Mathematical model for the natural history of human papillomavirus infection and cervical carcinogenesis

The authors constructed a Markov model as part of a systematic review of cervical cytology conducted at the Duke University Evidence-based Practice Center (Durham, North Carolina) between October 1997 and September 1998. The model incorporated states for human papillomavirus infection (HPV), low- and high-grade squamous intraepithelial lesions, and cervical cancer stages I-IV to simulate the natural history of HPV infection in a cohort of women from ages 15 to 85 years. The age-specific incidence rate of HPV, and regression and progression rates of HPV and squamous intraepithelial lesions, were obtained from the literature. The effects of varying natural history parameters on cervical cancer incidence were evaluated by using sensitivity analysis. The base-case model resulted in a lifetime cervical cancer risk of 3.67% and a lifetime cervical cancer mortality risk of 1.26%, with a peak incidence of 81/100,000 at age 50 years. Age-specific distributions of precursors were similar to reported data. Lifetime risk of cancer was most sensitive to the incidence of HPV and the probability of rapid HPV progression to high-grade lesions (two- to threefold variations in risk). The model approximates the age-specific incidence of cervical cancer and provides a tool for evaluating the natural history of HPV infection and cervical cancer carcinogenesis as well as the effectiveness and cost-effectiveness of primary and secondary prevention strategies.