Abstract
BACKGROUND: One or two-dose schedule for human papillomavirus (HPV) vaccination has been recommended by the World Health Organization and used in many vaccination programs. We aimed to comprehensively evaluate the effectiveness of quadrivalent HPV vaccine against high-grade cervical lesions by age at vaccination and number of doses received. METHODS: This cohort study included 2,200,495 females aged 10-35 years old who were residents of Sweden between 2006 and 2022, with 584,676 (26.6%) receiving at least one dose of quadrivalent HPV vaccine. We used Poisson regression models to estimate the incidence rate ratios (IRR) comparing the incidence rate of high-grade cervical lesions in relation to age at vaccination and doses. FINDINGS: In girls initiating vaccination before age 15, we observed IRRs of 0.42 (95% CI 0.33-0.52) after one-dose, 0.54 (0.47-0.63) after two-dose, and 0.50 (0.47-0.53) after three-dose. The IRRs were 0.60 (95% CI 0.52-0.70), 0.55 (0.49-0.62), and 0.54 (0.52-0.56) after one, two or three doses for girls who initiated vaccination age 15-17. For women who initiated vaccination after age 20, higher doses may be needed to achieve a statistically significant risk reduction. INTERPRETATION: Receiving one or two doses of HPV vaccines prior to age 17, especially for those initiating before age 15, has comparable effectiveness against high-grade cervical lesions with those who received three doses. FUNDING: Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare, and Karolinska Institutet.