Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: a randomized controlled trial.
OBJECTIVE
Human papillomavirus (HPV) virus-like particle (VLP) vaccines have demonstrated effectiveness in preventing persistent HPV infections. Whether protection lasts longer than 18 months and, thus, impacts rates of cervical intraepithelial neoplasia (CIN) 2-3 has not yet been established. We present results from an HPV16 L1 VLP vaccine trial through 48 months.


METHODS
A total of 2,391 women, aged 16-23 years, participated in a randomized, double-blind, placebo-controlled trial. Either 40 mug HPV16 L1 VLP vaccine or placebo was given intramuscularly at day 1, month 2, and month 6. Genital samples for HPV16 DNA and Pap tests were obtained at day 1, month 7, and then 6-monthly through month 48. Colposcopy and cervical biopsies were performed if clinically indicated and at study exit. Serum HPV16 antibody titer was measured by radioimmunoassay.


RESULTS
Among 750 placebo recipients in the per protocol population, 12 women developed HPV16-related CIN2-3 (6 CIN2 and 6 CIN3). Among 755 vaccine recipients, there were no cases (vaccine efficacy 100%, 95% confidence interval [CI] 65-100%). There were 111 cases of persistent HPV16 infection in placebo recipients and 7 cases in vaccine recipients (vaccine efficacy 94%, 95% CI 88-98%). After immunization, HPV16 serum antibody geometric mean titers peaked at month 7 (1,519 milli-Merck units [mMU]/mL), declined through month 18 (202 mMU/mL), and remained relatively stable between month 30 and month 48 (128-150 mMU/mL).


CONCLUSIONS
The vaccine HPV16 L1 VLP provides high-level protection against persistent HPV16 infection and HPV16-related CIN2-3 for at least 3.5 years after immunization. Administration of L1 VLP vaccines targeting HPV16 is likely to reduce risk for cervical cancer.


METHODS
I.
Mao
Constance
C
Department of Obstetrics and Gynecology and Epidemiology, University of Washington, Seattle, Washington 98104-2499, USA. cmao@u.washington.edu
Koutsky
Laura A
LA
Ault
Kevin A
KA
Wheeler
Cosette M
CM
Brown
Darron R
DR
Wiley
Dorothy J
DJ
Alvarez
Frances B
FB
Bautista
Oliver M
OM
Jansen
Kathrin U
KU
Barr
Eliav
E
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000032:analysis*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000517:prevention & control; D053918:Papillomavirus Vaccines; D012016:Reference Values; D018570:Risk Assessment; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination / Q000379:methods; D014765:Viral Vaccines / Q000008:administration & dosage*; D002578:Uterine Cervical Dysplasia / Q000517:prevention & control* / Q000821:virology
D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines; D014765:Viral Vaccines