Median Age at HPV Infection Among Women in the United States: A Model-Based Analysis Informed by Real-world Data

BACKGROUND: The US Advisory Committee for Immunization Practices (ACIP) recommended shared clinical decision-making for human papillomavirus (HPV) vaccination of individuals aged 27 to 45 years (mid-adults) in June 2019. Determining the median age at causal HPV infection and CIN2+ diagnosis based on the natural history of HPV disease can help elucidate the incidence of HPV infections and the potential benefits of vaccination in mid-adults. METHODS: Real-world data on CIN2+ diagnosis from the prevaccine era were sourced from a statewide surveillance registry in Connecticut. Age distribution of CIN2+ diagnosis in 2008 and 2009 was estimated. A discrete event simulation model was developed to predict the age distribution of causal HPV infection. The optimal age distribution of causal HPV infection provided the best goodness-of-fit statistic to compare the predicted vs real-world age distribution of CIN2+ diagnosis. RESULTS: The median age at CIN2+ diagnosis from 2008 through 2009 in Connecticut was 28 years. The predicted median age at causal HPV infection was estimated to be 23.9 years. There was a difference of 5.2 years in the median age at acquisition of causal HPV infection and the median age at CIN2+ diagnosis. CONCLUSIONS: Real-world data on CIN2+ diagnosis and model-based analysis indicate a substantial burden of infection and disease among women aged 27 years or older, which supports the ACIP recommendation to vaccinate some mid-adults. When natural history is known, this novel approach can also help determine the timing of causal infections for other commonly asymptomatic infectious diseases.