Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women.
BACKGROUND
The impact of the prophylactic vaccine against human papillomavirus (HPV) types 6, 11, 16, and 18 (HPV6/11/16/18) on all HPV-associated genital disease was investigated in a population that approximates sexually naive women in that they were "negative to 14 HPV types" and in a mixed population of HPV-exposed and -unexposed women (intention-to-treat group).


METHODS
This analysis studied 17 622 women aged 15-26 years who were enrolled in one of two randomized, placebo-controlled, efficacy trials for the HPV6/11/16/18 vaccine (first patient on December 28, 2001, and studies completed July 31, 2007). Vaccine or placebo was given at day 1, month 2, and month 6. All women underwent cervicovaginal sampling and Papanicolaou (Pap) testing at day 1 and every 6-12 months thereafter. Outcomes were any cervical intraepithelial neoplasia; any external anogenital and vaginal lesions; Pap test abnormalities; and procedures such as colposcopy and definitive therapy. Absolute rates are expressed as women with endpoint per 100 person-years at risk.


RESULTS
The average follow-up was 3.6 years (maximum of 4.9 years). In the population that was negative to 14 HPV types, vaccination was up to 100% effective in reducing the risk of HPV16/18-related high-grade cervical, vulvar, and vaginal lesions and of HPV6/11-related genital warts. In the intention-to-treat group, vaccination also statistically significantly reduced the risk of any high-grade cervical lesions (19.0% reduction; rate vaccine = 1.43, rate placebo = 1.76, difference = 0.33, 95% confidence interval [CI] = 0.13 to 0.54), vulvar and vaginal lesions (50.7% reduction; rate vaccine = 0.10, rate placebo = 0.20, difference = 0.10, 95% CI = 0.04 to 0.16), genital warts (62.0% reduction; rate vaccine = 0.44, rate placebo = 1.17, difference = 0.72, 95% CI = 0.58 to 0.87), Pap abnormalities (11.3% reduction; rate vaccine = 10.36, rate placebo = 11.68, difference = 1.32, 95% CI = 0.74 to 1.90), and cervical definitive therapy (23.0% reduction; rate vaccine = 1.97, rate placebo = 2.56, difference = 0.59, 95% CI = 0.35 to 0.83), irrespective of causal HPV type.


CONCLUSIONS
High-coverage HPV vaccination programs among adolescents and young women may result in a rapid reduction of genital warts, cervical cytological abnormalities, and diagnostic and therapeutic procedures. In the longer term, substantial reductions in the rates of cervical, vulvar, and vaginal cancers may follow.
Division of Research and Public Health, National Institute of Cancer, Bogotá, Colombia . nubia.munoz@free.fr
Nubia
N
Muñoz
Susanne K
SK
Kjaer
Kristján
K
Sigurdsson
Ole-Erik
OE
Iversen
Mauricio
M
Hernandez-Avila
Cosette M
CM
Wheeler
Gonzalo
G
Perez
Darron R
DR
Brown
Laura A
LA
Koutsky
Eng Hseon
EH
Tay
Patricía J
PJ
Garcia
Kevin A
KA
Ault
Suzanne M
SM
Garland
Sepp
S
Leodolter
Sven-Eric
SE
Olsson
Grace W K
GW
Tang
Daron G
DG
Ferris
Jorma
J
Paavonen
Marc
M
Steben
F Xavier
FX
Bosch
Joakim
J
Dillner
Warner K
WK
Huh
Elmar A
EA
Joura
Robert J
RJ
Kurman
Slawomir
S
Majewski
Evan R
ER
Myers
Luisa L
LL
Villa
Frank J
FJ
Taddeo
Christine
C
Roberts
Amha
A
Tadesse
Janine T
JT
Bryan
Lisa C
LC
Lupinacci
Katherine E D
KE
Giacoletti
Heather L
HL
Sings
Margaret K
MK
James
Teresa M
TM
Hesley
Eliav
E
Barr
Richard M
RM
Haupt
D000293:Adolescent; D000328:Adult; D052685:Alphapapillomavirus / Q000276:immunology*; D005260:Female; D005831:Genital Diseases, Female / Q000517:prevention & control / Q000821:virology; D014943:Global Health; D052140:Human papillomavirus 11 / Q000276:immunology; D052162:Human papillomavirus 16 / Q000276:immunology; D052161:Human papillomavirus 18 / Q000276:immunology; D052163:Human papillomavirus 6 / Q000276:immunology; D006801:Humans; D053208:Kaplan-Meier Estimate; D065006:Papanicolaou Test; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000494:pharmacology*; D012747:Sexual Partners; D012749:Sexually Transmitted Diseases / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D014412:Tumor Virus Infections / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D014626:Vaginal Smears; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology
D053918:Papillomavirus Vaccines