Human Papilloma Virus (HPV)-E6/E7 and Epidermal Growth Factor Receptor (EGF-R) Protein Levels in Cervical Cancer and Cervical Intraepithelial Neoplasia (CIN)

BACKGROUND: About 90% of cervical cancers and advanced cervical intraepithelial neoplasia (CIN II/III) are squamous epithelial cells with mRNA for human papillomavirus (HPV)16 and 18 and up-regulated epidermal growth factor receptor (EGF-R). Since presence of proteins rather than mRNA may be truly indicative of active infection or disease progression, establishing reliable methods for quantifying these proteins in cervical biopsies is important. METHOD: We have established an objective semi-quantitative immunofluorescent antibody assay to reliably assess the levels of HPV-E6/E7 and EGF-R proteins in the cervical biopsies from 12 normal women, five women with CIN I, 15 with CIN II/III and ten with cervical cancer. RESULTS: HPV-E6/E7 and EGF-R, when present, were specific to para-basal, basal and squamous epithelial cells (negative in stromal cells). Nine of ten women with cervical cancer and 15 (14 CIN II/III; 1 CIN I) of 20 women with CIN were positive for HPV-E6/E7. All 12 controls were HPV-negative. The controls and six women with CIN (four with CIN I) negative for HPV had low levels of EGF-R. The only exception was one woman with cervical cancer negative for HPV, with high levels of EGF-R. Levels of HPV-E6/E7 and EGF-R were significantly higher (P