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High-risk Human Papillomavirus E7 Oncoprotein Detection in Cervical Squamous Cell Carcinoma

Authors' Affiliations: ¹ Cell Metabolism and Differentiation Research Group, ² Molecular and Cellular Biology Division, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, ³ Tyrolean Cancer Research Institute and ⁴ Departments of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria; and ⁵ Division of Pathology and Morphologic Tumour Registry, National Health Laboratory, Luxembourg

Requests for reprints: Werner Zwerschke, Institute for Biomedical Aging Research and Tyrolean Cancer Research Institute, Rennweg 10, 6020 Innsbruck, Austria. Phone: 43-51258-391932; Fax: 43-51258-39198; E-mail: werner.zwerschke{at}oeaw.ac.at.

Purpose: Persistent infections by high-risk human papillomavirus (HPV) types are the main etiologic factor for cervical cancer. The objective of this study was to evaluate whether high-risk E7 oncoprotein is adequate as a marker for the detection of cervical cancer.

Experimental Design: HPV typing was done in biopsies from 58 cervical carcinoma and 22 normal cervical squamous epithelia. The HPV-16 E7, HPV-18 E7, and HPV-45 E7 oncoprotein levels were monitored by immunohistochemistry and compared with those of p16^INK4a and Ki67.

Results: Fifty-five (94.8%) tumors were high-risk HPV-DNA–positive (46 HPV-16, 2 HPV-16 and HPV-18, 4 HPV-18, 1 HPV-33, and 2 HPV-45). HPV-DNA could not be detected in three tumors (5.2%). High HPV E7 oncoprotein levels were shown in 57 cervical cancers (98.3%), without correlation between expression levels and tumor stages.

Conclusion: This is the first study which systematically analyzes the levels of the major HPV oncoproteins in cervical carcinomas demonstrating that the high-risk HPV E7 proteins are regularly expressed in these cancers. This suggests that high-risk E7 oncoproteins are necessary for cervical cancers and apparently essential as tumor marker.