Use of person-years of CIN III exposure as a surrogate outcome measure in cervical cancer screening trials.

BACKGROUND: The reluctance to perform randomised trials on still unresolved issues of the cervical screening programme is largely due to the view that using invasive cancer as an end-point would require huge and lengthy studies. However, by assuming that the incidence of invasive cancer is related to the number of women with CIN III, an estimate of person-years of CIN III can act as a surrogate outcome. METHODS: By having a reliable model for the development of CIN III and the errors involved in taking the smears and biopsies, the person-years of CIN III can be estimated from a smear and biopsy history. Methods for comparing resulting distributions of person-years of CIN III are discussed. Sensitivity analyses on the error rates of smear and biopsy results, and on the incidence of onset and regression of CIN III are performed. RESULTS: Estimates of person-years of CIN III were calculated for women with mildly abnormal smears in two screening programmes. 11% of women in the Cambridge programme and 21% in the Aberdeen programme were estimated to have been exposed to CIN III for more than 12 months. The greater estimated person-years of CIN III in the Aberdeen study reflects the more conservative treatment policy which was operating there. DISCUSSION: The use of person-years of CIN III as a surrogate outcome can provide a practical and meaningful assessment of strategies for cervical cancer screening. Using CIN III, in place of invasive disease, considerably reduces the study duration and sample size required.