J Gynecol Oncol.  2013 Jul;24(3):215-221. 10.3802/jgo.2013.24.3.215.

p16INK4a immunohistochemistry is a promising biomarker to predict the outcome of low grade cervical intraepithelial neoplasia: comparison study with HPV genotyping

• Nishio S
• Fujii T
• Nishio H
• Kameyama K
• Saito M
• Iwata T
• Kubushiro
• Aoki D

• KMID: 2288527
• DOI: http://doi.org/10.3802/jgo.2013.24.3.215

Abstract

OBJECTIVE
In cervical intraepithelial neoplasia (CIN), p16INK4a immunohistochemistry has been reported to be a useful diagnostic biomarker. However, limited information is available about the association between the p16INK4a immunohistochemistry and the outcomes of CIN. Here, we report p16INK4a immunohistochemistry as an effective biomarker to predict the outcomes of CIN.
METHODS
p16INK4a immunohistochemistry was performed in patients with CIN from January 2000 to August 2009. Among these patients, we have performed a retrospective analysis of the medical records to evaluate the outcome of CIN 1-2 and performed statistical analysis to determine the correlation between p16INK4a expression and the outcomes. We also performed HPV genotyping and analyzed the relation between the infecting human papillomavirus (HPV) genotype and the outcomes.
RESULTS
A total of 244 patients, including 82 with CIN 1, 60 with CIN 2, and 102 with CIN 3, were examined. The rate of p16INK4a overexpression increased with increasing CIN grade, 20.7% for CIN 1, 80.0% for CIN 2, and 89.2% for CIN 3, with significant differences between CIN 1 and CIN 2-3 group. In the 131 CIN 1-2 patients, the progression rate was significantly higher for the patients showing p16INK4a overexpression than for those not showing p16INK4a overexpression (p=0.005); the regression rate was also found to be significantly lower for the patients showing p16INK4a overexpression (p=0.003). High-risk HPV genotypes were detected in 73 patients (73.7%). Both progression and regression rates were not significantly different between the high-risk HPV-positive and HPV-negative groups (p=0.401 and p=0.381, respectively).
CONCLUSION
p16INK4a overexpression was correlated with the outcome of CIN 1-2, and p16INK4a is considered to be a superior biomarker for predicting the outcome of CIN 1-2 compared with HPV genotyping.

Keyword

Biomarker; Cervical intraepithelial neoplasia; Human papillomavirus; Immunohistochemistry; p16INK4a

MeSH Terms

Cervical Intraepithelial Neoplasia
Genotype
Humans
Immunohistochemistry
Medical Records
Retrospective Studies

Figure

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  Fig. 1 Patients. CIN, cervical intraepithelial neoplasia.

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  Fig. 2 p16INK4a immunohistochemistry of cervical biopsy specimens. Immunoreactivity for p16INK4a was classified as negative, weakly positive (A), moderately positive (B), or strongly positive (C) (microscope objective: ×10).

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  Fig. 3 (A) Kaplan-Meier analysis of the cumulative progression rate and follow-up periods in the patients with cervical intraepithelial neoplasia (CIN) 1-2. The progression rate for the patients showing p16INK4a overexpression was significantly higher than that for patients showing no p16INK4a overexpression (p<0.05). (B) The cumulative regression rate and follow-up periods in patients with CIN 1-2. The regression rate for the patients showing p16INK4a overexpression was significantly lower than that for the patients showing no p16INK4a overexpression (p<0.05).

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  Fig. 4 (A) Kaplan-Meier analysis of the cumulative progression rate and follow-up periods (mo) for patients with CIN 1-2 lesions with prevalent high-risk human papillomavirus (HPV) infection. The progression rate in patients with prevalent high-risk HPV was not significantly different from that in patients who were negative for high-risk HPV. (B) The cumulative regression rate and follow-up periods (mo) for patients with CIN 1-2 with high-risk HPV infection. The regression rate in the patients with prevalent high-risk HPV was not significantly different from that in patients who were negative for high-risk HPV infection.

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