 I want to extend a welcome to those who have joined us online also. I'm Steve Morrison, Senior Vice President here at CSIS. I head up the CSIS Global Health Policy Center. We're delighted to be hosting this major conference here today, the Global Experience in Addressing Cervical Cancer. And we're grateful to the many experts, several of whom came very long distance to be here with us today, who've come as presenters and as moderators. We're very reliant on our far-flung friends for the quality and success of programs and we're very grateful to all of you. And a special thanks to my colleague, Katie Peck, who's been the pivotal person pulling this program together over the last couple of months. She's done a really remarkable job with remarkable skill and grace and patience throughout and we're very grateful to her. I want to thank a number of other CSIS colleagues who've contributed to this, Sahil Angelo, Catherine Strifell, Addison Smith, Ariane Malacca, Travis Hopkins, Alexi Corey and Namio Thomas on our external relations and Jim Dutton on the copy editing. I want to emphasize that today we're issuing a paper, which I hope all of you have had a chance to pick up and hard copy. It's HPV vaccination in Japan, the continuing debate and global impacts. I'm going to take a minute just to say a few words about this paper since we're putting this out today. And then I want to say a few quick words about the conference and the flow of it and then introduce Dr. Ted Trimble, who's going to kick things off in just a moment. This paper that we've put out, it's authored by Heidi Larson and her colleagues at the London School of Hygiene and Tropical Medicine. It's available in hard copy, it's available online. Heidi will appear in the first panel in a three minute video to talk a bit about the work that she's undertaken. Let me just say a few quick words about this paper. It's a very important and it's a timely update to an analysis that these same authors put together and we published a year ago. It's in a very careful and detailed way. It documents the worsening situation in Japan surrounding HPV vaccine, which is a difficult, complex and confusing situation and attempts to untangle how and why anti-vaccine groups have strengthened their control of the narrative surrounding the HPV vaccine in the past year with quite a bit of influence over media and public attention. And they detail how the medical community itself has become dangerously split as certain personalities have come forward to support claims of adverse effects linked to the HPV vaccine, even in the absence of any evidence of association. There's some detail in this paper about countermeasures by the Ministry of Health and medical professional organizations that have proven to be only very partially effective and the problem of the absence of high level Japanese leadership to solve what is essentially a political problem, not a medical or scientific standoff. And there's some concrete and pragmatic recommendations, which Heidi will detail about reinstating an active recommendation and other measures to reassure and engage with the public and to de-stigmatize this. This report comes out just a few days before Prime Minister Abe's state visit to Washington early next week and the joint address, the address to a joint session of Congress. That visit is going to predominantly be about Asian security and about trade, about the Trans-Pacific Trade Partnership. We hope that there's space for consideration of what the government can and should do to restore an active recommendation in this period. There is a fear that the situation is drifting into a wakefield-like moment that as the scientific community becomes split and we see these claims about causal links that this becomes very, very difficult to reverse and may take years really to resolve. And that danger I think is something that if seen for what it is, can motivate folks to do more and better. Let me just talk a bit about the larger perspective that we're taking here in this conference. We're here not just to talk about Japan. We're here to talk globally about what has happened retrospectively in the last decade or longer and what lies ahead. And there's really three key points that we want to bring across. One is that this is a story of hope and rising success in the prevention treatment and control of cervical cancer globally. And there are several areas in which this is becoming quite apparent. Among policymakers, global specialists, private industry, media, there is a rising consciousness of the burden of cervical cancer and the need to make it a priority. And we'll hear more about that. Second related to that is that there are improved tools and continued evolving innovation. The HPV vaccine became available almost a decade ago in 2006. Innovations continue in screening, treatment, and care. We'll hear a great deal about that, including the pink ribbon, red ribbon initiative at the Bush Presidential Center. There's greater evidence of impact. Our data has improved. Some countries, we'll hear about the UK, Australia, Rwanda, Botswana have demonstrated remarkable progress and determination. Second big point is that this is a story of continued struggle and controversy. It is without, not without, some significant barriers that we need to acknowledge and think about. Here in the United States, uptake among girls and young women, adolescent girls and young women remain at a 32 or 33 percent level, 7 percent among boys. As recounted in the U.S. Presidential study issued in early 2014, a little over a year ago, those low numbers stem from a number of factors, from physician reluctance, from misinformation, from a misalignment of systems. And it's important to continue to remind ourselves of the need to move ahead in our own domestic setting here in the United States to remedy these problems. Sometimes, and I think this is true here in the United States and elsewhere, it's difficult to identify who owns, who in our government or who in multilateral institutions truly owns the issue of cervical cancer. There's a certain level of fragmentation around this and that people struggle with. Another factor is that by definition, adolescent girls and young women are a weak constituency. And the impacts of not receiving adequate prevention, timely screening and treatment are often not manifest for very long periods of time. So accountability has been a problem, drawing a connection between timely interventions and the health impacts. These are barriers that we'll hear more about today. In low and middle-income countries, we know that there's continued questions about capacity, institutional capacity, human capacity, financing, prioritization, questions around costs, access and equity. And we'll hear about those. Then, of course, because vaccines figure so prominently, there are issues around trust, confidence, hesitation that are very much specific to the cultures and societies and norms around sexuality that come into play that require a very sophisticated and grounded understanding of each situation we're dealing with. The third thing that we're trying to do is look ahead and ask, where does this leave us and what's the future going to look like? There's much progress to celebrate. There's much unfinished business that we want to mobilize around. And that's how we're going to proceed today. So we're going to begin with Dr. Ted Trimble, Director of the National Cancer Institute for Global Health who's going to come in over the course of 20 to 30 minutes, walk us through the big picture. And we've asked him to really do that scene setter for us in a brisk but fairly comprehensive way. We're not going to have a discussion around this. We're going to get that data up. And then we'll move to our first panel that Sally Cowell, Ambassador Sally Cowell, will be moderating, which is looking at the country experiences of advanced and evolving and emerging economies. We have an incredible array of speakers for that. Dr. David Salisbury from Chatham House, Dr. Aki Saito from Niigata University in Tokyo, Dr. John Andrus of Saban Institute and Dr. Melinda Wharton from CDC. After that, we'll move into an examination of the Pink Ribbon, Red Ribbon Initiative of the Bush Presidential Center. The first time really, since it was launched three and a half years ago, that such an occasion has been organized here. And we have the leadership, Dr. Duyan Oluwole. We have Sandy Thurman from OGAC, from the Office of Global AIDS Coordinator and Dr. Kennedy Lashimpe from the Cancer Disease Hospital in Osaka, who's joined us. And Lisa Cardia, senior fellow here at CSIS and head of the UN AIDS shop and co-chair of the board will be moderating that. Over lunch, we'll be looking at the developing country experience, at large, with Natasha Bill-Amoria from Gavi Alliance, along with John Yang from the Bill and Melinda Gates Foundation and Susan Wang from CDC. We'll close with a discussion of the future in which we'll bring together a number of prominent personalities from industry, Julie Gerberding from Merck, Donna Alton-Pole from GSK will come in by remote video and Steven Resch from the Harvard School of Public Health who's put together some terrific new data looking at projected costing for expanded delivery. So please join me in welcoming Dr. Ted Trimble to kick things off. Thank you. Thank you very much, Steve. I should start by saying my training is in obstetrics and gynecology and gynecologic cancer. And so I've screened many women for cervical cancer. I've treated women with cervical cancer with both surgery and radiation. And I've kind of held the hand of women with terminally ill from cervical cancer trying to help them die in dignity. So the fact that we now have so many interventions for cervical cancer is a mark of, I mean, a sign of hope for me. My talk is divided into these topics, covering the disease burden, some of the epidemiology and risk factors for the disease, what are interventions as well as some discussion of the uptake of the preventive HPV vaccines. Cervical cancer is the third most common cancer in women. It's a fourth leading cause of cancer deaths around the world. We think it is responsible for 7.5% of cancer deaths. And it may affect as many as 1% of women around the world if you look by age 75. According to the estimates from the WHO's International Agency for Research on Cancer, in 2012 there were more than 500,000 new cases and more than 250,000 deaths. And so that's a relatively high mortality to incidence ratio. This is a world map with the size of the countries inflated by their population. You can see both India and China are very big on this map. And if you look at Australia, it seems somewhat squeezed because population of Australia is relatively small to the land size. Now this is the global burden of cervical cancer. And again, you see the enormous burden in India, to a certain degree in China. You see a large burden in Southeast Asia. Again, Australia is very small. It's been squeezed, but you see in the US is small, higher burden in Mexico. So, and if we look at these figures are, you can see the in yellow is the incidence, in red is the mortality. And if you look in, let's say North America, about 14,000, almost 15,000 cases and about almost 6,000 deaths. And compare that with Africa, where you have 78,000 estimated cases and 61,000 deaths. If we know that in the developing world, probably more than 25% of cancers are associated with chronic infection. And here in yellow is the burden associated with human papillomavirus. The other bars are for helicobacter pylori which causes stomach cancer, for hepatitis B and C which causes liver cancer. And if you look down the chart, you see that in sub-Saharan Africa that yellow band is very broad. That's the burden of cervical cancer. In Central Asia, Pacific Islands, South America, that broad band is the impact of HPV and cervical cancer. We have seen some epidemiologic transitions. This shows breast and cervical cancer. You see four countries, Australia, China, Colombia and Uganda. And as the breast is in blue, cervical cancer is in red. And you can see that as both, as in Australia and China, Colombia, for example, we do see an increase in breast cancer, decrease in cervical cancer. If this is lung cancer rates on the left, cervical cancer rates on the right for a variety of countries. And you can see, for example, as tobacco smoking has gone down, lung cancer rates have gone down. And over the same time period, cervical cancer rates have gone down in the developed countries. So what are the risk factors for cervical cancer chronic HPV infection? I think it's really important that we understand that this is a very common infection that most men and women are exposed to the HPV virus at some point in their life. They clear that infection without adverse events. High risk subtypes are 16 and 18. We know that there are increased risk factors associated with cigarette smoking and immunosuppression, particularly among HIV positive individuals and those who have to take chronic steroids. There are also some reproductive and hormonal risk factors. One is high parity. And that's one reason why in the developing world we have seen decreased risk of cervical cancer because family sizes are smaller. And there's also an increased risk with long-term use of oral contraceptives. So in terms of interventions, today, as Steve mentioned, we can treat HPV infection, we can screen for and treat pre-invasive disease before it can progress to cancer. We can treat locally invasive cancer and we can treat the symptoms of progressive and metastatic cancer. And we've made this progress really over more than 100 years. I'd like to start the story with this slide from highlighting the contribution of Friedrich Sertuner, who was a German pharmacist. And he was the first person to isolate morphine. And of note, it was first sold by Merck, a company important to us now, in 1827. Another advance was in 1842 when this gentleman, Dominico Rigoni-Stern, looked at cancer deaths in his home city of Verona. I do not need to remind you that this is a site of where Shakespeare plays Romeo and Juliet, which is a story in part about, shall we say, adolescent sexual activity. But in any case, Dr. Rigoni-Stern noted that nuns were more likely to have breast cancer than other women. And the nuns were less likely to have cervical cancer than other women. So this was the first suggestion that cervical cancer might be associated with sexual activity. We've had treatment for cervical cancer for more than 100 years. The radical hysterectomy procedure was developed really around the 1890s by surgeons in Baltimore and Vienna. After the identification of radium by Marie Curie and Pierre Curie, who you see here, within two or three years it was being used topically to treat women with cervical cancer. We've had screening for cervical cancer for more than 50 years. This was developed by Dr. George Pappan-Nicholau. And over about a 15-year period, he evaluated Pap smear to see if it might be useful to look at a variety of gynecological conditions and identified it as something that could pick up a preinvasive disease. And this shows on the left, normal cervical cells. You see that the nuclei, the little black dots, are normal in size, and the cytoplasm, which is the pink or blue kind of misty material, is relatively large compared to the little dots. On the right-hand side is the abnormal pap smear, and you see there that the nuclei are very big, and the cytoplasm is relatively small in size to the nuclei. Now I also like to show a picture of his wife. She worked at Cornell with her husband, and as part of their combined research, she underwent daily pap smears for 20 years. So her contribution is major, and this shows her receiving an award from the King of Greece for her efforts. Now these are slides that, or a slide that my wife lent me, and my wife happens to be a GYN pathologist, immunologist and gynecologist working on therapeutic HPV vaccines. So this shows on the top the abnormal pap smear, a normal cervical biopsy, and a normal appearing cervix to physical exam. After HPV infection, we see changes in the cervix, both in the pap smear on top, in the cells in the cervix, in the middle, and then in the visual exam in the center. And then this is invasive cervical cancer all the way over on the right, with grossly abnormal cells in the pap smear on top, evidence of invasive disease in the center, and a very abnormal cervix in physical appearance. So treatment of invasive disease, we've learned that if we destroy or remove the abnormal cells, we can use a variety of techniques for that. We basically take out the small portion of the cervix, which you see here outlined at the bottom. Surgical treatment of invasive disease, for early stage disease, a hysterectomy will generally suffice for a radical hysterectomy is done for a slightly more advanced disease. We've learned about external radiation for invasive disease, combined with intracavitary radiation. This is a, it's not a short treatment. External beam is generally given for four to six weeks and the internal radiation can be over as short as 24 hours or as several outpatient doses. Another advance, I think, has been the development of effective hospice care and here I like to show the side of Dame Cecilia Saunders, who really helped us as a global community understand the importance of effective palliative care and linking that palliative care in the hospital to the hospice and in the home. So combining her efforts as well as the fact that we had morphine means that we can take good care of patients who were dying from cancer now. The causative agent, namely human papillomavirus, was identified by Harold Zerhausen. In 1976 he published his hypothesis that HPV causes cervical cancer. He started then to identify some of the different subtypes, including HPV6, HPV16, HPV18, and as most of you know in 2008 he was awarded the Nobel Prize for these efforts. And after we identified HPV as a causative agent, we could then study the molecular biology of cancer and learn that in fact this virus caused a variety of diseases. Cervix was one and the most important numerically, but it's also responsible for anal cancer or many anal cancers for some vaginal and vulvar cancers, some penile cancers, some cancers of the oropharynx as well. And this slide is similar to one I showed earlier, but it shows the worldwide incidents of cancers attributable to infected agents. So that includes stomach cancer, includes cervical cancer, includes liver cancer. And we do have vaccines now for cervical cancer with HPV as well as for a vaccine for hepatitis B which causes many cases of liver cancer. Primary prevention, abstinence from sexual activity, obviously in theory might work. Barrier protection during sexual intercourse does seem to reduce the risk of HPV transition. And we now have the development of prophylactic HPV vaccine. This came out of the work of four academic laboratories, one here in Georgetown, one at the National Cancer Institute, one at the University of Rochester, New York and at the University of Queensland. Those four groups then got together and jointly issued a non-exclusive license to Merck and Glaxo. This is Dr. Ian Frazier who has led the efforts at University of Queensland and was named Australian of the Year in 2006. And the Australians I think are very proud of his efforts and that may be why they have some of the highest vaccine rates in the world. This is our colleagues, Doug Lowy and John Schiller. Doug is now our acting director of the NCI. And they in December were given the US National Medal of Technology and Innovation by President Obama for their work in developing the HPV vaccine. This shows you what the vaccine looks like. It's what's called an empty viral capsid. It's constructed of the L1 protein. So the bad DNA which is normally inside the capsid is entirely missing. It's very efficacious in terms of reducing infection. It's given in, currently the recommendations are to give it in three doses over six months and before the onset of sexual activity. So this shows you the quadrivalent vaccine which is called Gardasil made by Merck contains four different of these virus-like particles for HPV 16, 18, 6 and 11. The bivalent called Cerverix made by Glaxo contains a mixture of two of the 16 and 18. Steve mentioned the US FDA approved Gardasil in 2006 and Cerverix in 2009. In this country, vaccination is recommended for boys and girls by the American Committee on Immunization Practice. It's been recommended by the WHO Strategic Advisory Group on Immunization. And it's been recommended by the Global Alliance for Vaccines and Immunizations. There've been extensive post-licensure safety surveillance in the United States and around the world reported from both Merck and Glaxo. What are some of the challenges? In the developed world, the cost is a challenge. It's $150 a dose for three doses plus the administration costs. In addition, we have not had until recently vaccines appropriate for adolescents, so we've had to build those, that infrastructure. There have been a number of studies looking at school-based approaches or clinic-based approaches. We do have some other adolescent vaccines, particularly for tetanus, whooping cough, ninja caucus. So we do have other vaccines now. We want to give our children of this age. And as we'll hear about today, societal and parental acceptance of the vaccine has been a challenge in some settings. This shows a variable uptake for the HPV vaccine. The red is the girls who've gotten one dose. The blue is girls who've gotten three doses. And you can see we have very high rates in the United Kingdom. And there, they are using a school-based approach, high rates in Australia, similarly a school-based approach. In the United States, we have lower rates and we are using a clinic-based approach. France is also using a clinic-based approach. If one looks at the trends in vaccination rates, you see that we are still behind compared to the other vaccines that are appropriate for this age. And you see that relatively high rates for the T-DAP, the other, meningococcal vaccines, and then the lower rates are for, in blue and red, are for girls. The dotted, I mean, the dashed line is those girls who've got at least one dose. The blue dots are girls who've got three doses. And similarly for boys, it's lower. For boys who've got at least one dose and boys who've got three doses. So we know that we have to figure out how to get more boys and girls vaccinated against HPV in the U.S. So I'd be happy to answer any questions if we have time. If not, we'll proceed with the program. Good morning, ladies and gentlemen. My name is Rosemary Segeir. I'm president of an organization called Hope for Tomorrow. Thank you so much, Doctor, for your wonderful explanation. I come, I'm best here in Washington, D.C., and I come from Kenya. Last year, for the last two years, we've lost about 10 families in Kansas, both men and women. And we didn't know, we came to know when it's over. So by the time they come from Kenya, they have to go to Kambala, to Uganda to go and get treatment. By the time they get there, they say we can't even, even rotation itself is, it was not possible for them to get because it's very expensive to go to Nairobi and to get treatment. So how do we work with you, especially looking at the prices, 150 affordable testing, affordable treatment and affordable, you know, equipments that can help people in the rural area because I focus in the rural areas of Kenya, DRC and other countries. How do we come, because there's killing people there and by the time they know it's already developed, no treatment, no vaccine, nothing. So I would like to know that how, if this could be affordable for the poor people, I can say, thank you. That's a great question. We are working closely with a number of partners in Kenya. We, last year we did organize a cancer stakeholders meeting in Kenya, bringing together the Ministry of Health and the Chemri and the US CDC, the various US universities working in Kenya to try to think about cancer control and try to figure out how we could help Kenya set up a cervical cancer screening, help improve access to treatment. I know this is a challenge, particularly for radiation therapy. The Moore University in Eldorette, they have the bunkers built for radiation but they have not been able to get the radiation unit in place. And I know earlier this spring, all the radiation machines in Kenyatta Hospital were broken. So this has been a big effort and we're trying to work with the International Atomic Energy Agency. But this one reason why we're having this meeting is to see how we can, as a global community, work to bring down the cost of HPV vaccines and certainly Gavi has been very effective or had a very effective partnership with Merck and Vlaxo on this. I know the Gates Foundation is trying to improve the infrastructure for other HPV vaccine manufacturer. We're trying to work, as I said, with the International Atomic Energy Agency to improve access to radiation therapy around the world. Dr. Trimmel, I'm Dr. Joe Geary and I work in Haiti. And I'm wondering if, is there some hint that one dose will provide some immunity with the bivalent vaccine? And also, is there a hint that giving the bivalent confers immunity against some of the other HPV viruses? Great questions. There is good data, particularly from a number of studies, including the NCI work in Costa Rica, that two doses is as good as three doses. And the European Medicines Agency has approved server X, I think, for two doses. And so we at the NCI are proposing a study that we hope will be able to get support from the Gates Foundation to join the money we would put into it that would actually randomize girls in Costa Rica, and I think the majority of the study will be in Costa Rica randomizing them between wonders versus two doses and between server X and Gardasil nine. And their goal is to have that study open in addition to Costa Rica and the United States, Haiti, and possibly a site in Africa as well. So we're excited about the data suggesting that one dose may be as effective as three doses. Thank you, Ted. That was really terrific. Ted will be with us over the course of the day, and so I hope we can pull you in on a number of other occasions over the course of the day, but please join me in thanking Ted. We're gonna move right away into the first panel, so I'd like to ask Ambassador Cowell, Aki, Melinda, John, and David to come forward. Well, you can all just come right up here. Well, good morning, and welcome to our first panel discussion of the day, and I believe we're, Katie's gonna kick us off with a message from Heidi Larson, who is the principal author on the report, which has been issued by CSIS today about what's been happening in Japan over the last year. Hi, I'm Heidi Larson. I'm sorry not to be with you at the meeting today. I just wanted to share a few words coming back recently from Japan, where I met with public health professionals, researchers, academics, the Ministry of Health to discuss the current situation of HPV vaccination in Japan. What really struck me was this absolute growing frustration among health professionals, particularly of Strikson. Hi, I'm Heidi Larson. I'm sorry not to be with you at the meeting today. I just wanted to share a few words coming back recently from Japan, where I met with public health professionals, researchers, academics, the Ministry of Health to discuss the current situation of HPV vaccination in Japan. What really struck me was this absolute growing frustration among health professionals, particularly of Strikson Gynecology and Pediatric Associations, who together are starting to connect. And I have here a petition of over 250 signatures that are saying, we need to change. We want support. They feel actually not just undermined, but really let down by the government's silencing of a proactive recommendation of what they believe is a really important vaccine. Did this petition ever make it into the media? No. And my second point is about the media and about the fact that today it's been largely absent these growing voices of positive support for HPV vaccine. And somehow these silent majority, as they were, who are starting to write the petition who are appealing for support to a more positive voice need to be captured by the media. How can we support that? And the other part of the media voice is that it can help build a confidence of political support. So the third point is about high-level political support to this issue. So we have the health professionals who are growing and increasing their positive sentiment. We need a media that listens to a multiple chorus of voices, including this emerging choir and chorus of the positive health professionals and others. And then the third thing is high-level political leadership that says that we support this. We give people the choice. We are not going to silence the proactive recommendation, but you have a choice. And we think this is a good thing if you want it. And this is a continuous cycle. There is no single solution to this issue. It needs a multiplicity of voices from high-level political leadership. Media attention to multiple voices and an engagement of the existing silent majority who are indeed quite positive about this vaccine. Thank you. Thank you. Up here on the stage, and then we're going to throw it open to all of you for questions. So I think we've already heard that today's event really comes at a critical time in the global fight against cervical cancer. As you're well aware, and Dr. Trimble already told us this morning, it's one of the few cancers that we know how to prevent it with vaccination. We know how to detect it early with tests like pap smears and also much more affordable tests like visual inspection with acetic acid and with HPVDNA testing. And when caught early, it's highly treatable. I listen to our colleague from Kenya and feel for these kinds of experiences because we know that in the United States, our five-year survival rate from cervical cancer is 91%. So highly treatable when caught early. And yet as Ted told us, 266,000 women lose their lives from cervical cancer every year and 87% of them live in low and middle income countries. And unlike in the United States where it tends to be a disease which takes women in their 60s and 70s, in low and middle income countries, they're women in the primes of their lives. They're 20s, 30s, and 40s, wives and mothers dying of a perfectly preventable disease when their families and their economies and their countries need them the most. So I present my own bias out here. What I'm mainly interested in is low and middle income countries where the burden is the greatest. And I will be asking the panel to not only tell us the experiences in the developed and emerging economies but also the lessons we can learn from the mistakes and the mistakes we may be able to avoid from the experience that we've had in these countries. So we need action very urgently and there's a tremendous amount to be learned from advanced and emerging countries which have not had significant resource constraints that we face in low and middle income countries. But that's not to say that we haven't faced obstacles in addressing cervical cancer. And our panelists will discuss this today. Even in the most high resource nations have faced significant barriers to implementing comprehensive cervical cancer vaccination programs. And as Ted mentioned in the United States, for instance, HPV vaccine coverage rates continue to hover around 30%. Heidi mentioned political will, the role of the media and also the medical community in the vaccine debate addressing cervical cancer. So that even in the wealthiest nations it remains an ongoing issue. Advancing the fight against cervical cancer challenges us to develop programs that reach women across their life cycle and develop life-saving messages and campaigns that are relevant for adolescents, parents, educators, NGOs and leaders at all levels of the health system. But by learning from experience in advanced economies health advocates and officials in low and middle income countries can better understand the obstacles that will have to be surmounted in the future to be successful. So our panelists this morning will share experiences from countries ranging from the US and the United Kingdom to Latin America, India and Japan. What has worked? What has worked well? And what are the areas we need to improve? My own organization, American Cancer Society has made cervical cancer our number one global priority. And we believe the issue merits prioritization on the post-2015 UN development agenda which is currently under study and under development. I think cervical cancer is very important for itself for the mortality and morbidity that it is presenting the world. But I also think it's tremendously important is a bridge between the communicable diseases and the non-communicable diseases and the way we may get the global development community to inch its way toward doing more on non-communicable diseases. So I'm really looking forward to a robust discussion here this morning. And I'd like to briefly introduce our panelists. Their biographies have been handed out to all of you and we are behind time. So I'm gonna be very, very brief. I'm gonna start with Dr. Andrews in part because he's gonna need to leave by 1030 at the latest to catch a flight. So Dr. Andrews, can we ask you for a few opening comments? Thank you very much, Sally. I'm delighted and honored to be here. I wanna thank the organizers. This is a topic near and dear to my heart because in a former life as the director of the PAHO Immunization Program and subsequently the deputy director, we worked very hard with our partners and member states to accelerate prevention and control of cervical cancer in Latin America. And what was always, and the Caribbean, what was always mind-boggling for me was the fact that in the U.S. and Canada and Europe, there were very effective screening strategies that were remarkable public health stories in preventing cervical cancer, but did not grab and did not take hold in the middle income countries that we were working. So it was always very hard. So it was a godsend when the first vaccines became available, especially when we consider the disease burden. PAHO currently estimates that some 68,000 women in Latin America and the Caribbean develop cervical cancer and greater than 20, 28,000 women died of this disease in the year 2012. In Brazil alone, their National Cancer Institute estimates 15,000 new cases and 4,800 deaths each year. Recognizing that cervical cancer is one of the leading cancer causes of premature mortality among women. And as Sally said, young women in their prime in countries of the Americas, I was very fortunate to have had the opportunity to work on PAHO's PROVAC initiative. PROVAC was about strengthening national capacity to make evidence-based decisions on the new vaccine. And it did so recognizing the importance of integrating the vaccination approach with the screening strategies. And we did so more than 10 years ago. Supported by the Bill and Melinda Gates Foundation, the mission, as I mentioned, continues to build national capacity to make these informed evidence-based decisions. And today, we now have 20 countries that have introduced the HPV vaccine into their national immunization program. Last year, in 2014, Brazil was one of the more recent countries to introduce the vaccine. And as a result, some 80% of our young girls living in the Western Hemisphere now have access to this life-saving vaccine. This intervention will have a major impact on the health of today's girls and tomorrow's women by preventing the infection and reducing the mortality. All evidence as well shows that the vaccine is safe and effective. As Ted mentioned, currently the HPV vaccines that are available target the two HPV oncogenic type 16 and 18 that cause about 70% of the cancer cases. The virus is transmitted by sexual contact causing infections that over time evolve into cervical cancer. And these vaccines are highly effective in preventing the infections with the virus as long as they are administered before the onset of sexual activity. And so to that end, the WHO recommends the target group for vaccination to be girls nine to 13 years of age who have not yet become sexually active. And because cervical cancer takes years to develop, the full effect of the vaccine will not be seen for some time in many countries. So in the meantime, young women who are not protected by the vaccine will continue to die. So accelerating access to this vaccine requires accelerating screening programs as well. The bottom line is that the vaccine does not replace screening tests for cervical cancer, whether it be a pap smear, the HPV antigen test or such techniques such as the visual inspection with acetic acid, a technique that many rural isolated communities may benefit the most, particularly in middle income countries. So with regards to the vaccine, there are a number of challenges. One key challenge has been to ensure the high vaccination coverage is achieved and maintained. Many countries are reaching 80 to 90% coverage with the first dose, but few are able to sustain that high level coverage with second dose. The PAHO Technical Advisory Group for Vaccine Preventable Diseases some few years ago and more recently the WHO Strategic Advisory Group of Experts recommended that only two doses rather than the original three recommended doses are needed, thus providing a huge cost savings for countries. However, despite this cost savings, many countries in our region are still using the three-dose strategy and are slow to convert. And it serves as an example for me that once policy, you fight that battle, get a policy decision, but to refine it may be even more difficult than getting the policy in place in the first place. So an important lesson learned. Sue Goldie and her team at Harvard, I know Steve Rush is here a few years ago did a study that estimated that approximately at $4 a dose vaccination becomes cost savings. In other words, when a country is able to introduce a vaccine at this cost, they will actually save money in the expense of cancer treatment and other costs. And I'm struck by these analysis. I think the effects of such analyses are immeasurable in terms of accelerating policy. Another example when the Caribbean countries found out that for every dollar they invested in the elimination of congenital rubella syndrome, they were saving $12 to $13 in the healthcare costs of these young babies who for the rest of their lifetime are gonna suffer from either mental retardation, hearing loss, you name it with the syndrome, that there was a cost saving. So the rest is history. The last congenital rubella syndrome case in the Americas was 2009. Another challenge in developing countries has been monitoring vaccine impact. More affluent countries have the resources and commitment to do this important work. And in these countries the vaccines impact so far has been very encouraging. In the United States, for example, infections by HPV types targeted by the vaccine have declined by half. And data from Australia and Denmark show a significant reduction in pre-cancerous cervical lesions in vaccinated women. However, few countries are monitoring vaccine impact on pre-cancerous lesions and general awards. And the anti-vaccine movements are growing. They're gaining ground. Even in Latin America and the Caribbean. So having accurate data on vaccine impact will provide useful ammunition against such movements, let alone reassure those high level political leaders that their nation's investment, their nation's financial resources are being well spent. And unfortunately, as I mentioned, these anti-vaccine movements in Latin America and the Caribbean are continuing to grow and be very active. They have misconceptions about many issues, including safety, duration of protection, and vaccine effectiveness to prevent cervical cancer. It was Mark Twain who once said something to the effect, you are entitled to your own conclusions, but to not to your own facts. And so to that end, we think there is an incredible need in all countries to have continuous, sustained, effective health communication that will also have highly effective advocacy and the other communication strategies to the public as well as to the health practitioners about the evidence and value of HPV vaccines. Such strategies will also help in sustaining the demand for vaccination. Globally, some 80% of the cancer deaths are occurring in developing countries when screening programs are not existent or if they exist, they're often fragmented and not functioning well. In reality, cervical cancer is a disease of poverty. Families living on the margin, struggling to get by with adequate shelter and food face incredible challenges when relatively young women, many of them mothers succumb to cervical cancer. Certainly the challenges exist, but we have the opportunity and certainly highly effective tools to overcome them. And regarding those opportunities, everyone in this room can ask themselves, what more can I do? What more can my agency do? What more can we do working together to ensure those girls most in need are receiving the HPV vaccine and that appropriate strategies are also accessible to all women at appropriate ages. In ending, I'd just like to share with you one of my favorite quotes, it's by E.B. White and he once said that civilization is organized kindness. Efforts to prevent and control cervical cancer certainly exemplifies organized kindness in the truest sense and it's gonna require and all of society approaches was mentioned by other speakers. And but together we can do it. So thank you madam. Thank you. Thank you. Next I'd like to introduce Dr. Akajito Saito, who's the professor and chairman of the department of pediatrics at Negata University Graduate School of Medical and Dental Sciences. And he'll talk to us about the cervical cancer situation in Japan. And I really thank him for coming all this way and also for putting himself on the spot in the middle of a very controversial season in his own country. So Dr. Saito. Thank you very much, sorry. It's a pleasure to be here today. And thank you very much for giving me the opportunity to be here. So I'm going to briefly summarize what's going on in Japan. The current HPV vaccines, data set issues which we have been facing. So this is the immunization schedule recommended by Japan Pediatric Society. As you can see here, the orange is the vaccines included in NIP, National Immunization Program. And the green one is called Voluntary Vaccine, which the patients need to pay out of pocket. For the last several years, it has been improving. We call it vaccine gap, which means that our immunization system is not well advanced compared to the one in other developed countries. However, the world's characters are a little bit small, but we have cable vaccine, we have pneumococcal conjugate vaccine, we have rotavirus vaccine, we have the IPV vaccine. And at the end, we have the HPV vaccine, yes. So we have the, this is recommended at between 11 and 12 years old. And it is included in NIP. So this vaccine, the HPV-2 was introduced in December 2009. And the government decided to provide temporal public funding, which helped the teenager to receive this vaccine without money out of pocket. Oh, I'm sorry. So then, yes, HPV-4 was introduced in August 2011. And after the introduction of HPV-2, four years later, both vaccines were introduced into the National Immunization Program. It was very successful. And however, things happened. And we'll tell you more on the next slide. The active recommendation was suspended in 2003 in June, which was a two months after the introduction into the National Immunization Program. So let me tell you what happened. Why suspended? Active recommendation was suspended from the patient side and government side. And the patient side, the major issue was the March 2013, 30 cases of chronic pain syndrome. We say complex regional pain syndrome were reported. And that image and video of the patients, especially the one with Estonia, was on TV and internet worldwide. It was a very significant impact for them. And the government decided to suspend active recommendation of HPV vaccine. And the cases were accumulated in September. It was reported 130 cases of CRPS or motor disturbance. And the government reviewed all the cases recorded and then concluded that it is a convergent disorder, not neurologic disease. It's not toxic mediated. It's not immunologic disease. So they ruled out the possible other causes. Differential diagnosis for this disease condition included macrophagic myofasciitis, fibromyalgia, chronic fatigue syndrome. Those diseases are difficult to make a diagnosis. But the government vaccine adverse event committee concluded this is not related to vaccine. However, the cases were accumulated in March 2014, 617 severe adverse events were reported, including these CRPS motor disturbance and among them 176 cases were accumulated. And then in August, still under the suspension, the government decided to establish a medical system to support those patients suffering from the diseases and also made a easier reporting system for patients. So government did their best to try to help them. So far, including mild cases, severe cases, related, unrelated, total of more than 2,500 cases are currently investigated. And as of today, active recommendation of HPV vaccine has been suspended. So this is that kind of summary what's going on in Japan right now. Thank you, Dr. Saito. We'll get to some questions about that. I'm sure both myself and other panel members. I'd like now to turn to Dr. David Salisbury, who is the Director of Immunization at the Department of Health in the United Kingdom, who will talk about some real success stories in the United Kingdom and Australia. UK. Can I do them myself? Thanks. What I do need to know is how to get on to the presentation. I'm not doing anything. That's a beautiful screen. Hi, I'm hot. Okay, okay, we're nearly there. No, can we go back please? You've already seen the presentation about twice. Okay, well, it's my pleasure to be here and in the space of a few minutes, I will try and fly through some of the key elements of the UK Immunization Program that I believe have led to its success. The background to all of this is that the program started in 2008-9 and the immunization is free for all females at less than 18 years. The program is provided in schools, apart from the very initial catch-up program for the oldest girls who were out of school but under the age of 18 and they were vaccinated in primary care. But after that part of the program finished, all of the HPV vaccinations provided in schools. The immunizations are provided by teams of school nurses that visit the schools at pre-arranged dates and they're now twice a year, whereas previously they were three times a year. The consent forms are sent home with the girls in advance of the schools being visited and the girls are asked to give the consent forms to their parents that they then read the information and they complete the consent forms and then bring them back to school and then that authorizes the program to go ahead for that girl. Now, many of those consent forms are probably still in satchels or in pockets somewhere and a number of them are probably up in trees but nevertheless it's a very effective way to get coverage returns on the girls. Now, the girls can give or withhold consent if they understand the consequences of so doing irrespective of age and that is established in UK law. So it doesn't matter how old the girl is, she can countermand her parents' wishes or she can acquiesce with her parents' wishes both to be vaccinated or not to be vaccinated and the data are uploaded to the Department of Health on a monthly basis on a semi-automated process. So within roughly a month of each month the national data are available by locality so that the program can be performed managed. Here's what we did. We started in 2008-09 and the vertical column at school year eight is for the 12 to 13 year old girls so every year they are vaccinated during the school year. In the first year of the program, 2008-09, if you now look at the right hand side you see that we vaccinated the oldest cohort that is the 17 year old girls before they left school after which time they would have graduated out of the program. Now, the reason you see that laid out on a grid like that is that we were planning to do the catch up over four years but in fact we did the hold of the catch up in effectively two years and so we vaccinated year 10, 11, 12 and 13 all in the second year of the program which was a huge undertaking so that by 2010 we were just doing one cohort a year with no catch up. Critically important was setting the communication agenda and we did this based on a great deal of communication research that we did before we started the program. We interviewed parents of 10, well no we first interviewed parents of eight, nine and 10 year old girls and established that they did not wish their girls to be vaccinated at that age and so we moved and reevaluated vaccinating at age 12 to 13 and found very strong support. So a great deal of communication work was done before the program and it identified the program that would be best accepted. So we identified the ideal and that's ideal for parents not necessarily for immunology but we identified the ideal age of vaccination, the key messages and we developed and evaluated the communication materials. Introducing the full HPV story led to confusion and indeed rejection. The cervical cancer story is significant and is easily understood. The key message was that HPV vaccine protects against cervical cancer. Parents were reassured that the vaccine will be part of the routine immunization program and they view immunization as protecting their children against disease they were not interested in the viruses. And so from all of this came talk about cancer and that was the key message that we communicated. I'll show you a series now of the advertisements that we used and along with all of the hard copy material there was a great deal of social media based material and I'm just going to show you for the greater part the hard copy material. I want you to look at the consistency of messaging in all of these advertisements. The key theme was armed for life. That didn't work in one part of the United Kingdom where it could not be used. And in Northern Ireland they said they needed a different strap line. And we were sensitive to that. But look at all of the girls and the logo you'll see that coming up in each time on their arms and essentially you see the key points in the text up on the left. So look again and you'll see the same sort of imagery the same colors, the same themes and the same story being reflected. Satellite TV in your bedroom and all of this came from market research. We asked girls what were they interested in what were key things in their lives. Satellite TV in their bedroom, skinny jeans and the vaccine against cervical cancer. Only one of these must haves is really a must have. Everything here is about cancer. Here for the older teenagers arm yourself for life again the same message and on the right life is full of difficult decisions and it lists some of those I think curly or straight hair. You'll just see some of those. And thankfully this isn't one of them protecting yourself against cervical cancer. And here the core piece of the web based material that girls could access look at the consistency of all of these messages in the colors that are used the fonts that are used and the logo that's used. If you go down to the bottom right hand side you put in when you were born and it tells you when you would have had your when you were due to have your doses of HPV vaccine. Here material for women who were of an age who were likely to have teenage daughters. And this builds on market research about the way in which girls and their mothers communicate or not. So the mother says how was school fine and how did your jab go fine and how did it feel fine and did you mom it's just a jab no problems. Okay then fine. And that came from the market research that these are two groups of people whose communication is often on a monosyllabic basis. Let's look at what we achieved. And what you're gonna see now are multiple graphs of coverage by cohort of girls. So the very first graph that you'll see is the first dose of vaccine given to the 12 to 13 year old girls at the very beginning. So we went into this program you could see the first dose being given over the autumn time and the first dose of the first cohort the very beginning of the program we're up at over 80% coverage. Second dose is pretty much the same as the first dose and the third dose not quite so good but it's still over 80% coverage for the very first time we use this vaccine. Second year not so bad that was the year of the flu pandemic so we weren't doing quite so well. Third year we're back up at well up into the 80s for the first dose, second dose, third dose. The next year we're even higher for the first dose look at the gap between first and second dose it's almost nothing and there's the third dose and then the most recent year with full year data there's the first dose look at that there's the second dose and then there's the third dose. Well you can do better than that and you can do better than that if you vaccinate in schools and there's the final 2013 data first dose 91%, third dose 86%. Why schools? Because you have an inbuilt catch up program. So left hand side shows you the year cohort middle column shows you the coverage of the third dose at the end of the school year and then on the right hand side you can see what happens when you go every year back into the schools. So if you go back into the schools every year you can get the girls who you didn't vaccinate the year before. So every year that you can do this you're gaining another between two and a half and five and a half percent coverage. So schools are the ideal place in which to provide this program. When I did a review of immunization with HPV by source of immunization you get two very clear communities of results. You get high coverage in those countries that vaccinate in schools. You get low coverage in those countries that vaccinate outside of schools. And I'm sorry there seems to be a conclusion slide missing but it doesn't matter. It really was to say that two things made the difference. The first was you just talk about cancer. It seems impossible to think that people would reject a vaccine that protects against cancer. And the second is you implement through schools. Thank you. Thank you. Well we've been all over the world. I know Dr. Lenders has to leave. I want to thank him for joining us this morning. We've been all over the world. We've looked at places where it's been very difficult. We've looked at places such as the United Kingdom where it's worked very well and what are some of the lessons from that. Now I'd like to bring us back home and ask Dr. Melinda Wharton who's the director of immunization services division at the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention to talk about the U.S. experience. Dr. Wharton. Thank you and I appreciate the invitation to be here even if I do have to follow David Salisbury. So in the United States we don't have a national health system. We have a system for pediatric immunization that's based on shared financing between the public and private sector. And this system really goes back to the early 1990s when the Vaccines for Children program was created which provides federally purchased vaccine for children and families who don't have insurance for our Medicaid as well as a small number of other children. And for families with insurance even before the Affordable Care Act insurance generally did a pretty good job of covering childhood immunization. Since the Affordable Care Act has passed and the provisions have been phased in it is even better. But between the two, the Federal Vaccines for Children program and the private sector insurance programs pediatric immunizations are generally covered. And so these financial issues of the cost of the vaccine should not be a major problem in coverage in the United States but it does complicate vaccine delivery. And the fact that we don't have a single payer is one of the reasons why we are not able to do as well as a country with a national health system can in terms of school-based delivery. This whole issue back who pays really is a big driver for us and somewhat of a limitation in terms of how vaccines are actually delivered. But in spite of that we do pretty well with childhood immunization. We generally have high coverage which we have been able to sustain over the years in spite of all of the vaccine safety issues that have played out in the public realm. So when we began to discuss vaccines for use in adolescence and in the United States it wasn't just HPV vaccine. It was also a tetanus diphtheria and a cellular pertussis vaccine dose that was envisioned to be given at 11 to 12 and also a meningococcal conjugate vaccine that was planned for the same age. When we began thinking about how to give these vaccines to adolescents a big unknown for us had to do with healthcare utilization. Were kids this age actually going to the doctor in a way that they could get vaccines from their healthcare provider? And certainly there is an anything like the well child visits that are such an important part of pediatric care for young children. But there were doctor visits. If not well child visits, there were sports physicals, there's other dermatology visits. There's all kinds of healthcare utilization that does go on at this age. And we thought that if providers were willing to take advantage of all of the visits available that we probably could at least get the first dose of the HPV series as well as these other vaccines given. And in fact, when these recommendations were made in 2005, 2006, it has become clear that we've done a really good job of getting the Tdap vaccine and the meningococcal vaccine added into our program. Now, we don't have the flip the switch and it happens kind of system that they've got in the UK. When we have a new recommendation for a vaccine it's implemented over several years. We have nice increases in coverage in most circumstances and after a few years we have high coverage. And that's really what's happened with the Tdap dose that's recommended 11 to 12 and it's what's happened with the meningococcal conjugate vaccine. We now have over 80% coverage with the tetanus diphtheria and mesolyl overtussis vaccine. We're close to that with meningococcal conjugate that you already saw our coverage data in Dr. Trimble's presentation. It just hasn't happened with HPV vaccine. Between 2011 and 2012 with coverage for girls for at least one dose or three more doses we had no change at all. And we were pretty well stalled out in around a third of girls had gotten all three doses and around half had gotten on this one dose. It was really very disconcerting to see for a life saving vaccine that we were doing so badly with incorporating it into our routine program. Of course we now recommend the vaccine not only for girls and young women but also for boys and young men routinely since 2011. There's three different products that are now licensed and recommended for use in the United States. And a lot of work around how we keep up and do better and I do think the complexity of our financing system and delivery based on healthcare provider visits is does make it more complicated than a national system that can do school-based clinics. But I don't think that's actually the primary problem because we're doing so much better with the other two vaccines. I think there is something specific about this one in the United States that has been difficult to implement in our routine national program. And that appears to be primarily the absence of routinely a strong provider recommendation. And unfortunately it frequently is presented as optional as something that's not needed the same way the other vaccines are needed. And so we've been working very hard with our colleagues in the American Academy of Pediatrics and with other partners to try to provide providers the support so that they're comfortable making that strong provider recommendation. You know, it is a really interesting question what the underlying causes of this are. And I think there's probably several things. One of them may be that some providers simply are not convinced that the vaccine is needed at the age we recommend it, which is 11 to 12. But of course they could be giving it at Old Regis and they're not really doing such a good job there either. I think that there is some reluctance on the part of providers to initiate a conversation about something that they don't really want to talk about. But of course they don't have to initiate that conversation. We don't get into big conversations about how meningococcal disease is transmitted before we get the vaccine and there's no reason to on this meter. So we're working to try to strengthen the provider recommendation. I am hopeful we'll make some progress. Our coverage in 2013 was a little higher but we'll see if we're able to. Well, the American Cancer Society recently received a grant from the CDC because we're such a grassroots organization out there and 5,000 communities across the country to begin to talk about to providers but also to parents. And I think the lesson that Dr. Salisbury presents to us that we need to be talking about cancer and this is a cancer vaccine. Maybe we need to get through. I would like to ask you one question and then ask the others a couple too. Do you think in shifting the focus from sort of just girls where it's been in countries to boys and girls, is that gonna help us or hurt us? Is that gonna take the specialness of this away? Well, I think that in terms of including things in a routine program any time everybody is included it makes it easier. On the other hand, by broadening the cancer discussion beyond cervical cancer to all of the HP-related cancers generally because they're less well-known with boys. I think that is a little bit more complicated and certainly our communication has been on the cancer message. There's, we've got some wonderful advertisements that show a young teen or preteen and if there were a vaccine against cancer wouldn't you give it to your child? And the answer to that absolutely should be yes but in fact it's not happening in Japan. Great, thank you. Dr. Psycho, let's turn it back to you. A little bit you outlined the situation in Japan. What do you think the lessons are that you've learned about correcting rumors or how has this become politicized and how could we unpoliticize it and how can we, I mean Dr. Anders who had to leave mentioned that there are now anti-vaccine, particularly anti-HPV vaccine movements growing. I've heard about them in France, certainly in Colombia and other Latin American countries. How can we prevent the Japanese experience from happening in other places? Can you advise us? Sure, before starting I just wanna to mention briefly about the background of the sensitivity to vaccine adverse event and adverse reaction in Japan. As you may know that historically we had issues related to safety of vaccine, including MMR vaccine, high incidence of aseptic meningitis caused by a month's component of the vaccine. We had issue with Japanese encephalitis vaccine. We had issue with simultaneous vaccination of heave and hemococortrait vaccine. When the issue happens then although all those vaccine were withdrawn from the schedule and then we fight against it. So basically Japanese tend to be very sensitive to adverse reaction or adverse events of the vaccines. So for this aspect we really have to think the things scientifically not emotion-based. Always we need a scientific-based evidence to see if to determine whether these vaccines need to be continued or not. So that's kind of baseline background that we have been always facing to the adverse reaction of these events of the vaccine. The other things that we are currently facing is the impact of media as I presented previously. We had the media presentation of the patient with dystonia and there was a pain syndrome after the vaccination. Japanese media, some Japanese media provide the images and videos without proof evidence or just from the one side of the aspect of the vaccines. Including mainstream media, correct? Right, right. So the main one was the one which was presented at the night national TV which was enough to impact on the influence, the public opinion about the vaccination. So we really have to watch on the media. We always need to focus on the safety of the vaccine at the same time we have to see the effectiveness of the vaccine, benefit of the vaccine. That's also very important to recognize that we have to also show the effectiveness of vaccines. And also the last thing I really want to show is the leadership of the government with support by the academia. I think they are not strong enough to determine the vaccine policy and actions in Japan. So we really have the government also with academic support has to develop a better system to determine the vaccine policy and actions with science evidence, not by emotionality. I have so many questions, but I want to give Dr. Salisbury a chance to make a comment here. So if I could, thank you. Two brief points. I understand that the Japanese government try to engage with the anti-HPV vaccine groups, not just from Japan, but on a wide basis. And I think that's a mistake. I think that you should not give oxygen to these groups. By doing so, you give them legitimacy, you give them a presence, you give them an apparent authority. And there is nothing that you will say that actually will persuade them anyway. And engaging was a mistake and it would have been better not to engage equally giving compensation, I think was a mistake, when the evidence that this was vaccine attributable did not exist. The third and a brief point was that I recall taking a telephone call at three o'clock in the afternoon, one afternoon, to say that a girl had died in less than an hour after she had received her HPV vaccine in school. And that was three o'clock in the afternoon. By six o'clock, it was the lead story on the national news. We did not suspend the program. We did not withdraw the vaccine. We gave a statement to say that, of course, our sympathy was with the family and we would not issue a further statement until we knew the cause of death but that the program would continue. The next day we had the result of the post-mortem and the girl had died of something entirely unrelated to her vaccination and the program continued and we did not at any point withdraw the vaccine or suspend the program and we had no deleterious impact. Equally during that first 24 hours, we agreed that no minister, no chief medical officer, I as director of the program, none of us would go on television or in the media until we knew the cause of death because we were gonna be faced with the camera and the question, can you guarantee that the vaccine did not kill this girl? And that's like, have you stopped beating your wife? Because you see, don't you have a fifth amendment which we don't, but it was unanswerable. And until we knew the cause of death, we were gonna hold our position and not put ourselves in the position of weakness. Thank you. Thank you. Before I open it to the floor, I'll ask just each of the panelists to comment briefly on one question and that's, we saw in Ted's slide, Ian Frazier, the Australian, one of the creators of an HPV vaccine and he was at the World Cancer Congress a few months ago in Melbourne and he put the goal of eliminating cervical cancer with HPV vaccines on par with polio eradication and showed how much money had gone into polio eradication, how much effort, how much world support and compared it to the number of polio cases there were and obviously our man from save and left but a tremendous discovery made a huge difference in health. Our HPV vaccines, that game changing and are we ready to envision and commit really to an end game for cervical cancer? Dr. Salford, let me start with you. Is the world ready for this fight? I'd like to think yes and there are interesting parallels in that for every thousand people infected with polio, only one is paralyzed. Similarly for HPV, for all those people infected, there are only a small number of cases of cancer but that doesn't detract from the benefit of trying to stop transmission. I'd like to think that would be very exciting and I'd be there voting for yes. Thank you, Dr. Salford. I think that this is, there's such potential for use of this vaccine in the countries that need it most that it would be wonderful if the vaccine could be utilized and really all the people in the world can't have this. Dr. Salford? Yes, I think I hope so. It is a wonderful concept that we can eliminate with vaccine. Sub-cancer will be, that is very great concept. At the same time, the current vaccine does not cover 100% of genotypes which causes sub-cancer. So we probably need a better vaccine to cover more genotypes. Right. Thank you for a great discussion and now I'd like to, Steve, do we have a few minutes for questions? I know we're to the end of our panel but we also started late so I know there are questions in the audience and you can direct them to any one of the panel members or to all of them. Can we start down here with the microphone? Thank you. Actually, I'm gonna take the opportunity. My name is Nimmi Rahmanajam. I'm a professor at Duke University in Global Health and Biomedical Engineering. I have two questions. One is a scientist developing technologies and one is a parent. As a scientist, I heard the first speaker talk about the importance of screening and that the vaccine is not a replacement for screening and I would like to hear an elaboration of that even though that speaker is not here. Maybe others could speak to that. The second is we know that there are a number of other diseases that are transmitted through sexual intercourse and that obviously the use of protective mechanisms for safe sex is not just for prevention of cervical cancer but other things and so given that that sort of transcends any particular transmission of any particular infection, how is that viewed given that the incidence of cancer, given that someone has an HPV infection is actually quite low? So I think we have two questions here. One about screening and vaccination and how do you work them together? Does one become more important than the other or how do you handle that? The second one is sort of philosophical, safer sex. What do we do? I mean one thing Ted didn't mention that I think is also important is male circumcision which we know has a tremendous effect in HIV. I think also has some effects in HPV but I'm not the medical person so I'd like to throw this out to those who are. Dr. Warren. Well we, of course screening continues to be very important as has already been pointed out. The current vaccines don't include all the types that are associated with cancer so we continue to recommend screening and I think at the beginning of the program when we first were grappling with how to use the vaccine there was concern that introduction of a vaccine would decrease people's understanding that these screening programs needed to continue and I think those issues have largely been worked through and really the screening is well integrated into women's health programs so I don't think that there's as much concern about that now in the US but certainly as countries are dealing with their screening recommendations it is something that is considered and incorporated into their planning. And of course safer sex is still very important for transmission of other diseases and this isn't really an issue that I've heard much discussed in the United States concern that the vaccine would in fact increase transmission of other diseases because of lack of abuse of the area of precautions. I think that the things are reasonably separated in most people's minds about this so that's not something that really I've heard a lot of discussion about. Further comment from Dr. Taito or Dr. Southford? I'm a pediatrician, I'm not the OB of GI end office so my comment is limited but for the screening is very important and Japanese screening rate is only up to 25% it's very low so it's very important to combine these vaccines and also second screening programs which needs to be provided well to the Japanese women. And I think the both needs to go together not only for the vaccine, not only for the screening now we have two tools so we can go. Comprehensive program of even as we introduce hopefully vaccine all over the world keeps screening. In relation to your second philosophic point sex and sneezes spread diseases but actually we're going the wrong way if we start to bring this into this discussion about sex and transmission parents didn't like it about HPV because when you started to say most people have been exposed to HPV at some point they all started to say you saying that I've had a sexually transmitted disease and the women looked at their husbands and their husbands looked at their wives this is a path to low coverage. Thank you another question here and then one in the back. Yeah, hi, good morning. First of all, thank you for the panel. I'm Yoke Silgarcia, EGIS Health Security and the former 13 Assistant Secretary for Health in the United States and I have Bruce Gellin here, expert in vaccine. I have a question from the policy perspective. I'm a former GYN and in the GYN practice treatment and diagnosis of HPV is the main state of many practices per se. Meanwhile from the policy perspective and from the government side this is a major cause for Medicaid insurance companies and managed care. We're talking called POSCOPY, we're talking laser labs, we're talking about all the diagnostics and treatment. Have you actually looked at the cost benefit of HPV to be able to get the Medicaid here in the United States agencies and Medicare which is the ultimate payer for this with the hysterectomy and find out a way to connect that economic impact to policy implementation at whatever level you want in school systems or actually at the local and state level. We have done cost benefit and cost effectiveness analysis as part of our policy formulation. In terms of this specific question about the impact on Medicaid and Medicare spending. I don't know that the specific thing you're suggesting has been done although I think it's worth us thinking through but we do have routine coverage through Medicaid for the vaccine up to age 18 through the Vaccines for Children program. So the ages in which the vaccine is routinely recommended it is covered through VFC for Medicaid children where we do have a gap in most states is with Medicaid is with coverage for young women and young men from 19 to the up to age limit. And so your point is a good one and I think we can think that through. All right, thank you. Question in the back here and I think we'll take one more after this one. Hello, great panel. I'm Nancy Harris from John Snow Inc. We pride ourselves on being evidence based and often it's evidence based about the vaccine but and I realize that the US is a very complicated health system and I don't know much about Japan but this is sort of a challenge to our American and Japanese colleagues in public health. We have very clear evidence that school based vaccinations work. Very, very clear. So maybe we need to start making evidence based programmatic decisions as well. I'm just that sort of a question and a statement. Go ahead and agree more. I think you've heard a whisper here that at least some of the panel agrees with you but myself in that camp. But in fact, we have done some work on school based immunization that they're, even if the payer issues can be surmounted, there are issues around, there are issues around lack of infrastructure delivery in our schools and even if that can be addressed, there are issues around the piece of paper in the back path. And it's not that that is insurmountable, generally but it is something that's very challenging in the US in those settings where there is a single payer in that school like the Vaccines for Children program that make it more complicated. It doesn't mean that it can't be done. We've done some work in that area. We've supported some work to assess this but it's not so simple for us. And we also I think don't really have the tradition now of school based immunizations delivering the way they do have in some other countries. So it is a little more complicated. It's not impossible but it's a little more difficult. Well, I think we can't find a way to get above 30% vaccination rates, we should think about the difficult question. We'll take one last question here. I think there's a mic there. Sorry. Jennifer Smith, University of North Carolina. I just wanted to second the comments that were just made by Melinda. We held a school-located vaccination discussion where we brought together individuals in the United States who are actually implementing school-based programs and some of the big issues, we actually are gonna be working on a manuscript, some of the biggest issues has been described over the really the reimbursement but there's a lot of individuals who really want to do this. I think one of the things as Nancy's mentioned is trying to identify how can you make a program that could be really effective in doing this and I think what we just found out in that meeting is with all of the barriers and obstacles, particularly around Medicaid reimbursement, there isn't a current model right now that we see that actually works. I think that we need to think more about school and then also more about pharmacies in the US. So, I see one more question I'm gonna take it and then we're gonna wrap up. It's a comment, not a question. Well, get vaccinated, vaccination programs. I have an 11 and a 13 year old daughter and actually the other two vaccines that are recommended for adolescent girls, the schools prevent you from being in the athletic program if you don't have those vaccines and the HPV vaccine wasn't even mentioned on the list that I got from the school saying that it was necessary so I did call the school up to find out why the HPV vaccine wasn't listed and they basically didn't have the authority to say that kids can't play sports without the HPV vaccine because somehow they felt it wasn't relevant but perhaps you don't have to give the vaccine in the school, maybe they could just add a line that says your daughter's also of age to receive the HPV vaccine and you should have a conversation with your doctor because then at least you're stimulating the thinking around it and it's not just completely absent. So, I would like to thank our panelists today for so thoughtfully sharing thoughtfully and frankly sharing their thoughts on cervical cancer prevention and control and also our audience for a robust discussion and I think from this discussion it's clear that no matter the country truly addressing cervical cancer is not for the faint of heart. It requires persistence and funding and the will to save lives that we can and we should be saving. So, I think they've all pledged to join us in the fight to do what's right for women throughout the globe not just in their own country and it's my hope that we can achieve real and meaningful progress in this fight against cervical cancer even in my lifetime. Thank you.