p16/ki-67 dual-stain cytology in the triage of ASCUS and LSIL papanicolaou cytology: results from the European equivocal or mildly abnormal Papanicolaou cytology study

BACKGROUND:

The objective of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual‐stain protocol, which simultaneously detects p16^INK4a and Ki‐67 expression in cervical cytology samples, for identifying high‐grade cervical intraepithelial neoplasia (CIN2+) in women with Papanicolaou (Pap) cytology results categorized as atypical squamous cells of undetermined significance (ASCUS) or low‐grade squamous intraepithelial lesions (LSIL).

METHODS:

Residual liquid‐based cytology material from 776 retrospectively collected ASCUS/LSIL cases that were available from a recent study evaluating p16 cytology and HPV testing were subjected to p16/Ki‐67 dual staining. The presence of 1 or more double‐immunoreactive cell(s) was regarded as a positive test outcome, irrespective of morphology. Test results were correlated to histology follow‐up.

RESULTS:

Sensitivity of p16/Ki‐67 dual‐stain cytology for biopsy‐confirmed CIN2+ was 92.2% (ASCUS) and 94.2% (LSIL), while specificity rates were 80.6% (ASCUS) and 68.0% (LSIL), respectively. Similar sensitivity/specificity profiles were found for both age groups of women aged <30 years versus women aged ≥30 years. Dual‐stain cytology showed comparable sensitivity, but significantly higher specificity, when compared with human papillomavirus (HPV) testing.

CONCLUSIONS:

The results of this study show that p16/Ki‐67 dual‐stain cytology provided a high sensitivity for the detection of underlying CIN2+ in women with ASCUS or LSIL Pap cytology results, comparable to the rates previously reported for HPV testing and p16 single‐stain cytology. However, the specificity of this morphology‐independent interpretation of p16/Ki‐67 dual‐stain cytology testing was further improved compared with the earlier p16 single‐stain cytology approach, which required morphology interpretation, and it is significantly higher when compared with HPV testing. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.