Our memories of

Mahabaleswar

CDC - Immunization Update 2006Satellite Internet Broadcast

December, 2006

Cervical Cancer Vaccine - HPV

Summarized from the CDC Broadcast by Dr. R.V.S.N.Sarma. M.D., M.Sc.,

Cervical Cancer

• Cervical cancer is the 2nd 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

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

InitialHPV

Infection

Cleared HPV Infection

Within 1 Year 1-5 YearsUp to Decades

PersistentInfection

CIN 2/3

Cervical Cancer

CIN 1

Natural History of HPV Infection

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%

40%

12%

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%

10%

90%90%

Global distribution of HPV types in cervical cancer

53%

15%

9%

6%

3%

14%

HPV 16

HPV 18

HPV 45

HPV 31

HPV 33

HPV others

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

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

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.

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 AIS8487 0 8460 53 100 (93,100)

HPV 6/11/16/18

related CIN7858 4 7861 83 95 (87, 99)

HPV 6/11/16/18

related genital warts

7897 17899 91 99 (94,100)

*Package insert: Gardasil® . . Integrated dataset; results in the per-protocol populations CIN – cervical intraepithelial neoplasia; AIS – adenocarcinoma in situ

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

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

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

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

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

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

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

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

US National Immunization Program

• Hotline (800) CDC-INFO

• Email nipinfo@cdc.gov

• Website www.cdc.gov/nip

• Broadcast Updates and Resources Web Page

www.cdc.gov/nip/ed/UpdatesandResources.htm