Immunological responses to cervical neoplasia : immunological status of patients with cervical carcinoma and HPV-specific cytotoxic lymphocyte responses in women with cervical neoplasia

Fiander, Alison Nina (1997) Immunological responses to cervical neoplasia : immunological status of patients with cervical carcinoma and HPV-specific cytotoxic lymphocyte responses in women with cervical neoplasia. University of Southampton, Doctoral Thesis.

Abstract

Half a million new cases of cervical cancer are diagnosed annually World-wide; with optimal management the five year survival is 58%. In Developing countries cervical carcinoma is the commonest female malignancy with a lifetime risk approaching 1 in 15. In the absence of adequate health care facilities, incidence and mortality figures equate. Alternate treatment modalities are therefore urgently awaited.

There is a close association between Human Papilloma Virus infection (HPV) and cervical carcinogenesis; the HPV E6 and E7 proteins interacting with the cellular regulatory proteins, p53 and Rb respectively. E6 and E7 are consistently expressed by neoplastic HPV-infected cells, serving as tumour-specific markers and as targets for immunotherapy. The importance of immunological control in HPV-associated disease is inferred from histological evidence of an immune response around regressing lesions and by the increased incidence of HPV-related disease in immunosuppressed individuals. However, there are few reports of HPV-specific T cell responses in the literature. Evidence of HPV-specific cytotoxic lymphocyte (CTL) activity presented here, in patients with cervical intraepithelial neoplasia.

Eight patients with late stage invasive disease were immunised with a recombinant vaccinia virus encoding HPV16 & 18 E6 and E7 genes. All patients mounted a serological reaction to the vector while three patients showed a definite anti-HPV serological response. Of three evaluable patients one showed an HPV-specific CTL response nine weeks after vaccination. No serious adverse events occurred and environmental release was contained. During the vaccine study evidence of immune compromise was noted amongst patients with cervical carcinoma. Systematic investigation for different disease stages revealed a pan T cell deficit, related to tumour load. This has implications for the safety and efficacy of future immunotherapeutic intervention.

This record has no associated files available for download.

Contributors

Download statistics