title: The increased detection of cervical intraepithelial neoplasia when using a second biopsy at colposcopy.
abstract: OBJECTIVE
  It has been suggested that colposcopy can miss a significant percentage of high-grade cervical intraepithelial neoplasia (CIN2+). Improved disease ascertainment was evaluated by taking multiple lesion-directed biopsies.
  
  
  METHODS
  In a cross-sectional multicenter study in the Netherlands and Spain, 610 women referred to colposcopy following abnormal cervical cytology results were included. Multiple directed biopsies were collected from lesions and ranked according to impression. A non-directed biopsy of normal-appearing tissue was added if fewer than four biopsies were collected. We evaluated the additional CIN2+ yield for one and two directed biopsies. Colposcopic images were reviewed for quality control.
  
  
  RESULTS
  In women with at least two lesion-directed biopsies the yield for CIN2+ increased from 51.7% (95%CI; 45.7-57.7) for one directed biopsy to 60.4% (95%CI; 54.4-66.2, p<0.001) for two biopsies. The highest CIN2+ yield was observed in women who were HPV16-positive, had high-grade squamous intraepithelial lesion (HSIL) cytology, and high-grade colposcopy impression. The yield increased from 83.1% (95%CI; 71.5-90.5) with one directed biopsy to 93.2% (95%CI; 83.8-97.3) with two directed biopsies. Only 4.5% additional CIN2+ were detected in biopsies not targeting abnormal areas on the cervix.
  
  
  CONCLUSIONS
  A second lesion-directed biopsy is associated with a significant increase in CIN2+ detection. Performing a second lesion-directed biopsy and using a low threshold for abnormality of any acetowhitening should become the standard clinical practice of colposcopy.
authors.affiliation: Department of Research and Development, DDL Diagnostic Laboratory, Visseringlaan 25, 2288ER Rijswijk, The Netherlands. Electronic address: jacolien.van.der.marel@DDL.nl.
authors.forename: J
authors.initials: J
authors.lastname: van der Marel
authors.affiliation: Department of Research and Development, DDL Diagnostic Laboratory, Visseringlaan 25, 2288ER Rijswijk, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: van Baars
authors.affiliation: Institut Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), C/Villaroel 170, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Rodriguez
authors.affiliation: Department of Research and Development, DDL Diagnostic Laboratory, Visseringlaan 25, 2288ER Rijswijk, The Netherlands.
authors.forename: W G V
authors.initials: WG
authors.lastname: Quint
authors.affiliation: Department of Research and Development, DDL Diagnostic Laboratory, Visseringlaan 25, 2288ER Rijswijk, The Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: van de Sandt
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, P.O. Box 7057, 1007MB Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Berkhof
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Schiffman
authors.affiliation: Institut Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), C/Villaroel 170, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Torné
authors.affiliation: Department of Pathology, CRESIB (Centre de Recerca en Salut Internacional de Barcelona), Hospital Clínic, C/Villaroel 170, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Ordi
authors.affiliation: Department of Research and Development, DDL Diagnostic Laboratory, Visseringlaan 25, 2288ER Rijswijk, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Jenkins
authors.affiliation: Division of Woman and Baby, Gynaecological Oncology, University Medical Center Utrecht, P.O. Box 85500, 3508GA Utrecht, The Netherlands.
authors.forename: R H M
authors.initials: RH
authors.lastname: Verheijen
authors.affiliation: Department of Obstetrics & Gynaecology, Erasmus University Medical Center, P.O. Box 2040, 3000CA Rotterdam, The Netherlands.
authors.forename: Th J M
authors.initials: TJ
authors.lastname: Helmerhorst
authors.affiliation: Department of Gynaecology, Roosevelt Kliniek, Rooseveltstraat 65, 2321CT Leiden, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Ter Harmsel
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, USA.
authors.forename: N
authors.initials: N
authors.lastname: Wentzensen
authors.affiliation: Institut Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), C/Villaroel 170, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Del Pino
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy / Q000379:methods; D002584:Cervix Uteri / Q000473:pathology*; D003127:Colposcopy / Q000379:methods*; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications / Q000473:pathology* / Q000821:virology; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000150:complications / Q000175:diagnosis / Q000473:pathology*; D002583:Uterine Cervical Neoplasms / Q000150:complications / Q000175:diagnosis / Q000473:pathology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000150:complications / Q000175:diagnosis / Q000473:pathology*
chemical_list: D004279:DNA, Viral
keywords: Biopsy; Cervical intraepithelial neoplasia; Colposcopy; Human papillomavirus