P16INK4a as an adjunct marker in liquid‐based cervical cytology

• Published in: International journal of cancer 2004-03, Vol.108 (6), p.871-876
• Main Authors: Sahebali, Shaira, Depuydt, Christophe E., Segers, Kurt, Moeneclaey, Liliane M., Vereecken, Annie J., Van Marck, Eric, Bogers, Johannes J.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biomarkers, Tumor - genetics; cervical cytology; Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Female; Genetic Markers; Genital system. Mammary gland; human papillomavirus; Humans; Immunohistochemistry - methods; Immunophenotyping; Investigative techniques, diagnostic techniques (general aspects); Mass Screening - methods; Medical sciences; molecular marker; p16INK4a; Papillomaviridae - metabolism; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; PCR; Polymerase Chain Reaction; ROC Curve; Sensitivity and Specificity; Uterine Cervical Neoplasms - diagnosis; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - virology
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.11589

Cytological screening for cervical cancer is hampered by high false negative rates. Inter‐observer reproducibility needs optimizing. The potential of p16INK4a 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 p16INK4a immunocytochemistry on a series of 291 patients selected from routine screening. Comparison of the number of p16INK4a 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. P16INK4a 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. © 2003 Wiley‐Liss, Inc.