1. INCREASING ADOLESCENT HPV UPTAKE Gale R Burstein, MD, MPH, FAAP Erie County Department of Health SUNY at Buffalo School of Medicine

2. QUESTIONS Let’s get to know each other!

3. Raise your hand if you work in a…. Community health center or physician office Health department Hospital School based health center College health Other

4. Raise your hand if you are a…… Physician NP or PA Nurse Health educator Other

5. Raise your hand if your clinical site offers HPV vaccine

6. Raise your hand if the estimated % of HPV vaccine refusers are 0~% ~25% ~50% >75%

7. Vaccines 2 FDA-licensed HPV vaccines Cervarix o bivalent HPV vaccine prevents HPV types 16/18 o licensed for ♀ Gardasil o quadrivalent HPV vaccine prevents HPV types 16/18 & 6/11 o licensed for ♂ & ♀

8. ACIP HPV recommendations All 11 and 12 yo ♀ and ♂ o Can begin as young as age 9 yrs Catch – up vaccines for all 13-21 yo ♀ and ♂ who not already vaccinated All 22-26 yo ♀ All MSM and immunocompromised ♂ o i.e., routine vaccination for 22-26 yo ♂ with risk factors Permissive recommendation for 22-26 yo ♂ without risk factors

10. ♂ HPV Cost Effectiveness Goal: estimate the cost-effectiveness of adding HPV of 12 yo ♂ to ♀ -only vaccination program for ages 12–26 yo in US Methods: o CEA o The HPV-associated outcomes: FDA-indicated: CIN; genital warts; cervical, vaginal, vulvar, & anal CA nonFDA-indicated: oropharyngeal & penile CA; RRP Chesson HW, et al. Vaccine 2011;29:8443–50.

11. CEA Findings HPV immunization of 12 yo ♂ cost-effective, particularly if o ♀ HPV4 coverage is low o all potential HPV vaccine health benefits included in analysis  ♀ coverage more efficient strategy than ♂ vaccination to  overall HPV health burden Chesson HW, et al. Vaccine 2011;29:8443–50.

12. Cost-effectiveness of male vaccination* Cost per QALY gained by vaccinating 12 year-old boys * Includes transmission effects to females “Indicated” outcomes include cervical outcomes, vaginal, vulvar, anal cancers, and genital warts. All outcomes include indicated outcomes plus oropharyngeal cancer, penile cancer, and recurrent respiratory papillomatosis. Lower coverage scenario: 30% 3-dose coverage at age 12 and 50% 3-dose coverage by age 26. Higher coverage scenario: 50% 3-dose coverage at age 12 and 70% 3-dose coverage by age 26. *Chesson HW, et al Vaccine 2011

13. Number of lifetime cancer cases averted by vaccinating 1 million males in a birth cohort Excludes indirect effects (herd immunity). Outcomes are not discounted. Results obtained from Chesson et al model, Vaccine 2011. Vaccine efficacy was assumed to be 90% against HPV 6/11 genital warts and 75% against HPV 16/18 cancers in males.

14. HPV Disease Burden It’s bad!!

15. Genital Warts—Initial Visits to Physicians’ Offices, United States, 1966–2011 NOTE: The relative standard errors for genital warts estimates of more than 100,000 range from 18% to 30%. SOURCE: IMS Health, Integrated Promotional Services ™. IMS Health Report, 1966–2011. 2011-Fig 53. SR

16. Human Papillomavirus—Prevalence of High-risk and Low-risk Types Among Females Aged 14–59 Years, National Health and Nutrition Examination Survey, 2003–2006 *HPV=human papillomavirus. NOTE: Error bars indicate 95% confidence intervals. Both high-risk and low-risk HPV types were detected in some females. SOURCE: Hariri S, Unger ER, Sternberg M, Dunne EF, Swan D, Patel S, et al. Prevalence of genital HPV among females in the United States, the National Health and Nutrition Examination Survey, 2003-2006. J Infect Dis. 2011;204(4):566-73 2011-Fig 52. SR

17. Genital HPV Prevalence Rates in Males Males aged 18–44 years in Tucson, Arizona (N = 290). High-risk/oncogenic HPV types included 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66. Low-risk/non-oncogenic HPV types included 6, 11, 26, 40, 42, 53, 54, 55,62, 64, 67–73, 81–84, IS39, CP6108. Giuliano AR et al. J Infect Dis. 2008;198:827–835. years (%)

18. Age-Specific Anal Canal HPV Prevalence Among Men Having Sex with Women Nyitray AR, et al. et al J Infect Dis. 2012;206(2):202-11

19. Nielsen et al, Int J Cancer In Press The Burden of Anal Cancer is Increasing Age standardized incidence rates of anal cancer in Denmark  US anal cancer rates (~2.7%/year); Rates ♀ >> ♂

20. Anal Cancer Affects Women and Men Estimated 5,820 ♀ and ♂ in US diagnosed with anal cancer in 2011 o 3,680 in ♀ and 2,140 in ♂ > 60% of anal CA cases and deaths occur in ♀ Anal CA can occur in heterosexual ♂ o 53% of male anal cancers occur in heterosexual ♂ ACS. www.cancer.org/Cancer/AnalCancer/DetailedGude/anal-cancer-what-is-key-statistics Last update: 10/25/2011 Nielsen IPV 2010 Daling et al Cancer 2004

21. Prevalence of Oral HPV Infection in the United States, 2009-2010 Gillison ML, et al. JAMA 2012;307(7):693-703.

22. Prevalence of Oral HPV Infection Methods 2009-2010 NHANES survey ♀ & ♂ aged 14 to 69 yrs Participants (N=5579) provided 30-sec oral rinse PCR and type-specific hybridization Demographic and behavioral data by standardized interview Gillison ML, et al. JAMA. 2012;307(7):693-703

23. Prevalence of Oral HPV Infection Results Prevalence all HPV types = 6.9% o HPV type 16 prevalence = 1.0% 85% of HPV-related OP cancers are positive for HPV-16 Bimodal pattern for age o 30-34 yo = 7.3% o 60-64 yo =11.4% ♂ ( 10.1%) >>♀ (3.6%); PR=2.8 Gillison ML, et al. JAMA. 2012;307(7):doi:10.1001/jama.2012.101

25. What sexual behavior was most associated with oral HPV? Oral sex Vaginal sex Any sex No sex

26. Oral HPV and Sex > 8 x higher in persons report ever having had sex (7.5%) vs not (0.9%)  with  # partners for any kind of sex (vaginal sex, or oral sex) More common among sexually experienced individuals who did NOT perform oral sex vs. sexually inexperienced individuals o consistent with transmission by other sexually associated contact (eg, deep kissing) Gillison ML, et al. JAMA. 2012;307(7):693-703

27. Gillison ML, et al. JAMA. 2012;307(7):doi:10.1001/jama.2012.101

28. Incidence rates for overall oropharyngeal cancer, HPV–positive oropharyngeal cancers, and HPV-negative oropharyngeal cancers during 1988 -2004 in Hawaii, Iowa, and Los Angeles. Chaturvedi AK, et al. J Clin Oncol

29. Oral HPV transmission??!! Unclear what types of oral contact are risk

30. Estimated average annual % and # of cancers attributable to HPV, by anatomic site and sex — United States, 2004–8 ANATOMIC AREA AVG ANNUAL # of CASES % attributable to HPV # attributable to HPV FEMALE Cervix11,9679611,500 Vagina72964500 Vulva3,136511,600 Anus3,089932,900 Oropharynx2370631,500 TOTAL:FEMALE21,2271,75417,880 MALE Penis1,04636400 Anus1678931,600 Oropharynx9356635,900 TOTAL:MALE11,55374907080

31. HPV IMMUNIZATION COVERAGE AND PREVALENCE AMONG 14-19 YR OLD ♀ PRE- VS POST-HPV VACCINE ERA Markowitz L E et al. J Infect Dis. 2013;208:385-393

32. ↓ ♀ HPV Among Following U.S. HPV4 Introduction, NHANES, 2003–2010 National Health and Nutrition Examination Surveys (NHANES) HPV prevalence data o vaccine era (2007–2010) vs prevaccine era (2003–2006) Analyzed vaccine types (HPV-6, -11, -16, or - 18) for 14–19 yr old ♀ Markowitz L E et al. J Infect Dis. 2013;208:385-393

33. HPV4 Coverage and Sexual Behavior among 14-19 yr old ♀ 34% reported >1 HPV4 o 63% of vaccinated had 3 doses % 14–19 yr old ♀ reported had sex similar in pre- vs post-vaccine eras o 2003–2006: 53.9% (95% CI, 50.8–56.9) o 2007–2010: 50.3% (95% CI, 45.0–55.5), (P =.24) o small, nonsignificant differences in lifetime # partners and race/ethnicity Markowitz L E et al. J Infect Dis. 2013;208:385-393

34. HPV4 Prevalence among 14-19 yr old ♀ pre- vs post-HPV vaccine era ????????

35. HPV4 Prevalence among 14-19 yr old ♀ pre- vs post-HPV vaccine Pre-vaccine era 2003–2006 : 11.5% Post-vaccine era 2007–2010 : 5.1% o 56% decline!!!!!! No significant decrease in non-vaccine type HPV prevalence

36. Prevalence of individual HPV types among ♀ aged 14–19 yrs, 2003–2006 and 2007–2010 Markowitz L E et al. J Infect Dis. 2013;208:385-393

37. HPV PREVALENCE AMONG SEXUALLY ACTIVE 14–19 YR OLD ♀ BY VACCINATION HISTORY

38. HPV prevalence in pre- vs post-vaccine era among sexually active 14-19 yr old ♀ Overall demographic and sexual risk behavior did not differ between 2 periods Overall HPV vaccine type prevalence 53% lower in post- vs pre-vaccine era 88% vaccine type prevalence ↓ among vaccinated ♀ Estimated >1 dose vaccine effectiveness = 82%

39. HOW ARE WE DOING WITH HPV IMMUNIZATION RATES?

40. Estimated Vaccination Coverage among 13-17 yr old, NIS-Teen, US, 2006-20012 2007-2011: ↑rates 6%/yr 2011-12: No change www.cdc.gov/mmwr/preview/mmwrhtml/mm6234a1.htm?s_cid=mm6234a1_w

41. HPV Vaccine Coverage ≥1 dose of any HPV vaccine ↑ from 25% in 2007 to 53% in 2011, o No change in 2012 (54%) If HPV vaccine given at visits when another vaccine given, vaccine coverage for ≥1 dose would be 93% Safety monitoring data continue to indicate that HPV4 is safe

42. Missed Opportunities % of unvaccinated ♀ with >1 missed opportunity for HPV vaccination ↑ from 21% in 2007 to 84% in 2012 o Missed opportunity = health care encounter on or after a girl's 11th birthday and on or after 3/23/2007 where ♀ received >1 vaccine but NOT HPV www.cdc.gov/mmwr/preview/mmwrhtml/mm6229a4.htm

43. Human papillomavirus (HPV) vaccination among females 19–26 yrs (≥1 dose), ever — National Health Interview Survey, U.S., 2010 www.cdc.gov/mmwr/preview/mmwrhtml/mm6104a2.htm#tab1

44. HPV vaccination among ♂ (≥1 dose), ever— National Health Interview Survey, U.S., 2010 Age% 19–26 yrs0.6 19–21 yrs0.3 www.cdc.gov/mmwr/preview/mmwrhtml/mm6104a2.htm#tab1

45. WHAT WE CAN DO!!!

46. #1: Education of parents 3 of 5 of parents’ main reasons for not vaccinating daughters indicate gaps in understanding o including why vaccination is recommended by age 13 years Parents reported vaccine safety concerns Updated CDC educational materials addressing these issues at www.cdc.gov/vaccines/who/teens/index.html www.cdc.gov/vaccines/who/teens/index.html

48. www.cdc.gov/vaccines/who/teens/products/print-materials.html

49. #2: Providers must ↑ consistency & strength of HPV vaccine recommendations Studies show that providers give weaker recommendations for HPV vaccine vs other adolescent vaccines o Especially young adolescents Provider counseling and recommendations greatly influence parental vaccine acceptance CDC developed a tip sheet available at www.cdc.gov/vaccines/who/teens/for-hcp- tipsheet-hpv.html www.cdc.gov/vaccines/who/teens/for-hcp- tipsheet-hpv.html

51. #3: missed vaccination opportunities must ↓ Health-care access is NOT main impediment ↑ missed opportunities during 2007–2012 due to ↑ coverage for other adolescents vaccines 2012 NIS-Teen shows 84% of unvaccinated ♀ had health-care visit where another vaccine given If the 3-dose HPV series was started at these visits, coverage for ≥1 dose would be 93%

52. Lessons Learned High HPV vaccination coverage with existing infrastructure and health-care utilization is possible! Using every health-care visit, including acute-care visits, to assess every adolescent's vaccine status can ↓ missed opportunities

53. Office systems changes strategies Use vaccination prompts in EMRs Check NYSIIS Nurse counsels for HPV4 before pt seen by provider Schedule appointments for 2 nd & 3 rd doses at 1 st HPV dose visit Use automated reminder-recall systems Assessment of practice-level vaccination rates with feedback to staff members

54. LHD Vaccination PROGRAM strategies Provider education o HEDIS measure Education of potential vaccine recipients Publicity to promote vaccination ↑ access to vaccination services in medical and complementary settings o Workplaces and pharmacies

55. HPV Resources www.cdc.gov/vaccines/who/teens/for-hcp/hpv- resources.html www.cdc.gov/vaccines/who/teens/for-hcp/hpv- resources.html www.cdc.gov/vaccines/who/teens/downloads/hcp- factsheet.pdf www.cdc.gov/vaccines/who/teens/downloads/hcp- factsheet.pdf www.health.ny.gov/prevention/immunization/providers /hpv_q_and_a.htm www.health.ny.gov/prevention/immunization/providers /hpv_q_and_a.htm www.health.ny.gov/publications/2110.pdf www.cdc.gov/vaccines/who/teens/for-hcp-tipsheet- hpv.pdf www.cdc.gov/vaccines/who/teens/for-hcp-tipsheet- hpv.pdf www.cdc.gov/vaccines/vpd-vac/hpv/downloads/dis- HPV-color-office.pdf www.cdc.gov/vaccines/vpd-vac/hpv/downloads/dis- HPV-color-office.pdf www.cdc.gov/vaccines/vpd-vac/hpv/downloads/PL-dis- preteens-hpv.pdf www.cdc.gov/vaccines/vpd-vac/hpv/downloads/PL-dis- preteens-hpv.pdf

56. QUESTIONS? 56