Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection.
OBJECTIVE
In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL/SILGARD) clinical program, 73% of women aged 16-26 were naïve to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical disease. Of the remaining women, 15% of had evidence of past infection with one or more vaccine HPV types (seropositive and DNA negative) at the time of enrollment. Here we present an analysis in this group of women to determine the efficacy of the HPV 6/11/16/18 vaccine against new cervical and external anogenital disease related to the same vaccine HPV type which had previously been cleared. Vaccine tolerability in this previously infected population was also assessed.


METHODS
18,174 women were enrolled into 3 clinical studies. The data presented comprise a subset of these subjects (n = 2,617) who were HPV seropositive and DNA negative at enrollment (for >or=1 vaccine type). In each study, subjects were randomized in a 1:1 ratio to receive HPV 6/11/16/18 vaccine or placebo at day 1, month 2 and month 6 (without knowledge of baseline HPV status). Procedures performed for efficacy data evaluation included detailed genital examination, Pap testing, and collection of cervicovaginal and external genital specimens. Analyses of efficacy were carried out in a population stratified by HPV serology and HPV DNA status at enrollment.


RESULTS
Subjects were followed for an average of 40 months. Seven subjects in the placebo group developed cervical disease, and eight subjects developed external genital disease related to a vaccine HPV type they had previously encountered. No subject receiving HPV 6/11/16/18 vaccine developed disease to a vaccine HPV type to which they were seropositive and DNA negative at enrolment.


CONCLUSIONS
These results suggest that natural HPV infection-elicited antibodies may not provide complete protection over time, however the immune response to the HPV 6/11/16/18 vaccine appears to prevent reinfection or reactivation of disease with vaccine HPV types. Vaccine-related adverse experiences were higher among subjects receiving vaccine, mostly due to increased injection site adverse experiences.
Olsson
Sven-Eric
SE
Karolinska Institute at Danderyd Hospital, Stockholm, Sweden. sven-eric.olsson@ds.se
Kjaer
Susanne K
SK
Sigurdsson
Kristján
K
Iversen
Ole-Erik
OE
Hernandez-Avila
Mauricio
M
Wheeler
Cosette M
CM
Perez
Gonzalo
G
Brown
Darron R
DR
Koutsky
Laura A
LA
Tay
Eng Hseon
EH
García
Patricia
P
Ault
Kevin A
KA
Garland
Suzanne M
SM
Leodolter
Sepp
S
Tang
Grace W K
GW
Ferris
Daron G
DG
Paavonen
Jorma
J
Lehtinen
Matti
M
Steben
Marc
M
Bosch
F Xavier
FX
Dillner
Joakim
J
Joura
Elmar A
EA
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
Maansson
Roger
R
Vuocolo
Scott
S
Hesley
Teresa M
TM
Saah
Alfred
A
Barr
Eliav
E
Haupt
Richard M
RM
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D002584:Cervix Uteri / Q000166:cytology / Q000473:pathology / Q000821:virology*; D005260:Female; D005500:Follow-Up Studies; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D006801:Humans; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000009:adverse effects / Q000276:immunology*; D010919:Placebos / Q000008:administration & dosage; D014844:Vulva / Q000473:pathology / Q000821:virology*; D055815:Young Adult
D000914:Antibodies, Viral; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D053918:Papillomavirus Vaccines; D010919:Placebos