Estimating the Natural History of Cervical Carcinogenesis Using Simulation Models: A CISNET Comparative Analysis.
2019
BACKGROUND: The natural history of human papillomavirus (HPV)-induced cervical cancer (CC) is not directly observable, yet the age of HPV acquisition and duration of preclinical disease (dwell time) impacts the effectiveness of alternative preventive policies. We performed a Cancer Intervention and Surveillance Modeling Network (CISNET) comparative modeling analysis to characterize the age of acquisition of cancer-causing HPV infections and implied dwell times for distinct phases of cervical carcinogenesis. METHODS: Using four CISNET-cervical models with varying underlying structures but fit to common U.S. epidemiological data, we estimated the age of acquisition of causal HPV infections and dwell times associated with three phases of cancer development: HPV, high-grade precancer, and cancer sojourn time. We stratified these estimates by HPV genotype under both natural history and CC screening scenarios, as screening prevents cancer development that impacts the mix of detected cancers. RESULTS: Median time from HPV acquisition to cancer detection ranged from 17.5-26.0 years across the four models. Three models projected that 50% of unscreened women acquired their causal HPV infection between ages 19-23 years, while one model projected these infections occurred later (age 34 years). In the context of imperfect compliance with U.S. screening guidelines, the median age of causal infection was 4.4-15.9 years later compared with model projections in the absence of screening. CONCLUSIONS: These validated CISNET-cervical cancer models, which reflect some uncertainty in the development of CC, elucidate important drivers of HPV vaccination and CC screening policies and emphasize the value of comparative modeling when evaluating public health policies.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
29
References
18
Citations
NaN
KQI