title: Evaluation of CINtec PLUS® testing as an adjunctive test in ASC-US diagnosed SurePath® preparations.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Edgerton
authors.forename: Cynthia
authors.initials: C
authors.lastname: Cohen
authors.forename: Momin T
authors.initials: MT
authors.lastname: Siddiqui
mesh_terms: D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D005260:Female; D061809:Human Papillomavirus DNA Tests; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*; D014626:Vaginal Smears
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen