Serious adverse events after HPV vaccination: a critical review of randomized trials and post-marketing case series

Abstract

This article critically reviews HPV vaccine serious adverse events described in pre-licensure randomized trials and in post-marketing case series. HPV vaccine randomized trials were identified in PubMed. Safety data were extracted. Post-marketing case series describing HPV immunization adverse events were reviewed. Most HPV vaccine randomized trials did not use inert placebo in the control group. Two of the largest randomized trials found significantly more severe adverse events in the tested HPV vaccine arm of the study. Compared to 2871 women receiving aluminum placebo, the group of 2881 women injected with the bivalent HPV vaccine had more deaths on follow-up (14 vs. 3, p = 0.012). Compared to 7078 girls injected with the 4-valent HPV vaccine, 7071 girls receiving the 9-valent dose had more serious systemic adverse events (3.3 vs. 2.6%, p = 0.01). For the 9-valent dose, our calculated number needed to seriously harm is 140 (95% CI, 79–653). The number needed to vaccinate is 1757 (95% CI, 131 to infinity). Practically, none of the serious adverse events occurring in any arm of both studies were judged to be vaccine-related. Pre-clinical trials, post-marketing case series, and the global drug adverse reaction database (VigiBase) describe similar post-HPV immunization symptom clusters. Two of the largest randomized HPV vaccine trials unveiled more severe adverse events in the tested HPV vaccine arm of the study. Nine-valent HPV vaccine has a worrisome number needed to vaccinate/number needed to harm quotient. Pre-clinical trials and post-marketing case series describe similar post-HPV immunization symptoms.

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  • 29 July 2017

    An erratum to this article has been published.

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Correspondence to Manuel Martínez-Lavín.

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The original version of this article was revised: The above article originally published with an error present in the 9-valent dose listed within the abstract. Originally reading “…For the 9-valent dose, our calculated number needed to seriously harm is 140 (95% CI, 796–53)…”, this should instead have read “…For the 9-valent dose, our calculated number needed to seriously harm is 140 (95% CI, 79–653)…” [bold text used to highlight problem area].

An erratum to this article is available at https://doi.org/10.1007/s10067-017-3782-7.

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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 36, 2169–2178 (2017). https://doi.org/10.1007/s10067-017-3768-5

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Keywords

  • Adverse events
  • Chronic fatigue syndrome
  • Fibromyalgia
  • HPV vaccine
  • Postural orthostatic tachycardia syndrome