The use of Ki67/p16 dual staining of cytology smears as a prognostic marker for identifying high grade Cervical Intraepithelial Neoplasia (CIN) has been suggested. In a group of women attending the Norwegian Cervical Cancer Screening Program, an automated staining protocol was used to test the clinical value of Ki67/ p16 dual staining alone or as an adjunct to cytology.
The CINtec PLUS kit was used for dual staining of liquid based PAP smears in residual specimens after cytology testing. The results were correlated with CIN grade 1, 2 or 3 in biopsies or HPV negative cytology as the clinical endpoint on average 184 days after cytology specimen collection.
In a total of 266 HPV positive women, 67% were CINtec PLUS positive. For detecting CIN2+ in the whole cohort (201) or the subgroup of non HPV16 or 18 positives (136), the sensitivity for CINtec PLUS was significantly higher than for cytology (0.88 versus 0.79), but not for CIN3 (0.94 versus 0.88). The specificity of cytology to detect ≤ CIN2 was significantly higher than for CINtec PLUS (0.35 versus 0.28), but not for detecting ≤CIN1 (0.35 versus 0.31). Using the CINtec PLUS as an adjunct to cytology increased the sensitivity for CIN3 (0.96) and CIN2+ (0.94), while the specificity was higher for CIN3 (0.40) and lower for CIN2+ (0.24).
Dual staining of p16 and ki67 as an adjunct to cytology is more sensitive and more specific to use for detection of CIN3, but less specific for CIN2+, as compared to CINtec PLUS or cytology alone.