Safety of human papillomavirus vaccines in healthy young women: a meta-analysis of 24 controlled studies

Abstract

BackgroundHuman papillomavirus (HPV) vaccines have been shown to be effective for the eradication of HPV and prevention of cervical cancer. However, the number of women who receive HPV vaccinations has decreased over the last several years in Japan, due to concerns about adverse reactions associated with the vaccines. We evaluated the safety of three types of HPV vaccines separately in young women and the difference in the risk of adverse reactions between HPV and other vaccines by conducting a meta-analysis.MethodsPrimary literature was retrieved from MEDLINE, the Cochrane Central Register of Controlled Trials, and Japana Centra Revuo Medicina. Prospective controlled studies with participants consisting exclusively of healthy women who received bivalent, quadrivalent, or 9-valent HPV (2vHPV, 4vHPV or 9vHPV) vaccines were included. Primary safety outcome was the incidence of solicited local and systemic symptoms, and unsolicited symptoms. When two or more studies were found for the same analysis, a meta-analysis was applied.ResultsA total of 24 controlled studies from 22 articles were included in our study. Of the 24 studies, 16 were placebo-controlled and eight were active-controlled (different HPV vaccine or hepatitis vaccine). Average ages of the participants ranged from 12 to 37 years. A significantly higher incidence of solicited local symptoms was observed following injection of HPV vaccines (2vHPV and 4vHPV) compared to placebo, but there was no difference between HPV vaccines [risk ratio (RR) for 2vHPV: 1.25, 95% confidence interval (CI): 1.09 to 1.43, RR for 4vHPV: 1.16, 95% CI: 1.11 to 1.20]. The incidence of solicited systemic symptoms was not different between HPV vaccines and placebo (RR: 1.04, 95% CI: 0.99 to 1.09). The incidence of unsolicited symptoms was significantly higher for 2vHPV vaccine compared to placebo (RR: 1.28, 95% CI: 1.01 to 1.63), but was not significantly different between 2vHPV and hepatitis B vaccines.ConclusionsHPV vaccines had significantly higher risk of any injection site symptom compared to placebo or other vaccines (hepatitis A and B vaccines), and the incidence of solicited local symptoms was no difference between 2vHPV vaccination and 4vHPV vaccination. However, the most adverse reactions were transient.

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“…Additionally, the risk of swelling as well as systemic symptoms was also lower with the QHPV vaccine. The study concluded that although the HPV vaccines were associated with an overall higher risk of injection site symptom compared to placebo or other (hepatitis A and B) vaccines, most of the adverse events were transient (Ogawa et al, 2017).…”

Addressing Human Papillomavirus Prevention During Pediatric Acute Sexual Assault Care

“…Concern regarding adverse effects of over-vaccination may have existed among both caregivers and healthcare providers relying on caregiver report, however this was not specifically assessed. To date, safety outcomes associated with errant HPV vaccination beyond evidence of solicited local symptoms following administration have not been reported (Ogawa, Takei, Ogawa, & Mirhara, 2017; CDC, 2017a). Furthermore, there is currently no outcome data suggesting HPV vaccination formulations are systemically dangerous or pose significant health risk.…”

Adverse events associated with human papillomavirus vaccines: a protocol for systematic review with network meta-analysis incorporating all randomised controlled trials comparing with placebo, adjuvants and other vaccines

“…Previous meta-analyses did not support the specified AEFIs with the use of HPVv 53–55. Although another research group recently suggested a high risk of topical reactions at the injection site,19 20 we must assess whether an adjuvant evokes such topical reactions.…”

“…Fatigue, weariness and hypoactivity during the observation period, which recent reports stated as adverse events during the observation period 19 20. The secondary outcomes include the following:…”