title: P16INK4a as an adjunct marker in liquid-based cervical cytology.
abstract: Cytological screening for cervical cancer is hampered by high false negative rates. Inter-observer reproducibility needs optimizing. The potential of p16(INK4a) as a biomarker for cervical lesions was examined in a study of liquid-based cytology (LBC), HPV DNA testing by MY09/MY11 consensus PCR and type-specific PCRs and p16(INK4a) immunocytochemistry on a series of 291 patients selected from routine screening. Comparison of the number of p16(INK4a) immunoreactive cells/1,000 cells exhibited a significantly higher mean count in HSIL (8.80 +/- 1.13) than other cytological groups. The mean count of LSIL (1.09 +/- 0.18) was significantly higher than that of the negative group (0.82 +/- 0.40). ASC-H and HSIL combined showed a significantly higher mean count (6.46 +/- 1.17) than negative, ASC, ASC-US and LSIL. The mean count of immunoreactive cells/1,000 cells was significantly higher in HPV16 positive samples (3.22 +/- 0.72) than in samples containing infections with types of unknown malignant potential (0.83 +/- 0.26) or HPV negative samples (1.17 +/- 0.41). The mean count in infections with other high-risk HPV types (2.55 +/- 0.52) was significantly higher than that in HPV negative samples. Receiver-operating characteristic curves yielded a test accuracy (area under curve) of 0.76, 0.79, 0.88 and 0.95 for ASCUS, LSIL, ASC-H/HSIL and HSIL, respectively. Thresholds for 95% sensitivity were at 0.005, 0.007, 0.098 and 0.445 immunopositive cells/1,000 cells for ASCUS, LSIL, ASC-H/HSIL and HSIL, respectively. The 95% specificity threshold for the detection of HSIL was at 1.87 immunopositive cells/1,000 cells. P16(INK4a) immunocytochemistry can be used as an adjunct to LBC in cervical screening, because it has a good diagnostic accuracy to discriminate HSIL and ASC-H from other lesions. It could be used as a surrogate marker of high-risk HPV infections.
authors.affiliation: Department of Pathology, University of Antwerp, Wilrijkstraat 10, B-2650 Antwerp (Edegem), Belgium.
authors.forename: Shaira
authors.initials: S
authors.lastname: Sahebali
authors.forename: Christophe E
authors.initials: CE
authors.lastname: Depuydt
authors.forename: Kurt
authors.initials: K
authors.lastname: Segers
authors.forename: Liliane M
authors.initials: LM
authors.lastname: Moeneclaey
authors.forename: Annie J
authors.initials: AJ
authors.lastname: Vereecken
authors.forename: Eric
authors.initials: E
authors.lastname: Van Marck
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Bogers
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis* / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016130:Immunophenotyping; D008403:Mass Screening / Q000379:methods; D027383:Papillomaviridae / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012372:ROC Curve; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005819:Genetic Markers