High-risk human papillomavirus E7 oncoprotein detection in cervical squamous cell carcinoma

Clin Cancer Res. 2007 Dec 1;13(23):7067-72. doi: 10.1158/1078-0432.CCR-07-1222.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antibodies, Viral / chemistry
  • Antibodies, Viral / immunology
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology*
  • Cell Cycle / physiology
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • DNA, Viral / analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Mice
  • Middle Aged
  • NIH 3T3 Cells
  • Neoplasm Staging
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification*
  • Papillomavirus E7 Proteins / analysis*
  • Papillomavirus E7 Proteins / biosynthesis
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / virology
  • Polymerase Chain Reaction
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology*

Substances

  • Antibodies, Viral
  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • Ki-67 Antigen
  • Papillomavirus E7 Proteins