ABSTRACT
Infection with high-risk genital human papillomavirus (HPV) types is a major risk factor for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The design of effective immunotherapies requires a greater understanding of how HPV-specific T-cell responses are involved in disease clearance and/or progression. Here, we have investigated T-cell responses to five HPV16 proteins (E6, E7, E4, L1 and L2) in women with CIN or cervical carcinoma directly ex vivo. T-cell responses were observed in the majority (78%) of samples. The frequency of CD4+ responders was far lower among those with progressive disease, indicating that the CD4+ T-cell response might be important in HPV clearance. CD8+ reactivity to E6 peptides was dominant across all disease grades, inferring that E6-specific CD8+ T cells are not vitally involved in disease clearance. T-cell responses were demonstrated in the majority (80%) of cervical cancer patients, but are obviously ineffective. Our study reveals significant differences in HPV16 immunity during progressive CIN. We conclude that the HPV-specific CD4+ T-cell response should be an important consideration in immunotherapy design, which should aim to target preinvasive disease.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/virology , Papillomaviridae/pathogenicity , Papillomavirus Infections/immunology , Uterine Cervical Neoplasms/immunology , Uterine Cervical Neoplasms/virology , Adult , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunotherapy , Male , Middle AgedABSTRACT
This paper describes the case of a malignant retroperitoneal paraganglioma with extensive metastases. The patient presented with a supraclavicular mass and an absence of hypertension. Exclusively raised dopamine metabolites were detected which may be a marker of a malignant process and account for the lack of hypertension.
