>> We have an amazing panel of experts for you today. If I introduce each with their full pedigree, we would not have time for any vaccine information. So you can find their bios at the end of slide 85 of the presentation. The slides will appear in the central window of your screen and will advance automatically, so you can keep both hands on your sandwich. We encourage you to ask questions throughout the presentation using the chat box window, or on the left side of the screen. We'll answer some of those questions at the end of the presentation. We'll post answers to all the questions we receive during the webinar to the AAP immunization webpage on aap.org, and we'll e-mail them to everyone who registered for the webinar with a link to the recorded webinar as well within two weeks. The slides used today will be available also on the AAP immunization webpage on the aap.org website within the next two weeks. We hope you will use these handouts to give an in-service at your work, so everyone understands the mission behind this vaccination. There is no CME available for watching this webinar. But you see here on this slide two web links for programs on HPV that do have associated CME credits. We're completely jazzed to let you know that today you are part of a huge gathering of people interested in preventing HPV-associated cancers, almost 700 people registered for today's webinar, including almost 250 registered nurses. So welcome. My name is Dr. Sharon Humiston, I'm a pediatrician at Children's Mercy in Kansas City, Missouri, and I'll be your moderator today. Our objectives for today are what is it to review the latest information on what is known about HPV? How good is the available HPV vaccine, How can we translate the HPV vaccine science to protection for our patients, and what are people asking about HPV? So let's start with our first objective. For this, we turn to Dr. Kristin Oliver, a pediatrician and public health specialist for the Icahn School of Medicine in Mount Sinai, New York City. Kristin, we've heard that HPV can cause cancers. But in the United States, just how common are cancers caused by HPV?

>> Thanks, Sharon. So right, we know HPV is so common that pretty much everybody is going to get it at some point in their life. And even though most cases of the infection are cleared, if the infection does persist, it causes a significant cancer burden. In the U.S. alone, that comes out to over 30,000 people with diagnose of the cancer caused by HPV every year. That's one case every 20 minutes. Or by the time we finish this webinar, three new cancer diagnoses. In American women, this translates to 19,000 cases of HPV-related cancer a year. The vast majority of those shown in dark blue on the left-hand pie chart here are cervical cancer cases, a little over 10,000. Women also get oropharyngeal, vaginal, vulvar and anal cancer from HPV infection. And don't forget the men. Because men also bear a significant burden from HPV-related cancer. The majority of cases in men shown here in light blue on the pie chart on the right are oropharyngeal cancer cases, about 9,000 a year. Men also get anal, penile and rectal cancer from HPV disease. Now, for both men and women, the burden of HPV-related cancer varies across the U.S. And here we're looking at a map of cervical cancer incidents per 100,000 by state. And in this map, the darker blue indicates a higher incidence rate. So you'll see a darker blue, higher incidence, in areas around Texas, Oklahoma, Arkansas, and up through parts of Appalachia. Cervical cancer deaths are also higher in this region. You'll see a similar trend for oropharyngeal cancer with men on the left and women on the right for HPV-related oropharyngeal cancer. Again, a higher incidence in the darker blue states. More concentrated this time in the southeast. And I want everybody to remember this pattern when we look later at HPV immunization rates. Now, I wanted to put HPV cancer into perspective. These are the other diseases that we're preventing with the adolescent immunization platform. And now, this is data for all age groups, so we're not talking just among adolescents, but among the entire population from birth through death. And you'll notice that cervical cancer incidents per year are the highest followed by pertussis and oropharyngeal cancer, all of which are significantly higher than cases of meningococcal disease every year. Taking this a step further and looking at the estimated average number of annual deaths of these diseases in the United States, again, across all age groups, you'll see over 4,000 women are dying every year from cervical cancer compared to 70 people per year for meningococcal disease, 7.5 specifically for Men B and 6 from pertussis. And this is going to be just tremendously satisfying to watch the incidents and death rates from HPV-related cancers drop as we increase HPV immunization rates to levels that are consistent with Tdap and Menactra. You may, if you've been paying close attention, have noticed that I did not include oropharyngeal cancer death rates on this graphic. And that's not because there isn't significant mortality associated with that cancer. It's just that it's very difficult to find specific data on specifically HPV-related oropharyngeal cancer. That's on an annual basis.

>> All right, thank you, Kristin. You raise a lot of really important points. In the pie charts you showed, the incidents of cancer probably caused by HPV, you showed these big blue swatches of light blue for oropharyngeal cancer. I'd like to know more about that. So we asked Dr. Mike Moore, a head and neck surgeon, to join us from UC Davis. Mike, what do primary care folks need to know about these oropharyngeal cancers?

>> Thanks very much, Sharon. As Kristin mentioned, I went over on her portion of the presentation, we're now learning that it's not just cervical cancer anymore. In fact, over the last three decades or so, there's been an increase in HPV-related oropharyngeal cancer by over 200%. And it's now close to passing. It's may have even passed, cervical cancer is the most prevalent HPV-related cancer in the United States. And so in this publication from 2010 in the Journal of Clinical Oncology, what you'll see is that the cervical cancer incidence is continuing to decline with improvements in prevention and screening techniques. But the incidence of the HPV-related oropharyngeal cancer continues to rise. The majority of that is made up of cancers developing in men. And so as I mentioned, most of these happen in men, and when you look here graphically, you do have a fair incidence in women, it's relatively low in comparison to what we see in the male population. But it can happen in young people who lack some of the other classic risk factors for head and neck cancer. When you look at the incidence in men, it's not only quite high, but it's been increasing in recent years. And in particular, can affect younger, healthy people that otherwise wouldn't be considered at high risk in their 30s, 40s, and even 50s, with those individuals being affected.

>> Couldn't we reduce the number of oropharyngeal cancers if we just caught it earlier in the pre-cancer stages like we're doing with cervical cancer?

>> Well, I think that's one of the biggest challenges. The short answer is where we stand now, probably not. Pap smear to identify pre-malignant lesions or early malignant lesions. And a lot of this also has to do with the fact of the area that is affected. So the palatine tonsils on the side, and then around the corner on the base of the tongue, the lingual tonsil tissue, only a portion of these areas are really seen on physical exam. In addition, just the particular behavior pattern of HPV-related oropharynx cancer, they often spread to lymph nodes within the neck very early in their course. And when the primary lesion is very small. So here is an example of right tonsil cancer that you're seeing on the left-handed picture. And in this individual, it could have been caught fairly early, but this is a pretty unusual scenario where the lesion is very readily visible just looking through the mouth. What we see is actually the most common presentation for HPV-related oropharynx cancer is actually a neck mass as you see on the other patient there. And that already indicates that it's presented at an advanced stage. So the treatment options are both surgical or non-surgical, depending on what is in the best interest of getting the patient's disease under control and causing the fewest side effects. And while these can be fairly successful, there is significant treatment related toxicity that results from them both, acute and chronic side effects, such as taste disturbance, severe dryness of the mouth and the throat, scar tissue or narrowing in the throat. And around 10% of people actually require a long-term feeding tube, either over a year, or sometimes even indefinitely. In addition to the impact on the patient, there's also a significant cost to society from the disease. When you look back at the 2004 to 2007 data, they showed that the societal cost was over $300 million at that time, and the incidence has actually more than doubled since then. So as you can see, there's really an evolving epidemic that we're seeing in front of our eyes. And it's really critical that we're having sessions like this and really appreciate everybody attending. The goal is to not only educate the public, but also practitioners, and there are many tools available for us to do that. This is just one example. There's a set of videos that have been developed through the American Cancer Society, and the links are free to view, and we strongly encourage you guys to check them out, and then also pass them on to your colleagues and your patients.

>> Thank you, Mike. I wanted to turn now to Dr. Rebecca Perkins. She's an OB/GYN from Boston University. Rebecca, you, in our personal conversations, have convinced me of the importance of the pre-cervical cancer in the HPV story. Please tell us about the OB/GYN perspective on all of this.

>> Sure, I'd be happy to. So I'm not a gynecologic oncologist. I don't see women with cancer. I just see the garden variety gynecological patient. And despite that, about one out of every five of my clinical visits is for disease caused by HPV. Most commonly, abnormal Pap smears or cervical pre-cancers. So what this graph shows is how HPV infection turns into pre-cancer, and then turns into cancer. So most people are infected with HPV in their late teens and early 20s. And then about five to ten years after the initial infection, they develop pre-cancer of the cervix. And that's 330,000 women a year treated for pre-cancers, so that cervical cancer can be avoided. And the most common age that we do this treatment is ages 25 to 29. If women do not get treated, the pre-cancer can go on to become cancer another decade or so down the line. So we start to see cervical cancers developing in the early 40s. And then there's another peak in the 60s. Next slide, please. When women develop a pre-cancer, you need to treat them by essentially cutting out the abnormal cells. So we can do this in the office under local anesthesia. And what we do is we essentially take a hot wire, an electrical cutter wire, and we move about one centimeter of the five centimeter cervix. And this is very effective. It works about 90% of the time. But we do see pretty convincingly in basically almost every site we look at, that when you remove part of the cervix, the purpose of which is to hold the baby inside until delivery, we start to see complications in terms of pre-term delivery, pre-term rupture of membrane, and complications of prematurity. So whenever I'm doing one of these procedures, I think, oh, this could have been prevented with a shot in the arm. Next slide, please. So HPV vaccination can really stop cervical cancer in its tracks by preventing that initial infection, that if it persists for years, goes on to cause first pre-cancer, and then cancer. Next slide. Next slide, please. Thank you. It's really important to vaccinate early. Because with any vaccine, it only works before the person has the disease. This is something we all know, but with HPV vaccine, I think somewhere it's gotten lost in the shuffle, especially with parents. So this is data from Australia where they got the HPV vaccination on board very early through the school and started vaccinating routinely at about age 12. And they found that when girls got their vaccine by age 14, they had a 75% lower chance of getting pre-cancer than if they got their vaccines at 15, 16 or 17 years of age. And it's actually substantially outperformed the clinical trial, which is something you almost never see. In real life, if vaccination occurs before 14, it works better than it did in clinical trial. Next slide. And this is more data from Australia, which is incredibly exciting, because it shows that not only is vaccination working, but that it's continuing to work. So this is data from the Pap smear registry in Victoria, Australia. And these lines show women of different ages and their likelihood of developing a pre-cancer. About through the middle, through 2008, that would be the pre-vaccine era and then when you start to see all those lines head south, that is the post-vaccine era. So you can see that in women under the age of 20, pre-cancers have nearly disappeared. They're also dropping very dramatically in women ages 20 to 24. And those women are not being vaccinated anymore. They only provided the catch up program for a couple of years. So these are women who got vaccinated and are now aging up into the overage groups. And now even the 25 to 29-year-olds are starting to show decline, showing that the vaccine is continuing to work. During this time, the gray line on the bottom and the pink line in the middle, the 35, 30 to 34-year-olds and 35 and over, there's no decline at all. It's a very, very exciting real world evidence of the effectiveness. Next slide, please. So without vaccination, this is what we see in the United States with costs and these are just related to cervical and general HPV. So we see about 1.4 million in cases of low grade cervical dysplasia, or low grade abnormal Pap smears. These women will require a some basis procedure called a colposcopy where we take biopsies of the cervix to make sure they don't have a high grade lesion. We'll see about 250,000 new cases of genital warts. We'll see about 330,000 new cases of the high grade cervical pre-cancers that require that leap procedure, that partial amputation, partial removal of the cervix in order to prevent cancer. And despite all of our best efforts, we will still see between 10 and 12,000 cervical cancers this year. And about one in three women, even in the United States, will die from their disease. But if we were to achieve the healthy people 2020 goal of 80% vaccination, a pyramid would look like this. Now, these levels of the pyramid have been redrawn based on actual published data on vaccine effectiveness. We would get rid of over 1/3 of our low grade abnormal Pap smears. Nearly all of our genital warts. At least half of our high grade lesions, and 3/4 of them if we actually vaccinate on time. And then we'd expect to see up to an 85% reduction in cervical cancer down the road.

>> Thank you very much. This has been a great review of the burden of HPV disease. So our next objective is to look at how good is the available HPV vaccine? So for this, we turn to our pediatric infectious disease specialist, Dr. Sean O'Leary from the Colorado School of Medicine in Denver. Sean, why have we switched to the 9-Valent HPV vaccine?

>> Great question, Sharon. Just for some background, the 9-Valent vaccine was recommended for use in February of 2015. And prior to that, there were two vaccines available, what they called the bivalent HPV vaccine containing two strains, covering two strains and the quadrivalent HPV vaccine with protection against four strains. Both of these vaccines covered HPV type 16 and 18. And those two strains are responsible for about 80% of all the cancers caused by HPV. The quadrivalent vaccine also covered type 6 and 11, which are the strains that cause most genital warts. So essentially, the 9-Valent vaccine covers the same types as the quadrivalent vaccine, plus types 31, 33, 45, 52 and 58. And by covering those strains, those strains are responsible for an additional 12% of cancers. And most of those cancers are in females. So a little more about the 9-Valent vaccine. This figure shows the comparison between the immune response for two doses of the 9-Valent vaccine compared to three doses in women. And this comparison is made because the original effectiveness studies on the bivalent vaccine and the quadrivalent vaccine were based on women ages 15 to 26. So they wanted to compare what it would look like to do two doses in the younger kids to the original effectiveness studies. So what this slide shows is that if anything, two doses in the younger ages is actually superior to three doses in the older ages, the 15 to 26. So the Y axis is the immune response. And the X axis is the different strains in the 9-Valent vaccine. So as you can see, for all of the strains, the immune response to this vaccine is actually higher in younger adolescents compared to the older ones. And then this slide is to point out that not only does the vaccine produce a robust immune response much better, in fact, than natural infection, but that that immune response lasts. And so this is showing follow-up five years. So what evidence do we have? What other evidence do we have for lasting immunity? So for the or three-dose schedule, we have no evidence of waning protection after a three-dose schedule. And so far, antibody persistence for the two-dose schedule appears to be very similar to the three-dose schedules. And then in terms of how long, at this point, we have data available through about 10 years for the bivalent vaccine and the quadrivalent vaccine. And there's longer follow-up that's ongoing through about 14 years right now in some studies. And based on those, we have no reason to believe that the immune response is just going to precipitably drop off. It looks like it's really--this vaccine provides a robust immune response that really lasts. We've had lots of questions about the new schedule. Basically, it boils down to when this series was started. If it started before the 15th birthday, you need two doses separated by a minimum of five months. After the 15th birthday, it's three doses, just like the old schedule. And then for immunocompromised people, it's three doses. This slide is for your reference, so this is about the immunocompromised patients. Basically, if you're wondering whether or not--so you have a patient that's immunocompromised and you're wondering, do they need two or three doses? I'd suggest, rather than memorizing this list, just reading the footnotes in the schedule, this is all on the adolescent immunization tool. Some kids that we consider immunocompromised for other vaccines may not be for HPV vaccines. For example, asplenia or sickle cell disease. Then here is the schedule written out with the minimum intervals. So the recommended dosing schedule for the two-dose series is 0 in 6 to 12 months. The minimum interval, which is what will be calculated in the immunization registry. And so if you have someone that got historical vaccination, the minimum interval is 5 months between doses 1 and 2. So now I want to move into some Q and A cases. And the way we're going to do that is rather than trying to coordinate an audience response system with 700 plus people, I'm going to have you just think about this and write it down for yourself, or make an answer in your mind. And then we'll go over the answer. So for case example number one, a boy is starting the HPV vaccine series on his 15th birthday. How many doses does he need in total? So I'm going to give you a few seconds to think about that. All right, so the correct answer is he needs three doses. Because he started on his 15th birthday. So it's on or after. So he needs the 0, 1 to 2 months and 6-month schedule. All right, next question. That was not a trick question. None of these are trick questions. All right, so case example number two. A 13-year-old has a history of two doses of HPV vaccine. The quadrivalent or 4-Valent HPV vaccine given at age 12 years, and a 9-Valent HPV vaccine given six months later. How many more doses are needed? Okay, so a 13-year-old got a quadrivalent and then a 9-Valent. Okay, so the correct answer here is actually zero. No further doses are recommended because she initiated the vaccination series before the 15th birthday and got two doses six months apart.

>> And it didn't matter that they were different, one was quadrivalent and one was 9-Valent.

>> Correct. Right now, you can--according to the recommendation, no matter what vaccine you started the series with, you can finish it with a 9-Valent. Case example number three. A 13-year-old had a history of two doses of HPV vaccines. She got the 4-Valent at age 11 and the 9-Valent given two months later. How many more doses are needed? All right, so is that 0, 1 or 2? So the correct answer is one more dose. She initiated the series before her 15th birthday, but she needs another dose because doses one and two were less than five months apart. And so for the third dose, you need a minimum of 12 weeks between doses two and three, and a minimum of 5 months between doses one and three.

>> That was great, Sean. Okay, so HPV causes bad disease, and a vaccine is really good. Kristin, have we finally reached the point where getting HPV vaccine is the norm in the United States?

>> We have. So in most places in the U.S., most adolescents are getting the HPV vaccine. Among 13 to 17-year-olds, over 60% of girls and over 50% of boys has started the series. And I talked earlier about variation and cervical and oropharyngeal cancer incidents and death in the U.S. And you'll notice looking at these maps, we also have variation in immunization rates. In this map here, the darker shade means higher levels of immunization. So higher, darker is better. And you'll notice again in the areas in the south where we saw before higher rates of HPV-related cancer burden, there's unfortunately lower rates of HPV immunization. And this is sort of consistent, again, with data for the boys shown here in blue. We'd really like to see the rates increase here in an effort to address this disparity and this burden. And obviously we also want to see rates increase across the country. And fortunately, there's lots of really effective strategies to do this that we're going to be discussing next.

>> Okay. I'm going to ask everyone to chime in for this objective. How can we translate the HPV vaccine science to actual protection for our patients? Sean, what strategy would you emphasize?

>> Yeah, so here I'm going to talk briefly about how to introduce the vaccine. And we have two studies that we can pull from on this. One was by a group in Seattle, and another was from a group in North Carolina. And both of these studies were published in pediatrics in the last few years. So the group in Seattle did an observational study looking at how providers introduced vaccines for children. And they made the observation that children were much more likely to be vaccinated if the provider introduced the vaccine in what they called a presumptive fashion, meaning saying something like "we've got some shots to do today," as opposed to "would you like to do some shots?" Dr. Brueller and Company then put this to the test in a randomized control trial for HPV vaccine. And they were able to show that doing what they called announcements, another way of saying the presumptive vaccine, or presumptive recommendation, was effective at increasing HPV vaccination rates. So what does that translate into practice? So what we recommend is basically same day, same way. So just saying for the vaccines, "your child needs three vaccines for the Tdap, HPV vaccine, and meningococcal vaccine." To do it a little bit longer, "today your child should have three vaccines. They're designed to predict meningitis, cancers caused by HPV, and tetanus, diphtheria, and pertussis."

>> Kristin, what strategy would you emphasize?

>> So there's really strong evidence that reminder recall strategies are effective to increase immunization rates for all immunizations for all age groups from infants through adults, adolescents, everybody. And now there's also very specific evidence for HPV vaccines to effective by these strategies. And what I mean by reminder recall is physicians and practices, identifying their patients who are either due or overdue for a vaccine, and then letting them know. So making telephone calls, sending letters, sending postcards, or now sending text messages. And so quickly here, two specific studies that looked at this. On the left, this is a study conducted in private in academic practices in New York City. And they found that patients who enrolled into the text message program, so agreed to get these text messages for the next dose of the HPV vaccine, either dose two or dose three, those patients those families were more likely to get the subsequent dose on time compared both to families who did not participate, and then also compared to a historical control group. The difference was 51% compared to 35%, getting that next dose on time. On the right was a study conducted at full private practices in Denver. And these are patients who were missing one of the vaccines in the adolescent series, either Tdap, Menactra or HPV. And these patients were randomized to either receive, they receive telephone and letter reminders, or just the usual care. And again, the group in black who got the intervention were more likely to get this needed vaccine dose than the control group. Importantly in this study, they also looked at cost effectiveness. And so some people may be saying, yikes, it's a lot of effort and a lot of cost to conduct these recalls. But, in fact, three of these practices saw a positive net revenue from the reminder recall efforts.

>> I know that some states are also sending reminders through their centralized immunization information system, their registry.

>> Absolutely.

>> I think, again, talk about cost effectiveness. Seems like it would be. Okay, Rebecca, I have heard you talk about provider prompt as a strategy for increasing immunization rates. Can you tell us more about that?

>> Sure. And provider prompts literally mean something to remind the provider. So if people have a sophisticated EHR and they know how to use it and people actually look at the pop-ups or best practice alerts, those are obviously a fantastic way to do it. A lot of practices either don't have a very functional EHR or they have one that's functioning, but their providers don't really know how to use it. And anything, a yellow sticky note, a checklist, a pre-printed note, this is literally anything that reminds the provider to vaccinate, works really well. Evidence from 14 studies showed a vaccination rate increase of an average of 6%.

>> Not a hit-it-out-of-the-park improvement, but a significant increase.

>> Right. And this is actually from one of the practices that we're working with right now. And I think this speaks to when you have a practice that's really interacting well with their electronic medical record and using the best practice alert. So this is a practice that was vaccinating at age 11, and doing a great job at starting their kids when they came in, but they had a population that just didn't come in that well. And so they found that by age 13, only half of them had actually finished the vaccine series, even when we were trying to recalculate based on the two dose data. And so they decided, well, why don't we just start at 10? It will give us an extra year to get vaccines into the kids. And their best practice alert went live in August, and you can see that by October, 100% of their residents were responding to that and vaccinating the kids at 10. And about 82% of the full-time pediatricians were responding to that alert and giving it at age 10 when nobody had been doing it before. So just really fast and really effective.

>> Okay. Sean, to wrap up this objective, tell us about your standing orders and the strategy for increasing immunization.

>> Yeah, so I'll talk about standing orders for a second. So what is a standing order? So essentially it's a single division order for all patients for recommended vaccines. And it stipulates that all patients meeting certain criteria should be vaccinated, and that usually will include an age, underlying medical condition, and then potential contraindications. So to do this, the nurse or medical assistant will track the immunization history of the patient, and then identify the eligible patient. And then they can educate the patients about the vaccination. And then alert the provider if the patient still has questions or wants to talk with the provider. And then the nurse or medical assistant can administer the vaccine. And in some cases, even before the provider has entered the room, or even outside of a provider visit. So what are the benefits? So standing orders have been shown to be effective in both adults and children across many, many studies. And for children, the use of standing orders is associated with immediate increase in vaccination coverage of 28%, which is really high. And by the way I review the literature, I think standing order, you could make an argument that standing orders are probably the most effective evidence-based method we have for increasing vaccination rates. You can overcome administrative barriers and save time. And when you think about what I talked about earlier with presumptive recommendation, the standing order is really the ultimate presumptive recommendation. And to illustrate this, I want to briefly talk about Denver Health. The Denver Health is a large safety net system here in Denver where I practice. And they care for about a third of all children in Denver. They've got I think actually now 9 community health center, 16 school-based health centers. And for years, they had kind of a typical immunization process with rates similar to the national average. What did they do? So they implemented a system of standing orders predicated on the idea of taking the provider out of the immunization equation from birth to adulthood. And I can hear the snickers from the nurses in the audience. But basically take the doctors out of it. And as I talked about earlier, they presented Tdap, HPV, and meningococcal vaccine as a standard bundle of vaccines. And they also tried to give the vaccines early in the visit. And providers are only involved in vaccine conversations if there's a refusal. And what I hear from the providers at Denver Health is that this is actually pretty rare. So their work was actually published in pediatrics a few months ago, achieving high adolescent HPV vaccination coverage. And you can see here that what they were able to achieve with standard orders. So they are able to go on the, you can see Tdap on the left. They went a little above the national average in the Colorado average. Meningococcal vaccine, they did better. But if you look at HPV for both initiation and completion, simply through the process I described, they are able to greatly go above and beyond what the national average and the Colorado average are with 90% initiation rates, and close to 2/3 completion rates.

>> It looks like they're up, that they weren't missing opportunities, that they were doing it at the same rate as their Tdap and their meningococcal vaccine.

>> Correct. Exactly. So simply by bundling it, using standing orders, putting the medical system and nurses essentially in charge, they were able to achieve these rates. So my recommendation for standing orders for practices, public health departments and et cetera is to consider implementing them, and particularly for the adolescent immunization bundle. Also, using standing orders allows more time for focusing on other important aspects of preventative and sick visits for those without significant vaccine concerns. And just remember that having standing orders is not a substitute for provider conversation for families with questions.

>> Okay. Well, this brings us to our last objective. And I want to go through some rapid fire answers to the frequently asked questions. But we're going to start with you, Kristin, at the 20,000 foot level, what do pediatricians need to know about coding and billing for HPV?

>> Sure. There's really three things you need to know to make sure you're getting the maximum reimbursement for the effort and cost of delivering immunizations. The first is to make sure you're purchasing your vaccine for the best possible price. And if you're not part of a large system, you may want to consider joining a group purchasing organization that can help you negotiate discounts. Next, you want to make sure that your private payer claims are being billed out with the appropriate vaccine product and vaccine administration code, including the NDC, or the National Drug Code. And finally, you want to make sure that you're getting appropriate payment from your payers. And this may also require some negotiation. This is a very simple overview of a complex area. So I wanted to also include some great AAP resources that have a lot more detail and can really help you better manage this process. All of these links to these resources are going to be available on the slides at the end.

>> All right, well, as people are getting--if they want to know more, they can go to these resources.

>> Exactly.

>> Okay, well, no webinar on HPV vaccine is complete without a discussion of vaccine safety. So Rebecca, I'm coming to you. Are there any alarming signals coming from HPV vaccine safety monitoring?

>> No, there are not. So the HPV vaccine is monitored continuously in 180 countries. At this point, that means over 170 million doses worldwide. The CDC has the VAERS system. And there's also European systems as well as WHO systems. In addition, when specific concerns have been raised by anyone, additional literature has been produced. So just to go through very quickly, the long-term safety data shows no increased risk of allergic reactions, anaphylactic Guillain-Barré syndrome, stroke, blood clots, appendicitis, seizures, adverse events related to the immune or central nervous system, venous, thromboembolism or blood clots, the study did two different studies, autoimmune disorders were studied in three different studies, including multiple sclerosis and other demyelinating diseases, as well as 60 other conditions studied specifically over and above the monitoring systems that are in place. The only side effects that have been shown are an increase in skin infections. Obviously, anytime you break the skin, there's a possibility of infection. And the same thing can occur with any vaccination.

>> Right, we have a lot more data on the quadrivalent vaccine because it's been given for longer, and it's given in more countries around the world. But when the 9-Valent and quadrivalent vaccines were compared in clinical trials, they looked essentially the same, except the arm might get a little bit more sore because of a higher antigen load.

>> All right. Well, I'm turning back to you, Kristin. This is one of the top questions. Why vaccinate at 11 to 12 years? Why not wait until kids are in their late teens?

>> So I love answering this question. Because I think it's really a slam dunk as far as the data we have to support given the vaccine at this age group, or even earlier. So first, there's a better immune response in these younger adolescents. So here you're looking at data from a non-inferiority immunogenicity study. And you see that ages 9 through 13 in the purple compared to ages 16 through 26 in the red, and ages 9 through 13 consistently higher antibody response. And this is for quadrivalent but there's similar data for the 9-Valent, as well. Point number two for this question, younger adolescents, they're just still coming to their doctor for preventative care visits. And these rates of preventative care visits decline as they get older. The decline starts around age 13, and this really gives us few opportunities to immunize these older adolescents. Third, as we've mentioned before, you really want to give the entire series before sexual activity begins. There's very little HPV exposure in 10 to 11-year-olds. But you see the start of sexual activity increases around 12 to 13. And the thing is, even though we think we know, we don't really have a predictive model for identifying which of our patients are going to fall into that 5% of 13-year-olds who are going to initiate sexual activity at that age. As Sean mentioned earlier, we have very good evidence that the duration of immunity for this HPV vaccine is going to be long and protective. And so you really can't vaccinate too early. You can only vaccinate too late. And as Rebecca discussed before, very good evidence when the series is complete before age 14, you have a much more effective vaccine at preventing cervical pre-cancer, again, from the Australia data. So now this is obviously more detail than I give most families when they ask this question. I start off with a really simple response. This summarizes all of this. "The vaccine just works better at younger ages. If Claire gets the vaccine today, she's only going to need two doses. If we wait until she's older, she might need three."

>> Okay. All right, last question. Sean, how should I handle it if I come across an actual HPV vaccine hesitant parent? What do I do?

>> Yeah, I'm sure that's never happened. Yeah, great question. So I'm going to go through a few cases. This will be a little rapid fire, but we're going to leave some time at the end for questions. So an 11-year-old girl comes into your office for well care, you offer the presumptive or announcement recommendation for the vaccine, saying, "great, you're here for your vaccines, we can go ahead and do her tetanus, diptheria and whooping cough vaccine, her HPV vaccine, and her meningitis vaccine." Hold on. The mom says, "we're okay with that tetanus shot and the meningitis one, but we're going to hold off on the HPV vaccine." So what do you do? So this is how I'm recommending handling this. And I'm going to give you a few slides on sort of how to have this conversation. I think we've talked a lot about the but of what we need to be able to be equipped with to talk with parents about vaccines. I'm going to talk a little bit about the how. So step one, ask the parent to share the concerns. "So you seem to have concerns about the HPV vaccine. Well, that's perfectly understandable. I've had a number of questions about this. Would you mind sharing what your particular concerns are?" So you've asked in a non-threatening way. "Well, I've heard it's a vaccine to prevent a disease that's transmitted by having sex. And she's a long way from having sex, right?" So that's a common concern. Okay, so then you reflect back. So you reflect back what the parent is saying. Make sure that you understand. You're showing empathy. You summarize what's been heard. And then you ask permission to make a recommendation. And I'll go through that. "So I can hear your concerns. She's too young for the HPV vaccine because it's transmitted by sexual activity. I completely get that. She is only 11, after all. I've thought a lot about this. Is it okay if I go over how I've come to think about this vaccine?" So asking that permission to share, the cognitive psychologist told me that's a crucial step. It makes people more receptive to what you're going to say than if you just said it. By just saying--

>> If you just said it, yeah, like if you just said it, it would feel like you're ramming it down my throat.

>> Exactly. So asking permission is a crucial step in the process. So then step three, here's what you don't say. "So, well, data shows that many adolescents will be having sex by middle school. And if you're worried about her having sex, studies have shown it won't increase the likelihood of her having sex," right? So that would be an example of just repeating the what. Like that's repeating what we know. So a better way of saying it is "I used to think of this vaccine as something to prevent a sexually transmitted disease. But I realized it's really about preventing cancer. Almost everyone gets this virus. So I think it's important for everyone." So there we've sort of pivoted these, you know, point out why we're giving the vaccine. And then you can make your personalized recommendation. "So if she were my daughter, I wouldn't hesitate to recommend this vaccine for her. And most of my parents now are getting the vaccine. Having said that, this is a decision only you and your daughter can make. What do you think?" So I'm going to go over sort of what the different principles I'm using here in a second. So you want to engage the patient respectfully and fully in discussion. You want to use empathy, collaboration, evocation, and then support for autonomy. And you want to use open-ended questions. And then using behavior change principles like emphasizing social norms. That's where I said, most of my patients are now getting this. Pivoting from debunking a myth that she's too young to focusing on the disease that's prevented rather than the negatives. You want to make a clear, strong and personalized recommendation.

>> Well, that was very helpful, you guys. And we're open now for questions. We actually have 14 minutes for questions. And so as Dana is getting ready with picking one from the side, I want to bring up something you said, Rebecca, about in the provider prompt slide, you talked about not only did they institute best practice prompts, but they also changed to 10 years old. And I've heard you talk about your enthusiasm for certain HPV vaccine series at age nine. Can you talk about that strategy? I know it's not routine recommendation. But just out of curiosity, I'm interested in your take on that.

>> So the reason is really purely practical. Because it is a multi-dose series. And now, you know, most people are going to be instituting it at annual visits. So it's now actually going to take longer to complete the series than it did before because you're looking at about 12 months to complete it instead of 6. And like Kristin said, adolescents aren't great about coming in for care. So basically 14 is our kind of hard stop date. If we want the vaccine to work as well as it can, we know they have to finish it before their 15th birthday. That's when you switch to three doses. That's when their rates of exposure go up. That's when the effectiveness of the vaccine goes down in basically every study that you look at. So if you start--and we also know that the antibody response is incredibly robust in younger adolescents. And it doesn't seem to wear off for as long as we have looked at it. So it's really along the lines of you can't vaccinate too early, only too late. So if you start at 9, you have 9, 10, 11, 12, if you manage to get that second dose in. And if you look at the populations of kids covered by any given clinic, a lot of them aren't coming in for annual visits. And it's just taking a really long time to get the series done and kids are getting missed, so starting earlier it's just a safety net, it just gives you more chances to get the series done.

>> Okay, now, so I'm going to open this up to anybody in the panel. Is there any data on the cases of HPV-related cancers among LGBTQ individuals? Can men who have sex with men transmit to each other? Anybody want to take that? We know that because almost everyone is going to be exposed to this virus at some time in their life, that we know, for example, that lesbian women, there was a question on an earlier webinar about do we have to protect lesbian women? And the answer is yes. Anybody have anything to add to that?

>> I think I actually may be the only provider who sees adults. So women who have sex with women, or who identify as lesbian, are less likely to get cervical cancer screening particularly. But are not less likely to get cervical cancer because it's very rare that they will never have had heterosexual sex. And also, HPV can be transmitted through manual genital contact, oral genital contact, as well as any shared objects. So certainly the need for HPV vaccination and cervical cancer screening is just as high in women who have sex with women. Men who have sex with men have very high rates of anal dysplasia, and anal cancer, as well.

>> While I have you Rebecca, can HPV be transmitted by means other than sexual contact? You brought up, and again, in previous webinar, you talked about having anal cancer in women. The most predictive thing is having HPV--or you say it, because you can get the statistic right.

>> So anal cancer is about twice as common in women as in men, which, again, is something we'd always look at twice. Because we tend to think of anal cancer as a disease of gay men, which it is not. And the most predictive risk factor for anal cancer in women is a history of cervical dysplasia. So about 10 years after a woman gets her lead procedure for cervical dysplasia, she starts to have a noticeable increase in her risk for anal cancer. Which if you think about the time clock, if you didn't actually treat her cervical dysplasia, she would be getting her cervical cancer then too. And does this mean that all the women were also having anal sex? No, it means that the vagina and the anus are anatomically quite close together. And HPV can be transmitted on the hand to another body part called autoinoculation, or another person.

>> Okay. If someone asked any associations between giving the meningitis vaccine with HPV vaccine or other vaccines, and facial palsy, anyone heard about any data related to that? I have not.

>> I don't think they've looked at that question specifically. But I also don't think there's been a specific signal of an increase in facial palsy for either of those vaccines or those vaccines given together.

>> While I have you Sean - can you talk about the incidence of syncope with HPV vaccines? Is it really different than with other adolescents vaccines? Are you more likely to faint after HPV vaccine than other adolescent vaccines?

>> Yeah, that's a great question. I think there was a misimpression that HPV vaccine causes fainting versus the other vaccines. The literature on actually fainting after needle sticks goes back to the 50s with blood banking and people donating blood. So we've known for a long time that people faint after they get a needle poked in their arm. And adolescents faint more than anybody else. So whenever you introduce a new vaccine among adolescents, you're going to see an increase in syncope. So the recommendation, a lot of people have interpreted as you need to watch kids 15 to 30 minutes after their HPV vaccination. No, you need to watch the adolescents 15 to 30 minutes after any vaccination. It's not just HPV. Any of them can cause fainting.

>> Okay, parents are concerned about three shots at age 11. So our piece practice gives Tdap at age 10, and allows us to give two vaccines a year later. And this seemed to increase acceptance at that practice. Is that consistent with recommendations?

>> Well, you can give the Tdap early. I think another approach that some people are taking, and anecdotally people are saying is working for them when they do it is actually giving the HPV vaccine earlier. Because if you look closely at the recommendation from ACIP, it's recommended to give at ages--initiate the series at ages 11 to 12. You may give the vaccine as early as age 9. And so what some providers are reporting is that they've switched their process to introduce HPV vaccine at age 9, and are getting that series complete before they're even due for Tdap or meningococcal vaccine at age 11. I think that's an individual practice decision at this point. But buyers are reporting that that's effective.

>> Well, and the thing about just giving two shots to an adolescent, it seems ironic because you give little babies many more than that in most visits, it would be lovely to have a combination vaccine that put all the adolescent vaccines together. But we're not there yet. Okay, our next question. If an adolescent gets sick, vaccine at age 14 years and 8 months, can she get--and then she waits 6 months later. So now she's past her 15th birthday for her second dose. Is that a complete series? Sean, do you want to take that one?

>> Yeah, I can tackle that one. So that is complete. They could wait, according to the current recommendations, they could wait six months or six years. And they only need one more dose. It's all based on when the series was initiated.

>> That would be wonderful.

>> But, you know, 6 to 12 months after the first.

>> Okay. Okay, someone asked, I may have missed this, but is it recommended to give a boost of HPV-9 if a teen has completed the series with HPV-4? So they got a full series of the quadrivalent. Do you go back and give one dose of 9? Do you give any doses of 9? Or are you done?

>> So that's a great question. And a lot of people are asking that question. The ACIP has not made a recommendation about this at this point. Some individual providers have decided to do that. We don't really have data on should it be one dose, should it be a two-dose series, should it be a three-dose series? We don't really know the answers to those questions. But I will say that some providers are kind of doing that. Some parents are requesting it. I think to do that, you have to consider that the insurance company might not pay for it. And so this may end up meaning that a parent gets stuck with a large bill or a practice ends up eating the cost.

>> Okay. I can take this question. Are there strong efforts to involve dentists in the promotion of the HPV vaccine at the recommended ages? This would be really good, since HPV infection can cause oral cancer. And that our pediatric dentist could get the point across. I know that some of our friends from the American Cancer Society are in the audience today, and that they are making a real effort to get the dentists, the pediatric dentists and adult dentists to get the message out. As well as American Academy of Pediatrics has been reaching out to a special interest group for dentists. So people have been thinking about having the dentist explain when they're doing--they're moving your tongue around. What they're looking for is oropharyngeal cancer. So why not tell people, gee, it's really important to get this vaccine? All right, are there any--

>> Oh, can you hear me?

>> Go ahead.

>> In Massachusetts we actually, we have an HPV coalition. And there is a very, very active dental group. We did a presentation at the Yankee Dental Conference, which is about 10,000 dentists have all over New England, and I think there were over 150 people at the three-hour HPV session. And this group has also developed a dentist toolkit. So if anyone is interested in having that tool kit to share with partners, please e-mail whoever the contact person is for this webinar, and I'll be sure to give that to you.

>> And this isn't a question that's directly related to what you just said. Is there any role for non-medical institutions in the community to promote immunization with HPV? And do you have any examples of non-medical institutions that are getting the word out? I know that there are faith-based organizations. Again, both through American Cancer Society and the AAP chapters are bringing together the state coalitions to get all of the stakeholders at the table. And so American Cancer Society, for example, has reached out to schools. And it's really important. We want this to be a normative activity. And for everybody to understand that this is now the new normal. And so yes, the answer is yes, and we need everybody on this webinar today to get involved with their state-based coalitions to get the job done, okay? A lot of parents are terrified of extreme side effects, such as sterility in women, and they say that it's a got more information, you know, that they've gotten information from the internet or from somebody tweeting, and now they've come up with a new concern that maybe, you know - Rebecca - like you showed that there is data on multiple sclerosis and CNS demyelination seizures, that there's data about a lot of things. But I can come up with something new tomorrow and tweet about it and scare people anew. What do you do with that?

>> I think that's one of the tougher questions because you need to come back with the safety data that there is. And also, you know, remind people that while someone can tweet about something that may or may not be true, we know that there are 30,000 people getting cancer every year from HPV that is undeniable. And if you, you know, stirred all of the people with cancer up in a huge auditorium, I mean, they would fill up a--all of the HPV people, all of the people from an HPV-related cancer who are either currently going through treatment or survivor, we'd fill up multiple football stadiums. And all of the people who think their child may have had a side effect, you know, might fill a small classroom. So I think trying to put it in proportion. But sometimes it's really hard if someone has an idea in their minds, even if you try to tell them the evidence sometimes it's still hard to change their mind.

>> I think that what you brought up before too about the choice isn't that you're either going to get the vaccine or nothing. No, most people are going to be exposed to wild type HPV, which we know really no causes--that there are certain types that are authigenic. And so even if you get a pre-cancer, the side effects of the treatment for pre-cancer is pretty important to your ability to carry a child to term. So I agree that we don't want to just ram the facts down somebody's throat, as Sean said earlier. You have to say, do I have permission to talk about? All right, well, we are now at the top of the hour. We are actually a little past the hour. And I want to thank our speakers today for a really good session. And for the audience, for your interest and participation. We've got so many good questions. This webinar has been presented by the AAP division of pediatric practice, department of primary care and subspecialty pediatrics. The webinar recording, slides, and all the unanswered questions will be archived in about two weeks from today on the AAP immunization website, or webpage, which is part of aap.org's website. So look for it there. Also, all attendees will receive the link. If you registered, you will get an e-mail with that. Again, thank you for participating. Have a happy and healthy day.