Abstract for: Application of System Dynamics to Inform a Model of Human Papillomavirus Vaccination Efficacy

The uncertainty of prior Human Papillomavirus (HPV) infection is a major limitation in evaluating the effectiveness of HPV vaccination within populations 19-26 years old. We used Systems Dynamics to simulate a prospective cohort of 100,000 women age 19 years old at entry. Using data from prospective natural history and vaccine efficacy studies, we followed these women for both the incidence of high-risk (16/18) HPV types and for Cervical Intraepithelial Neoplasia (CIN) grade 2 or higher. At 20 years of follow-up, we found that the relative risk (RR) for developing CIN2+ lesions in a vaccinated cohort of women exposed to high-risk HPV was 8.8 (95%CI: 7.8-10.0) when compared to a vaccinated cohort who were high-risk HPV naive (serology & DNA negative). We also found that the RR of developing CIN2+ lesions in women exposed to the vaccine after a resolved HPV infection was 0.32 (0.27, 0.37). The RR of developing CIN2+ lesions in women exposed to the vaccine after a persistent infection was 1.06 (1.02, 1.10). Thus, our model demonstrates the fundamental difference in CIN2+ lesion incidence between women who with past exposure to HPV 16/18 and naïve populations. Therefore, our model has important policy implications for future vaccination strategies.