Safety Profile of the 9-Valent HPV Vaccine: A Combined Analysis of 7 Phase III Clinical Trials

Pediatrics. 2016 Aug;138(2):e20154387. doi: 10.1542/peds.2015-4387. Epub 2016 Jul 15.

Abstract

Objectives: The overall safety profile of the 9-valent human papillomavirus (9vHPV) vaccine was evaluated across 7 Phase III studies, conducted in males and females (nonpregnant at entry), 9 to 26 years of age.

Methods: Vaccination was administered as a 3-dose regimen at day 1, and months 2 and 6. More than 15 000 subjects received ≥1 dose of 9vHPV vaccine. In 2 of the studies, >7000 control subjects received ≥1 dose of quadrivalent HPV (qHPV) vaccine. Serious and nonserious adverse events (AEs) and new medical conditions were recorded throughout the study. Subjects testing positive for pregnancy at day 1 were not vaccinated; those who became pregnant after day 1 were discontinued from further vaccination until resolution of the pregnancy. Pregnancies detected after study start (n = 2950) were followed to outcome.

Results: The most common AEs (≥5%) experienced by 9vHPV vaccine recipients were injection-site AEs (pain, swelling, erythema) and vaccine-related systemic AEs (headache, pyrexia). Injection-site AEs were more common in 9vHPV vaccine than qHPV vaccine recipients; most were mild-to-moderate in intensity. Discontinuations and vaccine-related serious AEs were rare (0.1% and <0.1%, respectively). Seven deaths were reported; none were considered vaccine related. The proportions of pregnancies with adverse outcome were within ranges reported in the general population.

Conclusions: The 9vHPV vaccine was generally well tolerated in subjects aged 9 to 26 years with an AE profile similar to that of the qHPV vaccine; injection-site AEs were more common with 9vHPV vaccine. Its additional coverage and safety profile support widespread 9vHPV vaccination.

Trial registration: ClinicalTrials.gov NCT00543543 NCT00943722 NCT01651949 NCT00988884 NCT01047345 NCT01073293 NCT01304498.

Publication types

  • Meta-Analysis

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Clinical Trials, Phase III as Topic
  • Edema / etiology
  • Erythema / etiology
  • Female
  • Fever / etiology
  • Follow-Up Studies
  • Headache / etiology
  • Humans
  • Immunization Schedule
  • Male
  • Outcome Assessment, Health Care
  • Pain / etiology
  • Papillomavirus Vaccines / administration & dosage
  • Papillomavirus Vaccines / adverse effects*
  • Pregnancy
  • Pregnancy Complications / etiology
  • Pregnancy Outcome
  • Young Adult

Substances

  • Papillomavirus Vaccines

Associated data

  • ClinicalTrials.gov/NCT00543543
  • ClinicalTrials.gov/NCT00943722
  • ClinicalTrials.gov/NCT01651949
  • ClinicalTrials.gov/NCT00988884
  • ClinicalTrials.gov/NCT01047345
  • ClinicalTrials.gov/NCT01073293
  • ClinicalTrials.gov/NCT01304498