Population-level impact and herd effects following human papillomavirus vaccination programs : a systematic review and meta-analysis

Human papillomavirus (HPV) vaccination programs were first implemented in 2007. We conducted a systematic review and meta-analysis to examine the population-level impact and herd effects following female HPV vaccination programs, to verify whether the high efficacy measured in randomized controlled clinical trials are materialising under real-world conditions. We searched Medline and Embase databases (01/2007-02/2014), and conference abstracts for time- trend studies examining changes, between the pre- and post-vaccination periods, in the incidence/prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts (AGW), and high-grade cervical lesions. We derived pooled relative risk (RR) estimates using random effect models. We stratified all analyses by age and gender. We performed subgroups analysis by comparing studies according to vaccine type, vaccination coverage and years since vaccination implementation. We assessed heterogeneity across studies using I2 and χ2 statistics. We performed trends analysis to examine dose-response between HPV vaccination coverage and each study effect measure. We identified 20 eligible studies, conducted in nine high-income countries, and representing >140 million person-years of follow-up. In countries with female vaccination coverage ≥50%, HPV-16/18 infections and AGW decreased significantly between the pre- and post-vaccination periods by 68% (RR=0·32, 95%CI[0·19;0·52]) and 61% (RR=0·39, 95%CI[0·22;0·71]), respectively, among females <20 years. Significant reductions in HPV-31/33/45 among females <20 years (RR=0·72, 95%CI[0·54;0·96]), and AGW among males <20 years (RR=0·66, 95%CI[0·47;0·91]) and older females (RR=0·68, 95CI[0·51;0·89]) were also observed, respectively suggesting cross-protection and herd effects. In countries with female vaccination coverage <50%, significant reductions were observed for HPV-16/18 infection (RR=0·50, 95%CI[0·34;0·74]) and AGW (RR=0·86, 95%CI[0·79;0·94]) among females