Cytologic Parameters of Cervical Cytology Specimens Associated with Discordant "Equivocal" Hybrid Capture II High-Risk HPV DNA Tests Results: A Cytologic/Histologic Review of 191 Cases
A Lagstein, KS Luckett, BM Smola, WD LeBar, D Newton, RT Pu, SM Knoepp. University of Michigan, Ann Arbor, MI
Background: The Hybrid Capture II (Qiagen) high-risk human papilloma virus (hrHPV) DNA test is an in vitro assay that performs qualitative and semiquantitative detection of hrHPV in cervical samples. Results are reported as a ratio of relative light units (RLUs) to a cutoff value (CO) or (RLU/CO), with a value of 1.0 separating negative from positive results. Per FDA labeling, values between 1.0 and 2.5 RLU/CO or "equivocal" specimens are retested and must show a value above 1.0 on retest to be resulted as a true positive specimen.
Design: We reviewed all hrHPV tests over a 27 month period at our institution, selecting 3 patient cohort subsets for corresponding cytologic and histologic comparison: a concordant "equivocal" group (1st hrHPV test between 1.0 and 5.0 RLU/CO with subsequent test positive), a discordant "equivocal" group (1st hrHPV test between 1.0 and 5.0 RLU/CO with subsequent test negative), and an unequivocal positive group (1st hrHPV test above 5.0 RLU/CO). We compared 46 ThinPrep pap tests from the discordant "equivocal" group with 29 ThinPrep pap tests each from the concordant "equivocal" and unequivocal positive groups. Finally, we examined available histologic follow-up corresponding to pap tests diagnosed as ASCUS in the discordant "equivocal" group.
Results: A total of 10,157 hrHPV tests were reviewed. Of these, 9395 (92.5%) were unequivocal positive or negative tests, 571 (5.6%) were concordant equivocal tests, and 191 (1.9%) were discordant equivocal hrHPV tests. Abundant blood and acute inflammation were associated with ThinPrep pap tests associated with an "equivocal" hrHPV test, with the discordant "equivocals" showing more profuse blood than concordant "equivocals" (p=0.014). Available follow-up histologic cervical biopsies from patients in the discordant "equivocal" group originally showing ASCUS cytology (n=12) were examined and showed high-grade CIN (CIN 2 or 3) in 25% of cases, and CIN 1 in 50% of cases.
Conclusions: Histologic follow-up from cervical cytology pap tests showing the most borderline of "equivocal" hrHPV tests (the discordant "equivocal" hrHPV test) reveals a highly significant degree of both low and high-grade dysplasia, suggesting that these cases are best managed as being unequivocally positive for hrHPV. The phenomenon of "equivocal" results in this cohort is most likely due to obscuring blood and inflammation in the cervical cytology specimens, and not lack of hrHPV.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 74, Tuesday Morning