Detection and pathological value of papillomavirus DNA and p16INK4A and p53 protein expression in cervical intraepithelial neoplasia

Abstract

The aim of the present study was to investigate human papillomavirus (HPV) infection and p16INK4A and p53 protein expression, to evaluate their roles in the pathological diagnosis and grading for cervical intraepithelial neoplasia (CIN). The detection of HPV DNA and p16INK4A and p53 protein expression were examined in a panel of clinical tissue samples using polymerase chain reaction or immunohistochemistry. In 104 cases, HPV16/18 DNA was identified in 49.0% and HPV6/11 DNA in 9.6% of cases. While in 203 cases, 74.4% positively expressed p16INK4A and 47.3% positively expressed p53. The expression of p16INK4A exhibited a significantly higher rate in the CIN I group than in the squamous metaplasia coupled with hyperplasia group (SMH; P<0.0001) and the CIN II–III group (P=0.005). A marked correlation was revealed between the band-like staining pattern of p16INK4A and HPV16/18 infection. On the contrary, p53 expression was not found to significantly correlate with CIN grade or the HPV16/18 infection status. These results suggested that p16INK4A expression correlates with a higher grade of CIN and may be used as a diagnostic marker to distinguish between CIN I and SMH, as well as between CIN I and CIN II–III.

The Association and Significance of p53 in Gynecologic Cancers: The Potential of Targeted Therapy

“…Clinically, immunohistochemical analysis of p53 has been performed in cervical lesions [39,40,41,42,43,44,45,46,47]. Silva et al summarized nine studies on p53 immunohistochemistry in cervical lesions [48].…”

“…Two studies demonstrated that the positive intensity and cells showing p53 expression were increased in accordance with the progression of CIN [40,44]. However, the remaining studies showed no significant differences among normal cervical epithelium, dysplasia, and cancer [39,42,43,44,45]. Dysfunction of p53 by E6 and E7 leads to the promotion of degradation, not TP53 mutation, so it may be difficult to detect p53 expression by immunohistochemistry.…”

The Role of Carcinogenesis-Related Biomarkers in the Wnt Pathway and Their Effects on Epithelial–Mesenchymal Transition (EMT) in Oral Squamous Cell Carcinoma

“…In recent studies, various biomarkers have been used to identify PMDs, including the kinase inhibitor of cyclin-dependence p16INK4a protein (p16) [16], nuclear protein ki67 [17], and the tumor suppressor p53 [18]. Additionally, functional dysregulation of genes of the wingless (Wnt) signaling pathway can promote PMD development and progression [19].…”

Epstein-Barr virus, human papillomavirus and herpes simplex virus 2 co-presence severely dysregulates miRNA expression

“…P16 regulates the cell cycle by acting as a cyclin-dependent kinase inhibitor and has been used as an alternative biomarker for HPV testing. 10 , 11 Thus, serum samples that were positive and negative for p16 (from previous a study) were also used as internal positive and negative controls for HPV testing. p16 kit-included positive and negative controls were considered as external controls (Bioassay Technology Laboratory, Yangpu, Shangai, China).…”