Results of a Randomized Trial on the Management of Cytology Interpretations of Atypical Squamous Cells of Undetermined Significance

Am J Obstet Gynecol. 2003 Jun;188(6):1383-92. doi: 10.1067/mob.2003.457.

Abstract

Objective: This study was undertaken to compare alternative strategies for the initial management of a cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS).

Study design: A total of 3488 women with a community-based ASCUS interpretation were randomly assigned to immediate colposcopy, triage that was based on enrollment HPV DNA testing and liquid-based cytology at a colposcopy referral threshold of high-grade squamous intraepithelial lesion (HSIL), or conservative management based on repeat cytology at a referral threshold of HSIL. All arms included 2 years of semiannual follow-up and colposcopy at exit. Loop electrosurgical excision procedure was offered to women with histologic diagnoses of cervical intraepithelial neoplasia (CIN) grade 2 or 3 at any visit or persistent CIN grade 1 at exit. The study end point was 2-year cumulative diagnosis of CIN grade 3.

Results: The 2-year cumulative diagnosis of CIN grade 3 was 8% to 9% in all study arms. The immediate colposcopy strategy yielded 53.6% sensitivity for cumulative cases of CIN grade 3 diagnosed over 2 years. The human papillomavirus (HPV) triage strategy referred 55.6% of women and detected 72.3% of cumulative cases of CIN grade 3. A conservative management strategy of repeat cytology at the HSIL threshold referred 12.3% of women while detecting 54.6% of cumulative CIN grade 3. To compare triage tests, we re-estimated the performance of HPV and cytology in successfully referring women with underlying CIN grade 3 (ie, ignoring the insensitivity we discovered in colposcopically directed biopsies). A single enrollment HPV test identified 92.4% of the women diagnosed with CIN grade 3. Serial cytology, even at an ASCUS threshold, would have required two visits to achieve similar sensitivity (95.4%) and would have referred 67.1% to colposcopy.

Conclusion: HPV triage is at least as sensitive as immediate colposcopy for detecting CIN grade 3 and refers about half as many women to colposcopy. Follow-up that used repeat cytology is sensitive at an ASCUS referral threshold but requires two follow-up visits and ultimately more colposcopic examinations than HPV triage.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alabama
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Carcinoma, Squamous Cell / virology
  • Cervical Intraepithelial Neoplasia / diagnosis*
  • Cervical Intraepithelial Neoplasia / pathology
  • Cervical Intraepithelial Neoplasia / surgery
  • Cervical Intraepithelial Neoplasia / virology
  • Colposcopy / standards*
  • DNA, Viral / genetics
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Oklahoma
  • Papillomaviridae / genetics*
  • Papillomaviridae / isolation & purification
  • Pennsylvania
  • Sensitivity and Specificity
  • Triage
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / surgery
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears / standards*
  • Washington

Substances

  • DNA, Viral