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. 2017 Jul 11;3:18.
doi: 10.1186/s40780-017-0087-6. eCollection 2017.

Safety of Human Papillomavirus Vaccines in Healthy Young Women: A Meta-Analysis of 24 Controlled Studies

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Free PMC article

Safety of Human Papillomavirus Vaccines in Healthy Young Women: A Meta-Analysis of 24 Controlled Studies

Yukari Ogawa et al. J Pharm Health Care Sci. .
Free PMC article

Abstract

Background: Human 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.

Methods: Primary 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.

Results: A 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.

Conclusions: HPV 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.

Keywords: Cervical cancer; HPV vaccine; Meta-analysis; Safety; Solicited local symptoms; Solicited systemic symptoms.

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
A study selection flow diagram. n: total number of articles. *We included 24 studied from 22 articles because 2articles [26, 47] included 2 studies each. Abbreviations: PMDA, Pharmaceutical Medicines Devices Agency
Fig. 2
Fig. 2
Summary of risk of bias for the 24 studies included in meta-analysis. The judgements were made by two of the study investigators. Symbols: +, low risk of bias; −, high risk of bias;?, bias risk is unclear
Fig. 3
Fig. 3
A forest plot of the present meta-analysis on the incidence of solicited local symptoms after administration of HPV vaccines (2vHPV and 4vHPV) compared to placebo injection. Risk ratios (RRs) and 95% confidence intervals (CI) are shown. The analysis was performed using the Mantel-Haenszel method with random effects model. Abbreviations: HPV, human papillomavirus; 2vHPV, bivalent human papillomavirus; 4vHPV, quadrivalent human papillomavirus
Fig. 4
Fig. 4
A forest plot of the present meta-analysis on the incidence of solicited systemic symptoms after administration of HPV vaccines (2vHPV and 4vHPV) compared to placebo injection. Risk ratios (RRs) and 95% confidence intervals (CI) are shown. The analysis was performed using the Mantel-Haenszel method with random effects model. Abbreviations: HPV, human papillomavirus; 2vHPV, bivalent human papillomavirus; 4vHPV, quadrivalent human papillomavirus
Fig. 5
Fig. 5
A forest plot of the present meta-analysis on the incidence of unsolicited symptoms after administration of 2vHPV compared to placebo or hepatitis vaccine. a 2vHPV versus Placebo, b 2vHPV versus Hepatitis vaccine. Risk ratios (RRs) and 95% confidence intervals (CI) are shown. The analysis was performed using the Mantel-Haenszel method with random effects model. Abbreviations: HPV, human papillomavirus; 2vHPV, bivalent human papillomavirus

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