A controlled trial of a human papillomavirus type 16 vaccine.
BACKGROUND
Approximately 20 percent of adults become infected with human papillomavirus type 16 (HPV-16). Although most infections are benign, some progress to anogenital cancer. A vaccine that reduces the incidence of HPV-16 infection may provide important public health benefits.


METHODS
In this double-blind study, we randomly assigned 2392 young women (defined as females 16 to 23 years of age) to receive three doses of placebo or HPV-16 virus-like-particle vaccine (40 microg per dose), given at day 0, month 2, and month 6. Genital samples to test for HPV-16 DNA were obtained at enrollment, one month after the third vaccination, and every six months thereafter. Women were referred for colposcopy according to a protocol. Biopsy tissue was evaluated for cervical intraepithelial neoplasia and analyzed for HPV-16 DNA with use of the polymerase chain reaction. The primary end point was persistent HPV-16 infection, defined as the detection of HPV-16 DNA in samples obtained at two or more visits. The primary analysis was limited to women who were negative for HPV-16 DNA and HPV-16 antibodies at enrollment and HPV-16 DNA at month 7.


RESULTS
The women were followed for a median of 17.4 months after completing the vaccination regimen. The incidence of persistent HPV-16 infection was 3.8 per 100 woman-years at risk in the placebo group and 0 per 100 woman-years at risk in the vaccine group (100 percent efficacy; 95 percent confidence interval, 90 to 100; P<0.001). All nine cases of HPV-16-related cervical intraepithelial neoplasia occurred among the placebo recipients.


CONCLUSIONS
Administration of this HPV-16 vaccine reduced the incidence of both HPV-16 infection and HPV-16-related cervical intraepithelial neoplasia. Immunizing HPV-16-negative women may eventually reduce the incidence of cervical cancer.
Koutsky
Laura A
LA
Department of Epidemiology, University of Washington, Seattle, USA. kouts@u.washington.edu
Ault
Kevin A
KA
Wheeler
Cosette M
CM
Brown
Darron R
DR
Barr
Eliav
E
Alvarez
Frances B
FB
Chiacchierini
Lisa M
LM
Jansen
Kathrin U
KU
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D004279:DNA, Viral / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines; D014412:Tumor Virus Infections / Q000453:epidemiology / Q000517:prevention & control*; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology
D000914:Antibodies, Viral; D004279:DNA, Viral; D053918:Papillomavirus Vaccines; D014765:Viral Vaccines