Lymphoproliferative response to fusion proteins of human papillomaviruses in patients with cervical intraepithelial neoplasia

Abstract

The cell-mediated immune response (CMI) to E6 and E4 fusion proteins of human papillomavirus type 16 (HPV-16), E6 fusion protein of HPV-18, and to control proteins similarly produced, was analysed in 29 patients with cervical intraepithelial neoplasia (CIN) and in 15 age-matched laboratory personnel using a lymphocyte proliferation assay (LPA). Compared to controls without any added proteins, a positive response (stimulation index greater than 2.0) to the highly purified E6 control protein was found in only one patient. Positive responses to the E4 control protein which contained beta-galactosidase were noted in three patients and two controls. With control proteins as baseline, the lymphocytes from nine patients (28%) and three laboratory personnel (20%) responded to at least on HPV fusion protein after 7 days in culture. Stimulation indices were low in both groups with a range of 2.06-4.69 and the difference in incidence of positive responses between the groups is not significant. Proliferative responses to HPV-1 and HPV-2 virion antigens were noted in 6/23 (26%) of the patients and 2/15 (18%) of the other group. No correlation between responsiveness and degree of dysplasia or presence of koilocytes was found in the patient group. The relevance of the low proliferative responses is discussed.