Pooled analysis on the necessity of random 4-quadrant cervical biopsies and endocervical curettage in women with positive screening but negative colposcopy

Controversy remains over whether random cervical biopsies and endocervical curettage (ECC) should be used in women with positive screening but negative colposcopy. Our paper aims to determine the indications for random biopsies and ECC among these screened positive women. Three thousand two hundred thirteen women with any positive screening test result but negative colposcopy, who received random 4-quadrant biopsies, were pooled from 17 population-based cervical cancer screening studies done in China from 1999 to 2008. The detection rates of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN grade 3 or worse (CIN3+) stratified by cytology and high-risk human papillomavirus (HR-HPV) status were assessed, as well as the false negative rates for CIN2+ and CIN3+ by random biopsies without ECC. Compared with women with negative cytology and positive HR-HPV, those with atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (ASC-US/LSIL) and negative HR-HPV had the equivalent lower risks of CIN2+ and CIN3+, but ascending risks were observed in the groups of ASC-US/LSIL and positive HR-HPV, and atypical glandular cells/atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion/high-grade squamous intraepithelial lesion or worse (AGC/ASC-H/HSIL+). If random biopsies were only taken without ECC, 9.3% of CIN2+ and 18.5% of CIN3+ would have been missed. For women with any positive screening but negative colposcopy, in areas with good cytological infrastructure, it was necessary to perform random biopsies plus ECC on those with cytological ASC-US/LSIL and positive HR-HPV, AGC, ASC-H, or HSIL+. In contrast, those with other results should be followed up.