Drug Safety

, Volume 41, Issue 5, pp 539–540 | Cite as

Comment on: “Safety of Human Papillomavirus Vaccines: An Updated Review”

  • Manuel Martínez-Lavín
Letter to the Editor

To the Editor,

In their updated literature review of HPV vaccine safety, Phillips et al. focused on the new 9-valent HPV vaccine, and on adverse events of special interest. Their conclusion was that “The risk–benefit profile for HPV vaccines remains highly favourable” [1]. Our recent analysis of the same scientific literature reached an opposite conclusion [2]. Our divergent opinion is based on the following reasoning.

The Phillips et al. review found no increased risk of death in bivalent HPV vaccine clinical trials [1]. Our analysis did [2]. The VIVIANE study compared 2871 women receiving aluminum placebo, with 2881 women injected with the bivalent HPV vaccine. The bivalent HPV vaccine group had more deaths on follow-up (14 vs 3, p = 0.012 by Fisher’s exact test). None of the deaths were believed to be related to vaccination [3].

Phillips et al. state: “Data from clinical trials reported a similar safety profile for the 9-valent HPV vaccine as for 4-valent HPV vaccine” [1]. Our...


Compliance with Ethical Standards


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

Conflicts of interest

Manuel Martínez-Lavín has no conflicts of interest that are directly relevant to the content of this letter.


  1. 1.
    Phillips A, Patel C, Pillsbury A, Brotherton J, Macartney K. Safety of human papillomavirus vaccines: an updated review. Drug Saf. 2017;41(4).
  2. 2.
    Martínez-Lavín M, Amezcua-Guerra L. Serious adverse events after HPV vaccination: a critical review of randomized trials and post-marketing case series. Clin Rheumatol. 2017;36(10):2169–78 (Erratum in: Clin Rheumatol).CrossRefPubMedGoogle Scholar
  3. 3.
    Skinner SR, Szarewski A, Romanowski B, Garland SM, Lazcano-Ponce E, Salmerón J, Del Rosario-Raymundo MR, Verheijen RH, Quek SC, da Silva DP, Kitchener H, Fong KL, Bouchard C, Money DM, Ilancheran A, Cruickshank ME, Levin MJ, Chatterjee A, Stapleton JT, Martens M, Quint W, David MP, Meric D, Hardt K, Descamps D, Geeraerts B, Struyf F, Dubin G. Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 4-year interim follow-up of the phase 3, double-blind, randomised controlled VIVIANE study. Lancet. 2014;84:2213–27.CrossRefGoogle Scholar
  4. 4.
    Joura EA, Giuliano AR, Iversen OE, Bouchard C, Mao C, Mehlsen J, Moreira ED Jr, Ngan Y, Petersen LK, Lazcano-Ponce E, Pitisuttithum P, Restrepo JA, Stuart G, Woelber L, Yang YC, Cuzick J, Garland SM, Huh W, Kjaer SK, Bautista OM, Chan IS, Chen J, Gesser R, Moeller E, Ritter M, Vuocolo S, Luxembourg A. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015;372:711–23.CrossRefPubMedGoogle Scholar
  5. 5.
    Blitshteyn S. Postural tachycardia syndrome following human papillomavirus vaccination. Eur J Neurol. 2014;21:135–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Brinth L, Theibel AC, Pors K, Mehlsen J. Suspected side effects to the quadrivalent human papilloma vaccine. Dan Med J. 2015;62:A5064.PubMedGoogle Scholar
  7. 7.
    Kinoshita T, Abe RT, Hineno A, Tsunekawa K, Nakane S, Ikeda S. Peripheral sympathetic nerve dysfunction in adolescent Japanese girls following immunization with the human papillomavirus vaccine. Intern Med. 2014;53:2185–200.CrossRefPubMedGoogle Scholar
  8. 8.
    Martínez-Lavín M, Martínez-Martínez LA, Reyes-Loyola P. HPV vaccination syndrome. A questionnaire-based study. Clin Rheumatol. 2015;34:1981–3.CrossRefPubMedGoogle Scholar
  9. 9.
    Palmieri B, Poddighe D, Vadalà M, Laurino C, Carnovale C, Clementi E. Severe somatoform and dysautonomic syndromes after HPV vaccination: case series and review of literature. Immunol Res. 2017;65:106–16.CrossRefPubMedGoogle Scholar
  10. 10.
    Chandler RE, Juhlin K, Fransson J, Caster O, Edwards IR, Norén GN. Current safety concerns with human papillomavirus vaccine: a cluster analysis of reports in VigiBase. Drug Saf. 2017;40:81–90.CrossRefPubMedGoogle Scholar
  11. 11.
    Exley C, Siesjö P, Eriksson H. The immunobiology of aluminium adjuvants: how do they really work? Trends Immunol. 2010;31:103–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Masson JD, Crépeaux G, Authier FJ, Exley C, Gherardi RK. Critical analysis of reference studies on the toxicokinetics of aluminum-based adjuvants. J Inorg Biochem. 2017. [Epub ahead of print].PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Rheumatology DepartmentNational Institute of CardiologyMexico CityMexico

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