Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial.
BACKGROUND
A randomised double-blind placebo-controlled phase II study was done to assess the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus (HPV) types associated with 70% of cervical cancers (types 16 and 18) and with 90% of genital warts (types 6 and 11).


METHODS
277 young women (mean age 20.2 years [SD 1.7]) were randomly assigned to quadrivalent HPV (20 microg type 6, 40 microg type 11, 40 microg type 16, and 20 microg type 18) L1 virus-like-particle (VLP) vaccine and 275 (mean age 20.0 years [1.7]) to one of two placebo preparations at day 1, month 2, and month 6. For 36 months, participants underwent regular gynaecological examinations, cervicovaginal sampling for HPV DNA, testing for serum antibodies to HPV, and Pap testing. The primary endpoint was the combined incidence of infection with HPV 6, 11, 16, or 18, or cervical or external genital disease (ie, persistent HPV infection, HPV detection at the last recorded visit, cervical intraepithelial neoplasia, cervical cancer, or external genital lesions caused by the HPV types in the vaccine). Main analyses were done per protocol.


RESULTS
Combined incidence of persistent infection or disease with HPV 6, 11, 16, or 18 fell by 90% (95% CI 71-97, p<0.0001) in those assigned vaccine compared with those assigned placebo.


CONCLUSIONS
A vaccine targeting HPV types 6, 11, 16, 18 could substantially reduce the acquisition of infection and clinical disease caused by common HPV types.
Villa
Luisa L
LL
Department of Virology, Ludwig Institute for Cancer Research, Sao Paulo, Brazil. llvilla@ludwig.org.br <llvilla@ludwig.org.br>
Costa
Ronaldo L R
RL
Petta
Carlos A
CA
Andrade
Rosires P
RP
Ault
Kevin A
KA
Giuliano
Anna R
AR
Wheeler
Cosette M
CM
Koutsky
Laura A
LA
Malm
Christian
C
Lehtinen
Matti
M
Skjeldestad
Finn Egil
FE
Olsson
Sven-Eric
SE
Steinwall
Margareta
M
Brown
Darron R
DR
Kurman
Robert J
RJ
Ronnett
Brigitte M
BM
Stoler
Mark H
MH
Ferenczy
Alex
A
Harper
Diane M
DM
Tamms
Gretchen M
GM
Yu
Jimmy
J
Lupinacci
Lisa
L
Railkar
Radha
R
Taddeo
Frank J
FJ
Jansen
Kathrin U
KU
Esser
Mark T
MT
Sings
Heather L
HL
Saah
Alfred J
AJ
Barr
Eliav
E
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000096:biosynthesis; D036022:Capsid Proteins; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines; D010919:Placebos; D014412:Tumor Virus Infections / Q000517:prevention & control; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology; D014765:Viral Vaccines / Q000627:therapeutic use*; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology
D000914:Antibodies, Viral; D036022:Capsid Proteins; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D010919:Placebos; D014765:Viral Vaccines