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Evaluating the Risk of Cervical Precancer with a Combination of Cytologic, Virologic, and Visual Methods

Divisions of ¹ Cancer Epidemiology and Genetics and ² Cancer Prevention, National Cancer Institute, NIH, Bethesda, Maryland and ³ Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, Oklahoma

Requests for reprints: Sophia S. Wang, Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 6120 Executive Boulevard, EPS MSC# 7234, Bethesda, MD 20892-7234. Phone: 301-402-5374; Fax: 301-402-0916. E-mail: wangso{at}mail.nih.gov

Several test modalities (cytologic, molecular, and visual) may be used for cervical cancer screening, triage, and follow-up. Although no currently available single test for cervical neoplasia can detect disease with both high sensitivity and specificity, combinations of available tests allow for improved risk prediction. We therefore evaluated the combination of liquid-based cytology (LBC), human papillomavirus (HPV) DNA testing, and visual inspection (cervicography), taken at a single point in time, to predict risk of subsequent cervical intraepithelial neoplasia 3 (CIN3) or cancer developing within 2 years in a triage population of 5,060 women referred for equivocal or mildly abnormal cytology. The concurrent administration of all three test modalities showed that combinations of these test modalities permitted clear and distinct risk stratification. Among HPV-positive women with high-grade LBC and high-grade cervicography results, 79.1 % [95% confidence interval (95% CI), 64.0- 90.0] were diagnosed with histologic CIN3 or cancer within 2 years, supporting a "see-and-treat" clinical application. Conversely, only 1.4% (95% CI, 0.7-2.5) of women with a negative HPV, normal cervigram, and second normal cytology result developed CIN3 or cancer. Because this low absolute risk was largely attributable to the negative HPV test, our results suggest a lack of benefit for a secondary or tertiary test result given an HPV-negative test result. Within HPV-positive women, however, we observed a steadily increasing absolute risk for cervical precancer/cancer with increasing numbers and severity of abnormal test results. We conclude that the clear discrimination of cervical cancer risk provided by multiple test modalities is consistent with our understanding of cervical etiology related to HPV natural history.

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