Efficacy and safety of prophylactic HPV vaccines. A Cochrane review of randomized trials

ABSTRACT

Introduction: Recently, the evidence on efficacy and safety of prophylactic HPV vaccines derived from randomized trials was published in the Cochrane database of Systematic reviews. A summary of this Cochrane review is presented below.

Areas covered: Only trials involving mono-, bi-, and quadrivalent HPV vaccines were included. Trials evaluating the nonavalent vaccine were excluded since women in the control group received the quadrivalent vaccine. Main efficacy outcomes were: histologically confirmed cervical precancer lesions distinguishing those associated with vaccine HPV types and any cervical precancer. Exposure groups were: women aged: 15–26 or 24–45 years being initially negative for high-risk HPV (hrHPV) or negative for the vaccine types and women unselected by HPV status.

Expert commentary: All evaluated vaccines offered excellent protection against cervical intraepithelial neoplasia of grade 2 or 3 (CIN2 or CIN3) and adenocarcinoma in situ associated with HPV16/18 infection in young women who were not initially infected with hrHPV or HPV16/18. Vaccine efficacy was lower when all women regardless of HPV DNA status at enrollment were included. In young women, HPV vaccination protected also against any cervical precancer but the magnitude of protection was lower than against HPV16/18 associated cervical precancer. Vaccine efficacy was lower in mid-adult (aged 24–45 years) women. No protection against cervical precancer was found in mid-adult women unselected by HPV DNA status at enrollment. Trials were not empowered to address protection against cervical cancer. Occurrence of severe adverse events or adverse pregnancy outcomes was not significantly higher in recipients of HPV vaccines than in women included in the control arms.

KEYWORDS:

• Cervical cancer
• HPV vaccines
• safety
• randomized clinical trials
• systematic review
• meta-analysis

Acknowledgments

The authors are very grateful for the support from Cochrane’s editorial office and the Cochrane Gynaecological Cancer group.

Declaration of interest

M Arbyn has received travel grants from MSD-Sanofi-Pasteur and GSK (ceased in 2008).

Authors of the Cochrane review were assessed by the Cochrane Funding Arbiter Committee after Cochrane received correspondence and feedback on the published protocol. Current authors were approved by this committee based on stringent Cochrane conflict of interest guidelines. An unrestricted grant was provided by Sanofi-Pasteur-MSD to the University of Ghent who co-ordinated the SEHIB study (Surveillance of Effects of HPV Immunization in Belgium). The grant was given in the framework of the EMA (European Medicine Agency) request to set up post-marketing surveillance of HPV vaccination effects in non-Nordic member states of the European Union. The Sciensano (employer of M Arbyn and L Xu, former name ‘Scientific Institute of Public Health’) collaborated with the University of Ghent to conduct the SEHIB study [47]. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed authorship of many papers in this field.

Additional information

Funding

M. Arbyn and L. Xu were supported by the COHEAHR Network (grant No. 603019), funded by the 7th Framework Programme of DG Research and Innovation, European Commission (Brussels, Belgium). M. Arbyn was also supported by the Belgian Cancer Centre and the Cochrane Gynaecological Cancer Review Group.