Association of Guillain–Barré Syndrome With Nonavalent Human Papillomavirus Vaccine: A Postmarketing Drug Safety Study

Introduction Human papillomavirus (HPV) vaccines prevent types of HPV responsible for most cervical cancers. While Guillain–Barré syndrome (GBS) has rarely reported postvaccination, a causal relationship remains unestablished. This study evaluates the association between the nonavalent HPV vaccine (9‐valent) and GBS using the Vaccine Adverse Event Reporting System (VAERS). Methods We analyzed VAERS data from January 1, 2016, to July 26, 2024, focusing on domestic reports for individuals aged 6–29 years. GBS cases were identified using the MedDRA preferred term code 10018767. Disproportionality was assessed via a 2 × 2 contingency table to calculate the proportional reporting ratio (PRR) and Yates’ chi‐squared ( χ 2 ) test. A signal was defined as PRR ≥ 2, χ 2 ≥ 4, and n ≥ 3. Results A total of 11 serious GBS cases were reported following HPV 9‐valent vaccination out of 14,367 total adverse events for the vaccine. Comparison with all other vaccines (1757 GBS cases) yielded a PRR of 0.79 (95% CI: 0.44–1.44) and a Yates’ χ 2 of 0.384 ( p = 0.535). Of the HPV 9‐valent–associated GBS cases, 64% occurred in females and 57% in the 6–17 age group. Most cases occurred 10–30 days postvaccination; no deaths were reported. Conclusions The findings indicate an absence of a disproportionality signal in VAERS, suggesting that GBS is not reported more frequently after HPV 9‐valent than other vaccines. However, this study is limited by a small number of cases and the inherent constraints of passive surveillance; thus, these results reflect reporting patterns and cannot establish causality or absolute incidence.