Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance.
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).


METHODS
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.


CONCLUSIONS
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.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000407:Alabama; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery / Q000821:virology; D003127:Colposcopy / Q000592:standards*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009825:Oklahoma; D027383:Papillomaviridae / Q000235:genetics* / Q000302:isolation & purification; D010414:Pennsylvania; D012680:Sensitivity and Specificity; D014218:Triage; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery / Q000821:virology; D014626:Vaginal Smears / Q000592:standards*; D014861:Washington; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery / Q000821:virology
D004279:DNA, Viral