E fficacy of quadrivalent human papillomavirus (types 6, 11, 16 and 18) vaccine (GARDASIL)

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

Total admission

160

surgical 77(48.1%)

medical 83(51.9%)

1030509 512

Participants underwentgynecologicalexaminations

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

Treatments for genital wartsointments

(5-FU, bleomycin, imiquimod,)

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.

Characteristics by vaccination group

not pregnant

no previous abnormal Pap smears

reported a lifetime history of four or fewer malesex partners

Participants and Methods

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 inthe 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 Japanesewomen aged 18–26 years. Quadrivalent HPV vaccine

couldsignificantly 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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