Comparison between the safety of the HPV vaccine versus placebo: a systematic review and meta-analysis of randomized clinical trials.

Objective: Human Papillomavirus (HPV) is a virus that targets epithelial tissues. Virtually all cases of cervical cancer are related to HPV, emphasizing the importance of vaccines in prevention. Although >200 million doses have been administered worldwide, concerns persist about adverse reactions. This study evaluated the safety of the HPV vaccine and the main adverse effects.

Data sources: The study was registered in the PROSPERO database (CRD42023365692). The systematic searches were conducted in the PubMed, Scopus, Embase, Cochrane, Science Direct, and Web of Science databases using the search strategy "HPV" AND "vaccine" AND "safety" NOT "COVID" from 01/01/2007 to 31/12/2022. Inclusion criteria were based on the PICOT strategy, focusing on studies with humans, vaccinated populations comprising children, adolescents, and adults, and Phase II/III randomized clinical trials. The PEDro scale was used to assess the quality of the studies.

Summary of findings: Eleven articles were qualified for qualitative synthesis and meta-analysis. The results indicated that HPV vaccination was associated with increased local reactions, fatigue, and myalgia compared to the placebo. However, there were no significant differences in serious adverse events, gastrointestinal reactions, cutaneous effects, headache, or fever between the vaccine and placebo groups.

Conclusion: Local reactions, fatigue, and myalgia were more prevalent in the HPV vaccine group; the overall safety profile of the vaccine was favorable. The HPV vaccine was deemed safe, mirroring the profile of adverse reactions seen with other vaccines. With its potential to prevent cancer, the benefits of HPV vaccination far outweigh the minimal risks.