Transcript Slide 1

Efficacy of quadrivalent human
papillomavirus
(types 6, 11, 16 and 18) vaccine
(GARDASIL)
inJapanese women aged 18–26
years
Hiroyuki Yoshikawa,1 Keiko Ebihara,2 Yoshiyuki Tanaka2,4 and Kiichiro
Noda3
A randomized double-blind placebocontrolled phase II trial (RCT) was
conducted to evaluate the efficacy of a
prophylactic quadrivalent vaccine targeting
the (HPV) types most frequently associated
with cervical cancer (types 16 ⁄ 18) and
genital warts (types 6 ⁄ 11) in Japanese
women aged 18–26 years
1030
assessed
for eligibility
509
512
randomized to
randomized to
placebo
vaccine
gynecological
examinations
Participants
underwent
cervicovaginal
sampling for HPV DNA
serum neutralizing
antibodies to HPV
Papanicolau testing
Human papillomavirus (HPV)-related genital
warts are considered to be the most
common sexually transmitted Disease.
HPV 6 and HPV 11 are found in over 90% of
anogenital warts cases
ointments
(5-FU, bleomycin,
imiquimod),
Treatments
for genital
warts
surgical treatments
(laser ablation)
electronic iron and liquid
nitrogen
In addition to leading to genital warts,
infection with HPV is known to lead to
cervical cancer. HPV has been detected in
99.7% of patients with cervical cancer and
HPV infection is considered to be a
necessary prerequisite of
the disease
A meta-analysis demonstrated that HPV16 and
18 were the most common types and together
were associated with 58.8% of cervical cancer
in Japan. Based on a recent report,
approximately 67.1% of cervical cancers in
Japan are considered to be
related to HPV types 16 and 18
HPV infection is seen as a
very important risk factor for
vulvar, vaginal and anal
cancers.
Participants and Methods
not pregnant
Characteristics
by vaccination
group
no previous
abnormal Pap
smears
reported a lifetime
history of four or fewer
male
sex partners
Participants were required to use
effective contraception during the
vaccination phase.
A 0.5 mL vaccine or
placebo was given
by IM injection at day
1, month 2 and
month 6.
Temperatures were also
recorded orally every day in
the evening for 4 days after
vaccination and the
participant was to note
adverse events by standard
diary card for 15 days
after vaccination.
Gynecological examination was done at day
1 and at months 7, 12, 18, 24 and 30. A ThinPrep
Pap test and external genital and cervical swabs
for PCR analysis of HPV were obtained from all
participants at day 1 and at months 7, 12, 18, 24
and 30.
Biopsy samples of external genital lesions
identified during the study were taken and serum
samples were obtained at day 1 and months 2, 3,
7, 18 and 30
Women underwent colposcopy if
they were diagnosed with atypical
squamous cells,low-grade
squamous intraepithelial lesions,
high-grade squamous
intraepithelial lesions or atypical
glandular cells.
Results
Combined incidence of persistent
infection or disease
with HPV 6, 11, 16 or 18 fell by 87.6%,
with HPV 6 or 11 by 73.1% and
with HPV 16 or 18 by 94.5%
in those assigned vaccine compared
with those assigned placebo
In addition, the vaccine was well
tolerated in Japanese
women aged 18–26 years.
Quadrivalent HPV vaccine could
significantly reduce the acquisition of
infection and clinical
disease caused by HPV types 6, 11, 16
and 18.
Discussion
We have shown that qHPV vaccine
is efficacious against HPV types
that cause cancer and genital warts
in Japan by observing a combined
primary end-point of both persistent
infection and genital disease.
Vaccine efficacy against this end-
point was 87.6% in the per-protocol
efficacy population. Furthermore,
efficacy with regard to HPV types
closely related to cervical cancer
(types 16 and 18) was 94.5% in the
per-protocol population
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