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• Moving Forward on HPV Vaccine Safety Concerns
  Benjamin D. Brooks, Megan Wijesinghe and Nicole .chipperijn
  Published on: 24 April 2024

• Published on: 24 April 2024

  Moving Forward on HPV Vaccine Safety Concerns

  • Benjamin D. Brooks, Professor Rocky Vista University
  • Other Contributors:
    • Megan Wijesinghe, Medical Student
    • Nicole .chipperijn, Medical Student

  Gøtzsche and Jørgensen claim that the European Medicines Agency (EMA) mishandled their investigation of the safety of the HPV vaccine regarding serious neurological adverse events from the administration of the HPV vaccine, such as postural orthostatic tachycardia syndrome (POTS) and chronic regional pain syndrome (CRPS). The authors highlight the insufficiency due to poor data analysis, conflicts of interest, poor research into aluminum adjuvants, and bias in analyzing the research 1. We want to discuss several key points on the safety of the HPV vaccine.
  Over 270 million doses of HPV vaccines have been administered since 2006. Many regulatory agencies have overseen the safety of the HPV vaccine, including the World Health Organization’s GACVS (Global Advisory Committee on Vaccine Safety) 2. Most regulatory agencies regard the HPV vaccine as safe and effective 3,4. The noted exception in this article is the Uppsala Monitoring Centre which identified safety signals for POTS and CRPS post-HPV vaccination 5.
  As of specific note from the paper, the majority of the evidence supporting an association with the HPV vaccine and POTS and CRPS in the article by Gøtzsche and Jørgensen was generated from data in Europe, including Denmark 1. A recent study showed no safety signal generally and specifically commented that the Denmark signal was not identified in their analysis, noting that 1,232,572 girls received the vaccine and 563 unique CRPS diagnoses (6). Concerns about...

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  Gøtzsche and Jørgensen claim that the European Medicines Agency (EMA) mishandled their investigation of the safety of the HPV vaccine regarding serious neurological adverse events from the administration of the HPV vaccine, such as postural orthostatic tachycardia syndrome (POTS) and chronic regional pain syndrome (CRPS). The authors highlight the insufficiency due to poor data analysis, conflicts of interest, poor research into aluminum adjuvants, and bias in analyzing the research 1. We want to discuss several key points on the safety of the HPV vaccine.
  Over 270 million doses of HPV vaccines have been administered since 2006. Many regulatory agencies have overseen the safety of the HPV vaccine, including the World Health Organization’s GACVS (Global Advisory Committee on Vaccine Safety) 2. Most regulatory agencies regard the HPV vaccine as safe and effective 3,4. The noted exception in this article is the Uppsala Monitoring Centre which identified safety signals for POTS and CRPS post-HPV vaccination 5.
  As of specific note from the paper, the majority of the evidence supporting an association with the HPV vaccine and POTS and CRPS in the article by Gøtzsche and Jørgensen was generated from data in Europe, including Denmark 1. A recent study showed no safety signal generally and specifically commented that the Denmark signal was not identified in their analysis, noting that 1,232,572 girls received the vaccine and 563 unique CRPS diagnoses (6). Concerns about the media role increased in case count, and most cases were self-resolving and limited 1.
  So, the question is how to rectify the disparity of conclusions between Uppsala and other regulatory agencies. Or maybe the discussion is misdirected? Gøtzsche and Jørgensen claim bias and poor scientific rigor in the trial design. An alternative to this hypothesis was noted by Uppsala Monitoring Center when they said variability in diagnosis terms (i.e., the ontology of vaccine adverse events) might not provide a coherent diagnosing paradigm and monitoring approach across clinical, regulatory, and industry entities, which was only alluded to by the authors. The Uppsala manuscript has an excellent analysis focused on adversomics, which is completely missing in the Gøtzsche and Jørgensen paper. The adversomics is THE important part of the Uppsala manuscript.
  During COVID-19, numerous tools were developed and used to assess vaccine responses for safety and efficacy. These tools could potentially identify people who have adverse events after vaccination. Immunogenomics, transcriptomics, epitope mapping, machine learning, etc., are available and could be used to identify the safety profile of all vaccines 6. We strongly advocate that with these current technologies, risk factors for POTS and CRPS could be identified (> GRADE 3 SAEs (Serious Adverse Event)) through the study of existing and future cases. We strongly advocate developing diagnostic criteria for POTS and CRPS by Brighton Collaboration, including consistent GRADE analysis and ontology. Regulatory agencies could require monitoring using these tools in serious adverse events cases for any vaccine to improve vaccine safety for rare SAEs. Instead of asking whether HPV is safe, maybe we should ask how high-risk patients can be identified pre-vaccination. The COVID-19 analysis suggests we could identify potential risk factors that lead to adverse events to adjuvants and the vaccine in general. We advocate for these approaches through regulatory requirements, including improved phase IV trials, active monitoring, and proper analysis.

  1. Gøtzsche PC, Jørgensen KJ. EMA’s mishandling of an investigation into suspected serious neurological harms of HPV vaccines. BMJ Evid-Based Med. 2022;27(1):7-10. doi:10.1136/bmjebm-2020-111470
  2. HPV Vaccine Safety, WHO. Accessed June 23, 2023. https://www.who.int/groups/global-advisory-committee-on-vaccine-safety/t...
  3. HPV Dashboard. Accessed June 23, 2023. https://www.who.int/teams/immunization-vaccines-and-biologicals/diseases...(HPV)/hpv-clearing-house/hpv-dashboard
  4. Bonanni P, Bechini A, Donato R, et al. Human papilloma virus vaccination: impact and recommendations across the world. Ther Adv Vaccines. 2015;3(1):3-12. doi:10.1177/2051013614557476
  5. Chandler RE. Safety Concerns with HPV Vaccines Continue to Linger: Are Current Vaccine Pharmacovigilance Practices Sufficient? Drug Saf. 2017;40(12):1167-1170. doi:10.1007/s40264-017-0593-3
  6. Cotugno N, Ruggiero A, Santilli V, et al. OMIC Technologies and Vaccine Development: From the Identification of Vulnerable Individuals to the Formulation of Invulnerable Vaccines. J Immunol Res. 2019;2019:e8732191. doi:10.1155/2019/8732191

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  Conflict of Interest:
  None declared.

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