Evaluation of CINtec PLUS® testing as an adjunctive test in ASC‐US diagnosed SurePath® preparations

The CINtec PLUS® system is an immunohistochemical cocktail composed of antibodies against p16^INK4a (surrogate of HPV infection) and Ki‐67 (proliferation marker) meant to improve the sensitivity and specificity for detecting high‐grade dysplasia (HGD). In the presence of dysplasia, a red chromogen marks Ki‐67 expression in the nucleus and a brown chromogen marks cytoplasmic p16^INK4a expression. Only cells showing dual staining are interpreted as positive. This retrospective study examined the performance of CINtec PLUS testing when performed on ASC‐US diagnosed samples. Comparison was made to high‐risk HPV DNA test results and colposcopic biopsy results. Technical considerations in the interpretation of this immunohistochemical stain are additionally discussed. CINtec PLUS showed modest sensitivity (64%) and specificity (53%) in identifying the presence of HGD at surgical biopsy. Positive and negative predictive values for HGD were 28% and 83%, respectively. HR‐HPV DNA test yielded sensitivity of 100% and specificity of 21%. During interpretation, squamous metaplasia and endocervical cells were seen to show individual staining for p16^INK4a or Ki‐67. Individual staining, when present within three dimensional cellular groups common to SurePath® preparations, can be time‐intensive to interpret necessitating thoughtful examination at high power. The Pap test with HR‐HPV DNA testing is a highly sensitive test. A specific test is needed to prevent false positives and over treatment. The CINtec® system provides a modest increase in specificity beyond HR‐HPV DNA testing. Future study of its appropriateness and cost‐ffectiveness in a treatment algorithm are warranted. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.