RESUMO
PURPOSE: Anogenital intraepithelial neoplasia is a chronic disorder associated with infection by high-risk human papillomavirus (HPV) types. It is frequently multifocal and recurrence after conventional treatment is high. Boosting HPV-specific cell-mediated immune responses may reduce progression to carcinoma and could lead to disease clearance. We have tested the safety, immunogenicity, and efficacy of a recombinant vaccinia candidate vaccine (TA-HPV) in women with anogenital intraepithelial neoplasia. EXPERIMENTAL DESIGN: Twelve women, aged 42-54 years with high-grade HPV-positive vulval or vaginal intraepithelial neoplasia of up to 15 years duration, completed a Phase II study of TA-HPV, a live recombinant vaccinia virus, expressing modified versions of the E6 and E7 open reading frames from HPV-16 and HPV-18. RESULTS: The vaccine was well tolerated. Five of 12 (42%) patients showed at least a 50% reduction in total lesion diameter over 24 weeks with 1 patient showing complete regression of her lesion. Overall, 83% of women showed some improvement with an average decrease in lesion size of 40%. All cases showed an increased IgG titer and T-cell response to the vaccinia virus. An IFN-gamma enzyme-linked immunospot assay using pooled 22-mer peptides spanning HPV-16 E6 and E7 showed an increased specific T-cell response after vaccination in 6 of the 10 cases available for testing. There was no increase in specific cytotoxic response to selected individual HLA class I-restricted HPV-16 E6/7 peptides. CONCLUSIONS: The results suggest that the vaccine may have an effect on HPV-positive vulval intraepithelial neoplasia/vaginal intraepithelial neoplasia and that additional studies are warranted to develop an effective therapeutic vaccine.
Assuntos
Vacinas Anticâncer/uso terapêutico , Carcinoma in Situ/terapia , Proteínas de Ligação a DNA , Papillomaviridae/genética , Infecções por Papillomavirus/terapia , Proteínas Repressoras , Vaccinia virus/genética , Neoplasias Vaginais/terapia , Neoplasias Vulvares/terapia , Adolescente , Adulto , Vacinas Anticâncer/efeitos adversos , Carcinoma in Situ/imunologia , Carcinoma in Situ/virologia , Feminino , Antígeno HLA-A2/imunologia , Antígeno HLA-A2/metabolismo , Humanos , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/imunologia , Papillomaviridae/imunologia , Proteínas E7 de Papillomavirus , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Segurança , Linfócitos T/imunologia , Linfócitos T Citotóxicos/imunologia , Neoplasias Vaginais/imunologia , Neoplasias Vaginais/virologia , Neoplasias Vulvares/imunologia , Neoplasias Vulvares/virologiaRESUMO
Liquid-based cytology (LBC) is currently being marketed as an alternative methodology to replace the conventional PAP smear in cervical cytology. A substantial body of literature exists in support of LBC, some of which is at least partially sponsored by product manufacturers. The majority of published literature in support of LBC employs Bethesda reporting terminology. In this study we have analysed published raw data and presented this in NHSCSP terminology. Claims relating to sensitivity, specificity and smear adequacy have then been considered with reference to this data. Our analysis of existing data does not support the nationwide implementation of LBC at present. Further studies are recommended in order to evaluate the place of this technology within the NHSCSP.
