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 ce rvical cytology conducted at the Duke University Evidence-based Practice Ce nter (Durham, North Carolina) between October 1997 and September 1998. The model incorporated states for human papillomavirus infection (HPV), low- an d high-grade squamous intraepithelial lesions, and cervical cancer stages I -IV to simulate the natural history of HPV infection in a cohort of women f rom ages 15 to 85 years. The age-specific incidence rate of HPV, and regres sion and progression rates of HPV and squamous intraepithelial lesions, wer e obtained from the literature. The effects of varying natural history para meters on cervical cancer incidence were evaluated by using sensitivity ana lysis. 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 in cidence of 81/100,000 at age 50 years. Age-specific distributions of precur sors were similar to reported data. Lifetime risk of cancer was most sensit ive to the incidence of HPV and the probability of rapid HPV progression to high-grade lesions (two- to threefold variations in risk). The model appro ximates the age-specific incidence of cervical cancer and provides a tool f or evaluating the natural history of HPV infection and cervical cancer carc inogenesis as well as the effectiveness and cost-effectiveness of primary a nd secondary prevention strategies.