High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up.
Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16-23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrollment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy = 100%; 95% CI:12-100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts.
Villa
L L
LL
Ludwig Institute for Cancer Research, R Prof Antonio Prudente 109, 01509-010 Sao Paulo, SP, Brazil. llvilla@ludwig.org.br
Costa
R L R
RL
Petta
C A
CA
Andrade
R P
RP
Paavonen
J
J
Iversen
O-E
OE
Olsson
S-E
SE
Høye
J
J
Steinwall
M
M
Riis-Johannessen
G
G
Andersson-Ellstrom
A
A
Elfgren
K
K
Krogh
G von
Gv
Lehtinen
M
M
Malm
C
C
Tamms
G M
GM
Giacoletti
K
K
Lupinacci
L
L
Railkar
R
R
Taddeo
F J
FJ
Bryan
J
J
Esser
M T
MT
Sings
H L
HL
Saah
A J
AJ
Barr
E
E
D000293:Adolescent; D000328:Adult; D052685:Alphapapillomavirus / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood; D003218:Condylomata Acuminata / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D002578:Uterine Cervical Dysplasia / Q000517:prevention & control; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*; D014626:Vaginal Smears; D014771:Virion / Q000276:immunology*
D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18