Risk of miscarriage with bivalent vaccine against human papillomavirus (HPV) types 16 and 18: pooled analysis of two randomised controlled trials.
OBJECTIVE
To assess whether vaccination against human papillomavirus (HPV) increases the risk of miscarriage.


METHODS
Pooled analysis of two multicentre, phase three masked randomised controlled trials


METHODS
Multicentre trials in several continents and in Costa Rica.


METHODS
26 130 women aged 15-25 at enrolment; 3599 pregnancies eligible for analysis.


METHODS
Participants were randomly assigned to receive three doses of bivalent HPV 16/18 VLP vaccine with AS04 adjuvant (n=13 075) or hepatitis A vaccine as control (n=13 055) over six months.


METHODS
Miscarriage and other pregnancy outcomes.


RESULTS
The estimated rate of miscarriage was 11.5% in pregnancies in women in the HPV arm and 10.2% in the control arm. The one sided P value for the primary analysis was 0.16; thus, overall, there was no significant increase in miscarriage among women assigned to the HPV vaccine arm. In secondary descriptive analyses, miscarriage rates were 14.7% in the HPV vaccine arm and 9.1% in the control arm in pregnancies that began within three months after nearest vaccination.


CONCLUSIONS
There is no evidence overall for an association between HPV vaccination and risk of miscarriage.


BACKGROUND
Clinical Trials NCT00128661 and NCT00122681.
Wacholder
Sholom
S
Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Rockville, MD 20852, USA. WacholdS@mail.nih.gov
Chen
Bingshu Eric
BE
Wilcox
Allen
A
Macones
George
G
Gonzalez
Paula
P
Befano
Brian
B
Hildesheim
Allan
A
Rodríguez
Ana Cecilia
AC
Solomon
Diane
D
Herrero
Rolando
R
Schiffman
Mark
M
D000022:Abortion, Spontaneous / Q000139:chemically induced*; D000293:Adolescent; D000328:Adult; D019496:Cancer Vaccines / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D052162:Human papillomavirus 16; D052161:Human papillomavirus 18; D006801:Humans; D030361:Papillomavirus Infections / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000009:adverse effects*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000517:prevention & control; D011252:Pregnancy Complications, Neoplastic / Q000517:prevention & control*; D011256:Pregnancy Outcome; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*; D055815:Young Adult
D019496:Cancer Vaccines; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18