Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24-45 years: a randomised, double-blind trial.
BACKGROUND
Although the peak incidence of human papillomavirus (HPV) infection occurs in most populations within 5-10 years of first sexual experience, all women remain at risk for acquisition of HPV infections. We tested the safety, immunogenicity, and efficacy of the quadrivalent HPV (types 6, 11, 16, 18) L1 virus-like-particle vaccine in women aged 24-45 years.


METHODS
Women aged 24-45 years with no history of genital warts or cervical disease were enrolled from community health centres, academic health centres, and primary health-care providers into an ongoing multicentre, parallel, randomised, placebo-controlled, double-blind study. Participants were allocated by computer-generated schedule to receive quadrivalent HPV vaccine (n=1911) or placebo (n=1908) at day 1, and months 2 and 6. All study site investigators and personnel, study participants, monitors, and central laboratory personnel were blinded to treatment allocation. Coprimary efficacy endpoints were 6 months' or more duration of infection and cervical and external genital disease due to HPV 6, 11, 16, 18; and due to HPV 16 and 18 alone. Primary efficacy analyses were done in a per-protocol population, but intention-to-treat analyses were also undertaken. This study is registered with ClinicalTrials.gov, number NCT00090220.


RESULTS
1910 women received at least one dose of vaccine and 1907 at least one dose of placebo. In the per-protocol population, efficacy against the first coprimary endpoint (disease or infection related to HPV 6, 11, 16, and 18) was 90.5% (95% CI 73.7-97.5, four of 1615 cases in the vaccine group vs 41/1607 in the placebo group) and 83.1% (50.6-95.8, four of 1601 cases vs 23/1579 cases) against the second coprimary endpoint (disease or infection related to HPV 16 and 18 alone). In the intention-to-treat population, efficacy against the first coprimary endpoint was 30.9% (95% CI 11.1-46.5, 108/1886 cases vs 154/1883 cases) and against the second coprimary endpoint was 22.6% (-2.9 to 41.9, 90/1886 cases vs 115/1883 cases), since infection and disease were present at baseline. We recorded no vaccine-related serious adverse events.


CONCLUSIONS
The quadrivalent HPV vaccine is efficacious in women aged 24-45 years not infected with the relevant HPV types at enrolment.


BACKGROUND
Merck (USA).
Muñoz
Nubia
N
National Institute of Cancer, Bogotá, Colombia. nubia.munoz@free.fr
Manalastas
Ricardo
R
Pitisuttithum
Punee
P
Tresukosol
Damrong
D
Monsonego
Joseph
J
Ault
Kevin
K
Clavel
Christine
C
Luna
Joaquin
J
Myers
Evan
E
Hood
Sara
S
Bautista
Oliver
O
Bryan
Janine
J
Taddeo
Frank J
FJ
Esser
Mark T
MT
Vuocolo
Scott
S
Haupt
Richard M
RM
Barr
Eliav
E
Saah
Alfred
A
D000328:Adult; D000367:Age Factors; D052685:Alphapapillomavirus; D003105:Colombia / Q000453:epidemiology; D004311:Double-Blind Method; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D010679:Philippines / Q000453:epidemiology; D012449:Safety; D013785:Thailand / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination / Q000009:adverse effects / Q000379:methods
D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D053918:Papillomavirus Vaccines