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 intraepithe lial neoplasia (CIN II/III) are squamous epithelial cells with mRNA for hum an papillomavirus (HPV)16 and 18 and up-regulated epidermal growth factor r eceptor (EGF-R). Since presence of proteins rather than mRNA may be truly i ndicative 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 immunofluorescen t antibody assay to reliably assess the levels of HPV-E6/E7 and EGF-R prote ins in the cervical biopsies from 12 normal women, five women with CIN I, 1 5 with CIN II/III and ten with cervical cancer. RESULTS: HPV-E6/E7 and EGF-R, when present, were specific to para-basal, ba sal and squamous epithelial cells (negative in stromal cells). Nine of ten women with cervical cancer and 15 (14 CIN II/III; I CIN I) of 20 women with CIN were positive for HPV-E6/E7. All 12 controls were HPV-negative. The co ntrols and six women with CIN (four with CIN I) negative for HPV had low le vels of EGF-R. The only exception was one woman with cervical cancer negati ve for HPV, with high levels of EGF-R. Levels of HPV-E6/E7 and EGF-R were s ignificantly 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-quanti tative immunofluorescent antibody assay for measuring levels of HPV-E6/E7 p roteins and EGF-R in archival cervical biopsies. Our data suggest an associ ation between HPV-E6/E7 and EGF-R.