p16^ink4a Is a Surrogate Marker for High-Risk and Malignant Cervical Lesions in the Presence of Human Papillomavirus

Abstract

Objective: To strengthen the role of high-risk human papillomaviruses (HPVs) in the development of cervical cancer, and the association between HPV and the cell cycle inhibitor gene p16^ink4a in cervical carcinogenesis. Methods: In this study, the association between p16^ink4a and the presence of HPV DNA in cervical lesions was investigated in a total of 177 cervical biopsies classified as benign (n = 42), low-grade squamous intraepithelial lesions (LSIL; n = 34), high-grade squamous intraepithelial lesions (HSIL; n = 48) and invasive cancer (n = 53). p16^ink4a expression was analyzed by immunohistochemistry while HPV DNA was localized by in situ hybridization. Results: No significant association was found between p16^ink4a expression and HPV presence in benign and LSIL samples. In HSIL and invasive cancer, a significant association was found between p16^ink4a overexpression and the presence of HPV DNA. Conclusion: Immunohistochemical p16^ink4a expression is associated with HPV infection in HSIL and cervical cancer, suggesting a role of p16 as a biomarker of HPV-associated cervical lesions.

High-Risk Human Papillomavirus in Esophageal Squamous Cell Carcinoma

“…Overexpression of cellular p16 INK4a has previously been linked with HPV oncogene activity, especially in cervical cancer (30,39), and has been used as a confirmatory test (40). We found that four of our eight HPV-positive ESCC cases overexpressed p16 INK4a .…”

“…INK4a overexpression, a widely accepted test for HPV oncogene expression (30). Tissue sections (4 μm) were mounted onto Superfrost Plus slides and stained with a monoclonal p16…”

The prevalence of human papillomavirus in oral premalignant lesions and squamous cell carcinoma in comparison to cervical lesions used as a positive control

“…This leads to an increase in the p16 INK4a tumor suppressor protein [18,19]. Immunohistochemical analysis of p16 INK4a is a reliable indicator of HPV-associated lesions and is useful as a marker of high-risk HPV in cervical dysplasia and SCC [19,[34][35][36][37]. Moreover, Gologan et al [38] have shown that p16 INK4a can be used as a potential marker to aid in the identification of the presence of dysplasia in oral lesions, and Cunningham et al [39] have described that the immunohistochemical detection of p16 INK4a is a potentially reliable assay for diagnosing HPV-induced oral high-grade dysplasia.…”

Cutaneous metastases from cervical squamous cell carcinoma in a 55 year-old woman: a rarely reported manifestation

“…Immunohistochemical markers for P16 may be used in these situations to help elucidate whether or not this tumor represents metastatic disease. P16/INK4a (CDKN2A), a cyclin-dependent kinase that is dysregulated in high-risk human papillomavirus (HPV) infection [19] , accumulates within infected cells, and is thus amenable to detection by immunohistochemical methods and is often utilized as a surrogate marker for infection with high-risk HPV strains and/or detection of HPV-related malignancies [22] . Figure 4 demonstrates that in the biopsies from our patient, the nests of tumor within the dermis stained strongly and diffusely for p16, while the overlying epidermis was completely negative, ruling out the presence of a second primary squamous cell carcinoma.…”