An analysis on the combination expression of HPV L1 capsid protein and p16^INK4a in cervical lesions

Abstract

Human papillomavirus (HPV) infection in cervix is the most important reason for cervical cancer, but only 2% cervical HPV infection will develop into cervical cancer. So how to identify patients at risk of progressive cervical lesions from those infected with HPV to avoid over treatment is a big issue in clinic. The aims of this study were to detect the expression of HPV L1 capsid protein and p16(INK4a) in cervical lesions and to investigate the combination expression of HPV L1 capsid protein and p16(INK4a) in cervical lesions and its diagnostic efficiency in clinic. Immunochemical method was used to detect the expression of HPV L1 capsid protein and p16(INK4a) in 169 cases of abnormal cytology. Histopathologic test was performed to identify cervical lesions of all the cases. chi(2) test and spearman's rank correlation were used for statistical analysis. The diagnostic sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), accuracy, and the area under the receive operating characteristic (ROC) curve (denoted by A(Z)) were calculated with SPSS 13.0. All the statistical tests were two sided at the 5% level of significance. L1 expression decreased (P < 0.001), but p16(INK4a) expression increased (P < 0.001) with histopathologic diagnosis increasing. The expression rates of HPV L1 capsid protein, p16(INK4a), and L1(-)/p16(+) in cervical intraepithelial neoplasia (CIN)2, CIN3, and squamous-cell carcinoma were statistically different from those in CIN1 (P < 0.001). The expressions of HPV L1 capsid protein, L1(+)/p16(+), L1(+)/p16(-), and L1(-)/p16(-) were negatively correlated with the severity of cervical lesions (P < 0.001), whereas the expressions of p16(INK4a) and L1(-)/p16(+) were positively correlated with the severity of cervical lesions (P < 0.001). The specificity and A(Z) of combining L1 with p16 (INK4a) were statistically higher than L1 or p16 (INK4a) alone (P < 0.05). L1 and p16(INK4a) are useful biomarkers for the early diagnosis of cervical lesions. The combination of L1 and p16(INK4a) has a higher diagnostic accuracy than L1 or p16(INK4a) alone in diagnosis of cervical lesions.

Immunostaining of p16INK4a/Ki-67 and L1 Capsid Protein on Liquid-based Cytology Specimens Obtained from ASC-H and LSIL-H Cases

“…In the current study, L1 capsid protein negativity in LBCS correlated with follow-up CIN2+ ( P =0.02). This result is consistent with a study in which L1 capsid protein expression in cervical cytology negatively correlated with cervical lesion severity 9.…”

“…Immunocytochemistry for the presence of L1 capsid protein was performed using the Cytoactive ® HPV L1 screening set (Cytoimmun Diagnostics GmbH, Pirmasens, Germany) according to manufacturer's protocols 9. The L1 antibody recognizes the major L1 capsid protein of 28 HPV types including types 6, 11, 16, 18, 31, and 45.…”

Differential Methylation of the HPV 16 Upstream Regulatory Region during Epithelial Differentiation and Neoplastic Transformation

“…These included: i.) HPV infected epithelium without any morphological changes and no obvious signs of viral replication [44], [45], ii.) cervical intraepithelial low grade lesions (sometimes referred to as flat condylomas) lacking diffuse p16 INK4a immuno-reactivity but displaying koilocytes or HPV 16 L1 capsid protein expression in superficial squamous cells as indicator for permissive HPV-infections and iii.)…”

Using Biomarkers as Objective Standards in the Diagnosis of Cervical Biopsies

“…Many studies 9, 12, 13, 16, 17, 20, 30 have provided evidence that Ki-67 and p16 INK4a immunohistochemistry are valuable adjunctive aids in the diagnosis of difficult cervical biopsies. However, virtually none of these studies take into account the realities of diagnostic variation and the confounding effect of autocorrelation.…”

“…Several candidate biomarkers, such as HPV L1, p16 INK4a , and Ki-67 as well as others, have been proposed for use on cytologic or histologic specimens based on promising preliminary results. 9, 13, 16, 17, 20, 30…”