Two-dose schedules for human papillomavirus vaccine: Systematic review and meta-analysis

Simpler schedules for human papillomavirus (HPV) vaccine delivery could improve vaccine coverage and the effectiveness of cervical cancer prevention. The objective of this study was to systematically review evidence about the effects of two-dose compared with three-dose schedules for human papillomavirus (HPV) vaccine and to describe the uptake of two-dose HPV vaccination schedules globally. We searched PubMed, the Cochrane Central Registry of Controlled Trials, trials registers, and manufacturers' databases from their earliest date to February 2016. We selected randomised controlled trials and controlled clinical trials that directly compared HPV vaccine schedules with two or three doses. We extracted data on immunological and clinical outcomes and used meta-analysis where appropriate. We also described the use of two-dose HPV vaccine schedules globally. We screened 1464 items and included seven eligible noninferiority trials in 11 countries. In randomised comparisons amongst adolescent girls (three trials), geometric mean concentrations (GMC) of antibodies against HPV16 and HPV18 were non-inferior or inconclusive, up to 24 months after a two-dose compared with a three-dose schedule. One trial with a clinical outcome found no persistent HPV infections occurred after either two or three doses. In non-randomised comparisons, GMC were non-inferior or superior in adolescent girls receiving the two-dose schedule compared with women receiving the three-dose schedule for at least 21 months after vaccination. By February 2017, 23 low and middle income and 25 high income countries had adopted a two-dose HPV vaccination schedule. A two-dose HPV vaccine schedule provides satisfactory immunological outcomes in adolescent girls, but uptake globally is limited, particularly in countries with the highest burden of cervical cancer.