Serious adverse events following human papillomavirus vaccination: A systematic review and meta-analysis of post-marketing evidence.
Hannah Brown, Sharifa Nasreen
✦ AI-curated · Sources linked
In 30 seconds
This systematic review and meta-analysis assessed serious adverse events (SAEs) reported after human papillomavirus vaccination in post-licensure observational studies and surveillance. Of 258 records identified, 24 articles were included: 15 in the meta-analysis and nine in narrative synthesis. The pooled rate across 14 studies reporting doses distributed was 0.04 (95% CI: 0.00, 0.35) per 1000 doses, with very high heterogeneity (I² = 99.98%). Narrative synthesis found no consistent evidence of increased SAE risk, although an increased risk of celiac disease was observed and considered potentially related to diagnostic unmasking.
Key findings
- The pooled SAE rate was 0.04 (95% CI: 0.00, 0.35) per 1000 doses across 14 studies.
- The pooled proportion of adverse events that were SAEs was 3.67% (95% confidence interval, CI: 1.19%, 7.30%); I² = 99.73%.
- Nine studies in the narrative synthesis showed no consistent evidence of increased SAE risk with HPV vaccination.
- An increased risk of celiac disease was observed, considered likely due to diagnostic unmasking rather than a causal association.
Why it matters
Post-marketing safety findings can inform discussions about vaccine safety and help contextualize concerns that may affect uptake of HPV vaccination. The review found a low pooled SAE rate and no consistent signal of increased risk, while also identifying substantial variation across studies and a celiac disease finding that merits further investigation. Standardized definitions and reporting remain important for interpreting surveillance evidence.
What to keep in mind
The pooled estimates had very high heterogeneity (I² = 99.73% and 99.98%), limiting consistency across studies. The evidence came from post-marketing observational studies and surveillance.