloma. But we see the potential impact of this vaccine, new vaccine with seven each oncogenic types in it, and we go back to the graph, we're going to be able to control HPV16 and the other types that are going to be included in the vaccine. That means that at the end, we're going to have a huge impact just looking at the types that we are eradicating with this vaccination. And those results are good. We already have data from different countries showing the impact on the pre-cancer and cancer control. But also, it's important to be clear that we only need one dose. The data of one dose versus two doses or three doses is very, very solid, showing that one dose has good protection. Antibody levels last for many years, and these antibody levels, even though here you can see the antibody levels are a little bit lower than two doses and three doses, it still is enough to control the disease. Here, the efficacy against persistent HPV infection and the 11-year follow-up from Amy Kramer here in NCI shows also the protection against 16-18, at least, with one dose was really, really good. That means when we start to talk about choosing wisely and according to our resources, one good investment is HPV vaccination. There are many challenges still, the price and the needs for implementation of this vaccine, but I think it's a good option that we need to see very seriously to control cervical cancer. Now, when we look at screening and treatment, the picture is a little bit more complicated. It's not only one shot, one visit. We are talking here about several visits. First, to reach the population in this graph, let's assume that here we have 100 women that are in need for screening. Only two of them are the ones that are really, really pre-cancer, histologically proven pre-cancer. It's two or three, depending on the different populations. We are going to have a prevalence of two or three histologically proven pre-cancer CIM trees, and we need to identify them. For that, we select a screening test. In the screening test, we hope to have those two detected, but we are going to have also some other positive. They do not have disease, but they are positive in the test. That's why we need a second step, a triage or diagnosis, where we hope just to have the two cases that are really pre-cancer, but that's difficult. In those cases, we provide the treatment. Of course, for the screening test, what we want is high sensitivity. We want to detect the two cases with really pre-cancer, and with a second step here, with a triage, we want high specificity to just, at the end, get only the two real cases. That has to be done in areas where we work. In this area, we limit the resources, lack of trained personnel, lack of access to care, and with procurement limitations. Some of the learnings here is, and we have to be very clear and upfront when we discuss about cervical cancer control, is that the strategy should be affordable and easy to implement. In the past, we tried, in the screening test, we tried different options, and some of them look simple, but the learning is that some of them are not simple at all. One good example is the Pap smear. We worked with Pap smear for many, many years, had impact in some places, but now we know that Pap smear only detects half of the cases of pre-cancer, and requires multiple steps, a lot of infrastructure training, and requires a pelvic examination. That's why we try to implement Pap smear in developing countries in multiple settings, and the results were not good. It looks simple because it's just a slide that you stay in and read in the microscope, but it's not that simple, and the impact is not going to be that big. The same happened with the visual inspection. With only Vinegar, I remember the first time in the 90s when we started to use visual inspection, oh, it's easy, it was simple, with a lot of enthusiasm. Yes, it's simple to do. You just apply Vinegar. This is a service before and after. You will see a change in the cervix, a significant change after the application of cervical cancer. Sorry, the acetic acid, and that's a negative result. And the same here, before and after the acetic acid, you see the changes, oh, that's a clear pre-cancer, easy to do. But the problem is that not all the cases are like this. Here you have magnification. In real life, you don't have magnification. It's just naked eyes, a small view of the cervix, and not all the cases have very clear acetyl weight changes there. I mean, I spent many years working on visual inspection. Actually, when we started to implement visual inspection, there were no training materials. We needed to create a training material for visual inspection. A lot of work on this, but at the end, we learned that it's not easy to implement, it's difficult to train people, multiple days because they are visiting multiple other things, and also the performance changed a lot from person to person. I mean, there are challenges there, and we are still detecting around half, in a good scenario, half of the cases. There is some optimal sensitivity. It's not reproducible. It's a lot of variation between the different health workers. The training took several days. There are some publications showing a huge, great performance of visual inspection. When you read the article, you see that some of them were trained for one month, two months, or multiple days, and that's not easy. That's not practical. It's almost impossible to do, and there is no good quality control for visual inspection either. That's why another option we have now is the HPV test with all the advantages that you already have, highly sensitive, you can screen less times in that life, in the life of a woman. The results are very reliable. Most of the times, very reliable, and we can use self-collected samples. That's possible. We have done that for almost 15 years, almost 20 years now. It's very acceptable, very well accepted by populations. We did the implementation of HPV testing in several projects in Africa, India, and Central America, and the acceptability of self-collection was very high in most of the places. Actually, the challenge we had was not with the population. The challenge we had was with the health workers, that we needed to convince them that really self-collection was a good option. Also, good learning is be careful at the time of evaluating the cost of a test. You're going to see tests that are presented as very cheap. In my experience, I was in charge of validating one of the low-cost tests. The idea was to have under $5. At the end, it was not under $5. The commercialization cost increased the price. It was simple. We were supposed to have no special training. We also learned that that was not the case, and portable, close to point of care. That was a work that took several years. This is the test. It's a current HPV test, multiple steps. In order to reduce cost, we got a test with multiple manual steps, and that created also an issue because we needed dedicated people. With some training on lab practices, the cost of the test has many components. How the reagents, how the sample collection, how the equipment, how that is possible. When we talk about cost of the test, we need to have clear what exactly that means. It's just the reagents. Okay, you have other components there that are on top of that cost. One of the consequences of the manual steps is that there were several steps where a failure could happen. We had also the increased risk of contamination because these manual steps, the sample from one well moved to the other part of the plate and created contamination. Again, cost of the test. It's very careful when you talk about that because it includes not only the manufacturing, it includes the shipping, the custom clearance, the storage, distribution, technical support, troubleshooting. There are many, many, many things in the cost of the test. I'm always very reluctant to have a precise number for a cost because there are many components in there. In order to avoid paying a high price, we try to skip the need of a local distributor. But in my experience, local distributor helps a lot when there are problems with equipments in the country. They are the ones that are coming and fixing the problems. In my experience, the final cost could be much higher than the actual manufacturing cost. The other learning here that comes from the time of the implementation of cryotherapy more than 25 years ago when we were told that cryotherapy was a good option. Actually, it was. But there were some assumptions about the settings where this was supposed to be implemented that the people implementing this didn't know that much about the setting. One of the things was that cryotherapy, because it's just quotation marks in there, it's just the gas that you need. You don't need electricity and that's very suitable because the people training us in those years assumed that in our countries, we didn't have electricity. Actually, that was a bad assumption, actually, because they didn't pay attention to the availability of the gas. In the 90s, the benefit, of course, the introduction of cryotherapy, easy to use, not those many side effects. Portable, I put there, underscore, because it's portable, the equipment, but the gas is not necessarily portable. The main message was that you don't need electricity, only need gas, and CO2 is cheap. That was the message. Our learning with the years is that needing gas was the problem, actually, and electricity was more available. Moving distance of gas is a problem. Procuring and filling and sending the gas to some places to be filled is a logistical problem. A percentage of countries, a population with access to electricity, of course, there is a variation. In some countries, you have very good access to electricity. Even in countries with lack of access to electricity or not that good, you have more access to electricity than access to gas. That means that it's going to be easier now to use equipments that require electricity. One of those equipments is the thermal ablation. I already exceeded my time, sorry. I tried to run my presentation. Now, we have devices for treatment that operates with batteries, rechargeable batteries, and you can charge these in any place, basically, where you have a point of access to electricity. The national electricity grid, you can have solar panels that are popular in some places as well. Any place where you can charge your cellular phone, you can charge this device. Also, there are LED devices that are also battery-powered that can help to provide treatment in some places. Now, at the time of choosing wisely about cervical cancer control, now we have options. Self-sampling for HIV testing, we have battery-powered treatments, and now we are working actively with artificial intelligence to do the evaluation of the cervix. There is no algorithm now. There is no AI algorithm now that is completely validated. Be careful. Because AI is not a magic box that does everything. There are many steps to train and validate AI here in the national cancer world. Instead, we are working on this. It's going to take still some time to get a validated algorithm. Thank you very much. Thank you so much.

cervical cancer

HPV vaccination

screening

treatment

technological advancements

resource distribution