Safety of Human Papillomavirus 9-Valent Vaccine: A Meta-Analysis of Randomized Trials

Abstract

Vaccination against human papillomavirus (HPV) has been progressively implemented in most developed countries for approximately 10 years. In order to increase the protection of the vaccines, a 9-valent vaccine (HPV9) was developed, which provides protection against nine types of the virus. Studies evaluating its safety are rare. Thus, we performed a meta-analysis of three clinical trials assessing adverse effects on women randomly vaccinated with HPV9 or tetravalent vaccine (HPV4), with the objective of analyzing whether the HPV9 is as safe as HPV4. An electronic data search was performed through the PubMed, Embase, Scopus, Web of Science, and SciELO databases. The studies selected 27,465 women who received one of the two vaccines. Pain (OR 1.72; 95% CI 1.62–1.82) and erythema (OR 1.29; 95% CI 1.21–1.36) occurred significantly more in the HPV9 group. However, there was no significant difference between the groups for the following adverse effects: headache (OR 1.07; 95% CI 0.99–1.15), dizziness (OR 1.09; 95% CI 0.93–1.27), and fatigue (OR 1.09; 95% CI 0.91–1.30), and the occurrence of serious events related to vaccination was similarly rare among those vaccinated. Therefore, our findings demonstrate that HPV9 in female patients is as safe as the tetravalent vaccine.

Safety profile of human papilloma virus vaccines: an analysis of the US Vaccine Adverse Event Reporting System from 2007 to 2017

“…Gardasil 9, by contrast, was associated with reports of predominantly mild adverse reactions mainly localized at the injection site. A similar result also emerged from a meta-analysis of randomized clinical trials of Costa et al, who showed that adverse reactions such pain and erythema occurred significantly more in the HPV9 group than in HPV4 [36].…”

Human Papillomavirus Vaccines: Successes and Future Challenges

“…In our earlier paper [1], we highlighted numerous studies attesting to HPV vaccine safety. Five years later, the safety profiles of the three HPV vaccines have been reviewed extensively, and the research continues to show they are safe, well tolerated, and have adverse effects similar to those experienced with other vaccines [12,13,113,114,115,116]. The most common adverse effects of the vaccines are soreness (pain), swelling, itching, and redness at the injection site, as well as syncope (fainting) [116].…”

“…(iv) There are more and more reports demonstrating long-term vaccine effectiveness [7,8,9,10], including a recent study showing that HPV vaccine prevents invasive HPV-related cancers beyond cervical cancer [11]. (v) There is an accumulated body of evidence that HPV vaccines are very safe [12,13,14]. Despite continued empirical evidence of the vaccines' safety and effectiveness, and the broad backing of HPV vaccination from the medical and scientific communities, many countries continue to report that HPV vaccine uptake rates are low or have dropped steeply, often related to incorrect attributions of harm [15,16,17,18].…”

Scientific Evaluation of the Court Evidence Submitted to the 2019 Human Papillomavirus Vaccine Libel Case and Its Decision in Japan

“…HPV-induced cancers, including cervical cancer and oropharyngeal cancer, are responsible for over 300,000 deaths annually worldwide ( 2 ), making HPV infection a major public health problem. Several HPV vaccines have been shown to safely and effectively prevent infection by cancer-causing HPV types, thus preventing the antecedent growths that inevitably lead to cervical cancer ( 3 , 4 ).…”