Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial.
OBJECTIVE
To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata).


METHODS
Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months' follow-up.


METHODS
Primary care centres and university or hospital associated health centres in 24 countries and territories around the world.


METHODS
17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy.


METHODS
Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6.


METHODS
Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied.


RESULTS
In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96% for cervical intraepithelial neoplasia grade I (95% confidence interval 91% to 98%), 100% for both vulvar and vaginal intraepithelial neoplasia grade I (95% CIs 74% to 100%, 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma.


CONCLUSIONS
Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up.


BACKGROUND
NCT00092521 and NCT00092534.
Depatment of Laboratory Medicine, Lund University, Malmö, Sweden. joakim.dillner@med.lu.se
Dillner
Joakim
J
Kjaer
Susanne K
SK
Wheeler
Cosette M
CM
Sigurdsson
Kristján
K
Iversen
Ole-Erik
OE
Hernandez-Avila
Mauricio
M
Perez
Gonzalo
G
Brown
Darron R
DR
Koutsky
Laura A
LA
Tay
Eng Hseon
EH
García
Patricia
P
Ault
Kevin A
KA
Garland
Suzanne M
SM
Leodolter
Sepp
S
Olsson
Sven-Eric
SE
Tang
Grace W K
GW
Ferris
Daron G
DG
Paavonen
Jorma
J
Lehtinen
Matti
M
Steben
Marc
M
Bosch
F Xavier
FX
Joura
Elmar A
EA
Majewski
Slawomir
S
Muñoz
Nubia
N
Myers
Evan R
ER
Villa
Luisa L
LL
Taddeo
Frank J
FJ
Roberts
Christine
C
Tadesse
Amha
A
Bryan
Janine T
JT
Maansson
Roger
R
Lu
Shuang
S
Vuocolo
Scott
S
Hesley
Teresa M
TM
Barr
Eliav
E
Haupt
Richard
R
D000293:Adolescent; D000328:Adult; D019496:Cancer Vaccines; D002278:Carcinoma in Situ / Q000517:prevention & control*; D003218:Condylomata Acuminata / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D006801:Humans; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines; D016896:Treatment Outcome; D014565:Urogenital Neoplasms / Q000517:prevention & control*; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control; D014625:Vaginal Neoplasms / Q000517:prevention & control; D014846:Vulvar Neoplasms / Q000517:prevention & control; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000517:prevention & control*
D019496:Cancer Vaccines; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D053918:Papillomavirus Vaccines