Resolving ASCUS without recourse to HPV testing: manual reprocessing of residual automated liquid-based cytology (ALBC) material using manual liquid-based cytology (MLBC)

We show that residual cell material from ThinPrep PapTest (Cytyc Corporation, Boxborough, MA) atypical squamous-cells of undetermined significance (ASCUS) cases may be manually reprocessed to triage women into actionable diagnostic categories (HSIL, LSIL, and Negative). Material remaining from each of 358 ThinPrep ASCUS cases was manually reprocessed as two slides, labeled "A" and "B." Interobserver agreement between case contributors (CCs) and three sequential reviewers (SRs) was analyzed with 186 cases (Study 1), and diagnostic reproducibility between SRs was examined with an additional 172 cases (Study 2). In Study 1, CCs classified 33% of cases as LSIL or greater, SRs classified 60% as LSIL or greater, and there was 58% diagnostic agreement between CCs and SRs. No "Negative" case assignment by one group afforded an "HSIL" assignment by the complementary group. In Study 2, there was 95% agreement between SRs A slide and B slide diagnoses with 54% of A slides and 55% of B slides classified as LISL or greater. Again, no "Negative" case assignment to one slide afforded an "HSIL" assignment to the complementary slide. Overall, 12.6% of the 358 cases showed HSIL, and all HSILs by one observer group were ASCUS or greater by the complementary observer group. Using manual reprocessing beyond the 21-day specimen outdate for HPV testing by the Hybrid Capture II High Risk HPV test (HR-HCII; Digene Corporation, Beltsville, MD), many ThinPrep ASCUS cases were reclassified as LSIL or HSIL. The 12.6% HSIL proportion of this study approximated the 11.5% CIN 2 or greater proportion of the ALTS ASCUS arm. Similar to ALTS, manual liquid-based cytology (MLBC) would have referred nearly 60% of women to colposcopy for a definitive diagnosis of HSIL or LSIL without resorting to HPV testing. These data demonstrate that many cases of automated liquid-based cytology (ALBC)-diagnosed ASCUS represent unrecognized SIL, which is present in the ALBC specimen vial at the time the ASCUS diagnosis is rendered.