Methods: We conducted a systematic review of evidence evaluating HPV vaccine schedules in which two doses were administered at an interval of at least 6 months (±4 weeks) to girls or boys aged 9–14 years. We used keyword search terms including “HPV vaccine,” “papillomavirus vaccine,” “two dose” and “two doses” to identify studies in Pubmed and clinicaltrials.gov. Relevant studies included primary data on health outcomes following two-dose schedules of any HPV vaccine. Benefits and harms were tabulated and quality of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluation (GRADE).
Results: We identified and reviewed 105 studies of interest, selecting 15 relevant studies for inclusion in evidence tables. Studies of each of the three licensed HPV vaccines have demonstrated non-inferior immunogenicity with two doses of HPV vaccine administered 6 months apart, compared with 3-dose schedules administered at 0, 1–2, and 6 months to women in the age group for whom efficacy was demonstrated in clinical trials. Using GRADE criteria, there is moderate evidence supporting two-dose schedules for HPV vaccination.