Drug Safety

, Volume 41, Issue 4, pp 329–346 | Cite as

Safety of Human Papillomavirus Vaccines: An Updated Review

  • Anastasia Phillips
  • Cyra Patel
  • Alexis Pillsbury
  • Julia Brotherton
  • Kristine MacartneyEmail author
Review Article


Human papillomavirus (HPV) vaccines are now included in immunisation programmes in 71 countries. Unfortunately, uptake has been impacted in some countries by reduced confidence in the safety of the HPV vaccine. In 2013, we published an extensive review demonstrating a reassuring safety profile for bivalent (2vHPV) and quadrivalent (4vHPV) vaccines. A nonavalent (9vHPV) vaccine is now available and HPV immunisation programmes have been extended to males in 11 countries. The aim of this updated narrative review was to examine the evidence on HPV vaccine safety, focusing on the 9vHPV vaccine, special populations and adverse events of special interest (AESI). The previous searches were replicated to identify studies to August 2016, including additional search terms for AESI. We identified 109 studies, including 15 population-based studies in over 2.5 million vaccinated individuals across six countries. All vaccines demonstrated an acceptable safety profile; injection-site reactions were slightly more common for 9vHPV vaccine than for 4vHPV vaccine. There was no consistent evidence of an increased risk of any AESI, including demyelinating syndromes or neurological conditions such as complex regional pain or postural orthostatic tachycardia syndromes. The risk–benefit profile for HPV vaccines remains highly favourable.



Catherine King, National Centre for Immunisation Research and Surveillance, assisted with the literature review. Anastasia Phillips was an employee of the National Centre for Immunisation Research and Surveillance at the time of writing this paper.

Compliance with Ethical Standards


No sources of funding were used to assist in the preparation of this study.

Conflicts of interest

Kristine Macartney, Anastasia Phillips, Alexis Pillsbury and Cyra Patel have no conflicts of interest that are directly relevant to the content of this study. Julie Brotherton is employed as the Director of the National HPV Vaccination Program Register, which is owned and funded by the Australian Government Department of Health. She has been an investigator on investigator initiated HPV epidemiology studies which have received unrestricted partial funding for laboratory components from Seqirus (cervical cancer typing study) and Merck (recurrent respiratory papillomatosis study) but has never received any personal financial benefits.

Supplementary material

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Supplementary material 1 (PDF 108 kb)
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Supplementary material 2 (PDF 79 kb)
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Supplementary material 3 (PDF 77 kb)
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Supplementary material 4 (PDF 49 kb)
40264_2017_625_MOESM5_ESM.pdf (50 kb)
Supplementary material 5 (PDF 56 kb)


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Anastasia Phillips
    • 1
  • Cyra Patel
    • 2
  • Alexis Pillsbury
    • 2
  • Julia Brotherton
    • 3
    • 4
  • Kristine Macartney
    • 1
    • 2
    Email author
  1. 1.The University of SydneySydneyAustralia
  2. 2.National Centre for Immunisation Research and Surveillance, Kids Research Institute, The Sydney Children’s Hospitals NetworkWestmeadAustralia
  3. 3.National HPV Vaccination Program Register, Victorian Cytology ServiceCarltonAustralia
  4. 4.The University of MelbourneMelbourneAustralia

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