Safety of human papillomavirus vaccines: a review

Drug Saf. 2013 Jun;36(6):393-412. doi: 10.1007/s40264-013-0039-5.


Vaccination to prevent human papillomavirus (HPV)-related infection leading to cancer, particularly cervical cancer, is a major public health breakthrough. There are currently two licensed HPV vaccines, both of which contain recombinant virus-like particles of HPV types 16 and 18 (which account for approximately 70 % of cervical cancer). One vaccine also protects against HPV types 6 and 11, which cause genital warts. The safety profile of both vaccines was assessed extensively in randomised controlled clinical trials conducted prior to licensure and has been further elucidated following licensure from surveillance and specific studies in large populations. This review aims to examine current evidence regarding the safety of HPV vaccines. In summary, both vaccines are associated with relatively high rates of injection site reactions, particularly pain, but this is usually of short duration and resolves spontaneously. Systemic reactions have generally been mild and self-limited. Post vaccination syncope has occurred, but can be avoided with appropriate care. Serious vaccine-attributable adverse events, such as anaphylaxis, are rare, and although not recommended for use in pregnancy, abnormal pregnancy outcomes following inadvertent administration do not appear to be associated with vaccination. HPV vaccines are used in a three-dose schedule predominantly in adolescent females: as such case reports linking vaccination with a range of new onset chronic conditions, including autoimmune diseases, have been made. However, well-conducted population-based studies show no association between HPV vaccine and a range of such conditions. Whilst this reassuring safety profile affirms the positive risk benefit of vaccination, as HPV vaccine use expands into more diverse populations, including males, ongoing safety assessment using well-conducted studies is appropriate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Evidence-Based Medicine*
  • Female
  • Humans
  • Male
  • Papillomavirus Infections / prevention & control
  • Papillomavirus Vaccines / adverse effects*
  • Papillomavirus Vaccines / therapeutic use
  • Pregnancy
  • Uterine Cervical Neoplasms / prevention & control
  • Uterine Cervical Neoplasms / virology
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / therapeutic use


  • Papillomavirus Vaccines
  • Vaccines, Synthetic