Question explored with the scientific record
Conversation so far
- 1 What benefit is the papaloma virus vaccine for young girls
- 2 What are the main risks or side effects, and how common are they?
- 3 What rare serious side effects are being watched, and what’s the evidence?
Answered on this page ↓
What rare serious side effects are being watched, and what’s the evidence?
The short version: the rare serious events being watched are autoimmune conditions, neurological disorders, and blood clots, but the evidence is mixed and the surveillance systems are weak.
The main rare events under surveillance are Guillain-Barré syndrome (GBS), autoimmune thyroiditis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes, venous thromboembolism (VTE), and postural orthostatic tachycardia syndrome (POTS). A 2026 systematic review of 29 studies found no consistent association between HPV vaccination and new-onset autoimmune diseases overall [2]. However, one French nationwide cohort of about 2.2 million girls reported a significantly increased risk of GBS, with an adjusted hazard ratio of 3.78 (95% CI 1.79-7.98), corresponding to about 1-2 extra cases per 100,000 vaccinated [2, 3]. This finding was not replicated in other large studies, including a UK self-controlled case series of 10.4 million doses that found a relative incidence of 1.04 (95% CI 0.47-2.28) [2].
A meta-analysis of the AS04-adjuvanted HPV vaccine found a 1.5-fold increased odds of autoimmune thyroiditis (OR 1.46, 95% CI 1.22-1.76) using one statistical method, but another method gave the opposite result (OR 0.68, 95% CI 0.57-0.81), making the finding unstable [4]. The same meta-analysis found no increased risk of inflammatory bowel disease (OR 1.11, 95% CI 0.75-1.66) [4]. A large South Korean cohort of 382,020 vaccinated girls found no association with any of 33 predefined serious adverse events, including Hashimoto's thyroiditis (adjusted rate ratio 1.24, 95% CI 0.78-1.94) [5].
| Rare event | Evidence summary |
|---|---|
| Guillain-Barré syndrome | Mixed: French cohort found 3.78x risk [2, 3]; UK study found none [2] |
| Autoimmune thyroiditis | Mixed: meta-analysis gave conflicting results [4] |
| Multiple sclerosis | No increased risk in Danish/Swedish cohort of ~4 million women [2] |
| Type 1 diabetes | No increased risk in French or Danish/Swedish cohorts [2] |
| Venous thromboembolism | No evidence of causal link in Alberta surveillance [6] |
| POTS | Signal in passive VAERS data, but absolute numbers small [1] |
The key limitation: these findings come almost entirely from passive surveillance (VAERS) and observational studies, not from randomized trials comparing vaccinated to genuinely unvaccinated girls over long periods. The French GBS finding is the strongest signal but has not been consistently replicated. The evidence does not include a prospective long-term safety trial designed to detect these rare events.
My call: the evidence shows no consistent increase in most rare autoimmune or neurological conditions, but the GBS signal from France warrants continued monitoring. Confidence: moderate.
Sources used 6
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Post-licensure safety monitoring of quadrivalent human papillomavirus vaccine in the Vaccine Adverse Event Reporting System (VAERS), 2009–2015
This study analyzes the safety of the quadrivalent human papillomavirus vaccine (4vHPV) using data from the Vaccine Adverse Event Reporting System (VAERS) from 2009 to 2015, finding no new or unexpected safety concerns.
DOI: 10.1016/j.vaccine.2018.02.034 -
Assessing the Risk of Autoimmune Diseases Following Human Papillomavirus Vaccination: A Systematic Review
This systematic review of 29 studies found no consistent association between HPV vaccination and new-onset autoimmune diseases across a broad spectrum of outcomes.
DOI: 10.69980/aj -
Human papillomavirus vaccination and risk of autoimmune diseases: A large cohort study of over 2 million young girls in France
This study investigates the association between human papillomavirus (HPV) vaccination and the risk of autoimmune diseases in a cohort of over 2 million young girls in France, finding no significant increase in risk except for a notable association with Guillain-Barré syndrome.
DOI: 10.1016/j.vaccine.2017.06.030 -
Meta‐analysis of the risk of autoimmune thyroiditis, Guillain‐Barré syndrome, and inflammatory bowel disease following vaccination with AS04 ‐adjuvanted human papillomavirus 16/18 vaccine
Meta-analysing 21 AS04-HPV-16/18 studies in females found no increased IBD risk, a 1.5-fold increased odds of (autoimmune) thyroiditis without a causal conclusion, and an unquantifiable GBS risk based on two cases.
DOI: 10.1002/pds.5063 -
Association between human papillomavirus vaccination and serious adverse events in South Korean adolescent girls: nationwide cohort study
In a nationwide linked cohort of South Korean girls aged 11-14, HPV vaccination was not associated with serious adverse events in cohort or self-controlled risk interval analyses, except an inconsistent migraine finding attributed to age and menstrual factors.
DOI: 10.1136/bmj.m4931 -
Adverse events following HPV vaccination, Alberta 2006–2014
Adverse events following HPV vaccination in Alberta are rare (37.4 per 100,000 doses) and there is no evidence of VTE causally related to HPV vaccination; observed VTE cases occurred in individuals with other risk factors.
DOI: 10.1016/j.vaccine.2016.02.040