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

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. Copyright (C) 2009 S. Karger AG, Basel