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 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.,
 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
 Natural History of HPV Infection
Up to Decades
Within 1 Year 1-5 Years

Persistent CIN Cervical

Infection 2/3 Cancer
Initial
HPV
Infection
CIN 1

Cleared HPV Infection

Cancer Attributable to HPV - 2006

Cancer Attributable
Cancer Cases Fraction
Cervical 12,000 100%
Anal 3,700 90%
Vulvar/vaginal 4,480 40%
Penile 1,000 40%
Oral/pharynx 10,000 12%
 HPV-associated Conditions
HPV 16, 18 Estimated %
Cervical cancer
- High/low grade cervical
70%
abnormalities
Anal, Vulvar, Vaginal, 30%-50%
Penile
Head and neck cancers 10%

HPV 6, 11
Low grade cervical 10%
abnormalities
90%
Genital warts 90%
RRP
Global distribution of HPV types in
cervical cancer

14%

HPV 16
3%
6% HPV 18

HPV 45
9% 53%
HPV 31

HPV 33

15% 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

• L1 VLPs made in insect cells –

GSK 16 and 18 - Cervarix
• i.m. 3 shots 0, 1 and 6 month
Insect Cell Culture

• VLPs made in yeast cells –

• Merck 16,18,11 and 6 -Gardasil
• i.m. 3 shots 0, 2 and 6 month

Yeast 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*
Vaccine Placebo
Endpoint N Cases N Cases Efficacy (95% CI)

HPV 16/18-related
8487 0 8460 53 100 (93,100)
CIN2/3 or AIS

HPV 6/11/16/18
7858 4 7861 83 95 (87, 99)
related CIN

HPV 6/11/16/18
7897 1
related genital 7899 91 99 (94,100)
warts
*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