The confounding effect of multi-type human papillomavirus infections on type-specific natural history parameter...

The natural history of human papillomavirus (HPV) from infection to cervical cancer differs between HPV types. Accordingly, type-specific natural history parameters are crucial for the mathematical models used to optimize the nearly life-long series of disease prevention measures. These parameters are estimated from genotyped data from trials and population level screening programs, typically one type at a time, which requires projecting the multiple-type data to the single type. To analyze impacts of such projection methods on the estimates, we compared estimating one type at a time using different projection methods with estimating all types together. We simulated genotyped data with chosen parameter values for two HPV types and analyzed the identifiability of the chosen values using the different estimation methods. We found the success of estimating one type at a time to be excessively sensitive to the data projection method, with potential to falsely identify the parameters at wrong values. Estimating all types together identified the parameters well. Our results were consistent both when trial and population level data were used. In conclusion, the potential confounding by multi-type infections has to be considered when choosing an estimation method for type-specific natural history parameters.