Welcome to the Epidemiology and Prevention of Vaccine Preventable Diseases Webinar Series

PB13 HPV

Welcome to The Epidemiology and Prevention of Vaccine Preventable Diseases webinar series. I’m Candice Robinson, a Medical Officer in the Immunizations Services Division of the National Center for Immunization and Respiratory Diseases, or NCIRD, at the CDC and I’ll be your moderator for today’s session. To participate in today’s program all you will need is an internet connection. Here are our learning objectives. At the conclusion of this session, the participant will be able to describe the different forms of immunity, describe the different types of vaccines, for each vaccine-preventable disease identify those for whom routine immunization is recommended. For each vaccine-preventable disease, describe the characteristics of the vaccine used to prevent the disease, describe an emerging immunization issue, locate resources relevant to current immunization practice, and implement disease detection and prevention health care services; for example, smoking cessation, weight reduction, diabetes screening, blood pressure screening, or in this case immunization services to prevent health problems and maintain health. Today is August 31, 2016, and on the agenda is The Epidemiology and Prevention of Vaccine-Preventable Diseases Pink Book, specifically the vaccine topic HPV which will be drawn from the chapter on Human Papillomavirus. This will be presented by Ms. JoEllen Wolicki, nurse educator in the Communication and Education Branch in the Immunization Services Division of the National Center for Immunization and Respiratory Diseases. Continuing Education or CE credit is available only through the CDC ATSDR training and continuing education online system at www2a.cdc.gov/TCEOnline. If you are watching this version live, CE credit for this session will expire on October 3, 2016. If you’re watching the enduring archive version, CE credit for the session expires on June 01, 2018. When obtaining CE, you will be required to provide a verification code. Watch and listen for the verification code during the course. Verification codes will not be given outside of this presentation. CDC, our planners and our presenters wish to disclose they have no financial interests or other relationships with the manufacturers of commercial products, suppliers of commercial services or commercial supporters. Presentations will not include any discussion of the unlabeled use of a product or a product under investigational use with the exception of Ms. Wolicki’s discussion of the use of HPV vaccine in a manner recommended by the Advisory Committee on Immunization Practices, or ACIP, but not approved by the Food and Drug Administration. CDC does not accept any commercial support.

1 A list of resources for HPV will be available and the web page www2.cdc.gov/vaccines/ed/pinkbook/pb13.asp. If you have a question during this presentation and related to this presentation, please type your question into the QA pod. I will collect these questions during the presentation and then we will address them during the question and answer period which will follow Ms. Wolicki’s presentation. I will now turn the session over to Ms. JoEllen Wolicki. Thank you Dr. Robinson. As she mentioned earlier, today we will be discussing Human Papillomavirus Disease and Vaccines including the nonvalent vaccine. This chapter begins on page 175 of the Epidemiology and Prevention of Vaccine Preventable Disease text or what we commonly know as the Pink Book. Human Papillomavirus is the most common sexually transmitted infection in the United States. Human Papillomaviruses are small double-stranded DNA viruses. More than 150 HPV types have been identified. The relationship of cervical cancer and sexual behavior was suspected for more than 100 years and was established by epidemiologic studies in the 1960’s. In the early 1980’s, cervical cancer cells were demonstrated to contain HPV DNA. Epidemiologic studies showing a consistent association between HPV and cervical cancer were published in the 1990’s. The first vaccine to prevent infection was licensed in 2006. Most people with HPV do not develop symptoms or health problems from it. In fact, in 90% of cases the body’s immune system clears HPV naturally within 2 years, but sometimes HPV infections are not cleared and can cause disease. HPV types differ in their tendency to infect cutaneous, mucosal or genital epithelium. With more than 150 HPV types identified, approximately 40 infect the genital area. Genital HPV types are categorized according to their epidemiologic association with cervical cancer. High risk types can cause low grade cervical cell abnormalities and high grade cervical cell abnormalities that are precursors to cancer. In addition to cervical cancer, HPV infection also is the cause of some cancers of the vulva, vagina, penis and anus as well as cancer of the oropharynx. Low risk types like 6 and 11 can cause benign or low grade cervical cell changes or genital warts. Infection with one type of HPV does not prevent infection with another. Of persons infected with mucosal HPV, 5% to 30% are infected with multiple types of the virus and there is no way to know who will go on to develop cancer or other health problems. A small portion of infected persons become persistently infected. Persistent infection is the most important risk factor for the development of cervical cancer precursor lesions. The most common clinically significant manifestations of persistent HPV is cervical, intraepithelial, neoplasia or CIN. Within a few years of infection low grade CIN or CIN-1 may develop which may also resolve spontaneously and the infection clears. Persistent HPV infections, however, may progress directly to high grade CIN called CIN-2 or CIN- 3. High grade abnormalities are at risk of progression to cancer. A small portion of high

2 grade abnormalities spontaneously regress. If left undetected and untreated years or decades later, CIN-2 or CIN-3 can progress to cervical cancer. As noted earlier, most HPV infections are asymptomatic and result in no clinical disease. Most people never know that they have been infected. Women may find out that they are infected because of abnormal PAP test, with a positive HPV test, or a diagnosis of genital warts. Men may find out because of a genital warts diagnosis as well. Clinical manifestations of HPV infection are outlined on this slide and include anogenital anal genital warts, recurrent respiratory papillomatosis, cervical cancer precursors and cancers including cervical, anal, vaginal, vulvar, penile and oropharyngeal cancer. This slide outlines the average number of cancers probably caused by HPV per year in the United States. A large majority of cancers caused by HPV are brought about by 1 or 2 types; HPV-16 or HPV-18. Together these types cause about just over 30,000 cases of cancer in the United States each year with about 11,600 HPV cancers occurring in men and 19,200 HPV cancers occurring in women. An HPV associated cancer is a cancer that is diagnosed in a part of the body where HPV is often found. These are outlined in the first column of the table. These parts of the body include the cervix, anus, penis, vagina, vulva and oropharynx which is the back of the throat including the base of the tongue and the tonsils. We clearly see that the predominant HPV cancer in women is cervical cancer and the predominant HPV cancer in males is oropharyngeal cancer. HPV infection occurs throughout the world. Humans are the only natural reservoir of HPV. HPV is transmitted by direct usually sexual contact with an infected person, even when the infected person has no signs or symptoms. It is important to note, sexual intercourse is not needed to acquire HPV infection. HPV is presumably communicable during the acute infection and during persistent infection. This issue is difficult to study because of the inability to culture the virus. Communicability can be presumed to be high because of the large number of new infections estimated to occur each year.

Studies of newly acquired HPV infection demonstrate that the infection occurs soon after onset of sexual activity. In a prospective study of college women, the cumulative incidents of infection was 40% by 24 months after first sexual intercourse. HPV-16 accounted for 10.4% of these infections. 25% of cervical cancers occur in women who are between 20 and 39 years of age. As noted earlier, anogenital HPV infection is believed to be the most common sexually transmitted infection in the United States. An estimated 79 million persons are infected and an estimated 14 million new HPV infections occur annually with half of these in persons 15 through 24 years of age. About $8 billion are spent each year to manage the outcomes of HPV infections, primarily for the management of abnormal cervical cytology and treatment of cervical neoplasia. This exceeds the economic burden of any other sexually transmitted infection except hHuman iImmunodeficiency vVirus.

3 Most cases of death from cervical cancer can be prevented through detection of precancerous cervical changes by a PAP test. HPV vaccination does not eliminate the need for continued PAP test screening since cervical cancers can be caused by HPV types that are not included in the vaccine. Since 2012, all organizations have recommended that screening should begin at age 21 years. While there are slight differences in other aspects of the recommendations, all groups recommend screening in women ages 21 to 65 with a PAP test every 3 years. For women age 30 to 65 years who want to lengthen the screening interval, screening can be done with a combination PAP test and HPV testing or co-testing every 5 years. When we talk about HPV disease, the focus is usually on the cases of cervical cancer but every year millions of women will be diagnosed with low or high grade cervical dysplasia. Each of these women and their families are faced with the emotionally trying news of an abnormal PAP test, subsequent diagnostic tests, and waiting to hear whether or not they have cancer. Preventing cancer is better than treating it. Preventing the infections that can lead to cancer is even better. This statement is required by Section 317 of the Public Health Service Act 42 USC 243. Correct and consistent condom use may have a protective effect on HPV acquisition, reduce the risk for HPV-associated diseases, and mitigate the adverse consequences of infection with HPV. Three HPV vaccines are licensed in the United States. These vaccines are inactivated vaccines. The antigen for the vaccines is the L1 protein of HPV produced by using recombinant DNA technology. L1 proteins self-assemble into non-infectious, non- oncogenic, non-cancer causing units called virus-like particles abbreviated VLP. These vaccines do not contain any virus DNA and therefore are not infectious and cannot cause actual disease or cancer. This table shown on the slide outlines the 3 vaccine products currently available. In the first row you see the 3 different vaccines with their brand name, and please note the recommended ACIP abbreviations for each of the different vaccines; the bivalent vaccine 2vHPV or Cervarix is licensed for females 9 through– 26 years. The quadrivalent vaccine 4vHPV or Gardascil is licensed for females and males 9 through– 26 years of age. The same is true for the 9-valent vaccine 9vHPPHV or Gardascil 9. It is licensed for females and males 9 through– 26 years. All 3 vaccines protect against types 16 and 18. The quadrivalent vaccine provides protection to types 6 and 11 in addition to 16 and 18. The 9-valent vaccine protects against the same 4 types as the quadrivalent vaccine with 5 additional cancer causing types 31, 33, 45, 52, and 58. The quadrivalent and 9-valent vaccine are produced by the same manufacturer. HPV vaccines are intended to prevent cancer, primarily cervical cancers, but cancer can take decades to develop following HPV infection. Clinical trials using cancer as the end point would take many years to complete, so a clinical trial using cancer as the outcome is not very practical. Instead, other end points were used to determine vaccine efficacy such as persistent HPV infection and cancer precursors we spoke about earlier.

4 Bivalent and quadrivalent HPV vaccines were studied in large efficacy and safety trials that included more than 15,000 females 15 through– 26 years of age. Half of the participants received the vaccine, the other half received a placebo. Both vaccines were found to be highly effective. The vaccine efficacy was more than a 95% reduction of cervical cancer precursors among the vaccinated group as compared to the unvaccinated group. Among females, efficacy against external genital lesions was 99% for the quadrivalent vaccine. Although high efficacy among persons without evidence of infection with HPV types included in the vaccines was demonstrated in clinical trials of both bivalent and quadrivalent HPV vaccine, there is no evidence of vaccine effectiveness or any therapeutic effect on existing infection or disease. Vaccinated participants infected with one or more vaccine HPV types prior to vaccination were protected against disease caused by the other vaccine types. Prior infection with one HPV type did not diminish efficacy of the vaccine against other HPV vaccine types. 9vHPV was licensed in the United States in December 2014. Originally the vaccine was approved for use in females 9 through– 26 years of age and males 9 through– 15 years of age. Males 16 through– 26 years were not part of the original submission to the FDA. Additional studies with older male adolescents and adults were conducted and submitted to FDA. 9-valent vaccine was approved for older male adolescents and adults in December 2015. As noted earlier, this vaccine targets the HPV types included in the quadrivalent vaccine as well as an additional 5 types shown here on the slide in yellow. 9-valent vaccine has been shown to be noninferior immunogenicity to quadrivalent vaccine for all serotypes and age groups and approximately 97% effective against the 5 additional HPV types in the vaccine. In the United States, approximately 64% of invasive HPV-associated cancers are attributable to HPV 16 or 18. All three vaccines protect against these types. 11% of HPV-associated cancers are attributable to the 5 additional types in 9vHPV. The 5 additional types account for 14% of HPV-associated cancers in females and 4% of HPV-associated cancer in males. For cervical precancer lesions or CIN-2 or worse, approximately 50% are caused by HPV type 16 or 18, and 25% by the other 5 HPV types. 9-valent HPV can be administered at the same clinical visit with other routine vaccines administered to adolescents; Tdap or meningococcal conjugate vaccine, for example. The safety profile is similar to that of the quadrivalent vaccine. The duration of protection following HPV vaccine is not known. A subset of participants who received bivalent vaccine and quadrivalent vaccine have been followed for many years with no evidence of waning protection. Ongoing studies of vaccinated populations including those that received 9-valent vaccine will continue to be followed for any evidence of waning immunity. This slide is the 2016 childhood immunization schedule. The line in the red box indicates the HPV schedule. Schedule footnotes highlight recommendations in greater detail.

5 HPV immunization recommendations span both childhood and adult immunization schedules. These schedules show the adult immunization schedule age related figure, figure 1. Again, HPV vaccine is highlighted by the red box. This slide shows figure 2 of the 2016 adult immunization schedule. Those at increased risk based on medical or other indications and immunization recommendations for these populations. Again, HPV is highlighted by the red box. Now, here are the current ACIP recommendations. ACIP recommends routine vaccination at age 11 or 12 for boys and girls. The vaccination series can be started beginning at age 9 years. Routine catch-up is recommended for females age 13 through– 26 years and males age 13 through– 21 years who have not been vaccinated previously or who have not completed the 3-dose series. Vaccination is recommended for men who have sex with men and immunocompromised men including those with HIV infection through age 26 years. HPV vaccine is recommended for all women through age 26 and males age 22 through– 26 may be vaccinated. So the 3-dose series can be started at age 26 even if it will not be completed before the patient turns 27 years of age. This is a frequently asked question that we receive here at CDC. An incomplete series should be completed regardless of the age of the patient; that is even if the patient is older than 26 years of age. Females can be vaccinated with any of the 3 vaccine products. Males should be vaccinated with either quadrivalent or 9-valent vaccines. Regardless of the HPV product used the schedule is the same. The 2 nd dose should be administered 1-2 months after the 1st dose and the 3rd dose 6 months after the 1st dose. The minimal interval between the 1st and 2nd doses of HPV vaccine is 4 weeks. The minimum recommended interval between the 2nd and 3rd dose of vaccine is 12 weeks, and the minimum interval between the 1st and the 3rd dose is 24 weeks. Following an accelerated schedule using minimum intervals is not recommended. ACIP recommends following the recommended schedule of 0, 1-2, and 6 months. There is one additional HPVHVP vaccine interval issue that is frequently asked. ACIP has not defined a maximum interval between HPV vaccine doses. If the vaccine schedule is interrupted and the interval between doses is longer than recommended, you should just continue the series where it was interrupted. It is not necessary to add doses or restart the series because of an extended interval between doses. Just pick up where the series left off and complete the needed doses. HPV vaccine should be administered at the same visit as other age-appropriate vaccines such as Tdap, influenza, and quadrivalent meningococcal vaccines. Administering all indicated vaccines at a single visit increases the likelihood that adolescents and young adults who receive each of the vaccines on schedule. Prevaccination testing such as PAP tests, screening for high risk HPV DNA, type specific HPV test, or HPV antibody or pregnancy testing is not needed nor recommended to determine if HPV vaccine can be administered. Patients should be

6 advised the vaccine will not have a therapeutic eaffect on existing HPV infection, genital warts or cervical lesions as we talked about earlier. There is no data on the schedules that include multiple products. The response to types 16 and 18 are likely to be similar when multiple products are used to complete the series. Protection against types other than 16 and 18 is probably reduced if fewer than 3 doses of quadrivalent of 9-valent vaccine is received. ACIP recommends providers use the same product for all 3 doses in the series whenever possible. But ACIP also recognizes that providers may not know or may not have the product previously administered. If providers do not know or do not have the previously administered product available, ACIP recommends providers administer the product available based on product indications. Females may receive any of the 3 HPV vaccine products. Males should only receive the quadrivalent of 9-valent HPV vaccine products. The HPV work group of ACIP recognized that there are many questions regarding these 3 products and developed supplemental information and guidance for providers regarding the use of 9-valent HPV. This FAQ document is posted on the ACIP web page and is very helpful. I recommend that you share this document with staff. There are a variety of what ACIP calls special situations with HPV vaccines. Vaccine can be administered to females 26 years of age or younger with an equivocal or abnormal PAP test, a positive HPV DNA test, meaning they are currently infected, or those with genital warts. Remember, as noted earlier, these women should be informed that the vaccine will have no effect on existing disease or infection. Females who are breastfeeding may be vaccinated also. HPV is an inactivated vaccine so it may be administered to immunocompromised persons for whom vaccination is recommended, including those with an HIV infection. ACIP prefers a conservative approach to the vaccination of pregnant women. The vaccine has not been causally associated with adverse pregnancy outcomes or with adverse effects on the developing fetus, but data on vaccination during pregnancy are limited. HPV vaccine is not recommended for use during pregnancy. If a woman is found to be pregnant after initiating the vaccination series, completion of the series should be delayed until after the pregnancy. If a vaccine dose has been inadvertently administered during pregnancy, there is no indication for medical intervention. A pregnancy registry has been established for 9-valent HPV vaccine and should be notified if the vaccine is inadvertently administered to a pregnant woman. Contact information for this registry is in the 9-valent HPV package insert. The bivalent and quadrivalent vaccine pregnancy registries have been closed with concurrence from FDA. Vaccination during pregnancy with any of the 3 vaccine products can be reported to the respective manufacturer and to the Vaccine Adverse Event Reporting system. HPV vaccine should not be administered to persons with a history of severe allergic reaction to a vaccine component or following a prior dose. GardasilGuardicil and GardasilGuardicil 9 are contraindicated for persons with a history of severe allergy to

7 yeast. Anaphylactic allergy to lLatex is a contraindication to Cervirax vaccine in a manufactured filled syringe since the tip cap may contain natural rubber Latex. A moderate or severe acute illness is a precaution to vaccination and vaccination should be deferred until symptoms of the acute illness improve. A minor acute illness such as diarrhea or a mild respiratory tract infection with or without a fever is not a reason to defer vaccination. The most common adverse reactions reported during clinical trials of HPV vaccines were local reactions at the site of injection. These included pain, redness or swelling at the injection site. Local reactions generally increased in frequency with doses 2 and 3. A similar proportion of recipients reported an elevated temperature. However, reports of fever did not increase significantly with subsequent doses. A variety of systemic adverse reactions were reported by vaccine recipients including nausea, dizziness, headache, malaise and myalgia. However, these symptoms occurred with equal frequency among both vaccine and placebo recipients. No serious adverse events have been associated with any HPV vaccine based on monitoring by CDC and FDA. Now let’s talk about vaccination rates. Despite increases in other routinely recommended adolescent vaccines, vaccination coverage estimates for Human Papillomavirus vaccine remained low in 2015 and continue to lag behind rates for Tdap and quadrivalent meningococcal conjugate vaccine. The strong coverage rates for Tdap and meningococcal conjugate vaccine demonstrate that not only are most preteens and teens getting to the doctor, but they are also getting at least one of the recommended adolescent vaccines. The chart on this slide demonstrates had HPV vaccine been administered during healthcare visits when another vaccine was administered, vaccination coverage for at least 1 dose could have reached 91.3% by age 13 for adolescent girls born in 2000. High HPV vaccination coverage with existing infrastructure and healthcare utilization is possible in the United States. Taking advantage of every healthcare encounter including acute care visits to assess every adolescent’s vaccination status can help minimize missed opportunities. Additional strategies to improve HPV vaccination rates include using vaccination prompts available through electronic health records or checking local and state immunization information systems to assess vaccination needs at every encounter so that an opportunity to provide the vaccine is not missed. Communicating about HPV vaccine during the health encounter is very important to vaccine acceptance and can sometimes be a challenge. Several qualitative evaluations have been done regarding this issue. Common themes found from these studies show that the vaccine is often presented as optional whereas other vaccines indicated for adolescents were recommended. Also some providers expressed mixed or negative opinions about the vaccine. When parents expressed reluctance to the vaccine or asked questions, providers were hesitant to engage in discussion. Finally, some providers shared the parents’ view that it was acceptable to delay vaccination until the teen was older.

8 Studies have been conducted and consistently show that a strong recommendation from you as their healthcare provider is the single best predictor of vaccination for any vaccine including HPV vaccine. In the 2014 NIS teen, nearly 15% of all parents who said that they would not be getting their child vaccinated against HPV in the next 12 months stated this was based on not receiving a recommendation as one of their top reasons. We can see based on this data, a strong recommendation for vaccination with HPV is very important. Recommend HPV when discussing other adolescent vaccines making it a part of your standard procedure. Recommend all indicated vaccines in the same way on the same day. Additional strategies found to increase vaccination rates include those we’ve already discussed; using vaccination prompts available through electronic health records, checking local and state immunization information systems to assess vaccination needs, implement a system for sending out reminders of doses due and a recall for those who miss an appointment. Consider using standing orders if they would be appropriate in your practice. Series completion also can be promoted through scheduling appointments for 2nd and 3rd doses before patients leave the facility. Don’t miss opportunities to vaccinate. In the last bullet on this slide I’ve included a web address where you can find many tools to help you with HPV vaccination and talking with teens and parents. Here are some of the resources I just mentioned. The HPV web portal is where all our materials can be found and we encourage all of you to visit this site and make use of the various items there to educate patients and to educate staff about HPV vaccine. It’s important to note that you want everyone in your office to be giving the same message to your patients and recommend vaccination. All HPV vaccines should be stored in the refrigerator between 2º - 8º C or 36º - 46º F. Store these vaccines in their original packaging as they need to be protected from light. Administer HPV vaccines 2vHPV, 4vHPV and 9vHPV via intramuscular injection using a 1to 11/2 inch -1/2” needle 23 to – 25 gage. Always use professional judgment to determine the correct needle length for your patient. The preferred site is the deltoid muscle in the upper arm but the vastus lateralis located in the thigh may also be used. Always follow aseptic a septic technique when preparing and administering vaccines. A new needle and syringe should be used for each injection. A single dose vial is for one patient only. An adhesive bandage may be applied to the site if bleeding occurs. And as we mentioned earlier, HPV vaccine can be administered during the same clinical visit as other indicated vaccines such as flu or meningococcal B vaccine. Syncope has been reported among adolescents and we frequently get asked questions about this. Syncope does occur among adolescents who received HPV and other vaccines recommended for this age group. 70% of syncopal episodes occurred within 15 minutes of vaccination. Recipients should be seated during vaccine administration

9 and ACIP recommends clinicians should consider observing recipients seated for at least 15 minutes after vaccination to prevent any injuries. There is a list of HPV resources available on the net conference web page. The link is on this slide. Included is information for healthcare providers on vaccine recommendations, administration and vaccine storage and handling. Of note, there is a link, a standing order template for HPV vaccine developed by the Immunization Action Coalition. As mentioned earlier, a best practice is using a standing order if it’s appropriate for your facility. It also helps to keep everybody on the same page in your facility. For parent and patient materials and information on recommendations, disease and vaccination safety are outlined. Partners in other programs will find links to resource materials such as matt articles, video and audio resources. I encourage you all to review these helpful materials. Now I would like to turn the conference back to Dr. Robinson …..

Thank you very much, Ms. Wolicki. On the screen you will see continuing education credit information including the verification code for today’s course. Please make note of this verification code as it will not be given outside of this presentation. Today’s verification code is 2016-HPV, and this verification code applies to both the live program and the enduring program. I will repeat the verification code is 2016-HPV. There also is a resource pod on your screen where you can click on files to obtain instructions for CE. Now I will review some of the questions that we’ve received during the program. Please continue sending these questions to the QA pod. I will remind listeners to make sure your question is related to today’s content. So our first question. Some parents resist HPV vaccination of their 11 or 12 year old because they are not sexually active or because they feel that the vaccine will give the child permission to engage in sexual activity. How do we counter this position? Thank you for this question. It’s a really good question and one that I think we all can relate to. Explaining to the parent that vaccination starting at 11 to 12 years of age will provide the best protection possible long before the start of any kind of sexual activity. That’s very important to get across to parents is that really for the best protection we want to give the child this vaccine long before they are going to engage in any sexual activity. Another thing that you might want to mention to them is that this is a 3-dose series that is given over at least 6 months, maybe even longer to get in. So it’s not just one dose and go. I think sometimes parents get confused by that because the Tdap vaccine is a 1-dose vaccine so I think sometimes when you’re in there and you’re talking to them and the adolescent is giving you the eye because they want to leave, things can get kind of muddled. So it’s very important that parents know that it’s 3 doses to provide protection and this is going to nna need to be given over a period of

10 time. So one dose at 11 to 12 is not going to protect them and they need to give them time to get it in. It is standard practice to vaccinate people before they are exposed to the infection as with the case for measles and other recommended child vaccines, so we’re really not doing anything any different than any of our other vaccination recommendations. Similarly, we want to vaccinate the children before they get exposed to HPV. Studies of HPV vaccine indicate that younger adolescents respond better to the vaccine than older adolescents and young adults. And finally, there is no evidence that receipt of HPV vaccine increases the chance that a child will become sexually active. Great. Thank you very much. Our next question is if a person already has HPV, so they’ve already been found to be HPV positive and they’re within the recommended age range, can they still get the vaccine? That’s a really good question and one that I know can get very confusing for people because usually we give them the vaccine to protect them against the disease, so if they’re already had the disease they may not need the vaccine, but that’s not the case with HPV. HPV has over 150 types, as we mentioned earlier, so even if they have the disease, they may not have been infected with one of the vaccine types and so they will mount a response to those types and even if they have one of the vaccine types, while it will not treat or they can’t use it for any treatment of the disease, they will mount a response to any types that they have not been exposed to. So I would say it’s critical that you want to get HPV vaccine into these people. Thank you very much. The next question is, I’ve read that HPV vaccine should not be administered to pregnant women. Do we need to perform a pregnancy test prior to administering these vaccines to our patients? Currently we just ask about pregnancy prior to providing the vaccine. That’s true. They’re right. HPV vaccines are not recommended for use in pregnant women but the vaccines have not been associated causally with any adverse outcomes of pregnancy or adverse events in the developing fetus. So if a woman is found to be pregnant after initiating the vaccine series, the remainder of the 3-dose series should be delayed until after completion of the pregnancy. There is no need for any type of medical intervention. What we need to do is just stop, put a pause on it, we’re gon ing tona hit the pause button, we’re goning to na stop the series right now, we’re gonnagoing to wait for the completion of the pregnancy and then we’re just goning to na —once she’s no longer pregnant we’re just goning tona pick up where we left off and start and complete the series. Pregnancy testing is not needed before vaccination. So currently what they’re doing now is just asking about pregnancy prior to providing the vaccine is perfectly appropriate and a good idea. Thank you very much. Our next question. We’ve been told that Cervarix is no longer being produced and that quadrivalent is no longer being produced and that only 9-valent HPV is currently available.

11 While that’s true that they are in the process of decreasing and no longer producing it, we still right now have a market that all three products are available. So it’s very important to make sure that your staff is knowledgeable about the product that you currently have in your inventory and that you certainly double check and make sure that you’re following the indications for the product in your inventory. That being said, because of this we’re in the process of transitioning over to the 9-valent vaccine. If this is a new vaccine product for your office, again, it’s extremely important that the staff within your office are knowledgeable about the indications, they’re knowledgeable about how it should be administered, all of those things, how it should be stored and handled. Whenever a new product is in an office, it’s very important to make sure staff are up to date about that vaccine and knowledgeable about it. Great. Thank you very much. And I would add to that, you know, even when companies decide that a vaccine is no longer produced, there may still be doses of that vaccine that have not yet expired. So even if the company does cease to produce it, you may still as Ms. Wolicki pointed out, have doses of that vaccine in your inventory that are not yet expired that may still be administered according to the recommendations. So it’s important, as Ms. Wolicki pointed out, to be familiar with what’s in your inventory and what you have available to vaccinate your patients with. Right. Transition periods are always complicated and they always get a little confusing for staff. So that’s why I think it’s important to touch base with them, like you said, Dr. Robinson. I think that’s a really good point. Thank you. Our next question is kind of a follow-up to the previous question about pregnant women. We inadvertently gave HPV vaccine to a woman who didn’t know she was pregnant at the time. How should we complete the schedule? Well, first of all it’s goinggonnagoing to to depend on the product that you gave or your actions that you’re going to gonnagoing to take at this point. The formal pregnancy registries for the quadrivalent and the bivalent vaccines have been closed. However, Merck has established a registry for women who inadvertently received 9vHPV during pregnancy. So you should certainly contact the registry and let them know that. You’re gonnagoing to put the series on pause and you’re gonnagoing to complete the series when she is no longer pregnant. After the pregnancy is completed you’re gonnagoing to administer the remaining doses of the series using the usual schedule. HPV2 assuming 1-2 months have passed since HPV1, you’re gonnagoing to give HPV3 six months after HPV1 but no earlier than 12 weeks after HPV2. Of course, this is considered a vaccine administration error and you’re gonnagoing to want to inform the patient, you’re gonnagoing to want to reassure her about the safety data and the fact that there have been no adverse outcomes for either the pregnancy or the fetus and you can certainly report it to the Vaccine Adverse Event Reporting system also.

12 Thank you very much. Our next question that we’ve gotten from multiple people is if we have a patient who has completed a series of bivalent or quadrivalent HPV vaccine, are additional doses of 9-valent vaccine recommended for those persons who have already completed the series with one of the other vaccines? Thank you for that question. That’s an excellent, excellent question. Currently there is no ACIP recommendation for additional doses of 9-valent HPV for persons who have completed a series with the bivalent or the quadrivalent vaccine. So there’s no recommendations for any additional doses. Not one dose, not two dose, or not even a completed series of three. Great. Our next question we received is why is bivalent HPV not recommended for males? Actually, I’ll weigh in on this one. So bivalent vaccine is active against type 16 and 18 which mainly cause cervical cancer and a lot of the other strains covered in the quadrivalent of 9-valent vaccine are also active against the HPV strains that cause genital warts and other HPV-associated cancers such as anal cancer, etc. So the bivalent is not recommended for the males because they do not get the benefit of prevention of HPV strains that cause other HPV- associated cancers. Our next question that came in is can vaccination with HPV vaccine be started at 9 years of age? That’s a really good question and certainly the vaccine is licensed down to that age group. It certainly can be started at the provider’s discretion. So if they have a child that’s 9 years of age and feel that that child is at risk for an HPV infection, the vaccine can certainly be given as early as 9 years of age. The series can be started and completed. Absolutely, and I would also add to that, if that child has had a high risk exposure in the past, so if they’ve had a history of sexual abuse or anything like that, they should actually be started at 9 years if they have that history. However, even if they don’t have that history, at the discretion of the provider it can absolutely be started at age 9 so thank you very much. That’s a really good point, Dr. Robinson, that certainly if they have had any diagnosis or if you’re aware of any information that would put these children at risk for an HPV infection, the vaccination should be started. Thank you. We received this question. Are PAP smears still necessary for women who receive HPV vaccine? I get this question a lot. I have two daughters so I get this question a lot especially from their friends. They sort of like to think that this is a get out of jail free card for PAP smears but it’s not. So vaccinated women still need to see their healthcare provider for periodic cervical cancer screening. The vaccine does not provide protection against all the types of HPV that cause cervical cancer. So even vaccinated women may still be at

13 risk for some of the cancers from HPV. So again, the cervical cancer screening, the PAP smears are very important to continue as a preventative health measure. Thank you. Our next question is if we have a male who comes into our office who is over 21 and they don’t say that they’re a male who has sex with other men or anything like that, can they still receive HPV vaccine? Do they have to declare one of these high risk conditions to receive the vaccine? That’s a really good question and, no, they don’t have to declare one of those high risk criteria for being vaccinated. The vaccine is certainly licensed for that age group. It may be given to that age group. That being said, it’s not recommended by ACIP for those persons. So one of the things that you might want to talk about with them is the fact that their insurance carrier may not cover the vaccine and let them know that they may potentially have to pay for the vaccine, but they certainly can be vaccinated. Thank you very much. I think that’s all the time we have for questions. We will answer any questions that we did not get to during this presentation will be posted on the web site along with the resources for your review. I will provide some continuing education credit information. Please go to the web page www2a.cdc.gov/TCEOnline to obtain credit. Today’s live CE event course number is WC2645-083116. To repeat, WC2645-083116. That is today’s date and differentiates this presentation from others in the series. CE credit for the live course will expire on October 3, 2016. You can also search for the enduring archive course number which is different. It lasts until June 01, 2018, and note that course number is WD2645-083116. You will also need the verification code which is 2016-HPV. This verification code, again, applies to both the live program and the enduring program. I will repeat the verification code is 2016-HPV. For help with the online system available 8:00 a.m. to 4:00 p.m. Eastern time, please dial 1-800-41-TRAIN. This corresponds to 1-800-418-7246, or you can email [email protected]. If you have additional questions that you didn’t ask on today’s program, you may email us at [email protected]. We’ll try to respond to those as quickly as possible. And like I said earlier, we will post questions and answers that we didn’t get to at www2.cdc.gov/vaccines/ed/pinkbook/pb13.asp. You can also call immunization questions at 1-800-CDC-INFO or 1-800-232-4636 from 8 a.m. to 8 p.m. Eastern time Monday through Friday. Additional resources include the Pink Book and the website for the Pink Book is www.cdc.gov/vaccines/pubs/pinkbook/index.html. It’s available online or you can purchase a hardcopy at the link for the Public Health Foundation Learning Resource Center. Our CDC vaccine home page is www.cdc.gov/vaccines/default.htm. Our resource guide for healthcare personnel entitled CDC Immunization Resources for You and Your Patients is listed at www.cdc.gov/vaccines/ed/downloads/imz-resources.pdf. That concludes our program. I want to thank Ms. JoEllen Wolicki for the presentation covering today’s topic in

14 great detail and for answering your questions. Thank you very much and have a great day from Atlanta.