E2 ModerateModerate confidencePEM not requiredObservationalPeer-reviewedMachine draft
Hospital Records of Pain, Fatigue, or Circulatory Symptoms in Girls Exposed to Human Papillomavirus Vaccination: Cohort, Self-Controlled Case Series, and Population Time Trend Studies.
Thomsen, Reimar Wernich, Öztürk, Buket, Pedersen, Lars et al. · American journal of epidemiology · 2020 · DOI
Quick Summary
This large Danish study looked at whether the HPV vaccine (which prevents cervical cancer) was linked to symptoms like pain, fatigue, or heart problems in girls. Researchers compared vaccinated and unvaccinated girls over 14 years and found no increase in hospital visits for these symptoms in vaccinated girls. The symptoms they tracked increased over time in both vaccinated and unvaccinated children, suggesting other factors were responsible.
Why It Matters
This study directly addresses concerns about vaccine safety and post-vaccination symptom clusters resembling ME/CFS-like conditions. For ME/CFS patients and researchers, understanding whether common vaccinations trigger or exacerbate disease is crucial for public health policy and identifying true disease triggers versus coincidental temporal associations.
Observed Findings
- Incidence rate ratios for pain, fatigue, and circulatory symptoms in vaccinated versus unvaccinated girls were close to 1.0 across all measured outcomes.
- Self-controlled case series analyses found no temporal association between HPV vaccination and subsequent symptom development.
- Population time trend analysis showed steady increases in hospital records for pain, fatigue, and circulatory symptoms in both girls and unvaccinated boys, independent of HPV vaccine introduction in 2009.
- No clustering of outcomes in the period following vaccination rollout.
Inferred Conclusions
- HPV vaccination is not causally linked to hospital-diagnosed diffuse autonomic or pain symptoms in girls.
- The temporal increase in these symptoms over the study period reflects factors unrelated to HPV vaccination introduction.
- Public concern about vaccine-associated diffuse symptoms is not supported by this population-level evidence.
Remaining Questions
- Does HPV vaccination affect symptom development or severity in girls with pre-existing autoimmune or autonomic conditions?
- What explains the population-level increase in these symptoms over time if not vaccination?
- Are milder symptoms not requiring hospitalization associated with vaccination, and if so, at what frequency?
What This Study Does Not Prove
This study cannot rule out rare or severe vaccine adverse events occurring outside hospital care, nor does it address whether vaccination might unmask or worsen pre-existing ME/CFS in susceptible individuals. Hospital records capture only moderate-to-severe cases, missing mild or undiagnosed cases managed in primary care. Observational data cannot prove causation if unmeasured confounding exists.
Tags
Symptom:Orthostatic IntolerancePainFatigue
Phenotype:Pediatric
Method Flag:Weak Case DefinitionMixed Cohort
Metadata
- DOI
- 10.1093/aje/kwz284
- PMID
- 31899791
- Review status
- Machine draft
- Evidence level
- Single-study or moderate support from human research
- Last updated
- 8 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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