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.