Risk of miscarriage with bivalent vaccine against human papillomavirus (HPV) types 16 and 18: pooled analysis of two randomised controlled trials

BMJ. 2010 Mar 2;340:c712. doi: 10.1136/bmj.c712.

Abstract

Objective: To assess whether vaccination against human papillomavirus (HPV) increases the risk of miscarriage.

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

Setting: Multicentre trials in several continents and in Costa Rica.

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

Interventions: 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.

Main outcome measures: 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.

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

Trial registration: Clinical Trials NCT00128661 and NCT00122681.

Publication types

  • Meta-Analysis
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Spontaneous / chemically induced*
  • Adolescent
  • Adult
  • Cancer Vaccines / adverse effects*
  • Double-Blind Method
  • Female
  • Human papillomavirus 16
  • Human papillomavirus 18
  • Humans
  • Papillomavirus Infections / prevention & control
  • Papillomavirus Vaccines / adverse effects*
  • Pregnancy
  • Pregnancy Complications, Infectious / prevention & control
  • Pregnancy Complications, Neoplastic / prevention & control*
  • Pregnancy Outcome
  • Risk Factors
  • Uterine Cervical Neoplasms / prevention & control*
  • Young Adult

Substances

  • Cancer Vaccines
  • Papillomavirus Vaccines
  • human papillomavirus vaccine, L1 type 16, 18

Associated data

  • ClinicalTrials.gov/NCT00122681
  • ClinicalTrials.gov/NCT00128661