1. Our memories of Mahabaleswar

2. CDC - Immunization Update 2006 Satellite Internet Broadcast December, 2006 Cervical Cancer Vaccine - HPV Summarized from the CDC Broadcast by Dr. R.V.S.N.Sarma. M.D., M.Sc.,

3. Cervical Cancer Cervical cancer is the 2 nd leading cancer amongst women worldwide 500,000 new cases and 300,000 deaths due to Ca Cx >99% related to human papilloma virus (HPV) infec. HPV infect epithelial cells including the genital tract HPV type 16 related to half of these cases HPV –18, -45, -31, -33, -52, -58 and -35 together with HPV-16 responsible for 90% of all cervical cancers worldwide

4. Human Papillomavirus More than 100 types – More than 60 cutaneous types  Can lead to skin warts –40 mucosal types  High risk types (particularly 16 and 18) –cervical cell abnormalities –certain anogenital cancers  Low risk types (particularly 6 and 11) –cervical cell abnormalities- usually resolve spontaneously and do not lead to cancer –genital warts –respiratory papillomatosis

5. Initial HPV Infection Cleared HPV Infection Within 1 Year1-5 Years Up to Decades Persistent Infection CIN 2/3 Cervical Cancer CIN 1 Natural History of HPV Infection

6. Cancer Cervical Anal Vulvar/vaginal Penile Oral/pharynx Cancer Attributable to HPV - 2006 Cancer Cases 12,000 3,700 4,480 1,000 10,000 Attributable Fraction 100% 90% 40% 12%

7. HPV-associated Conditions HPV 16, 18 Cervical cancer - High/low grade cervical abnormalities Anal, Vulvar, Vaginal, Penile Head and neck cancers HPV 6, 11 Low grade cervical abnormalities Genital warts RRP Estimated % 70% 30%-50% 10% 90%

8. Global distribution of HPV types in cervical cancer

9. Human Papilloma Virus Vaccine Contains the L1 protein from four types of HPV (16, 18, 6, 11) Produced using recombinant DNA technology L1 proteins self assemble into non- infectious units called virus-like particles (VLPs) VLPs are highly immunogenic

10. HPV Vaccines Yeast Cell Culture L1 VLPs made in insect cells – GSK 16 and 18 - Cervarix i.m. 3 shots 0, 1 and 6 month VLPs made in yeast cells – Merck 16,18,11 and 6 -Gardasil i.m. 3 shots 0, 2 and 6 month Insect Cell Culture

11. HPV vaccine news headlines “Vaccine prevents most cervical cancers.” - New York Times, October 7, 2005. Vaccine proves 100 percent effective in preventing cervical cancer – Seattle Times, October 6, 2005. “Promising new vaccines could wipe out cervical cancer. But they must be administered to preteens, and some groups oppose that.” – Philadelphia Inquirer, July 4, 2005. “OK Roll up your sleeve; new vaccines are arriving but the economics are still a challenge” – Business Week, July 25, 2005.

12. Efficacy of HPV Vaccine Among 16-26 year-old Females* Endpoint Vaccine N Cases Placebo N Cases Efficacy(95% CI) HPV 16/18-related CIN2/3 or AIS 8487 08460 53 100(93,100) HPV 6/11/16/18 related CIN 7858 47861 83 95(87, 99) HPV 6/11/16/18 related genital warts 7897 1 7899 91 99(94,100). *Package insert: Gardasil ®. Integrated dataset; results in the per-protocol populations CIN – cervical intraepithelial neoplasia; AIS – adenocarcinoma in situ

13. Human Papillomavirus Vaccine Efficacy High efficacy among females without evidence of infection with vaccine HPV types No evidence that the vaccine had efficacy against existing disease or infection Prior infection with one HPV type did not diminish efficacy of the vaccine against other vaccine HPV types

14. HPV Vaccine Schedule Approved for females 9-26 year of age 3 doses at 0, 2, and 6 months Minimum intervals: –4 weeks between doses 1 and 2 –12 weeks between doses 2 and 3

15. HPV Vaccine – Provisional ACIP Recommendations Routine vaccination of ♂ at 12 years of age The vaccination series can be started as young as 9 years of age at the clinician's discretion Vaccination is recommended for females 13-26 years of age who have not been previously vaccinated Ideally vaccine should be administered before onset of sexual activity Females who are sexually active should be vaccinated

16. HPV Vaccine – Special Situations* Females 26 years of age or younger with, equivocal or abnormal Pap test, positive HPV DNA, and genital warts may be vaccinated Vaccine will have no effect on existing disease or infection *Provisional ACIP recommendation, June 2006

17. HPV Vaccine – Special Situations* Females 26 years of age or younger who are lactating/breastfeeding or are immuno-compromised may be vaccinated NOT recommended for pregnant women *Provisional ACIP recommendation, June 2006

18. Screening for Cervical Cancer Why get screened? Screening was developed to detect abnormal cervical cells in the early stages when it is easy to remove them Who should be screened? Women from 25-65 years Once every 3 years

19. HPV Vaccine and Cervical Cancer Screening Cervical cancer screening recommendations have NOT changed for females who receive HPV vaccine –30% of cervical cancers caused by HPV types are not prevented by the quadrivalent HPV vaccine –Vaccinated females could subsequently be infected with non-vaccine HPV types –Sexually active females could have been infected prior to vaccination Providers should educate women about the importance of cervical cancer screening

21. Adding up the facts HPV is present in the majority of sexually active adults Presence of HPV does not indicate promiscuity HPV is short lived and asymptomatic in most adults If high risk HPV (16 and 18) persists – can cause Ca CX Cervical cancer kill 200,000 women worldwide annually 70% of Ca Cx is due to HPV 16 and 18 types HPV vaccine given at age 11, eliminates 70% of Ca Cx HPV vaccine does not replace screening for Ca Cx HPV vaccine in men prevents Ca Penis and genital warts Rapid adoption of HPV vaccine is right and essential

22. US National Immunization Program Hotline(800) CDC-INFO Emailnipinfo@cdc.gov Websitewww.cdc.gov/nip Broadcast Updates and Resources Web Page www.cdc.gov/nip/ed/UpdatesandResources.htm