title: Clinical and pathological heterogeneity of cervical intraepithelial neoplasia grade 3.
abstract: OBJECTIVE
  Cervical intraepithelial neoplasia grade 3 (CIN3), the immediate cervical cancer precursor, is a target of cervical cancer prevention. However, less than half of CIN3s will progress to cancer. Routine treatment of all CIN3s and the majority of CIN2s may lead to overtreatment of many lesions that would not progress. To improve our understanding of CIN3 natural history, we performed a detailed characterization of CIN3 heterogeneity in a large referral population in the US.
  
  
  METHODS
  We examined 309 CIN3 cases in the SUCCEED, a large population-based study of women with abnormal cervical cancer screening results. Histology information for 12 individual loop electrosurgical excision procedure (LEEP) segments was evaluated for each woman. We performed case-case comparisons of CIN3s to analyze determinants of heterogeneity and screening test performance.
  
  
  RESULTS
  CIN3 cases varied substantially by size (1-10 LEEP segments) and by presentation with concomitant CIN2 and CIN1. All grades of CINs were equally distributed over the cervical surface. In half of the women, CIN3 lesions were found as multiple distinct lesions on the cervix. Women with large and solitary CIN3 lesions were more likely to be older, have longer sexual activity span, and have fewer multiple high risk HPV infections. Screening frequency, but not HPV16 positivity, was an important predictor of CIN3 size. Large CIN3 lesions were also characterized by high-grade clinical test results.
  
  
  CONCLUSIONS
  We demonstrate substantial heterogeneity in clinical and pathological presentation of CIN3 in a US population. Time since sexual debut and participation in screening were predictors of CIN3 size. We did not observe a preferential site of CIN3 on the cervical surface that could serve as a target for cervical biopsy. Cervical cancer screening procedures were more likely to detect larger CIN3s, suggesting that CIN3s detected by multiple independent diagnostic tests may represent cases with increased risk of invasion.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, United States of America. yanghan@mail.nih.gov
authors.forename: Hannah P
authors.initials: HP
authors.lastname: Yang
authors.forename: Rosemary E
authors.initials: RE
authors.lastname: Zuna
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Joan L
authors.initials: JL
authors.lastname: Walker
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Landrum
authors.forename: Katherine
authors.initials: K
authors.lastname: Moxley
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gold
authors.forename: S Terence
authors.initials: ST
authors.lastname: Dunn
authors.forename: Richard A
authors.initials: RA
authors.lastname: Allen
authors.forename: Roy
authors.initials: R
authors.lastname: Zhang
authors.forename: Rodney
authors.initials: R
authors.lastname: Long
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D003127:Colposcopy; D004598:Electrosurgery; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D008403:Mass Screening; D008875:Middle Aged; D060787:Neoplasm Grading; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012725:Sexual Behavior; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000601:surgery; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000473:pathology* / Q000601:surgery