Association of Nonavalent Human Papillomavirus Vaccine with Abdominal Pain Symptoms: A Post-Marketing Drug Safety Study

Human papillomavirus vaccines protect against the types of this virus that most often cause cervical cancer. These vaccines must be safe for the population’s use. It is important to detect any adverse event possibly related to vaccination. Abdominal pain has occasionally been reported following HPV vaccination, but its clinical relevance and causal relationship remain unclear. Therefore, this study aimed to assess the association between the 9-valent HPV vaccine and abdominal pain symptoms using simple epidemiological measures applicable in clinical settings.

The Vaccine Adverse Event Reporting System database was searched for data on all vaccines and their adverse effects, especially the relationship between the human papillomavirus nonavalent vaccine and abdominal pain symptoms, from January 1, 2016, to November 29, 2024. A 2x2 table was designed, and from this, the proportional reporting rate, odds ratio, and Yates’ chi-squared test were calculated.

Among 15,005 reports related to the HPV vaccine, 127 (0.85%) involved abdominal pain. For other vaccines, 9,970 of 1,229,411 reports (0.81%) mentioned abdominal pain. The PRR and OR were both 1.04, and Yates’ Chi-squared = 0.204 (p = 0.651), indicating no statistically significant difference.

PRR and OR are practical tools for early signal detection of potential adverse effects. In this case, they suggest abdominal pain is not disproportionately associated with HPV vaccination.

No statistically significant association was observed between the 9-valent HPV vaccine and abdominal pain compared to other vaccines, supporting its favorable safety profile based on current VAERS data.