Inappropriate gold standard bias in cervical cancer screening studies

✍ Scribed by Robert G. Pretorius; Yan-Ping Bao; Jerome L. Belinson; Raoul J. Burchette; Jennifer S. Smith; You-Lin Qiao

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: French
• Weight: 103 KB
• Volume: 121
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.22991

✦ Synopsis

Abstract

As acetic acid‐aided visual inspection (VIA) and colposcopic‐directed biopsy miss small ≥cervical intraepithelial neoplasia (CIN) 2, inflation of sensitivity of VIA may occur when colposcopic‐directed biopsy is the gold standard for ≥CIN 2. To determine whether such inflation occurs, we reviewed 375 women with ≥CIN 2 from the Shanxi Province Cervical Cancer Screening Study II. These women had positive self or physician‐collected tests for high‐risk human papillomavirus or abnormal cervical cytology and had VIA followed by colposcopy with directed biopsy and endocervical curettage (ECC). If a cervical quadrant had no lesion, a random biopsy at the squamocolumnar junction within that quadrant was obtained. Sensitivity of colposcopic‐directed biopsy was higher for ≥CIN 2 involving 3–4 cervical quadrants (81.3%) than for ≥CIN 2 involving 0–2 quadrants (49.0%, p < 0.001). Sensitivities of VIA, cytology of ≥ASC‐US, ≥LSIL, and ≥HSIL were higher for ≥CIN 2 involving 3–4 quadrants than for ≥CIN 2 involving 0–2 quadrants. When a colposcopic‐directed biopsy gold standard was compared with that of a 5‐biopsy standard (which included ≥CIN 2 from colposcopic‐directed biopsy, random biopsy, or ECC), the sensitivity for ≥CIN 2 of VIA was inflated by 20.0% (65.9% vs. 45.9%, p < 0.001). Sensitivities of other screening tests were not affected. Similar inflation of sensitivity of VIA was found with an endpoint of ≥CIN 3 (70.4% vs. 52.0%, p = 0.0013). Inflation of sensitivity of VIA depended upon agreement between colposcopic‐directed biopsy and the screening tests as measured by kappa. Studies of VIA that used colposcopic‐directed biopsy as the gold standard require reevaluation. © 2007 Wiley‐Liss, Inc.