Objective:

This report compares new technologies for cervical cytological screening with conventional Papanicolaou (Pap) test screening in terms of diagnostic accuracy, costs, effectiveness, and cost-effectiveness in adult women of average cervical cancer risk

Search Strategy:

Published literature on the accuracy of cervical cytological screening, costs of screening and treatment, and cost-effectiveness were identified in MEDLINE, CINAHL, CancerLit, EconLit, HealthSTAR, and EMBASE databases.

Selection Criteria:

Diagnostic test studies were included if they compared cervical cytology diagnosis with concurrent colposcopy or biopsy and provided estimates of sensitivity and specificity. For the new technologies, studies were also included that used a cytology reference standard and allowed estimation of either sensitivity or specificity. Articles on costs and health outcomes were selected if they assessed the effect of screening on life expectancy or quality of life, number of cases of cervical cancer, or total health care costs.

Data Collection and Analysis:

For diagnostic test studies, paired reviewers independently abstracted sensitivity and specificity data from each study. Quality scores were assessed on blind interpretation of screening test results, histological reference standard, verification of test negative subjects, description of disease spectrum, avoidance of bias in sample selection, publication type, and source of support. Diverse articles on costs and health outcomes were summarized and quality-scored according to criteria published by an expert panel.

Supplemental analyses include a meta-analysis to generate summary estimates of Pap test discrimination; cost analysis using claims databases to generate costs of treatment and screening; and a Markov model to estimate the effectiveness and costs of different technologies and clinical strategies.

Main Results:

Conventional Pap smear screening, based on the few studies that avoided severe biases, showed specificity of 98 percent (95 percent confidence interval (CI); 97-99 percent) and sensitivity of 51 percent (95 percent CI; 37-66 percent). The sample prevalence of disease is strongly related to between-study variability in Pap test sensitivity and specificity and may reflect bias. Other indicators of study quality were not significant when prevalence was controlled. The Pap test is more accurate when a high-grade squamous intraepithelial lesion threshold is used with the goal of detecting a high-grade lesion than when lower thresholds, such as a low-grade squamous intraepithelial lesion (LSIL) or atypical squamous cells of uncertain significance (ASCUS), are used with the goal of detecting low- or high-grade dysplasia. Few studies of the new technologies used histology or colposcopy as a reference standard or allowed estimates of both sensitivity and specificity. In studies using a cytology reference standard, each of the new technologies appears to significantly improve sensitivity relative to conventional Pap smear screening; however, little information is available on the effects on specificity.

Cost-effectiveness ratios from published models comparing Pap smear screening with no screening fall into an acceptable range, but these models used parameters that overstate Pap test accuracy.

Base case estimates of the incremental cost-effectiveness of conventional Pap screening every 3 years compared with no Pap screening is $4,097 per life-year saved. A technology applied to the initial step in Pap screening that reduces the false negative rate by a factor of 0.6 at an incremental cost per slide of $10 has an incremental cost of $22,010 per life-year saved when performed every 3 years. With more frequent screening intervals, the cost per life-year saved is greater than $50,000. Technologies that allow 100 percent rescreening of slides initially read as normal by conventional Pap screening, at a reduction in false negative rate of 0.85 or higher, are more effective than technologies that improve initial screening with a reduction of 0.6. At these reductions in false negative rate, with identical incremental costs of $10 per slide and a screening interval of every 3 years, the cost per life-year saved of rescreening technologies compared with improved initial screening is $45,375. Findings were relatively insensitive to assumptions about cervical cancer incidence, cost of technologies, diagnostic strategies for abnormal screening results, and age at onset of screening. Findings were sensitive to both the reduction in false negative rate (i.e., improvement in sensitivity) and the relative specificity of the technologies compared with conventional Pap.

Conclusions:

Estimates of the sensitivity of the conventional Pap test are biased in most studies; based on the least biased studies, sensitivity is near 50 percent, much lower than generally believed. Newer technologies improve sensitivity compared with conventional Pap screening; however, there are no precise estimates for their effect on specificity. Under assumptions favorable to improved initial screening technologies and rescreening technologies, either approach can result in acceptable cost per life-year saved at 3-year Pap screening intervals. However, the imprecision in estimates of effectiveness and cost of the new technologies makes drawing firm conclusions about their relative cost-effectiveness problematic.