Abstract

ObjectiveThe accuracy of colposcopy-guided biopsy is key to the success of colposcopic triage in cervical cancer screening programs. However, there is no widely adopted biopsy guideline up to date. Our study aimed to determine whether multi-quadrants biopsy improves the yield of cervical lesions.MethodsEleven population-based cervical cancer screening studies were conducted in China. Cytology, high-risk human papillomavirus (hrHPV) testing and visual inspection were performed for primary screening. Females positive on one or more tests were referred for colposcopy and biopsy. The proportion of detected cervical intraepithelial neoplasia (CIN)2+ and yields by quadrant lesion-targeted biopsy or 4-quadrant random biopsy were compared.ResultsAmong 4,923 females included, 1,606 had quadrant lesion-targeted biopsy, and 3,317 had 4-quadrant random biopsy. The cumulative CIN2+ yield increased from 0.10 for only one quadrant-targeted biopsy to 0.21, 0.34, and 0.58 for at most two, three and four quadrants targeted biopsies. Among hrHPV positive females with high-grade squamous intraepithelial lesion (HSIL)+ cytology, the cumulative CIN2+ yield of a second targeted biopsy in another quadrant was significantly increased (P<0.05). Among hrHPV-negative females, the yield of 4-quadrant random biopsies was 0.005, and the yield by lesion-targeted biopsies was 0.017. For hrHPV positive females who had 4-quadrant random biopsy, the additional CIN2+ yield for HSIL+, low-grade squamous intraepithelial lesion (LSIL) cytology, or abnormal visual inspection via acetic acid and Lugol’s iodine (VIA/VILI) were 0.46, 0.11, 0.14.ConclusionsA 4-quadrant random biopsy is recommended only for hrHPV positive females with HSIL cytology, and is acceptable if hrHPV positive with LSIL cytology or with abnormal VIA/VILI. Our findings add evidences for an objective and practical biopsy standard to guide colposcopy in cervical cancer screening programs in low- and middle-income countries.

Highlights

  • Cervical cancer ranks fourth for both incidence and mortality worldwide among females, especially in low- and middle-income countries [1] where effective preventive interventions are inaccessible for most women [2]

  • Definitive diagnosis of cervical intraepithelial neoplasia (CIN) or cancer is obtained through colposcopy with biopsy followed by histopathology examination, which makes colposcopy the central link between primary screening and therapy decisions

  • The 24 CIN2+ cases found by endocervical curettage (ECC) alone will not be further discussed here

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Summary

Introduction

Cervical cancer ranks fourth for both incidence and mortality worldwide among females, especially in low- and middle-income countries [1] where effective preventive interventions are inaccessible for most women [2]. It has been shown that high-quality screening program with adequate coverage can reduce cervical cancer incidence and mortality [3,4,5]. In low- and middle-income countries, the lack of experienced personnel for colposcopy may lead to failure of a screening program. To address the limitations of colposcopic directed biopsy, some have recommended additional random biopsies from normal-appearing area [10,11]. Studies in the U.S and European countries recommended to take additional biopsies when multiple lesions are present, whereas untargeted biopsies from normal appearing areas added detection of very little disease [13,14]

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