Two-dose strategies for human papillomavirus vaccination: how well do they need to protect?

BACKGROUND: Two-dose human papillomavirus (HPV) vaccine schedules may provide short-term protection but their long-term population impact is unknown. METHODS: Two models of HPV transmission and associated cervical disease (squamous and glandular, neoplasia and cancer) were fitted to data from England and Canada on HPV epidemiology, sexual behaviour, cervical screening outcomes and cervical cancer incidence. RESULTS: Models suggest that at 40-80% coverage, if two-dose schedules protect vaccinees for 20 years, then the benefits of the third dose are small. If two doses protect for 10 years, then the third dose may prevent as many cancers as the first two. At 80% coverage, numbers needed to receive a third dose to prevent an additional cancer are 5900-110,000 (England), 3000-5100 (Canada) with 20 years two-dose protection, and 2000-5300 (England), 760-950 (Canada) with 10 years two-dose protection. CONCLUSION: Results enable decision makers to quantify risks associated with two-dose schedules despite remaining uncertainties in vaccine duration and cross-protection.