Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: Baseline results from a randomized trial

Background: More than 2 million U.S. women receive an equivocal cervical cytologic diagnosis (atypical squamous cells of undetermined significance [ASCUS]) each year, Effective colposcopy triage strategies are needed to identify the minority of women who have clinically significant disease while avoiding excessive follow-up evaluation for others. Methods: The ASCUS/LSIL (i.e., low-grade squamous intraepithelial lesion) Triage Study (ALTS) is a multicenter, randomized trial comparing the sensitivity and specificity of the following three management strategies to detect cervical intraepithelial neoplasia grade 3 (CIN3): 1) immediate colposcopy (considered to be the reference standard), 2) triage to colposcopy based on human papillomavirus (HPV) results from Hybrid Capture 2(TM) (HC 2) and thin-layer cytology results, or 3) triage based on cytology results alone. This article summarizes the cross-sectional enrollment results for 3488 women with a referral diagnosis of ASCUS, All statistical tests are two-sided. Results: Among participants with ASCUS, the underlying prevalence of histologically confirmed CIN3 was 5.1 %. Sensitivity to detect CIN3 or above by testing for cancer-associated HPV DNA was 96.3% (95% confidence interval [CI] = 91.6% to 98.8%), with 56.1% of women referred to colposcopy, Sensitivity of a single repeat cytology specimen with a triage threshold of HSIL or above was 43.1% (95 % CI = 35.6% to 52.9 %), with 6.9% referred. Sensitivity of a lower cytology triage threshold of ASCUS or above was 85.3% (95% Ct = 78.2% to 90.8%), with 58.6% referred. Conclusions: HC 2 testing for cancer-associated HPV DNA is a viable option in the management of women with ASCUS, It has greater sensitivity to detect CIN3 or above and specificity comparable to a single additional cytologic test Indicating ASCUS or above.