The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16-26 years.
BACKGROUND
Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated.


METHODS
We enrolled 17,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotyping was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of 6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types.


RESULTS
Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval [CI], 13.9% to 59.0%) and of CIN1-3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/33/45/52/58 infection and CIN1-3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2-3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31.


CONCLUSIONS
HPV-6/11/16/18 vaccine reduced the risk of CIN2-3/AIS associated with nonvaccine types responsible for approximately 20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18-related disease, because women may have >1 CIN lesion, each associated with a different HPV type.


BACKGROUND
ClinicalTrials.gov identifiers: NCT00092521 , NCT00092534 , and NCT00092482.
Brown
Darron R
DR
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. darfrow@iupui.edu
Kjaer
Susanne K
SK
Sigurdsson
Kristján
K
Iversen
Ole-Erik
OE
Hernandez-Avila
Mauricio
M
Wheeler
Cosette M
CM
Perez
Gonzalo
G
Koutsky
Laura A
LA
Tay
Eng Hseon
EH
Garcia
Patricía
P
Ault
Kevin A
KA
Garland
Suzanne M
SM
Leodolter
Sepp
S
Olsson
Sven-Eric
SE
Tang
Grace W K
GW
Ferris
Daron G
DG
Paavonen
Jorma
J
Steben
Marc
M
Bosch
F Xavier
FX
Dillner
Joakim
J
Joura
Elmar A
EA
Kurman
Robert J
RJ
Majewski
Slawomir
S
Muñoz
Nubia
N
Myers
Evan R
ER
Villa
Luisa L
LL
Taddeo
Frank J
FJ
Roberts
Christine
C
Tadesse
Amha
A
Bryan
Janine
J
Lupinacci
Lisa C
LC
Giacoletti
Katherine E D
KE
Sings
Heather L
HL
James
Margaret
M
Hesley
Teresa M
TM
Barr
Eliav
E
D000293:Adolescent; D000328:Adult; D052685:Alphapapillomavirus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D030361:Papillomavirus Infections / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control / Q000821:virology; D055815:Young Adult
D053918:Papillomavirus Vaccines