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To evaluate the impact of different strategies of human papillomavirus (HPV) vaccination on the burden of cervical cancer in Singapore. The incidence of cervical cancer was calculated using a Markov model with inputs based on Singapore data for the prevalence of HPV infection, socioeconomic characteristics and screening prevalence. The evaluation was performed for 10 scenarios: no screening, current opportunistic cytology screening, ideal optimal screening, universal adolescent HPV vaccination at 12-years old alone and with catch-up cohorts and combinations of screening and vaccination. (1) The model prediction showed that cervical cancer cases were reduced by 6.5% using opportunistic screening, by 34.3% using optimized screening and by 63.9% with a universal HPV vaccination at 12 years of age. (2) Adding optimized screening, but not opportunistic screening, to a universal adolescent HPV vaccination program caused a moderate further reduction in cervical cancer cases. (3) No difference was discernable in the impact of vaccination introduction between the age groups <20, 20-24 and 25-29 years old. (4) The time required to halve the incidence of cervical cancer was 42 years for universal vaccination at the age of 12 but could be shortened by including catch-up cohorts of women up to 40-years old. A universal HPV vaccination program introduced between the ages of 12-29 is superior to cytology screening in reducing the burden of cervical cancer. However, in the next four decades of post-vaccination era, optimizing the screening program remains the most important measure for cervical cancer prevention. [ABSTRACT FROM AUTHOR]