Ladies and gentlemen, dear friends, dear colleagues, welcome to the first session in the afternoon. It is a master session, master session on cervical carcinoma. Let's move forward together. This master session has two parts. We are now in part one. We will discuss the prevention, strategies, and treatment of early-stage disease altogether. It's my pleasure here to chair this session with my colleague, Professor Sarikapan from Thailand. Professor Sarikapan, you know, is the chair of FIGO Women's Cancer Committee, and I am currently chairing the ESGO Prevention Committee. So happy and proud to be here. We have a lot of presentations, and I just wanted to ask you to be really interactive for your questions. Be never shy and make an interactive session altogether. And now, our first speaker is very important historically, Sarikapan, because during the whole IGCS CTOE, the first time we will start with a voice of our patient, a cervical cancer survivor. We invite Olivia Archbold to share her journey with us as the first speaker. Olivia. Welcome, welcome, Olivia. Thank you. And first hurdle over, getting up the steps without falling. It's always a winner. So good afternoon, everyone. My name is Olivia. I'm married to Paul, and we have three wonderful boys aged 12, 14, and 15. Like many of you, I work in healthcare, but today I'm speaking not as a professional, but as a person on the receiving end of a cancer diagnosis. In the next few minutes, I hope to share with you some of my experiences from the time of diagnosis with cervical cancer. I was diagnosed when I was 44 in November 2020, almost exactly four years ago. Initial treatment involved a radical hysterectomy on the 8th of December 2020, less than a month after my formal diagnosis. The procedure went well. However, post-operative complications due to clotting led to readmission to hospital. The wound had to be reopened and a vacuum pump was required, which involved undischarged daily nursing visits for nearly a month. Further, I required a catheter for the same period as my bladder stopped functioning. As you can imagine, the impact of this on our small children at Christmas was enormous. They were only aged 8, 9, and 11 at the time. I'll never forget our middle child's letter to Santee that year, as he wrote, if the cancer could be taken away, Santee, that's all I really want. But then in small print, he did have, he wanted a surprise and large Lego. These complications subsequently led to a slight delay in receiving chemo and radiation. I began a cycle of 25 fractions of radiotherapy in February 2021, over a period of five weeks with once weekly chemo. The memory of the side effects of chemo still haunts me and I want to go, but we'll pass that. On completion of the treatment, it was, I found a huge sense of release. I felt I could do anything. The cancer was gone. This sense of joy was short-lived as the reality of a post-cancer trajectory kicked in. I wasn't expecting it. I expected to be fighting fit in no time. You see, prior to my cancer diagnosis, I was full of energy, possibly too full of energy and way too bubbly that my friends at times would have said, I'd love to remove your Duracell batteries, Olivia. I trained and I ran competitively from 5Ks to half marathons and I juggled the demands of three healthy, active sporting boys with my career in palliative care. You can imagine how busy that is. And even whilst I'm here, my oldest boy who's 15 is competing in a pentathlon that I'm dying to get down there to check how he's going. Into that pre-cancer life, now through extreme fatigue, bowel toxicity and a requirement to use dilators daily amongst other things, loss of femininity and intimacy with my gorgeous husband. Also add induced menopause and all that goes with it, including ever-changing HRT regimes. Suddenly I went from feeling 44 years young and bubbly to feeling 44-year-old, very, very old. Our family home also changed. It went from an access all areas to suddenly mummy locking doors for privacy. That was one small adaptation for my young children. Thankfully, my professional self meant that the skills to mitigate other impacts on our children by knowing the language, how to talk and communicate to children about cancer. Something which is not lost to me for a second. It was possibly one of the hardest and saddest conversations myself and Paul had with our kiddos that Christmas. I also missed out on many of our children's experience and they missed having me. At least I keep telling myself they missed having me. Christmas, holidays, sporting activities or even much simpler things such as staying awake long enough to read them their bedtime stories, which you can imagine I was probably the most animated person in the bedroom with our kids as we read stories. But thankfully, we're gradually coming back to the wonderfulness of the madness. Another strand of my life that was impacted was my profession. I obviously had a lot of time off work, missing out on opportunities for promotion and development. I currently have no entitlements to sick leave requiring me to try and juggle saving some annual leave for those unexpected minor illnesses, especially as we come into the Christmas period and flu season. The obvious financial costs that go with that for the majority of my recovery, I was on unpaid sick leave, which meant we had to defer mortgage payments and also the impact on our future pensions. And there's the ongoing life impact to this day of appointments and scans, which I'll be forever grateful for. And I do need for reassurance that the cancer remains gone, but they do need to be factored into my life planning. I'm glad to say that only recently, life finally feels like it's returning to close to normal. Finally, I would like to thank the organisers of today's event for allowing me to share my experience and such wonderful opportunities for patients to be heard. To Yvonne for helping me to keep it together and not cry too much. And I'm forever grateful to all involved in my care, especially my wonderful consultant, Ghani Oncologist, and his team who had me every step of the way. Thank you. Thank you very much, Olivia, for your bravery and openness, sharing your story. Your words remind us of why our effort is to improve cervical cancer care. And we are deeply grateful to your participation and hope you feel comfortable through our session. And now, our first speaker following Olivia will be Dr. Lata Balasubramanian from India. She will address innovative vaccination strategies. Can a less expensive vaccine be the answer? Dr. Balasubramanian, the floor is yours, please. Chairpersons and delegates, good afternoon. What a story of hope and courage. And that is exactly what we want to prevent. So my talk will be on the less expensive vaccine options. We were part of 12 centers in India, which did the phase two, phase three trial of the Cervavac. So vaccines we know produce a serological response, the adjuvants enhance immune response, and the long-lived plasma cells produce HPV-specific persistent IgG antibodies. But with countries rolling out the HPV vaccination program, there is an increased demand along with a high cost of vaccines. And as long as the LMIC cannot roll out national immunization programs, we will be nowhere close to global elimination of cervical cancer. So this was a multi-center study across 12 centers with cohort one, nine to 14 years, two doses were given six months apart. And cohort two, 15 to 26 years, three doses. Girls and women randomized to Cervavac, which was the Serum Institute vaccine versus the quadrivalent vaccine. Boys, which was the other strength of the study, boys were given Cervavac only. Both the Cervavac and the comparator vaccine have the same HPV type, 6, 11, 16, and 18 in a similar concentration. And demonstration of seroconversion and antibody teeters were adequate as per the WHO regulations. Immune bridging studies were done where the younger age group vaccine efficacy is demonstrated by demonstrating similar or higher antibody teeters in girls and women. We know that vaccine efficacy has already been shown in older adolescents and women as well. They were randomized to Cervavac or the comparator using a variable block randomization. All males, as I mentioned, received Cervavac only. The outcomes were non-inferiority of immune response by geometric mean teeters of the IgG antibodies compared to the comparator vaccine teeters of 15 to 26 years at seven months. And adverse events were also looked at. There was a robust immune response, almost twice the comparator vaccine, as you can see at the GMT ratios. This was seen with both the boys and the girls. There was 100% seroconversion, very similar to the quadrivalent vaccine. And the systemic, the adverse events, both the local events and the solicited systemic events were very similar. So to summarize the results of the study, the geometric mean fold rise was more than 1,000 fold, indicating a robust immune response. 100% seroconversion in both the boys and girls. And solicited adverse effects were 49% of girls in the Cervavac arm versus 48 of the comparator arm. In India, 14 in 1,000 girls are likely to develop cervical cancer without the HPV vaccine. Modeling studies show that vaccinating at age 10 will reduce lifetime risk of cervical cancer by 79% and will prevent nearly 1 million probable deaths due to cervical cancer. So can we really afford to wait? But the vaccines, the current vaccines, are expensive. LMICs have a large burden in deaths due to cervical cancer. We not only need an adequate supply, we also need an affordable vaccine, and this will encourage LMICs to roll out national HPV immunization programs. Cervavac could well become part of the Gavi vaccines, which will further reduce the cost of the vaccine, and this will ensure that 90% of adolescent girls will be vaccinated. So this is a comparison of costs. Costs will depend upon the country, the procurement, the way the vaccines are procured, and you can see that if we go with Gavi or the PAHO, the cost of the vaccine comes relatively less. But cost is not the only consideration. It is important we create awareness. We need to focus on the vaccine as one that prevents cervical cancer and not focus on HPV STI. It is important we build capacity with medical societies, civil societies, and the public. We have to ensure that we have a strong recommendation from our medical professionals. So in India, we will be looking at the single versus two doses of Cervavac as well, and hopefully we will have the results in a couple of years, which will ensure that logistics of rolling out an HPV vaccination program is easier. It is very important that we have clarity of messages. We do not want our ongoing vaccination program to take a hit if communication is not correct. It is very important that logistics and the cold chain are maintained, and very important that we have a stockpile of vaccine to ensure uninterrupted supply of the vaccine. So this is the current planned strategy. So the current plan is to go ahead with a multi-age cohort, which will be at about 68 million doses per year, and an annual vaccination of 10-year-old girls, which will be about 12 million a year. We will, however, wait for the single or the double dose clarity. That is something that is still ongoing. Discussions are still ongoing regarding this. So this is something from India, and we hope that once we have the data from the single dose study from the Cervavac, we will be able to offer it to all the LMIC countries, and this will be one step forward towards global elimination. Thank you very much. Thank you so much, Leita. Please have a seat. Also, thanks for your efforts for the world, for the Cervical Cancer Elimination Programme coming from India. We have another speaker from the UK, Maggie Krishnak, you all know from the Colposcopy Federation. Maggie, can you join us and let us know your opinion on these vaccination strategies? Welcome. Thank you very much, Murat. I want to talk a bit about the real-life experience of HPV vaccination in Scotland. Thank you very much, Olivia, for your really powerful and emotional talk, because when I was a medical student, we did not even know that HPV was the cause of cervical cancer, and now I have two adult daughters who are vaccinated against HPV, for which I am immensely grateful. So, Scotland is the upper third of the United Kingdom, but we only have 10% of the population, so a small country. The immunisation programme started in 2008, so that's girls born in 1990, and since 2008, we've moved from a three-dose to a two-dose, then a single-dose programme. We've gone from the bivalent to the quadrivalent, and now the non-availant vaccine, and in 2019, we started vaccinating boys as well. We had a catch-up campaign for the first three years, although the uptake in the catch-up was 65%, and that was three doses of the bivalent vaccine. So, the WHO sets us really very hard pillars to achieve, 90% uptake of HPV vaccination. So, even in a small country like Scotland, with a national health service, our uptake rate has been running above 80%. There was a reduction when we moved from three doses to two doses, and a further reduction when we moved to vaccinating boys, because we've had lower uptake in boys than we've had in girls. So, it takes a lot of work to maintain even 80% uptake of the vaccine. However, with that uptake, we've seen dramatic effects on HPV-related disease. So, we have seen near disappearance of HPV vaccine 16 and 18, and with a clinically validated test, that's only 0.5 prevalence now of those HPV types, and we've seen cross-protection against 31, 33 and 45. So, that's 90% of cervical cancers in Scotland. We've already reported on a 90% reduction in high-grade CIN as a result of vaccination, and the good news for that is that we have seen the biggest impact in women in the lowest socioeconomic groups, because of the ability to deliver vaccine within a school-based programme. And although the gold line are the girls who had the vaccine, they rapidly saw a reduction in CIN. Even in the unvaccinated girls, with 80% uptake, we've seen this herd protection, with a reduction in all grades of CIN, even in the unvaccinated girls. So when we look at the under 30-year-olds coming to colposcopy, we have seen falling numbers of referrals, particularly with high-grade disease. Although you can see when we changed to primary HPV screening in 2020, that did result in an increase in referrals in that first screening round. So not surprisingly, when we look at the disease we detect at colposcopy in the vaccinated cohorts or the cohorts who are offered the vaccine, we've seen rapidly declining rates of high-grade CIN, but also low-grade CIN, and almost disappearance of glandular and invasive disease. And that has meant that we are doing a fraction of the number of treatments for CIN at the clinics. So for these vaccinated girls, they're just about disappearing. So within Scotland, we have seen almost elimination of vaccine types of HPV, 90% reduction in pre-cancer. And in this year, the cancer registry were able to confirm that there were no cervical cancers detected in women who had received the HPV vaccine. Now, of course, Australia were the first country to adopt HPV vaccination and have declared they will be the first country in the world to eliminate cervical cancer. Although I would say no one has won that race until everyone gets over the winning line. So we really need to see HPV vaccination as a means by which we will eliminate not only cervical cancer, but other HPV-related cancers in LMIC, where the real need to eliminate cancer sits. So thanks very much. And finally, I would just say if you're interested more in the prevention of pre-cancer, I'd direct you to the IFCPC website. Thank you very much. Thank you. Thank you so much, dear Maggie. Please have your seat in the table. Dear friends, it's now time to discuss these new strategies on vaccination. And of course, we can also ask about screening. After this first Q&A session, we will move forward toward the invasive cancer treatment early stages. Any comments or questions from the audience? We have a new vaccine, Indian vaccine. Let me ask the first question to you. It's a really important initiative to have a new vaccine, seeing the really cheap cost. But how about the production capacity? Is it just for India? Or can you make it more global and sustainable for the whole developing countries? So as of now, we have a new industry coming up. And once that is ready, and hopefully that facility will be ready by mid-next year. And once that is ready, the anticipated capacity is about at least 70 million a year. But initially, the doses will be for India. And once we get the MAC done, the Multi-Age Cohort done, then it will be available to other countries. So that is the current plan. Yeah. I mean, 70 million is really a huge, huge number. And I hope if this capacity really becomes possible, then many African countries, Southeastern Asian countries can have the access for cheap vaccines, I think. And the cost is really, really very, very cheap. Any question? Yes, there is. Please. Thank you. I'm Chris Borgfell, professor in Linköping, Sweden. I congratulate on the great vaccine production and your tests. I wonder, in India, of course, you have HPV 16 and 18, mostly, as we do have. But why don't you broaden the vaccine? Have you thought of having those 9-valent vaccine types also in your vaccine? So the 9-valent vaccine is work in progress. As of now, we have enough data for the Cervavac, which is a quadrivalent vaccine. So 9-valent vaccine, the development is still on. It's on the pipeline. It's in the pipeline. Very, very good. Do you know any other initiatives to have a vaccine production in the Asian countries? Because we are in a shortage since MSD and GSK are not that, they need competition. That's what I am going for. I'm sorry, I didn't understand your question. Do you know any other initiatives taking, as you have done, it's great you've done this, but we need more vaccine production in the world? Not only HPV, but other vaccines. Also, we need this type of initiatives. Yes, that's right. Do you have any study other than HPV vaccine? So we don't have a formal study, but the Serum Institute does produce a lot of vaccines and they do supply it globally. That is apart from HPV as well. That's great. And the second question also is that why don't you include boys also, since we know that there's an increase in this HPV in men. They have HPV cancer in their mouth and the tongue and so on. Have you considered that? As per WHO recommendations, the most cost effective will be vaccinating the girls. So that is initially what we will be doing. Yes, that is something definitely to be kept in consideration. But in this study, they have data also for the boys. You know, for male vaccination, only quadrivalent and non-ovalant vaccine has the data, and now the third data for the males is coming from India. Thank you. Yes. Thank you for this presentation. I have one question related to vaccine in India. With all the efforts, I'm not sure whether how many people were vaccinated in India, but maybe a few millions. Don't you think that it is a very bigger task to think that we will vaccinate 70 million people in the country? Because I personally feel that in India, cervical cancer vaccine uptake is more of a demand side problem. There's not much of demand. With all the efforts, people are still hesitant to take vaccine. And I don't want to say, but I'm very skeptical because it should not happen in the COVID way. Because, you know, COVID, there was a supply, but there was no demand from the people's side. So at the same time, what is your take that apart from producing the vaccine, what is the strategy that you will be taking in different states, provinces in India to increase the demand? Because I see even the educated people, even medical community, if I say the vaccine uptake is not even 10%. So your take on this. Thank you. So the HPV vaccine is slightly different because it's an adolescent vaccine. But India has done very, very well with vaccines from zero to two years of age. So our vaccine uptake is about almost more than 90% in these areas. Once there is a governmental decision to roll out the HPV vaccination program, so there will be awareness creation that happens at all levels. And as you very rightly said, the demand has to be created. But any vaccine, and as of now, we've never had problems with introduction of vaccines when the government has authorized it. So, and the logistics, the planning is in place. So it is only a question of a policy decision that needs to be done. But I take your point, communication is very, very important, and I would be very happy to hear Dr. Maggie Crookshank's thoughts on how it was done in Scotland as well. Thank you. Thank you. You would like to add something, Maggie? Yeah, I completely agree with you that communication is so key to this. And when we have seen things like the anti-vax campaigns in Ireland here with the regret campaign and in Japan, which decimated the HPV vaccination program. And in Scotland, there was a lot of work done around communication before the HPV vaccination program. We have issues around rurality, people living on islands, very conservative religious groups. So as well as all the standard information, there were documentaries on television with journalists looking at both sides, trying to understand the pros and cons. Scottish government took a very proactive response to any concerns. So as well as passive monitoring of reported side effects, they actively looked at the diagnosis of chronic neurological conditions, autoimmune conditions, chronic pain conditions, and were able to show there were no increase in these in the vaccinated cohorts. The only diseases that increased over time were obesity and diabetes, and that was seen equally in boys as it was in girls. And equally, there was a big scare story in the press where a girl got vaccinated in England and died that night. It turned out she had a mediastinal tumour. But very quickly, it was put out in the press to clarify that this was not related to the vaccine, just a chance finding. But it really needs that proactive approach. Yeah. Actually, we have no time to discuss more, and we need to go to the other speakers. Let the ladies. Hear the questions. There's one. Yes. Thank you. Thank you for your presentations. And I'm Lou Erickson from Canada. I just wanted to clarify for the Scottish program, is this an opt-in program for the students in school or an opt-out program? Where in Canada, for instance, it's an opt-in program. Parents have to sign that they want to go ahead with this. So we're just curious what the program is like for Scotland. So in Scotland, it's done through the school-based program where the school nurses go in. Leaflets are sent home to parents that they can consent to it. But the age of consent in Scotland, if you have capacity to consent, is 12. So even if your parents don't sign the form, a 12-year-old is able to consent to vaccination, which is different from England around the ages of consent. Thank you very much for this wonderful session. Thank you, Lata and Maggie, for your insightful presentation and perspective. And not only the HPV vaccination that we should remember, it's screening as well. So thank you very much. You can join the audience. And now, shall we move on to the practical case presentation? This will give us a closer look at early-stage cervical cancer management and highlight the complexities and decision clinicians face. So I would like to invite Dr. Lata to come up to the stage and give us a brief presentation. Dr. Emma Alanson from Australia will share her case presentation. Dr. Alanson, the stage is yours, please. Thank you very much for inviting me to give this talk. So this is a case of early cervical cancer that touches on some of the issues raised by the previous wonderful speakers and certainly will be followed up by Marie Plante's talk next. I have no disclosures. So this woman presented to our unit. She was 33 years old and had no significant history. She'd been referred after seeing a general gynecologist, having had her first ever cervical screening test, which showed non-1618 positive oncogenic HPV. And we do primary HPV screening with reflex cytology in Australia. And her reflex cytology showed a high-grade squamous lesion with possible microinvasion. She was nulliparous, but clearly expressed a desire for fertility. She, despite being 33, had no previous cervical screening test. We have access to screening readily available in Australia, and it's been reported on throughout the morning today. And sort of more concerning, and I think highlighting the fact that having a screening program does not necessarily equal access to a screening program, she'd seen a care provider for contraception and management of an ectopic pregnancy in the two years prior. The HPV vaccine was rolled out in Australia in 2007, and she would have been 17 at the time, so she did miss school-based vaccination and would have needed to actively seek the catch-up vaccine. So at colposcopy, there was coarse mosaicism at 12 o'clock, which was biopsied, and a dense acetyl white epithelium at 6 o'clock, which was biopsied. And these biopsies showed CIN3. She proceeded to a Letts excision, which measured seven millimeters deep and showed a moderately differentiated squamous cell carcinoma. The depth of invasion was seven millimeters, and it involved the deep stromal margin. So this was the point at which the patient came to our unit, and she had a multidisciplinary team meeting review. The pathology was reviewed, confirmed to be a grade 2 SCC with no LVSI. She had a PET scan, which showed some focal change at the cervix post her Letts, but no avid nodal disease. And an MRI pelvis showed no residual disease, and there is a screenshot there of that. She was an apparent stage 1b1, and a discussion was had at that meeting about the options. Clearly, the options could have been a radical hysterectomy or trachelectomy and pelvic nodes, whether they be sentinel or full nodes, a simple hysterectomy and nodes or conan nodes. She desired fertility, and so the consensus of our unit was to undertake a cone biopsy given the positive margin and laparoscopic sentinel node plus full node dissection, which is unit procedure for us. The cone biopsy results would clearly determine any further surgical management. So some discussion about the cone biopsy at primary treatment. It's obviously a whole talk in and of itself, and there is obviously some variations in guidelines around the world, but this is a patient who desired fertility, who had a depth of invasion less than 10 millimeters and a tumor size less than 2 centimeters. Negative nodes on imaging, appreciating we didn't have the final pathology on those nodes next. LVSI in brackets, because we understand that there are some variations in whether LVSI is or isn't an indication for fertility sparing treatment, and ideally, obviously, you want your negative margins and may need a repeat cone, as was the case here. So she underwent a type 3 excision, a cone biopsy that measured 20 millimeters deep, and that showed no residual malignancy, some focal CAN3, which was well clear of the margins. She had laparoscopic sentinel nodes, which mapped on each side. There were two nodes in the left sided packet, both of which were negative, and a full pelvic node dissection, all of which were negative. So there's obviously lots of components to this case, and I look forward to the next talk, but I think there are some key messages. Even when we have a national vaccination program, screening clearly remains critical, especially for those outside who are aged outside of the program. The presence of a robust screening program, which we very clearly have in Australia, doesn't always equal access for a whole host of complicated reasons, both patient, clinician, political, and health system based. The role of opportunistic screening in patients who present for other reasons cannot be underestimated, and there was a great opportunity that was missed in this patient. The cohort of patients with cervical cancer who desire fertility need MDT consideration to those options. However, clearly there are less radical options that exist that we must consider. So thank you from our wonderful team on the west coast of Australia. Thank you very much, Dr. Alanson, for the interesting and comprehensive presentation. Take a seat on the stage, please. And ladies and gentlemen, our next speaker, Dr. Marie Planté from Canada. She's the PI of the famous SHAPE trial. She will discuss the role of simple hysterectomy for early stage cervical cancer. This approach is a key This approach is a key option for patients. Dr. Planté will share her perspective and expertise on how to best implement this surgical technique. Dr. Planté, please. Well, first, thanks to the program committee for inviting me to speak to you today. Oh, there it is. No. Okay, I'll go here. Okay. So I assume most of you have either read here, heard or read the simple hysterectomy or SHAPE trial, which was published in the New England Journal of Medicine in February of 2024. And in a nutshell, it's a prospective randomized trial which compares simple to radical hysterectomy in patient with what we now call the SHAPE criteria, which are low risk disease defined as the usual histology, lesions under two centimeters, and importantly with limited depth of invasion. And what the data showed is that the three-year pelvic recurrence rate was not inferior with simple hysterectomy compared to radical hysterectomy. And that data actually compares with other prospective clinical trials such as GOG278 and CONSERVE. And I think it is worth revisiting briefly CONSERVE because it is important to understand the differences between those trials. So I don't know why I'm having difficulty advancing the slides. Anyway, so in CONSERVE, patients had to have a full cold knife colonization to determine eligibility. And then the colonization had to have negative margins for cancer but also negative margins for high-grade lesions. Adenograde 3s were excluded. LVSI positive were also excluded. The other criterias were similar. Very briefly again, on the left-hand side, if patients had colonization with negative margins in order to preserve fertility, they proceeded with having lymph node evaluation. Two had positive lymph nodes. And in the follow-up, one patient actually recurred despite having had negative margins on the cone. In the middle section were patients who met the criteria of the colonization but did not want to preserve fertility. They underwent simple hysterectomy. Three patients had positive nodes. And despite again negative margin on the cone, one patient had residual disease higher up in the canal, which reemphasized the fact that even negative margin is not a guarantee that there's nothing left. But none of those patients recurred. And so based on those criteria, NCCN had issued guidelines to say that it is acceptable to do a simple hysterectomy extrafacial as long as patient meet all the conserved criteria, which you see listed on the slide. There's recently Dr. Covins presented at the ASGRO meeting in March results of GOG 278. Almost an identical design as conserved, but there are three differences, which is worth mentioning. Number one is LVSI was included. Patients could have a leap, not necessarily a cone. And margins could be positive for pre-invasive disease but not for invasive disease. And again, patients could either have a cone and lymph node or hysterectomy and lymph nodes. So I put together this table to help you compare those three trials. And I put in yellow that simple hysterectomy results across those three trials. And you can see the numbers. They're different. The types of study is different. In GOG 278, there was a pretty high rate of 1A disease of 45%, whereas only 8% in shape. Conversely, 92% of 1B1 disease in shape. Lymph nodes, again, positive as expected under 5%. But again, what is very different between those three trials is the status of the margins of the pre-hysterectomy leap cone, which had to be negative in GOG and conserved, but could be either negative or positive in shape. And so if we look at residual disease in the hysterectomy specimen, it had to be very low in GOG, there was only one in conserved, but it was 46% of patients with residual disease in the hysterectomy specimen for shape. So in terms of recurrence in GOG and conserved, there were none in the simple hysterectomy patients. It was 3% in shape, most likely because of a higher proportion of 1B1, and also because of the positive residual disease in hysterectomy specimen. But again, if you look at the death, it's very low in both arms. So I think it is fair to say that simple hysterectomy in low-risk disease is safe. What I get asked all the time, well, can we do minimally invasive surgery in those cases? Well, unfortunately, when we designed the shape trial, we did not know that surgical approach was going to be such a big issue. So it was not mandated as a randomization factor, so surgeons could decide whatever they wanted to do. And so as you can see, it turns out that 77% of patients in shape had MIS surgery, and only 23% had open surgery. So we asked the question, well, let's look at the simple hysterectomy group of patients from shape and compare open versus MIS. And this is a publication that's been submitted for publication. And as you can see, there were very few open cases. Most of them were MIS. But we saw no difference in clinical outcome between those two surgical approaches, as you can see here. Now, please be reminded that this is a subgroup analysis. This was not randomized in terms of surgical approach. There were only 57 open surgery and very few events. So that sort of limits the power of the conclusion. The second question I get asked all the time is, well, should a leap cone with negative margins be done prior to MIS, simple hysterectomy? Well, then again, we decided to go back in the database, and Sven Manner is actually leading this publication, which is almost ready to be submitted. And we looked specifically at patients in the shape trial who had a pre-hysterectomy leap cone with negative margins. And we identified 174 patients. We had two recurrences only. It turns out both were MIS, one after simple hyst, one after RAD hyst. But there were no extra pelvic recurrences and no extra cervical cancer deaths. And then I went back in the database of GOG, CONSERVE, and SHAPE and looked, again, specifically, simple hyst, MIS with a leap cone prior to hysterectomy with negative margins. You can see the numbers. The probability of the recurrence is not zero, but it's very low. So in summary, so far, I think it's fair to say that SHAPE confirmed that simple hysterectomy is safe, as long as we keep in meeting the SHAPE criteria, and that SHAPE does not provide a definitive evidence that MIS simple hyst is safe, simply because the numbers were small. However, the risk of recurrence following pre-hysterectomy cone or leap with negative margins appears to be very low. So there is a need to confirm the data in a large-perspective trial. And that's coming up. It's called the LASH trial out of Gemali in Italy. It's a large-perspective, non-randomized trial which will collect over nearly 1,000 patients. Patients meeting the SHAPE criteria, negative margins of the cone is recommended, not mandatory, but strongly recommended, and patients will undergo simple hysterectomy and lymph node assessment. So we look forward to this study that will provide us with a lot of data. So we thought we had it all figured out, but not quite. Most of you, I suspect, have seen the updated publication of the LAP trial in Journal of Clinical Oncology, and it confirms what we know, that is, that the outcome of patients who were operated on by MIS in that particular trial were significantly worse. But what's interesting in this publication is they separated out the data according to tumor size under two centimeters, and you can see that still the outcome of MIS patients, even in small lesions, were statistically quite a bit worse, by almost 9%. And what I find unusual is if you look at the three-year mark in the LAP trial, the three-year recurrence rate was 92%. And if I look back at SHAPE with a simple hyst by MIS, the three-year disease free is 96. Is that unusual? And my explanation is perhaps that in SHAPE, it was not only the under two centimeters, but it was also the low risk criteria that were included. Another interesting thing of the updated report is they separated out according to cone biopsy. On your right-hand side, even though we don't have the status of the cone margins, you could see that patients who had a cone biopsy and MIS surgery had survival or outcomes similar to open surgery. And there's been a whole host of different studies and meta-analysis and systematic reviews and all whatnot to compare outcomes of MIS and open. This one suggests that MIS is better. The GORILLA trial suggested that, well, we cannot guarantee that MIS is safe even for under two centimeters. This is another big analysis of 4,000 radhis suggesting better survival, less recurrence despite MIS. The SUCCOR trial shows that prior colonization and MIS, similar outcome with open surgeries, about the same thing that the updated trial report just mentioned, and so on and so forth. So retrospective data have consistently reported conflicting results with regards to the issue of pre-hysterectomy cone and MIS, and we look forward to the last trial. And so I would like to leave you with, I would say, my three messages. Number one, investigate and select patient for less radical surgery very carefully. Remember that it's not all the lesions on the two centimeters that are candidates for simple hyst. Please stay within the shape, low-risk criteria. Don't stretch the elastic. You'll get burned or your patient's gonna wind up with radiation. If you plan to do MIS for simple hysterectomy, I would believe that a pre-op leap cone with negative margins appears to be safer, and there should be no evidence of disease higher up in the canal, so I would suggest you do an MRI. And remember that negative margins does not guarantee that there's no disease left, so I would suggest that you be careful, close the cervix, no uterine manipulator, play it safe. And lastly, and I think this is important, if a patient shows up in your office with a small-volume lesion, well under two centimeters, performing a pre-hysterectomy leap cone with negative margins might be actually the way to go. Why? Because if you remove entirely the lesion with your leap cone and negative margins, it provides you with an objective assessment of tumor size. You know exactly what size the lesion is. You have the depth of invasion in the LVSI, and that allows you to then properly select the type of hysterectomy, whether this patient truly fits low-risk disease, can have a simple hyst, otherwise, rat hyst, and it also helps you determine or select the surgical approach, MIS or open. But if a patient shows up in your office with a large, bar-key lesion of three or four centimeters, a cervical biopsy alone is sufficient to establish the diagnosis, and please, there's no need or indication or benefit to do a leap cone in those patients. Thank you very much. Thank you so much, dear Mary. Please have your seat at the table. I think it's a quite debatable topic, and we need to discuss after the several other presentations. Dear friends, usually, IGCS and many other societies, altogether, we do good surgical trainings and training hubs we have, but we have a problem in eliminating the cervical cancer is about the radiotherapy. We have important challenges, and how we can solve these problems, especially in low-middle-income countries. Let's talk a little bit about the radiotherapy, and it's my pleasure to invite Dr. Chopra here to introduce us the best solutions of radiotherapy in these countries. Thank you very much for your kind invitation. These are my disclosures. Last couple of years have changed a lot for gynecological cancers, and since 2021, with the advent of major trials, the standards of radiotherapy are changing, and we know from PARSA study, which was purely a cervical cancer study, that image-guided IMRT reduced adverse events in absolute rates by 20%. EMBRACE, a prospective 25-center, 1,400-patient clinical trial, led to 10% to 12% increase in local control in advanced-stage cervical cancer, and because it was a single-arm prospective study, we followed it up with a meta-analysis of 5,000 patients where we included comparison between point A versus volume-based brachytherapy. It demonstrated a 10% increase in disease-free survival, suggesting that good-quality radiotherapy alone can improve survival and reduce toxicity. However, it's very important to define that in 2024, when so much is changing, what is standard radiotherapy, not only in LMICs but on control arms of so many clinical trials that will get presented in the next session. So standard radiotherapy should include image-guided IMRT and whenever applicable, nodal-dose escalation. Image-based brachytherapy should be the standard with doses more than 85 gray. A good program has intracravitory interstitial implants in up to 40% patients, and low-middle-income countries where there is advanced disease, this should look around 70%. And concurrent weekly platinum five cycles and treatment should be under 50 days. These are the quality standards. So these quality standards can get up and down in entire LMICs, they are quite stiff. And when we looked into India's situation and we last year published this in Lancet about how to make these changes happen, just like vaccination, it's a large country and how do you transition. And what we realized was that if you have to move to all these advanced treatments, it would lead to doubling of staff, tripling of time and cost, and we could be in a situation that there is a capacity loss and you make waiting lists for radiotherapy. And this constituted 17% of the world's population with cervical cancer. So we looked into it and now making access possible, we think that there are at least four pillars that should go into improving access. One is to use resource-pairing strategies, financial impact modeling, very important for national cancer control programs, integration of automated workflows, and to augment training in brachytherapy. So first thing actually came because all the clinical trials that have been completed for cervical cancer have three or four fractions of brachytherapy HDR where patients receive weekly. And in Tata Memorial Center, from this standard way of doing trial, which we did in our neoadjuvant trial and chemoradiotherapy trial, we moved to giving two implants and four fractions, and we had prospective clinical trials. But when COVID pandemic came, it put us almost in an emergency situation that you do less implants and deliver more fraction. That means your effort goes down in doing an implant and you could deliver more fractions. But this was considered non-standard. So we went ahead and in 1,300 patients in Tata Memorial Center, from 2010 to 2023, we compared if this strategy is safe for our patients. So this is what is the international standard, Embrace-1. And a certain local control, which is 90%, but in blue is the GI adverse events and yellow is the GU adverse events. And when looked into our COVID cohort of patients which had accelerated fractionation, the adverse events are very similar and so is the local control, and it became our new standard. And when we imputed this data into the national situation in India, we realized that all the red states could actually become yellow and green, barring few, if you change the fractionation, because there is 50% reduction in workload and 100% increase in treatment capacity. And it was a very simple solution with the data. So next step was us to look into many low-middle-income countries, and this was an IAEA collaborative project where we had 14 countries, and you can read out the names here. We went into them and got data from these countries to model their workflows for advanced brachytherapy. And what we realized was that we expand the India model to low-middle-income countries. This is a complex figure, which I will try to explain a bit, that most of the centers which were actually facing a deficit could be in an enhancement zone where the bars are under the index line, and some countries would need financial investment. So this was a very, very positive thing because without cost investment, just changing your strategy, there's a 100% expansion of capacity. And then in India also, after doing PARSER trial, despite being lead author, we could not get it into optimal recommendations IMRT because it's way too expensive. So we did a national cost modeling and a longitudinal cost analysis, and what we realized was that IMRT, which the incident cost is expensive, when you see patients longitudinally, actually it reverses itself. So it's a huge lesson for resource-stratified guidelines not to go with incident cost, but see the longitudinal trajectory of the patient, and then determine for their healthcare system. And this is a good example for even resource-stratified guidelines to have high-end procedures incorporated in optimal setting. The third pillar that we have been using to enhance is AI because there is shortfall of working staff. Once you do brachytherapy implants, there's treatment planning, and there is another three and four hour of process that follows a doctor. So what we started doing for IMRT is that we built, through computing, an AI-based model which would do treatment planning, state-of-the-art IMRT planning, and then we tested this model in collaboration with Denmark and McGill in Canada to see how this performs against best human physicists worldwide, 69 centers, and in all cases, this AI model trumped the best human physicist. And what humans can do in four hours, it takes 40 minutes or even less a time for model. And in Tata Memorial from 2020, we converted our entire treatment planning for EBRT with automation, and this model we made available for free worldwide use. Any center that wishes to use is most welcome to contact us. And similarly, for automated gynecological brachytherapy planning in a collaboration with Erasmus University, there is a university-based automated planning model that we tested both for performance and for time optimal utilization. And again, you can see that when clinicians were blindedly given what machines had generated, in 80% of the situations, they preferred automated. And you can see the drastic fall in time and resource efficiency that automation can bring. And finally, we come to training. We have a lot of surgical learning curves which are there, but none for brachytherapy. So this is a learning curve that we recently established at Tata Memorial Center for accreditation for brachytherapy to provide good quantity. I will not go into the complexity of this slide, but these are 25 or 30 variables or elements that a trainee must pass on to perform good quality brachytherapy. And we start with now evaluating our trainees with this learning curve. So I would like to conclude by saying that despite very high quality and fancy drugs and trials that are coming in, high quality radiotherapy remains the strongest backbone for cure of cervical cancer, and we must not forget that. We should augment workflows by using abbreviated fractionation and automation. Projecting national needs for radiotherapy are must, and many LMICs lack that in their national cancer control programs. Skill development is needed, and I would like to acknowledge that I have only included our data, but there is much, much effort by many people in the audience here representing various societies that are listed on this slide. And my apologies if I've missed on various initiatives that are already there in this direction. Thank you very much. Okay. Thank you very much, Supriya, for highlighting the challenges and solution in this specific area of RT in low middle income country for cervical cancer. And now we have mentioned upon surgery and radiotherapy in early cervical cancer already. Now let's move to our next presentation, which will explore the practical issue of fertility sparing in patients with cervical cancer, the topic that will hold very important for young women. And ladies and gentlemen, please welcome Professor Nao Suzuki, please. Hi, good afternoon, ladies and gentlemen. This is Nao Suzuki from Tokyo, Japan. I'm happy to be here today, so thank you very much, Sherika-Pam, for introducing me. And I have no, nothing to disclosure, so I'm going to review the current status of fertility sparing treatment for the young cervical cancer from, not only from the oncologic perspective, but also reproductive medicine perspective. The current topics of fertility preservation treatment for cervical cancer patients are discussed in the six points shown on this slide. So reproductive and outcome, and oncologic outcome, of course, and safety of fertility sparing surgery with more non-invasive approach. And neoadjuvant chemotherapy followed by fertility sparing surgery at the patient's tumor greater than two centimeter and ovarian toxicity. Oocyte pickup for oocyte and embryo cryopreservation, and also ovarian tissue cryopreservation and ovarian tissue transplantation, and finally, ovarian transplant position. However, this lecture will last only 10 minutes, so therefore, I would like to report only a small portion. This slide shows the 2023 updated version of ESGO-ESTRO-ESP guidelines for the management of fertility preservation treatment for the patients with young cervical cancer. Fertility spring therapy is an oncologically-valid alternative to radical hysterectomy for young patients with cervical cancer less than two centimeters, which is scar cell carcinoma and HPV-related adenocarcinoma, who want to preserve the option to have children. Before initiating fertility spring therapy, consultation at an oncology center and discussion in a multidisciplinary tumor board is recommended. So according to this guideline, fertility spring procedures comprise of colonization, simple tracheotomy, radical vaginal tracheotomy, and abdominal radical tracheotomy. The indications for colonization and simple tracheotomy are FIGO 2018, T1A1 and T1A2 tumors, regardless of the status of positive lymphobascular space invention. And T1B1 with negative lymphobascular space invention. Simple tracheotomy is indicated for patients with a high probability of being able to secure a sufficient margin of restriction without deep invasion of the stroma. The indications for radical vaginal tracheotomy and abdominal radical tracheotomy are T1B1, positive lymphobascular space invention. This slide showed the content of a paper published in 2024 that compared the prognosis of fertility spring surgery and standard surgery for early cervical cancer. This study found that the survival outcomes within five years of diagnosis of patients aged 45 years or younger with early stage cervical cancer with a tumor measuring four centimeter in diameter and who underwent fertility spring surgery was similar to those who underwent standard surgery. But risk of recurrence must be comprehensively discussed with the patient. This slide showed the content of the German Fertility Study reported in 2023. In this study, patients aged 18 to 40 years old and FIGO 2018 stage 1A with positive lymphobascular space invention were 1A2 and more stage of cervical cancer who underwent any type of fertility spring procedures were recruited. Almost half of the patients had stage 1B1 cervical cancer. After a median follow-up of 72 months, 7% of the patients experienced recurrence of whom 2.6% died because of the disease. The most common site of the recurrence was cervix and pevic node. The risk of recurrence was three times higher in patients with tumors larger than two centimeter in size than in patients with smaller tumors illicit of the treatment radicality. The recurrence risk in patients with tumors two centimeter or less in size did not differ between patients who underwent radical tracheotomy and patients who underwent non-radical cervical procedures regardless of tumor size, subcategory or lymphobascular space invention. This slide is from a 2024 paper for that summarized reproductive outcome model for this study in Germany. Of the 733 patients, 49.7% attempt to conceive during median follow-up of 72 months and 22.6% patients achieved a successful pregnancy. 89.5% of the patients became pregnant naturally. The overall success rate of pregnancy in women who attempt subsequent pregnancy after undergoing Fertility Surgery was 45.6% with a significant difference between non-radical procedures which is 63.2% and radical tracheotomy, 25.7%. In conclusion, the FATES study shows significantly lower pregnancy rate and an increased risk of preterm delivery following radical tracheotomy when compared to non-radical procedures. Importantly, non-radical procedures did not result in an increased risk of recurrence in patients with tumors two centimeter or less in size. Conversely, less favorable outcomes have been reported in patients treated for tumors larger than two centimeter, including a high incidence of preterm birth in earlier gestational weeks and lower mean birth weight. The FATES study supported that less radical surgery can achieve comparable oncological outcomes while preserving fertility more effectively. This slide shows an Italian retrospective analysis of patients who underwent IVF, ET treatment following Fertility Surgery for early stage survival cancer. As a result, non-radical group with uterine arteries being spared had a significantly higher live birth rate, this is 83%, compared to the radical group, 17%. So reduced implantation rate may be the key factor explaining worse IVF outcome in patients with uterine artery ligation. Decreased radicality and uterine artery sparing is advocated to optimize reproductive outcomes. According to the European guidelines, in more advanced cases, various fertility preservation proposals such as ovarian transposition, oocyte, embryo, and ovarian tissue cryopreservation and egg donation should be discussed with the patients. The aim of the fertility preservation should be to offer the most efficient approach in accordance with the legal country's basic regulation while not increasing the oncological risk. This is the most important. So next I will talk about ovarian tissue cryopreservation and ovarian tissue transplantation. The donor of OTC and OTT dates back 129 years. This slide is a case report paper submitted by Dr. Morris to the Medical Record in 1906. The recipient is 21 years old and the donor is 30 years old. A 20 years old woman had symptoms of menopause and her menstruation resumed due to ovarian tissue transplantation, after which she got livers. The issues are that it is just here's the information, of course, 100 years ago, and this is about the refusal of immunity to allergenic OTT. However, Dr. Morris in United States achievement are significant because OTT to human was done 100 years ago. And Dr. Parrot's achievement regarding first report of OTC and OTT in mice lead to the research result of Dr. Gosling of England. A more effective OTC method using slow-feeding technology was developed by Dr. Gosling in England and leading to the successful OTC and OTT using sheep. Thereafter, Professor Oktay in Turkey succeeded in obtaining embryos from the transplanted ovaries in human and reported to Lancet in 2004. And finally, Professor Jacques Donnet of Belgium reported the world's first successful live birth achievement in 2004. This slide summarizes evidence of bionic researchers in the area of Israel, Belgium, and the United States. According to this paper, menstruation resumption rate was 94%. Pregnancy rate was 50%. Live birth rate was 41.7%. And miscarriage rate was 6%. But 65% of patients were blood cancer patients. The diseases which ovary contain tumor cells for example, leukemia, ovarian cancer, borderline ovarian tumor, and non-Hodgkin lymphoma become control indicated for ovarian tissue cryopreservation because of the minimum residual disease. We can see cancer cells in the ovarian cortex in the patients with leukemia and non-Hodgkin lymphoma as seen here. But OTC is possible when it has no time or sufficient time until starting cancer treatment. Therefore, leukemia and non-Hodgkin lymphoma actually are one of the most appropriate indication for ovarian tissue cryopreservation. So is OTC and OTT indicated for survival cancer? According to European guideline, ovarian preservation should be discussed with women in reproductive age with skeletal cell carcinoma can be considered in HPV-associated adenocarcinoma and is not recommended for HPV-independent adenocarcinomas. I will introduce a report on OTC and OTC for patients with survival cancer. In 2024, Professor Okutai reported a review of the OTC, OTT for GYN cancer patients. Among the GYN cancers, cervical cancer accounted for 29% and 52% of OTC and OTT, respectively. This slide shows information on five cervical cancer patients for whom continuous ovarian stimulation and oocyte retrieval was possible. So oocyte retrieval was unsuccessful in one patient with cervical cancer and the remaining four patients were able to obtain embryos, but three of them did not go on the embryo transfer. So what is the impact of surgical manipulation on the uterus in ovarian tissue transplantation? Is it because most cervical cancer patients had OTT on the abdominal wall? What is the significance of OTC and OTT for cervical cancer patients? So adequate discussion and careful handling are needed. So in GYN cancers, there is a high risk of tumor cells being mixed in with the ovaries, so there is an urgent need to develop new technologies and techniques to avoid the risk of malignant minimal deleterious disease, just as leukemia and ovarian cancer. I'm also sorry that I cannot share information about the three studies we are currently conducting due to the time available for the lecture. This is the last slide. This is my take-home message. Fertile spleen surgery is a non-critically valid alternative to radical hysterectomy for young patients with cervical cancer. The tumor size is less than two centimeters, which is skeletal cell carcinoma and HPV-related adenocarcinoma. Less radical surgery, which is colonization and simple vaginal tracheotomy, can achieve comparable oncological outcomes while preserving fertility more effectively. Fertile spleen surgery may be an option for select patients with tumors up to four centimeters in size, but the risk of recurrence must be comprehensively discussed with the patients. The safety and efficacy of ovarian tissue preservation and ovarian tissue preservation in GYN cancer, including cervical cancer, has not yet been established. So GYN oncologists should not only do surgery, but also should be involved in subsequent medical care, including ART and fertility preservation treatment, since the goal of the fertility spleen surgery is to try to obtain a live birth, and this is our patients. Thank you for your attention. Thank you, thank you so much, Professor Suzuki. Please join us on the table. We are a little bit delayed, but I also want to invite Professor Hiawua Wu. Are you here? Professor Hiawua Wu. Am I reading? Maybe my, Shanghai. Shanghai. You wanted to discuss? I think he's not here. Okay, otherwise we can start our discussions. The questions and answer sections, and we have around five minutes more to discuss. Yes. Yes, please. Thank you for great presentation. I am Kenrochi Kazawa from Japan. I have one question about current indication about the radical tracheotomy after shape. If patients meet criteria, entry criteria of shape or GOG278, those patients are enough for simple hysterectomy. They don't need radical hysterectomy. Okay. Maria, maybe. Is it clear, the question? No, there's a lot of echo. The patient is suitable according to the shape criteria for fertility preservation. Should you, but will you move forward with simple hysterectomy, or should you offer still simple colonization, right? Yes, simple tracheotomy or simple colonization is enough. Or simple tracheotomy. For cervical cancer under two centimeter. It's difficult to hear. Well, I guess, you know, if the data out of shape trial shows that there's comparisons of outcome between a simple hysterectomy and a radical hysterectomy, and if the patient does not want to, wants to preserve fertility, it suggests that we can move from radical tracheotomy to simple tracheotomy in those cases, as long again as they meet, you know, the lowest criteria. I don't know whether I'm answering your question, because I'm not sure I heard completely well. So, if patient over entry criteria of shape or GOG278, we should perform radical tracheotomy. That we should offer a tracheotomy? Yeah, radical tracheotomy. Well, obviously, if the patient does not want to preserve fertility, and but she really wants to preserve her uterus, I guess it could be offered. But if she does not want to preserve fertility, I would probably recommend a definitive hysterectomy. Why? Well, the follow-up of patients after a tracheotomy remains challenging. Sometimes they have stenosis, the Pap test is not easy to do, ECC, et cetera. And then there's always the worries that if you leave some cervix, you potentially leave endocervical glands that might be still contaminated with HPV, which probably explains why there are more recurrences after a colon than after a simple hysterectomy. And that's probably why. Yeah, that would at least would be my theory. I get your point, thank you. Dr. Suzuki, any comment on that? I mean, simple colonization, simple tracheotomy, radical tracheotomy, how we can differentiate three groups. Yeah, as I presented, so you said that the tumor size is less than two centimeters. And if this patient is just for the shift trial criteria, we can do the colonization, I think, or simple radical tracheotomy. Yeah, this is my opinion, yeah. Thank you. Thank you for your answer. Thank you. But if the tumor size is greater than two centimeters, we should do the tracheotomy, not colonization. But it depends on the areas of the eye. We do the radical tracheotomy or like simple tracheotomy, I think. Thank you very much. Okay, the second question, is it Nassar Fahd or? Yes. Yes, yeah, Professor Nassar. Like a plant. Thank you very much for a nice presentation. In the era of molecular profiling, in the era of molecular profiling, do you think one of the reason that some of these patients had recurrences, in spite of the best surgical treatment and best surgical selection, maybe the molecular profile of those patients had recurrences where it was different than the other patients? Is there any molecular profile that you use to choose these patients? No, not currently, but in the future, there might be some ways or some tools to determine if there's still presence of like circulating tumor DNA, for instance, or cervical scrapes with hypermetallation that may be predictive. I think that if a patient had a leap cone or let's call it a large cone, and she remains HPV positive during follow-up, I really worry about, obviously, those cases because I worry about the risks of recurrences. Yeah. Can I just add a comment? Yeah, sure. So for surgical, I think it's already said that currently we don't have any established, but for radiotherapy, we just published the molecular profiling aligned to TCGA using two or three pathways. And there we observed that when patients have PD-L1 positive tumors, despite the best radiotherapy, and if you have lower doses, there is excessive relapse. And second thing that comes is the AKT pathway, and it's unpublished data as of now. So some patients may actually have 100% local control even in cervical cancer. So I think very soon, in a couple of years, there will be more data going also in the direction of molecular classified, at least from radiotherapy perspective, and that could possibly be adopted for surgical cohorts also. Thank you. Thank you very much. That was my point, that if we continue doing surgical trial and years and years, and we do not consider molecular profiling, we are back to the same points again. So I recommend we should consider that one. Thank you. Thank you. And last question. Thanks, I'm Paul Cohen from Western Australia. First of all, I'd like to thank the panel and the speakers for some really excellent talks and discussion. I have a question for Marie, and Marie, I apologize for this question in advance. In the supplementary appendix, in the forest plot, if you look at the adenocarcinoma adenosquamous subgroup, the upper bound of the 95% confidence interval crosses your 4% threshold for non-inferiority. So I'm just interested to know if you have a different discussion with patients with adenocarcinoma? No, not specifically, but you are right, that's the only subgroup where it crosses the one. Of course, the numbers are lower with adenocarcinomas, and we lump as well with the adenosquamous. And adenosquamous are perhaps a different beast, perhaps a little bit more aggressive. So I don't think that we would have enough cases to run a separate analysis, but there's that. And then we don't necessarily mix together like adenocarcinoma in the grade, for instance, if you have an adeno grade three, is that the same thing as an adeno grade one? I mean, those are all sort of factors that might have played a role. I'd like to ask. Thanks. Question? Ah, okay, let's get it. I will ask how many minutes. Please. Hi, I'm Diego Detto from Argentina. Mary, the question is for you. If you decide to do a vaginal trachelectomy, do you perform some kind of surclash, laparoscopic or vaginal surclash, after doing the vaginal trachelectomy? Surclash. After trachelectomy. Right, I don't, no more. Even if you do a vaginal trachelectomy? Yes, but I should say that currently in my practice, if patients have larger lesions, I give them neoadjuvant chemo to shrink it down to small lesions. So I very seldom, more rarely, do radical trachelectomies anymore. And so following simple trachelectomy, I don't tend to put in a surclash, and our data has shown excellent obstetrical outcome and delivery toward terms. It depends, at the end of the day, after your trachelectomy, how much cervix is left. I mean, if you're up very high up near the isthmus, I think you're probably safer to put in a surclash. But if you have a good length of cervix left, personally, I don't anymore. Thank you. At least on a routine basis. Yes, Professor Fratt, yes. I wonder, do you use double-step procedure during the radical trachelectomy? I mean, just taking the sentinel lymph node and waiting, ultrastaging, then after that, do you use just, you can directly use the frozen section? I think the purest answer would be to do it two-step, right? So you do your lymph node, you wait for the final pathology, and you're sure they're node negative before to proceed with fertility preservation. That, I think, would be purest. But then that means going to the OR twice, which is already hard in my center to get in there once. So I think that the compromise there is to do sentinel node mapping with a frozen section. I understand that you may miss some, like, you know, small volume metastasis, but usually 50%, at least, of the lymph node metastasis will be picked up on frozen section. And I think that's as best you can do it in one setting. Okay, thank you very much for, I would like to thank, sincere thank, to the speaker, panelists, and the audience as well. We have had an insightful session today, and through our collaboration, I think, we can make it to eliminate cervical cancer according to the context of our situation. And now, let's give the big hand to the panelists. And may I thank you, all the audience, and may I close the session. Thank you very much.

cervical carcinoma

prevention

early-stage treatment

fertility-preserving

Cervavac vaccine

HPV vaccination

SHAPE trial

simple hysterectomy

radiotherapy challenges

fertility-sparing treatments

molecular profiling

treatment stratification