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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
  1. S.-H. Song*,
  2. H.-M. Park,
  3. D.-W. Eom,
  4. J.-K. Lee*,
  5. N.-W. Lee*,
  6. A.-R. Kim§,
  7. J.-Y. Hur*,
  8. K.-W. Lee*,
  9. Y.-K. Park* and
  10. H.-S. Saw*
  1. *Department of Obstetrics and Gynecology, School of Medicine, Korea University, Seoul, Republic of Korea; Departments of
  2. Obstetrics and Gynecology and
  3. Pathology, School of Medicine, Ulsan University, Gangneung, Republic of Korea; and
  4. §Department of Pathology, School of Medicine, Korea University, Seoul, Republic of Korea
  1. Address correspondence and reprint requests to: Ho-Suk Saw, MD, PhD, Department of Obstetrics and Gynecology, School of Medicine, Korea University, Guro Hospital Guro-Dong, Guro-Gu, Seoul 152–703, Republic of Korea. Email: sawhs{at}korea.co.kr

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.

  • conization
  • HPV
  • Ki-67
  • p16 (INK4a)
  • viral load

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