title: Multiple biopsies and detection of cervical cancer precursors at colposcopy.
abstract: OBJECTIVE
  Women with abnormal cervical cancer screening results are referred to colposcopy and biopsy for diagnosis of cervical cancer precursors (high-grade squamous intraepithelial lesions [HSILs]). Colposcopy with a single biopsy can miss identification of HSILs. No systematic study has quantified the improved detection of HSIL by taking multiple lesion-directed biopsies.
  
  
  METHODS
  The Biopsy Study was an observational study of 690 women referred to colposcopy after abnormal cervical cancer screening results. Up to four directed biopsies were taken from distinct acetowhite lesions and ranked by colposcopic impression. A nondirected biopsy of a normal-appearing area was added if fewer than four directed biopsies were taken. HSIL identified by any biopsy was the reference standard of disease used to evaluate the incremental yield and sensitivity of multiple biopsies.
  
  
  RESULTS
  In the overall population, sensitivities for detecting HSIL increased from 60.6% (95% CI, 54.8% to 66.6%) from a single biopsy to 85.6% (95% CI, 80.3% to 90.2%) after two biopsies and to 95.6% (95% CI, 91.3% to 99.2%) after three biopsies. A significant increase in sensitivity of multiple biopsies was observed in all subgroups. The highest increase in yield of HSIL was observed for women with a high-grade colposcopic impression, HSIL cytology, and human papillomavirus (HPV) type 16 positivity. Only 2% of all HSILs diagnosed in the participants were detected by biopsies of normal-appearing transformation zone.
  
  
  CONCLUSIONS
  Collection of additional lesion-directed biopsies during colposcopy increased detection of histologic HSIL, regardless of patient characteristics. Taking additional biopsies when multiple lesions are present should become the standard practice of colposcopic biopsy.
authors.affiliation: Nicolas Wentzensen, Barry I. Graubard, Sholom Wacholder, and Mark Schiffman, National Cancer Institute, Bethesda, MD; Joan L. Walker, Katie M. Smith, Rosemary E. Zuna, Cara Mathews, S. Terence Dunn, Roy Zhang, Katherine Moxley, Erin Bishop, Meaghan Tenney, and Elizabeth Nugent, University of Oklahoma Health Sciences Center, Oklahoma City; and Michael A. Gold, Tulsa Cancer Institute and University of Oklahoma School of Community Medicine, Tulsa, OK. wentzenn@mail.nih.gov.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.affiliation: Nicolas Wentzensen, Barry I. Graubard, Sholom Wacholder, and Mark Schiffman, National Cancer Institute, Bethesda, MD; Joan L. Walker, Katie M. Smith, Rosemary E. Zuna, Cara Mathews, S. Terence Dunn, Roy Zhang, Katherine Moxley, Erin Bishop, Meaghan Tenney, and Elizabeth Nugent, University of Oklahoma Health Sciences Center, Oklahoma City; and Michael A. Gold, Tulsa Cancer Institute and University of Oklahoma School of Community Medicine, Tulsa, OK.
authors.forename: Joan L
authors.initials: JL
authors.lastname: Walker
authors.affiliation: Nicolas Wentzensen, Barry I. Graubard, Sholom Wacholder, and Mark Schiffman, National Cancer Institute, Bethesda, MD; Joan L. Walker, Katie M. Smith, Rosemary E. Zuna, Cara Mathews, S. Terence Dunn, Roy Zhang, Katherine Moxley, Erin Bishop, Meaghan Tenney, and Elizabeth Nugent, University of Oklahoma Health Sciences Center, Oklahoma City; and Michael A. Gold, Tulsa Cancer Institute and University of Oklahoma School of Community Medicine, Tulsa, OK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gold
authors.affiliation: Nicolas Wentzensen, Barry I. Graubard, Sholom Wacholder, and Mark Schiffman, National Cancer Institute, Bethesda, MD; Joan L. Walker, Katie M. Smith, Rosemary E. Zuna, Cara Mathews, S. Terence Dunn, Roy Zhang, Katherine Moxley, Erin Bishop, Meaghan Tenney, and Elizabeth Nugent, University of Oklahoma Health Sciences Center, Oklahoma City; and Michael A. Gold, Tulsa Cancer Institute and University of Oklahoma School of Community Medicine, Tulsa, OK.
authors.forename: Katie M
authors.initials: KM
authors.lastname: Smith
authors.affiliation: Nicolas Wentzensen, Barry I. Graubard, Sholom Wacholder, and Mark Schiffman, National Cancer Institute, Bethesda, MD; Joan L. Walker, Katie M. Smith, Rosemary E. Zuna, Cara Mathews, S. Terence Dunn, Roy Zhang, Katherine Moxley, Erin Bishop, Meaghan Tenney, and Elizabeth Nugent, University of Oklahoma Health Sciences Center, Oklahoma City; and Michael A. Gold, Tulsa Cancer Institute and University of Oklahoma School of Community Medicine, Tulsa, OK.
authors.forename: Rosemary E
authors.initials: RE
authors.lastname: Zuna
authors.affiliation: Nicolas Wentzensen, Barry I. Graubard, Sholom Wacholder, and Mark Schiffman, National Cancer Institute, Bethesda, MD; Joan L. Walker, Katie M. Smith, Rosemary E. Zuna, Cara Mathews, S. Terence Dunn, Roy Zhang, Katherine Moxley, Erin Bishop, Meaghan Tenney, and Elizabeth Nugent, University of Oklahoma Health Sciences Center, Oklahoma City; and Michael A. Gold, Tulsa Cancer Institute and University of Oklahoma School of Community Medicine, Tulsa, OK.
authors.forename: Cara
authors.initials: C
authors.lastname: Mathews
authors.affiliation: Nicolas Wentzensen, Barry I. Graubard, Sholom Wacholder, and Mark Schiffman, National Cancer Institute, Bethesda, MD; Joan L. Walker, Katie M. Smith, Rosemary E. Zuna, Cara Mathews, S. Terence Dunn, Roy Zhang, Katherine Moxley, Erin Bishop, Meaghan Tenney, and Elizabeth Nugent, University of Oklahoma Health Sciences Center, Oklahoma City; and Michael A. Gold, Tulsa Cancer Institute and University of Oklahoma School of Community Medicine, Tulsa, OK.
authors.forename: S Terence
authors.initials: ST
authors.lastname: Dunn
authors.affiliation: Nicolas Wentzensen, Barry I. Graubard, Sholom Wacholder, and Mark Schiffman, National Cancer Institute, Bethesda, MD; Joan L. Walker, Katie M. Smith, Rosemary E. Zuna, Cara Mathews, S. Terence Dunn, Roy Zhang, Katherine Moxley, Erin Bishop, Meaghan Tenney, and Elizabeth Nugent, University of Oklahoma Health Sciences Center, Oklahoma City; and Michael A. Gold, Tulsa Cancer Institute and University of Oklahoma School of Community Medicine, Tulsa, OK.
authors.forename: Roy
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Nicolas Wentzensen, Barry I. Graubard, Sholom Wacholder, and Mark Schiffman, National Cancer Institute, Bethesda, MD; Joan L. Walker, Katie M. Smith, Rosemary E. Zuna, Cara Mathews, S. Terence Dunn, Roy Zhang, Katherine Moxley, Erin Bishop, Meaghan Tenney, and Elizabeth Nugent, University of Oklahoma Health Sciences Center, Oklahoma City; and Michael A. Gold, Tulsa Cancer Institute and University of Oklahoma School of Community Medicine, Tulsa, OK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Moxley
authors.affiliation: Nicolas Wentzensen, Barry I. Graubard, Sholom Wacholder, and Mark Schiffman, National Cancer Institute, Bethesda, MD; Joan L. Walker, Katie M. Smith, Rosemary E. Zuna, Cara Mathews, S. Terence Dunn, Roy Zhang, Katherine Moxley, Erin Bishop, Meaghan Tenney, and Elizabeth Nugent, University of Oklahoma Health Sciences Center, Oklahoma City; and Michael A. Gold, Tulsa Cancer Institute and University of Oklahoma School of Community Medicine, Tulsa, OK.
authors.forename: Erin
authors.initials: E
authors.lastname: Bishop
authors.affiliation: Nicolas Wentzensen, Barry I. Graubard, Sholom Wacholder, and Mark Schiffman, National Cancer Institute, Bethesda, MD; Joan L. Walker, Katie M. Smith, Rosemary E. Zuna, Cara Mathews, S. Terence Dunn, Roy Zhang, Katherine Moxley, Erin Bishop, Meaghan Tenney, and Elizabeth Nugent, University of Oklahoma Health Sciences Center, Oklahoma City; and Michael A. Gold, Tulsa Cancer Institute and University of Oklahoma School of Community Medicine, Tulsa, OK.
authors.forename: Meaghan
authors.initials: M
authors.lastname: Tenney
authors.affiliation: Nicolas Wentzensen, Barry I. Graubard, Sholom Wacholder, and Mark Schiffman, National Cancer Institute, Bethesda, MD; Joan L. Walker, Katie M. Smith, Rosemary E. Zuna, Cara Mathews, S. Terence Dunn, Roy Zhang, Katherine Moxley, Erin Bishop, Meaghan Tenney, and Elizabeth Nugent, University of Oklahoma Health Sciences Center, Oklahoma City; and Michael A. Gold, Tulsa Cancer Institute and University of Oklahoma School of Community Medicine, Tulsa, OK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Nugent
authors.affiliation: Nicolas Wentzensen, Barry I. Graubard, Sholom Wacholder, and Mark Schiffman, National Cancer Institute, Bethesda, MD; Joan L. Walker, Katie M. Smith, Rosemary E. Zuna, Cara Mathews, S. Terence Dunn, Roy Zhang, Katherine Moxley, Erin Bishop, Meaghan Tenney, and Elizabeth Nugent, University of Oklahoma Health Sciences Center, Oklahoma City; and Michael A. Gold, Tulsa Cancer Institute and University of Oklahoma School of Community Medicine, Tulsa, OK.
authors.forename: Barry I
authors.initials: BI
authors.lastname: Graubard
authors.affiliation: Nicolas Wentzensen, Barry I. Graubard, Sholom Wacholder, and Mark Schiffman, National Cancer Institute, Bethesda, MD; Joan L. Walker, Katie M. Smith, Rosemary E. Zuna, Cara Mathews, S. Terence Dunn, Roy Zhang, Katherine Moxley, Erin Bishop, Meaghan Tenney, and Elizabeth Nugent, University of Oklahoma Health Sciences Center, Oklahoma City; and Michael A. Gold, Tulsa Cancer Institute and University of Oklahoma School of Community Medicine, Tulsa, OK.
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.affiliation: Nicolas Wentzensen, Barry I. Graubard, Sholom Wacholder, and Mark Schiffman, National Cancer Institute, Bethesda, MD; Joan L. Walker, Katie M. Smith, Rosemary E. Zuna, Cara Mathews, S. Terence Dunn, Roy Zhang, Katherine Moxley, Erin Bishop, Meaghan Tenney, and Elizabeth Nugent, University of Oklahoma Health Sciences Center, Oklahoma City; and Michael A. Gold, Tulsa Cancer Institute and University of Oklahoma School of Community Medicine, Tulsa, OK.
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy / Q000379:methods* / Q000706:statistics & numerical data; D002584:Cervix Uteri / Q000473:pathology*; D003127:Colposcopy / Q000379:methods* / Q000706:statistics & numerical data; D005260:Female; D005838:Genotype; D054884:Host-Pathogen Interactions; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000502:physiology; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000821:virology; D012017:Referral and Consultation / Q000706:statistics & numerical data; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000473:pathology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000821:virology