title: The expression of p16 (INK4a) and Ki-67 in relation to high-risk human papilloma viral load and residual disease after conization with positive margins.
abstract: The purpose of this study was to investigate the correlations between high-risk human papillomavirus (HPV) load and p16 (INK4a) or Ki-67, and to identify biomarkers that may predict residual disease after conization with positive margins. The following samples were analyzed: 49 paraffin-embedded specimens from patients with cervical intraepithelial neoplasia (CIN), including 12 CIN 2 conization specimens and 37 CIN 3 conization specimens. Immunohistochemical analysis was performed with antibodies to p16 (INK4a) and Ki-67. Hybrid Capture II testing was used to detect high-risk HPV DNA. The mean HPV loads within each of the p16 (INK4a)-staining cases were 9.5 (relative light units/positive control) RLU/PC for negative staining, 531.8 RLU/PC for 1+ staining, 140.2 RLU/PC for 2+ staining, and 545.1 RLU/PC for 3+ staining. HPV loads differed significantly according to p16 (INK4a) expression (P = 0.0021). The mean HPV loads within Ki-67 staining cases were 28.2 RLU/PC for 1+ staining, 189.6 RLU/PC for 2+ staining, and 563.3 RLU/PC for 3+ staining. HPV loads differed significantly according to Ki-67 expression (P = 0.0259). The expression of p16 (INK4a) (P = 0.0012) and Ki-67 (P = 0.0006) were significantly associated with the CIN grade. In univariate and multiple logistic regression analysis, age, parity, cytology, lesion grade in the cone, high-risk HPV load, and the expression of p16 (INK4a) and Ki-67 were not significantly associated with residual lesions after conization with positive margins (P > 0.05). In conclusion, high-risk HPV load showed significant differences according to the expression of p16 (INK4a) and Ki-67, while none of the prognostic factors were significantly associated with residual disease after conization with positive margins.
authors: Department of Obstetrics and Gynecology, School of Medicine, Korea University, Seoul, Republic of Korea.
authors: S-H
authors: SH
authors: Song
authors: H-M
authors: HM
authors: Park
authors: D-W
authors: DW
authors: Eom
authors: J-K
authors: JK
authors: Lee
authors: N-W
authors: NW
authors: Lee
authors: A-R
authors: AR
authors: Kim
authors: J-Y
authors: JY
authors: Hur
authors: K-W
authors: KW
authors: Lee
authors: Y-K
authors: YK
authors: Park
authors: H-S
authors: HS
authors: Saw
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D019092:Conization / Q000379:methods; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008875:Middle Aged; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D012306:Risk; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery / Q000821:virology*; D019562:Viral Load; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology / Q000601:surgery / Q000821:virology*
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen