Staining characteristics of p16INK4a: Is there a correlation with lesion grade or high-risk human papilloma virus positivity?

Abstract

Aim: The aims of this study were to evaluate the efficiency of p16INK4a in showing cervical lesions and to determine any relationship between lesion grade and high-risk human papilloma virus (HR-HPV) infection and p16INK4a staining characteristics. Methods: Immunohistochemical analysis of p16INK4a was performed on 13 low-grade squamous intraepithelial lesions (LSIL), 22 high-grade squamous intraepithelial lesions (HSIL), 23 squamous cell carcinoma (SCC) and 25 normal tissue samples. The distribution, staining pattern and intensity of p16INK4a expression were assessed and correlated with HR-HPV positivity determined by real-time polymerase chain reaction. Results: All HSIL and SCC cases, but only 46.2% of LSIL cases, were positive for p16INK4a. Although positive staining of p16INK4a in showing HR-HPV-positive lesions was statistically significant (P = 0.000), we could not find a significant correlation for distribution (P = 0.319), staining pattern (P = 0.057) or intensity (P = 0.057) of p16INK4a in showing HR-HPV in cervical epithelium. These parameters were correlated only with the increasing grade of the lesion (P = 0.000). Conclusions: p16INK4a is a highly sensitive marker of cervical intraepithelial neoplasia and cervical cancer. There is a good correlation between p16INK4a expression and cervical lesion grade and HR-HPV positivity. The distribution, staining pattern and intensity of this marker are significantly correlated with the increasing grade of cervical lesions, suggesting that diffuse distribution, full thickness staining pattern and strong intensity of this marker are highly supportive of HSIL and cervical cancer, while focal distribution, scattered/basal staining pattern and weak intensity suggest LSIL. However, these parameters are not correlated with HR-HPV status in cervical lesions.