INTRODUCTION: Targeted colposcopic biopsy has imperfect sensitivity for cervical precancer, with a clinically important risk of missing CIN2 plus. This study compared a prespecified single primary targeted biopsy strategy with strategies that add systematic four quadrant biopsies and endocervical curettage.
METHODS: : This paired diagnostic accuracy study evaluated nested index strategies within the same patients. Strategy A was the prespecified primary targeted biopsy from the most suspicious lesion. Strategy B1 included all targeted biopsies plus systematic four quadrant biopsies. Strategy B2 included B1 plus endocervical curettage. Reference standard was excision histology or 12 month follow up verification. The primary endpoint was the paired sensitivity difference for CIN2 plus.
RESULTS: Among 268 reference standard evaluable patients, reference CIN2 plus prevalence was 61 of 268 (22.8%). Sensitivity for CIN2 plus was 75.4% for Strategy A (46 of 61), 91.8% for Strategy B1 (56 of 61), and 95.1% for Strategy B2 (58 of 61). Compared with Strategy A, sensitivity increased by 16.4 percentage points for Strategy B1 (p=0.00195) and by 19.7 percentage points for Strategy B2 (p=0.00049). Endocervical curettage contributed an additional 2 detections among reference positive patients (3.3 percentage points; p=0.50). Specificity for CIN2 minus was 99.5% for all strategies. Patient based number needed to sample was 26.2 for four quadrant biopsies and 67 for endocervical curettage.
DISCUSSION AND CONCLUSION: Adding systematic four quadrant biopsies to targeted biopsy substantially increased CIN2 plus detection without an observed specificity penalty in this dataset. Endocervical curettage provided a smaller incremental yield overall, supporting selective use in higher risk profiles.
Keywords: colposcopy, cervical intraepithelial neoplasia, targeted biopsy, endocervical curettage, diagnostic accuracy