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Background Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. HPV can cause genital warts and multiple types of cancers in females. HPV vaccination is recommended to youth age 11 or 12 years before sexual initiation to prevent onset of HPV-related diseases. For females who have not been vaccinated previously, catch-up vaccines are recommended through age 26. The extent to which catch-up vaccines are beneficial in terms of disease prevention and cost-effectiveness is questionable given that some women may have been exposed to HPV before receiving the catch-up vaccination. This study aims to examine whether the cutoff age of catch-up vaccination should be determined based on an individual woman’s risk characteristic instead of a one-size-fits-all age 26. Methods We developed a microsimulation model to evaluate multiple clinical outcomes of HPV vaccination for different women based on a number of personal attributes. We modeled the impact of HPV vaccination at different ages on every woman and tracked her course of life to estimate the clinical outcomes that resulted from receiving vaccines. As the simulation model is risk stratified, we used extreme gradient boosting to build an HPV risk model estimating every woman’s dynamic HPV risk over time for the lifetime simulation model. Results Our study shows that catch-up vaccines still benefit all women after age 26 from the perspective of clinical outcomes. Women facing high risk of HPV infection are expected to gain more health benefits compared with women with low HPV risk. Conclusions From a cancer prevention perspective, this study suggests that the catch-up vaccine after age 26 should be deliberately considered.