1. You are the key to cervical cancer prevention– update on current projects Rebecca B. Perkins MD MSc Associate Professor of Obstetrics and Gynecology Boston University School of Medicine/ Boston Medical Center 11/6/15

2. Presenter Disclosure Information Rebecca Perkins  I, Rebecca Perkins, have been asked to disclose any significant relationships with commercial entities that are either providing financial support for this program or whose products or services are mentioned during my presentations.  I have no relationships to disclose.  I may discuss the use of vaccines in a manner not approved by the U.S. Food and Drug Administration.  But in accordance with ACIP recommendations. MIAP 2014

3. Common misperceptions about HPV vaccination  Myth #1: HPV is rare and causes few serious problems  Myth #2: Most HPV goes away on its own  Myth #3: HPV vaccines have no direct benefit for boys  Myth #4: HPV vaccines are not safe  Myth #5: It’s fine to delay HPV vaccination until the parent or provider thinks the child is at risk for having penetrative vaginal-penile intercourse  Myth #6: HPV vaccines don’t work

4. Myth #1: HPV is rare and causes few serious problems  3 million Americans seek medical care for HPV each year  27,000 develop HPV-related cancers  HPV currently causes as many deaths annually as measles did in the pre-vaccine era

5. Average Number of New Cancers Probably Caused by HPV, by Sex, United States 2006-2010 CDC, United States Cancer Statistics (USCS), 2006-2010 Women (n = 17,600) Oropharynx n=1,800 10% Anus n=2,600 15% Cervix n=10,400 59% Vagina n=600 3% Vulva n=2,200 13% Men (n = 9,300) Anus n=1,400 15% Oropharynx n=7,200 77% Penis n=700 8%

6. HPV-Associated Cervical Cancer Incidence Rates by State, United States, 2006-2010 www.cdc.gov/cancer/npcr 4,ooo women die from cervical cancer in the US each year

7. Myth #2: Most HPV goes away on its own

8. Infection remains dormant for decades, then reactivates later in life as immune system declines  700 women aged 35-60  Only 13% of incident infections attributed to new sexual partners  85% of incident infections occurred during periods of abstinence or monogamy Early vaccination can prevent initial infection Rostich Cancer Res 2012, Gravitt JID 2013 Infections may be lifelong

9. Myth #3: HPV vaccines have no direct benefit for boys HPV is responsible for 70% of oropharyngeal cancers - More common in men - No screening test available

10. HPV-related tongue and tonsil cancers have more than doubled in the past 20 years Chaturvedi, J Clin Oncol, 2010

11. Oropharyngeal Cancer 11,000 cases annually, 7,000 in men Will be more common than cervical cancer by 2020 http://www.ghorayeb.com/OropharyngealCarcin oma.html J Clin Oncol 29:4294-4301. © 2011 by American Society of Clinical Oncology

12. Myth #4: HPV vaccines are not safe

13. Coincidence doesn’t mean cause  Bad things will happen to adolescents– the question is whether they happen more frequently after HPV vaccination Clothier, Med J Aust, 2013

14. HPV Vaccine Adverse Events (AEs)  170 million doses worldwide (Europe, Australia)  Most commonly reported AEs were mild  For serious AEs reported, no unusual pattern or clustering that would suggest that the events were caused by the HPV vaccine  These findings are similar to the safety reviews of MCV4 and Tdap vaccines  >62 million doses of HPV vaccine distributed in US since 2006

15. Studies on Gardasil (vs unvaccinated) have shown that vaccinated females are not more likely to develop:  2011- allergic reactions, anaphylaxis, Guillain–Barré Syndrome, stroke, blood clots, appendicitis, or seizures (than unvaccinated or who received other vaccines)  2013 – (almost 1 million girls) blood clots or AEs related to the immune & CNS  2014 – (>1 million women) venous thromboembolism or blood clots  2012 and 2014 – (2 studies) autoimmune disorders  2015 - MS or other demyelinating diseases 2012 - vaccine may be associated with skin infections where the shot is given during the two weeks after vaccination and fainting on the day the shot is received Vichnin, An Overview of qHPV safety: 2006-2015, PIDJ, 2015

16. Myth #5: It’s fine to delay HPV vaccination until the parent or provider thinks the child is at risk for having sex 80% of people will be exposed to HPV You can’t predict who or when 59% of physicians report “risk”-based vaccination

17. HPV Transmission  Most common route is sexual intercourse  genital-genital, anal-genital, oral-genital, manual-genital  Nearly 50% of high school students have already engaged in sexual (vaginal-penile) intercourse  1/3 of 9th graders and 2/3 of 12th graders have engaged in sexual intercourse  24% of high school seniors have had sexual intercourse with 4 or more partners Jemal A et al. J Natl Cancer Inst 2013;105:175-201

18. HPV is found in virgins  Study examined the frequency of vaginal HPV and the association with non-coital sexual behavior in longitudinally followed cohort of adolescent women without prior vaginal intercourse  HPV was detected in 46% of women prior to first vaginal sex  70% of these women reported non-coital behaviors that may in part explain genital transmission Shew, J Infect Dis. 2012

19. MYTH #6: HPV VACCINES DON’T WORK

20. Markowitz, et al. JID 2103 *weighted prevalence 33% of girls received 3 vaccines Prevalence of vaginal HPV decreased 56% 20 56% decline HPV Vaccine Impact: US

21. Genital warts among females by age group, CA Family PACT 2007-2010 * * * * P trend <.05 -10.0% -34.8% +10.1% +9.4% * Bauer, et al AJPH 2012

22. Near-disappearance of genital warts in Australia following introduction of HPV vaccination 70% vaccination rate Ali H et al. BMJ 2013;346:bmj.f2032 ©2013 by British Medical Journal Publishing Group Percent reporting genital warts 93% reduction in girls <21 82% reduction in boys <21

23. Vaccination by age 14 is twice as effective against cervical dysplasia Gertig DM, BMC Med 2013 % Reduction in cervical dysplasia 5 years after vaccination, by age at vaccination Age at vaccination Percent dysplasia reduction

24. Without vaccination, annual burden of genital HPV in U.S. females: 3 million cases, $7 billion American Cancer Society. 2008;. Schiffman Arch Pathol Lab Med. 2003; Koshiol Sex Transm Dis. 2004; Insinga, Pharmacoeconomics, 2005 10,400 new cases of cervical cancer 4,000 deaths 330,000 new cases of cervical dysplasia Requiring treatment 1.4 million new cases of LSIL (CIN1) 350,000 new cases of genital warts

25. Extrapolating the prior pyramid with projections of vaccine efficacy based on Australian data Cervical cancer 46% reduction in of cervical dysplasia requiring treatment 75% if vaccination by age 14 35% reduction in CIN1 92% reduction in genital warts

26. Impact of HPV vaccine on oral HPV infection 7,466 women 18-25 years of age randomized to receive HPV or hepatitis A (control) vaccine  5,840 gave oral specimens at the end of the 4-year study  Control vaccine group:15 HPV 16/18 infections  HPV vaccine group: 1 HPV 16/18 infections 26 Herrero R, et al. Reduced prevalence of oral human papillomavirus (HPV) 4 years after bivalent HPV vaccination in a randomized clinical trial in Costa Rica. PLOS ONE 2013;8:e68329 Estimated vaccine efficacy against oral HPV infection: 93.3%

27. HOW CAN WE MAKE SURE EVERYONE IS PROTECTED? In summary: HPV exposure is ubiquitous HPV causes many cancers HPV vaccine is safe HPV vaccine is effective

28. Evidence-based effective recommendation Effective framing  “Today your child is due for 3 vaccines: Tdap, HPV, and meningococcal.”  HPV is framed as important  Many parents just say yes– because they trust their provider!  Making the job harder  “Today your child is due for the Tdap and meningococcal vaccines. We should also talk about the HPV vaccine…”  HPV is framed as “something different”  Parents sense confusion and the provider’s job gets harder Effective framing works at least 10 times better! Opel DJ, Pediatrics, 2013

29. CDC campaign Direct to provider advertising in medical journals Presentations at regional and national provider conferences - ACOG - AAFP -AAP - NAP NAP

30. CDC Federal Funding of 6 New Projects  Academic Pediatric Association  Promote partnerships, train providers and resident faculty  https://www.academicpeds.org/ https://www.academicpeds.org/  American Academy of Pediatrics  Education and training for pediatric offices, includes QI activities, interface with immunization registries and outreach to state AAP chapters  http://www2.aap.org/immunization/http://www2.aap.org/immunization/  American Cancer Society  Increase rates at safety net clinics and CHCs by identifying best interventions. Outreach to state health departments and other agencies  www.cancer.org www.cancer.org MDPH 2015 30

31. CDC Federal Funding of 6 New Projects MDPH 2015 31 American Cancer Society – Roundtable Project − Convene stakeholder organizations involved with cancer prevention: immunization, healthcare delivery, public health, etc. Pilot projects will focus on overcoming barriers − www.cancer.org www.cancer.org National Area Health Education Centers (AHEC) Network –Train clinicians across disciplines nationwide, work with state health departments, inventory resources and develop resources needed –http://www.nationalahec.orghttp://www.nationalahec.org National Association of City and County Health Officers (NACCHO) –Build capacity for local health departments to implement HPV recommendations –http://www.naccho.org/http://www.naccho.org/ 11 more states/projects funded by CDC

32. ACS Grant: provider training to improve HPV vaccination rates Intervention components repeated contacts Education individualized feedback strong quality improvement incentives Pilot study results New grant Expands intervention to 5 more FQHCs Training in brief motivational interviewing Perkins et al, Vaccine, 2015

33. Conclusions Vaccinating all adolescents with HPV vaccines will save lives and improve health For more information, including free resources for providers and patients: cdc.gov/vaccines/teens cdc.gov/vaccines/teens