1. The HPV Vaccine Our Best Shot to Prevent Cervical Cancer Harold C. Wiesenfeld, MD,CM Department of Obstetrics, Gynecology and Reproductive Sciences-University of Pittsburgh Magee-Womens Hospital of UPMC Allegheny County Health Department, Pittsburgh, PA

2. Impact of Cervical Cancer United States: – Annual number of cases: 12,000 – 4,000 women die from cervical cancer each year (>10 per day) Worldwide: – Annual incidence: ~500,000 – Second most common cause of cancer death in women – ~270,000 deaths each year

3. HPV-Attributable Cancer Cases per Year

5. PAP Smears have Cut Cervical Cancer by 70% but ….. % of US Women > 25 Years old who have had a PAP Smear in the Last 3 Years National Center for Health Statistics, 2013

6. Winer, R. L. et al. Am. J. Epidemiol. 2003 157:218-226; doi:10.1093/aje/kwf180 Cumulative Incidence of HPV Infection from time of first sexual intercourse

7. Incident HPV Infection in Men Partridge et al J Infect Dis 2007 62.4% 240 heterosexual male university students 18-20 years old Univ of Washington, Seattle 2003-2006

8. Cumulative Incidence CIN 3/CA single HPV test at entry (HC II) Kaiser study 20514 women Khan et al JNC 2005;97:1072Pap NL/ASC/LSIL

9. HPV is Associated with ORAL CANCERS ORAL HPV- UNITED STATES 2009-2010 (NHANES) Prevalence of HPV by genotype

10. HPV Vaccine Gardisil – Quadrivalent vaccine- 4 strains of HPV Cervarix – Bivalent vaccine- 2 strains of HPV Gardisil FDA approved in 2006 Both provide immunity against HPV 16 and 18 HPV 16 and 18 cause 70% of cervical cancers

11. Prophylactic Efficacy: GARDASIL Was 100% Efficacious Against HPV 16- and 18-related CIN 2/3 or AIS Populationn GARDASIL Cases n Placebo Cases Efficacy95% CI Protocol 005*755075012100%65.1–100 Protocol 00723102301100% -3734.9– 100 FUTURE I2,20002,22219100%78.5–100 FUTURE II5,30105,25821 100% † 80.9–100 Combined protocols 8,48708,46053100% † 92.9–100 *Evaluated only the HPV 16 L1 VLP component of GARDASIL. † P-values were computed for the prespecified primary hypothesis tests. All p-values were 0% (FUTURE II); and efficacy against HPV 16/18-related CIN 2/3 is >25% (combined protocols).

12. General Population Impact: GARDASIL Reduced HPV 16- and 18-related CIN 2/3 or AIS HPV 16- or 18- Related CIN 2/3 or AISN GARDASIL or HPV 16 L1 VLP Cases N Placebo Cases % Reduction95% CI Prophylactic Efficacy* 9,34219,4008198.8%93–100 HPV 16 and/or HPV 18 Positive at Day 1 --121--120-- General Population Impact † 9,8311229,89620139.0%23–52

15. Fig 1 Proportion of Australian born women diagnosed as having genital warts at first visit, by age group, 2004-11. Hammad Ali et al. BMJ 2013;346:bmj.f2032 Works best in younger women, i.e. before sexual onset

16. HPV Vaccine- Current Recommendations March 2015 FEMALES: – Routine vaccination ages 11-12 – Recommended ages 13-36 MALES: – Routine vaccination ages 11-12 – Recommended ages 13-26 Vaccination through age 26: – Men who have sex with men – Immunocompromised

18. Overcoming Barriers to HPV Vaccination Fears/Concerns and Facts/Reality – No access to vaccine 85% of potential recipients had another vaccine – Vaccine is not safe Pre- and post-licensure data support safety – Not sold on vaccines Vaccines one of the greatest successes of modern medicine (e.g. polio) – Will encourage risky sexual behavior Studies confirm NO increase in risky sexual behavior after vaccination – My child is not/will not be at risk for STDs 47% of teens have had sexual intercourse 1 out of 3 teens have had sex in the previous 3 months 1 out of 6 teens have had 4 or more partners in their life Almost 1 in 2 did not use condom Nearly half of the 19 million STDs each year are in young people (15-24 years) Background check of future son-in-law? Chlamydia- Allegheny County 2013

19. Cervical Cancer Overview of the Problem

20. HPV Vaccine FDA approved for: Prevention of cervical cancer and cervical “pre-cancer” Prevention of vulvar and vaginal cancers Prevention of anal cancer Boys and Men