Setting the target for a better cervical screening test: Characteristics of a cost-effective test for cervical neoplasia screening

Objective: To determine the potential effects on costs and outcomes of changes in sensitivity and specificity with new screening methods for cervical cancer.

Methods: Using a Markov model of the natural history of cervical cancer, we estimated the effects of sensitivity, specificity, and screening frequency on cost-effectiveness. Our estimates of conventional Papanicolaou test sensitivity of 51% and specificity of 97% were obtained from a meta-analysis. We estimated the effect of reducing false-negative rates from 40–90% and increasing false-positive rates by up to 20%, independently and jointly. We varied the marginal cost of improving sensitivity from $0 to $15.

Results: When specificity was held constant, increasing sensitivity of the Papanicolaou test increased life expectancy and costs. When sensitivity was held constant, decreasing specificity of the Papanicolaou test increased costs, an effect that was more dramatic at more frequent intervals. Decreased specificity had a substantial effect on cost-effectiveness estimates of improved Papanicolaou test sensitivity. Most of those effects are related to the cost of evaluation and treatment of low-grade lesions.

Conclusion: Policies or technologies that increased sensitivity of cervical cytologic screening increased overall costs, even if the cost of the technology was identical to that of conventional Papanicolaou smears. These effects appear to be caused by relatively high prevalence of low-grade lesions and are magnified at frequent screening intervals. Efficient cervical cancer screening requires methods with greater ability to detect lesions that are most likely to become cancerous.

Carcinoma of the cervix is one of the most common malignant conditions in women in many parts of the world. Papanicolaou smears detect preinvasive and early invasive disease and have led to significant reductions in its incidence and associated mortality in many countries.1 In the United States, the incidence of and mortality rate associated with cervical cancer have declined steadily; National Cancer Institute Surveillance, Epidemiology, and End Results registry data show a 43% decrease in incidence and a 46% decrease in mortality from 1973 to 1995.2 No such reductions occurred in countries in which cytologic screening is not widely available.3

In the United States and other countries in which screening is widely available, at least 40% of cases of cervical cancer occur in the 5–15% of women who have never been screened.4–6 Despite evidence that many cases are attributable to inadequate screening or inadequate follow-up of abnormal results, attention has been increased toward reducing false-negative results in women who are screened.

Several adjunctive technologies intended to reduce false-negative results of conventional smears have been approved by the U.S. Food and Drug Administration. Recent evaluations by our group7 and the Blue Cross/Blue Shield Technology Evaluation Center8 found that the cost-effectiveness of adjunctive technologies is directly related to frequency of screening. However, limitations in the extant evidence on sensitivity, specificity, and cost of new technologies do not permit reliable estimates of the cost-effectiveness of individual new tests. Therefore, we applied a comprehensive model of cervical cancer to identify circumstances in which new technologies could be cost-effective.