Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial.
BACKGROUND
Vaccination against the most common oncogenic human papillomavirus (HPV) types, HPV-16 and HPV-18, could prevent development of up to 70% of cervical cancers worldwide. We did a randomised, double-blind, controlled trial to assess the efficacy, safety, and immunogenicity of a bivalent HPV-16/18 L1 virus-like particle vaccine for the prevention of incident and persistent infection with these two virus types, associated cervical cytological abnormalities, and precancerous lesions.


METHODS
We randomised 1113 women between 15-25 years of age to receive three doses of either the vaccine formulated with AS04 adjuvant or placebo on a 0 month, 1 month, and 6 month schedule in North America and Brazil. Women were assessed for HPV infection by cervical cytology and self-obtained cervicovaginal samples for up to 27 months, and for vaccine safety and immunogenicity.


RESULTS
In the according-to-protocol analyses, vaccine efficacy was 91.6% (95% CI 64.5-98.0) against incident infection and 100% against persistent infection (47.0-100) with HPV-16/18. In the intention-to-treat analyses, vaccine efficacy was 95.1% (63.5-99.3) against persistent cervical infection with HPV-16/18 and 92.9% (70.0-98.3) against cytological abnormalities associated with HPV-16/18 infection. The vaccine was generally safe, well tolerated, and highly immunogenic.


CONCLUSIONS
The bivalent HPV vaccine was efficacious in prevention of incident and persistent cervical infections with HPV-16 and HPV-18, and associated cytological abnormalities and lesions. Vaccination against such infections could substantially reduce incidence of cervical cancer.
Harper
Diane M
DM
Department of Obstetrics and Gynecology, Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH, USA. diane.m.harper@dartmouth.edu
Franco
Eduardo L
EL
Wheeler
Cosette
C
Ferris
Daron G
DG
Jenkins
David
D
Schuind
Anne
A
Zahaf
Toufik
T
Innis
Bruce
B
Naud
Paulo
P
De Carvalho
Newton S
NS
Roteli-Martins
Cecilia M
CM
Teixeira
Julio
J
Blatter
Mark M
MM
Korn
Abner P
AP
Quint
Wim
W
Dubin
Gary
G
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D002213:Capsid / Q000276:immunology; D036022:Capsid Proteins; D002584:Cervix Uteri / Q000821:virology; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D009500:Neutralization Tests; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines; D002577:Uterine Cervical Diseases / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control* / Q000821:virology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D002578:Uterine Cervical Dysplasia / Q000821:virology
D000914:Antibodies, Viral; D036022:Capsid Proteins; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D014765:Viral Vaccines