A randomized trial on the management of low-grade squamous intraepithelial lesion cytology interpretations

OBJECTIVE: This study was undertaken to compare alternative strategies for the initial management of low-grade squamous intraepithelial lesion (LSIL) cytology. STUDY DESIGN: A total of 1572 women with a community-based LSIL interpretation were randomly assigned to immediate colposcopy, triage 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 main study end point was 2-year cumulative diagnosis of CIN grade 3. RESULTS: The 2-year cumulative diagnosis of CIN grade 3 was approximately 15% in all study arms. The HPV triage arm was closed early because more than 80% of women were HPV positive, precluding efficient triage. The immediate colposcopy strategy yielded 55.9% sensitivity for cumulative cases of CIN grade 3 diagnosed over 2 years. A conservative management strategy of repeat cytology at the HSIL threshold referred 18.8% of women while detecting 48.4% of cumulative CIN grade 3. At lower cytology thresholds, sensitivity would improve but would ultimately yield unacceptably high referral rates. CONCLUSION: LSIL cytology is best managed by colposcopy initially, because there was no useful triage strategy identified. Management of these patients, after colposcopy to rule out immediately overt CIN grade 2 or 3, needs to be determined.