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Screening intervals and the risk of carcinoma in situ of the cervix Phillips, Norman


This study examines the effect of length of interval between routine tests on the risk of carcinoma in situ (CIS) of the uterine cervix using cohort data from the B.C. population. CIS is a symptomless disease only detected by screening. Because of this, special methods are required for estimating incidence rates. Some case-control studies have used prevalence odds ratios to estimate the relative risk of disease, usually invasive cancer, from length of screening interval. But duration of disease is related to interval length and hence prevalence rates cannot be used to estimate relative risk. A multivariate model is fit to the incidence data using Poisson regression, and prevalence rates are fit with a logistic regression model. The results for prevalence odds ratios indicate a positive association between screening interval length and risk of disease whereas the results for relative risk indicate a negative relationship. Theoretical screening models are considered to examine the consequences of a case-control paradigm in which controls are matched with cases on the basis of having had a screen near the date of diagnosis of the case, the matching period. As the matching period shortens, the distribution of interval lengths for controls converges to the underlying distribution, whereas the distribution of interval lengths for cases equals the distribution of lengths of intervals which span a point in time. The latter distribution favours longer intervals. The difference is not due to the sampling of controls but, rather, to the relation between interval length and duration of disease. A matched case-control study is simulated with the cohort data, and a conditional likelihood logistic regression model is fit. The results agree with those of a logistic regression analysis of prevalence rates indicating a positive relation between interval length and risk of disease. When the sampling of controls is weighted by interval length the odds ratios approximate the relative risk. A possible explanation of the surprising result that screening interval length is inversely related to risk of diagnosis of CIS is that more cases are cured with time by the natural regression of disease than by treatment of earlier stages of disease. On the other hand, incidence rate is negatively related to recency and frequency of prior negative screens, possibly because of the occurrence of false negative tests. However, the effect of regression predominates and the unavoidable conclusion is that less frequent screening decreases the risk of diagnosis of CIS.

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