HPV9 Vaccine for the Prevention of Human Papillomavirus–Related Cancers

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HPV9 Vaccine for the Prevention of Human Papillomavirus–Related Cancers

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The human papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the United States (Centers for Disease Control and Prevention [CDC], 2013). HPVrelated disease is a significant public health concern both in the United States and globally. There are more than 100 different strains of HPV, and more than 40 are transmitted sexually and infect mucosal surfaces (CDC, 2013).

HOLLY B. FONTENOT HEIDI COLLINS FANTASIA Persistent infection with HPV has been identified as the causative factor in the development of invasive cervical cancer (Clifford, Smith, Plummer, Muñoz, & Franceschi, 2003; Schiffman, Castle, Jeronimo, Rodriguez, & Wacholder, 2007). HPV infection has also been identified as

Abstract Human papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the United States, with approximately 79 million Americans currently infected. Persistent infection with HPV has been identified as the causative factor in the development of invasive cervical cancer as well as other oral and genital cancers in women and men. The quadravalent HPV4 vaccine has been available since 2006. In December 2014, the U.S. Food and Drug Administration (FDA) approved the HPV9 vaccine that provides coverage for five additional oncogenic strains of HPV that are not included in the first generation vaccine. DOI: 10.1111/1751-486X.12223 Keywords HPV | HPV9 vaccine | human papillomavirus | sexually transmitted infection

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the cause of anal-genital and/or oral condylomas (genital warts) as well as other cancers for men and women, including anal, penile, oropharyngeal, vulvar and vaginal cancers (CDC, 2013; Dunne et al., 2014). In December 2014, the U.S. Food and Drug Administration (FDA) approved HPV 9 valent recombinant vaccine (HPV9; Gardasil 9®) for the prevention of diseases caused by nine strains of HPV (6, 11, 16, 18, 31, 33, 45, 52 and 58; FDA, 2014). This vaccine covers an additional

HPV vaccination has been identified as the primary preventive strategy to reduce the rates of HPV infection and HPV-related cancers

Holly B. Fontenot, PhD, RN, WHNP-BC, is an assistant professor in the William F. Connell School of Nursing at Boston College in Chestnut Hill, MA, and a women’s health nurse practitioner at the Sidney Borum Jr. Health Center in Boston, MA. Heidi Collins Fantasia, PhD, RN, WHNP-BC, is an assistant professor in the College of Health Sciences, School of Nursing, at the University of Massachusetts Lowell in Lowell, MA, and a nurse practitioner for Health Quarters in Beverly, MA. Dr. Fontenot reports no conflicts of interest or relevant financial relationships. Dr. Fantasia discloses that she is a member of the women’s health advisory board for Actavis Pharma, for which she receives financial consideration. Actavis Pharma had no involvement in the creation of this article. Address correspondence to: Heidi_ [email protected].

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five oncogenic strains of HPV not included in the quadravalent HPV4 (6, 11, 16 and 18; Gardasil®) vaccine that has been in use since 2006. This column will provide an overview of HPV9, prescribing and vaccine administration information and implications for nursing practice.

Overview of HPV and FirstGeneration HPV Vaccines Approximately 79 million Americans are currently infected with HPV and there are 14 million new cases each year (CDC, 2015a). HPV is primarily spread by vaginal, anal or oral sex, and can be transmitted even if an infected individual has no signs or symptoms (CDC, 2014). HPV vaccination has been identified as the primary preventive strategy to reduce the rates of HPV infection and HPV-related cancers. It’s estimated that in the United States, approximately 21,000 HPV cancers could be prevented by vaccination each year (CDC, 2014). Currently, the CDC and Advisory Committee on Immunization Practices (ACIP) recommend routine HPV vaccination for all males and females ages 11 to 12 with routine recommended catch up vaccination for females though age 26 and males through age 21. Males also may be vaccinated through age 26, and vaccination is recommended for men who are immunocompromised and who have sex with men (CDC, 2011; Markowitz et al., 2014). The first generation of HPV vaccines include HPV4 and HPV2 (Cervarix®) and these vaccines

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prevent the two primary oncogenic types of HPV (16 and 18). HPV4 also offers protection against two nononcogenic types of HPV (6 and 11). Types 16 and 18 are the known cause of 70 percent of cervical cancers in women and Types 6 and 11 are the known cause 90 percent of genital warts in men and women (CDC, 2015a). These current vaccines (on the market for nearly 10 years) have been demonstrated to be both safe and effective. As of 2012, more than 46 million doses of primarily HPV4 have been distributed in the United States and studies have not identified any serious safety concerns. Vaccine efficacy in clinical trials of youth who had not been previously exposed to targeted HPV types shows 93 percent to 100 percent efficacy in preventing cervical, vulvar and vaginal precancers in women and 75 percent efficacy in prevention of anal precancers in men (CDC, 2015a).

Overview of HPV9 This new second-generation HPV vaccine, HPV9, is expected to add additional cancer protection. With the addition of coverage for five more oncogenic types of HPV (Type 31, 33, 45, 52 and 58) beyond the current HPV4 vaccine, HPV9 has the potential to prevent 90 percent of cervical cancers as compared to HPV4 and HPV2, which covered for 70 percent of these cancers (FDA, 2014; Joura et al., 2015). The added five types are the cause of approximately 20 percent of cervical cancers that were not covered in the first-generation vaccines (FDA, 2014). According to Joura et al. (2015), HPV9 efficacy for the five additional types (31, 33, 45, 52 and 58) was 96.7 percent and the antibody response to the previous four HPV types (6, 11, 16 and 18) was noninferior to HPV4. It’s estimated that HPV9 will provide approximately 97 percent reduction in HPV-related disease (Luxembourg, 2014a). Safety was also reported as similar to HPV4, showing comparable tolerability and adverse experience profiles.

Dosage and Administration HPV9 is supplied as a single dose vial or prefilled syringe. The dose is 0.5 mL intramuscularly per individual injection (Merck & Co., Inc., 2014). Injection sites include the deltoid area of the arm or high anterolateral thigh. The vaccine is in a suspension and must be shaken well prior

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to injection. HPV9 is administered as a three-dose series at 0, 2 and 6 months, exactly the same as for HPV4 (Merck & Co., Inc., 2014). It should be refrigerated and can be administered immediately after removal. There is no need to bring the vaccine to room temperature prior to administration.

Drug Interactions Individuals who are taking immunosuppressive medications may have a decreased immune response to HPV9. This could result in reduced vaccine efficacy. If possible, clients and their health care providers should consider postponing the vaccine series until a full immune response is most likely (Merck & Co., Inc., 2014). There are no contraindications to administering HPV9 with other scheduled immunizations, including Tdap, meningococcal, influenza and hepatitis B vaccines (CDC, 2015a).

Contraindications

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HPV9 is contraindicated for individuals who are allergic to yeast, which is a vaccine component. Individuals who

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Box 1.

HPV9 Pregnancy Registry 1-800-986-8999 (for women exposed at time of conception or during pregnancy)

had a hypersensitivity or anaphylactic reaction to a previous dose of HPV9 or HPV4 shouldn’t continue to receive additional doses (Merck & Co., Inc., 2014). Consistent with general recommendations for all vaccines, HPV9 can be given during episodes of mild illness, but should be postponed if a client is reporting moderate to severe acute illness (CDC, 2015a).

Adverse Effects The most common adverse reactions are those consistent with vaccine administration in general, and may include syncope and local injection site reactions. Localized reactions can include pain, erythema, induration and swelling. In a large international clinical trial, 90 percent of HPV9 injection site adverse events were mild to

moderate with slightly higher injection site swelling, redness, itching and pain compared to the first-generation HPV4 vaccine (90.7 percent vs. 84.9 percent; Joura et al., 2015). Other systemic reactions that have been reported include headache, fever, nausea and dizziness. These adverse effects are similar to the currently available first-generation HPV vaccines (CDC, 2015a; Merck & Co., Inc., 2014). Researchers have not found an association between the firstgeneration HPV4 vaccine and the development of multiple sclerosis or other demyelinating diseases (Scheller et al., 2015).

Special Populations HPV9 is identified as a category B medication. Animal studies haven’t shown any evidence of fetal harm or impaired fertility although no adequate, wellcontrolled studies have been done with women (Merck & Co., Inc., 2014). HPV9 vaccination isn’t recommended during pregnancy, and women who are pregnant should wait until after birth to start or complete the series. If a woman receives vaccination during pregnancy she should enroll in the Pregnancy Registry established by Merck & Co., Inc. (see Box 1). It’s not known if the HPV9 vaccine is excreted in breast milk; therefore, decisions to breastfeed after receiving the vaccine should be made in consultation with a health care provider. Safety of the HPV9 vaccine has been established in children, adolescents and young adults between the ages 9 and 26. The HPV9 vaccine is not approved for women beyond the age of 26 and hasn’t been studied in the geriatric population (Merck & Co., Inc., 2014).

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As of March 2015, the ACIP updated HPV vaccine recommendations to include HPV9. The new HPV9 recommendations follow the same recommendations set for HPV4 (Petrosky et al., 2015). It will be important for nurses to continue to follow updates in vaccine recommendations and check the CDC or ACIP websites for new recommendations as additional guidelines for health care providers are expected to be released in late 2015 or 2016. Questions remain regarding the following: (1) transitions to this new vaccine, cost structures and how HPV9 will roll out to the public for use, (2) if or how to transition clients to the new vaccine when they’re mid-dose in the vaccine series and (3) if vaccination with HPV9 after previous vaccination with HPV4 will be recommended. It’s expected that HPV9 will eventually replace HPV4 and that insurance will cover HPV9, but nurses should follow updates as companies make them available. A clinical trial has evaluated safety of HPV9 for those who have already received HPV4, and findings highlight HPV9

Adolescents and their parents often have busy schedules, so it’s important to set up reminder systems, including electronic health record reminders, emails, texts or phone calls to help to facilitate three-dose completion

as having an acceptable safety profile as well as an adequate immunogenic response to the new types in HPV9 for those with prior HPV4 threedose completion (Luxembourg, 2014b). Current rates of HPV vaccination and threedose completion in the United States are far below national goals. Healthy People 2020 goals are to increase three-dose HPV vaccination

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completion rates to 80 percent for both young males and females (Office of Disease Prevention and Health Promotion, 2015). Current national vaccination rates for adolescent females (ages 13 to 17 years) receiving ≥ 1 dose are 57.3 percent and 37.6 percent receiving ≥ 3 doses. For males (ages 13 to 17 years) rates are even lower, with only 34.6 percent receiving ≥ 1 dose and 13.9 percent receiving ≥ 3 doses (Stokley et al., 2014). Also, state by state rates differ ranging from 28.8 percent to 73 percent for ≥ 1 doses, and vaccine initiation and completion is reported to be lower in Southern states as compared to the national average (Jemal et al., 2013). In the United States the overall incidence rates for cancers have declined; however, incidence rates for two HPVrelated cancers (oropharyngeal and anal) are on the rise (Jemal et al., 2013). Nurses can help to reduce disparities in HPV vaccination initiation and completion and address national public health goals by routinely recommending HPV vaccination to all eligible clients. Researchers have reported that recommendation by a health care provider is a main predictor for adolescent HPV vaccination, but barriers still exist (Conroy et al., 2009; Reiter,

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Implications for Nursing Practice

Brewer, Gottlieb, McRee, & Smith, 2009). Adolescents and their parents often have busy schedules, so it’s important to set up reminder systems, including electronic health record reminders, emails, texts or phone calls to help to facilitate three-dose completion. It’s also important to help to establish practice protocols to monitor all clients, especially adolescents, immediately postvaccine injection for syncope or any other adverse events. The vaccine should be administered while the client is seated or lying down, and clients should be encouraged to wait in the office for 15 minutes after injection to be monitored for dizziness or syncope (CDC, 2015a). Nurses are positioned to be leaders in health education by providing accurate and timely HPV information to clients and parents. As part of overall health education on the vaccine, evidence-based information about vaccine effectiveness and safety is essential. Anticipatory guidance may be helpful to dispel concerns about common side effects, such as pain and discomfort at injection site. The safety of the firstgeneration HPV4 vaccine has been established over the past 10 years and no significant safety concerns have been established (CDC, 2015a). Safety of the HPV9 vaccine has been documented using this data. Any actual or suspected adverse events should be reported to the Vaccine Adverse Event Reporting System (VAERS) that has been

established by the CDC and the FDA (see Box 2). Lastly, nurses should promote routine HPV vaccination at the CDCrecommended age (11 to 12 years) with other routinely recommended vaccinations for that age frame (Tdap and Meningococcal vaccines; CDC, 2015b). If older adolescents or young adults are seeking catch up vaccination through age 26, this might also be a good time for nurses to take the opportunity to discuss safer sexual behaviors, such as delaying sexual activity, limiting lifetime sexual partners and using condoms consistently. HPV vaccination is recommended prior to sexual debut before sexual exposure to HPV can occur, but can be given after the onset of sexual activity (CDC, 2011). If infection with one or more types of HPV has already occurred, the vaccine will not eliminate existing disease or make it worse (CDC, 2015a), but it may offer protection for additional types of HPV the client hasn’t been exposed to. Despite HPV vaccination status, nurses need to reinforce routine cervical cancer screenings per national guidelines for all women and encourage clients to follow-up appropriately related to Pap testing.

Conclusion In December 2014, the FDA approved a new HPV vaccine that offers a potential to further reduce the burden of HPV-related cancers, especially cervical

Box 2.

Vaccine Adverse Event Reporting System (VAERS) Adverse events related to the HPV9 vaccine can be reported three ways: 1. Online form: vaers.hhs.gov/index 2. Printed form faxed to (877) 721-0366 3. Printed form mailed to: VAERS P.O. Box 1100 Rockville, MD 20849-1100

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cancers. This new HPV9 vaccine includes HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58, and will most likely be available to the public in 2015. The new vaccine increases protection against cervical cancers from 70 percent to 90 percent. Nurses need to be ready to answer questions from clients, parents and other health care providers related to the HPV9 vaccine and the benefits it offers. According to Trottier (2012), “HPV vaccine, one of the most remarkable discoveries of the past decade, is currently implanted all around the world and is expected to prevent a substantial proportion of cervical and other HPV-related cancers in the future” (p. 12). The first generation of HPV vaccines have demonstrated efficacy in reducing the burden of HPV-related diseases and cancers nationally and internationally (Brotherton, et al., 2011; Markowitz et al., 2013) and now researchers will be monitoring the global impact of the new second-generation HPV9. NWH

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information for clinicians—Fact sheet. Atlanta, GA: Author. Retrieved from www.cdc.gov/std/hpv/stdfact-hpvvaccine-hcp.htm Centers for Disease Control and Prevention (CDC). (2015b). 2015 Recommended immunizations for children from 7 through 18 years old. Atlanta, GA: Author. Retrieved from www.cdc. gov/vaccines/who/teens/downloads/ parent-version-schedule-7-18yrs.pdf Clifford, G. M., Smith, J. S., Plummer, M., Muñoz, N., & Franceschi, S. (2003). Human papillomavirus types in invasive cervical cancer worldwide: A meta-analysis. British Journal of Cancer, 88(1), 63–73. doi:10.1038/ sj.bjc.6600688 Conroy, K., Rosenthal, S. L., Zimet, G. D., Jin, Y., Bernstein, D. I., Glynn, S., & Kahn, J. A. (2009). Human papillomavirus vaccine uptake, predictors of vaccination, and self-reported barriers to vaccination. Journal of Women’s Health, 18(10), 1679–1686. doi:10.1089/ jwh.2008.1329 Dunne, E. F., Markowitz, L. E., Saraiya, M., Stokley, S., Middleman, A., Unger, E. R. … Iskander, J. (2014). CDC grand rounds: Reducing the burden of HPV-associated cancer and disease. Morbidity and Mortality Weekly Report, 63(4), 69–72. Food and Drug Administration (FDA). (2014). FDA approves Gardasil 9 for prevention of certain cancers caused by five additional types of HPV (press release). Silver Spring, MD: Author. Retrieved from www. fda.gov/NewsEvents/Newsroom/ PressAnnouncements/ucm426485. htm?source=govdelivery&utm_ medium=email&utm_ source=govdelivery Jemal, A., Simard, E. P., Dorell, C., Noone, A. M., Markowitz, L. E., Kohler, B., … Edwards, B. K. (2013). Annual Report to the Nation on the Status of Cancer, 1975-2009, featuring the burden and trends in human papillomavirus (HPV)-associated cancers and HPV vaccination coverage levels. Journal of the National Cancer Institute, 105(3), 175–201. doi:10.1093/jnci/djs491 Joura, E. A., Giuliano, A. R., Iversen, O. E., Bouchard, C., Mao, C., Mehlsen, J., … Luxembourg, A. (2015). A 9valent HPV vaccine against infection and intraepithelial neoplasia in women.

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New England Journal of Medicine, 372(8), 711–723. doi:10.1056/NEJMoa1205044 Luxembourg, A. (2014a). 9-Valent HPV (9vHPV) vaccine program key results. Presented at Advisory Committee on Immunization Practices (ACIP) Meeting, February 2014. Summary Report: 9-valent HPV vaccine clinical trial data. Department of Helath and Human Services, Centers for Disease Control and Prevention, Advisory Committee on Immunization Practices (ACIP) Summary Report, February 26=27, 2014. Atlanta, GA. Retrieved from www.cdc.gov/vaccines/acip/meetings/ downloads/min-archive/min-2014-02. pdf Luxembourg, A. (2014b). 9-Valent HPV (9vHPV) vaccine program key results— Part II. Retrieved from www.cdc.gov/ vaccines/acip/meetings/downloads/ slides-2014-06/HPV-02luxembourgpost.pdf Markowitz, L. E., Dunne, E. F., Saraiya, M., Chesson, H. W., Curtis, C. R., Gee, J., … Unger, E. R. (2014). Human papillomavirus vaccination: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity & Mortality Weekly Report: Recommendations and Reports, 63(RR–05), 1–30. Markowitz, L. E., Hariri, S., Lin, C., Dunne, E. F., Steinau, M., McQuillan, G., & Unger, E. R. (2013). Reduction in human papillomavirus (HPV) prevalence among young women following HPV vaccine introduction in the United States, National Health and Nutrition Examination Surveys, 2003–2010. Journal of Infectious Diseases, 208(3), 385–393. doi:10.1093/ infdis/jit192 Merck & Co., Inc. (2014). Highlights of prescribing information (GARDASIL 9). Whitehouse Station, NJ: Author. Retrieved from www.merck.com/ product/usa/pi_circulars/g/gardasil_9/ gardasil_9_pi.pdf Office of Disease Prevention and Health Promotion. (2015). Healthy people 2020 topics & objectives: Immunization and infectious diseases. Washington, DC: U.S. Department of Health and Human Services. Retrieved from www.healthypeople. gov/2020/topics-objectives/topic/ immunization-and-infectious-diseases/ objectives

Petrosky, E., Bocchini, J., Hariri, S., Chesson, H., Curtis, R., Saraiya, M., … Markowitz, L. E. (2015). Use of 9-valent human papillomavirus (HPV) vaccine: Updated HPV vaccination recommendations of the advisory committee on immunization practices. Morbidity & Mortality Weekly Report: Recommendations and Reports, 64, 300–304. Reiter, P., Brewer, N. T., Gottlieb, S. L., McRee, A. L., & Smith, J. S. (2009). Parents’ health beliefs and HPV vaccination of their adolescent daughters. Social Science & Medicine, 69(3), 475–480. doi:10.1016/j.socscimed.2009.05.024 Scheller, N. M., Svanström, H., Pasternak, B., Arnheim-Dahlström, L., Sundström, K., Fink, K., & Hvidd, A. (2015). Quadrivalent HPV vaccination and risk of multiple sclerosis and other demyelinating diseases of the central nervous system. Journal of the American Medical Association, 313(1), 54–61. doi:10.1001/ jama.2014.16946 Schiffman, M., Castle, P. E., Jeronimo, J., Rodriguez, A. C., & Wacholder, S. (2007). Human papillomavirus and cervical cancer. Lancet, 370(9590), 890–907. Stokley, S., Jeyarajah, J., Yankey, D., Cano, M., Gee, J., Roark, J., … Markowitz, L. (2014). Human papillomavirus vaccination coverage among adolescents, 2007–2013, and postlicensure vaccine safety monitoring, 2006–2014—United States. Morbidity and Mortality Weekly Report, 63(29), 620–624. Trottier, H. (2012). Epidemiology of mucosal human papillomavirus (HPV) infections among adult and children. In D. V. Broeck (Ed.), Human papillomavirus and related diseases—From bench to bedside: Research aspects (pp. 3–18). Retrieved from www.intechopen. com/books/human-papillomavirusand-related-diseases-from-benchto-bedside-research-aspects/ epidemiology-of-mucosal-humanpapillomavirus-hpv-infections-amongadult-and-children

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