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 < 0.001 vs. controls) in women with advanced CIN II and III (P< 0.05 vs. controls in CIN I) and cervical cancer. The HPV-E6/E7 and EGF-R levels correlated significantly (r = 18.98; P < 0.001, by linear regression analysis).
Conclusion: We have established a highly specific and sensitive semi-quantitative immunofluorescent antibody assay for measuring levels of HPV-E6/E7 proteins and EGF-R in archival cervical biopsies. Our data suggest an association between HPV-E6/E7 and EGF-R.