Safety of human papillomavirus 6, 11, 16 and 18 (recombinant): systematic review and meta-analysis

Pedro Luiz Spinelli Coelho,Gustavo Lacerda Da Silva Calestini,Fernando Salgueiro Alvo,Jefferson Michel De Moura Freitas,Paula Marcela Vilela Castro,Tulio Konstantyner

doi:10.1016/j.rppede.2015.08.017

Pedro Luiz Spinelli Coelho, Gustavo Lacerda Da Silva Calestini + Show 4 more

Open Access

https://doi.org/10.1016/j.rppede.2015.08.017

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Abstract

ObjectiveTo identify and quantify the adverse effects associated with the recombinant human papillomavirus (types 6, 11, 16 and 18) vaccine in adolescents. Data sourceSystematic review of randomized clinical trials from PubMed, SciELO and Lilacs databases. Articles investigating the safety of the vaccine in subjects under 18 years and comparing the recombinant human papillomavirus types 6, 11, 16 and 18 vaccine with a control group were included. Meta-analyses were performed for the outcomes of pain, erythema, swelling and fever, using clinical trials with maximum Jadad score. Data synthesisFourteen studies were included. The most common adverse effects related to the human papillomavirus vaccine were effects with no severity (pain, erythema, edema, and fever). Five studies were used for the meta-analyses: pain–risk difference (RD)=11% (p<0.001); edema–RD=8% (p<0.001); erythema–RD=5% (p<0.001); fever–RD=2% (p<0.003). ConclusionsThe recombinant human papillomavirus types 6, 11, 16 and 18 vaccine was safe and well tolerated. The main adverse effects related to vaccination were pain, erythema, edema and fever. The low frequency of severe adverse effects encourages the administration of the vaccine in the population at risk.

Highlights

At least 80% of deaths from cervical cancer occur in developing countries, most of them in the poorest regions of the world, such as Southern Asia, Sub-Saharan Africa and parts of Latin America
The objective of this study is to identify and quantify the adverse effects associated with the administration of the human papillomavirus quadrivalent recombinant vaccine, as a tool to determine the safety of its use in adolescents
The selected articles were described according to the results shown in each of the randomized controlled trials (RCTs), disclosing prevalence data and characteristics of the identified adverse effects

Summary

Introduction

Cervical cancer is the second most common type of cancer that affects women worldwide, with an incidence of approximately 500,000 cases and 270,000 deaths each year. The disease is often detected at advanced stages due to the lower efficiency of screening strategies in the initial stage and treatment options that are not always effective.3---6 At least 80% of deaths from cervical cancer occur in developing countries, most of them in the poorest regions of the world, such as Southern Asia, Sub-Saharan Africa and parts of Latin America. Cervical cancer is the second most common type of cancer that affects women worldwide, with an incidence of approximately 500,000 cases and 270,000 deaths each year.. At least 80% of deaths from cervical cancer occur in developing countries, most of them in the poorest regions of the world, such as Southern Asia, Sub-Saharan Africa and parts of Latin America. In those areas, which receive only 5% of the resources for cancer in the world, cervical involvement is responsible for 15% of all cancer deaths.. 35---40 types of HPV can infect the genital epithelium. The infection may be transient and not clinically detectable, but can cause genital warts and a variety of pre-malignant and malignant anogenital lesions in both genders.9---14 Studies show that the peak incidence of HPV infection occurs 5---10 years after the first sexual intercourse (between 15 and 25 years old),15---19 and infection persistence by an oncogenic HPV type is crucial in the pathogenesis of cervical cancer.2,20---22 it becomes possible to prevent the disease onset through vaccination before the start of sexual activity.19,23---26

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