Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia.
dc.contributor.author | Daayana, Sai | |
dc.contributor.author | Elkord, Eyad | |
dc.contributor.author | Winters, U | |
dc.contributor.author | Pawlita, M | |
dc.contributor.author | Roden, R | |
dc.contributor.author | Stern, Peter L | |
dc.contributor.author | Kitchener, Henry C | |
dc.date.accessioned | 2010-08-10T15:28:23Z | |
dc.date.available | 2010-08-10T15:28:23Z | |
dc.date.issued | 2010-03-30 | |
dc.identifier.citation | Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia. 2010, 102 (7):1129-36 Br J Cancer | en |
dc.identifier.issn | 1532-1827 | |
dc.identifier.pmid | 20234368 | |
dc.identifier.doi | 10.1038/sj.bjc.6605611 | |
dc.identifier.uri | http://hdl.handle.net/10541/109412 | |
dc.description.abstract | BACKGROUND: Vulval intraepithelial neoplasia (VIN) is a premalignant condition, which is frequently associated with type HPV16 infection, and multifocal disease has high rates of surgical treatment failure. METHODS: We report a phase II clinical trial of the topical immunomodulator, imiquimod, for 8 weeks, followed by 3 doses (weeks 10, 14 and 18) of therapeutic human papillomavirus (HPV) vaccination (TA-CIN, fusion protein HPV16 E6E7L2) in 19 women with VIN grades 2 and 3. Histology and HPV testing of biopsies were performed at weeks 0, 10, 20 and 52. Intralesional infiltration of T-cell subsets and lymphocyte proliferation for HPV systemic immune responses were also assessed. RESULTS: Lesion response (complete regression of VIN on histology) was observed in 32% (6 out of 19) of women at week 10, increasing to 58% (11 out of 19) at week 20 and 63% (12 out of 19) at week 52. At this time, 36% (5 out of 14) of lesions showed HPV16 clearance and 79% (15 out of 19) of women were symptom free. At week 20, after treatment with imiquimod and vaccination, there was significantly increased local infiltration of CD8 and CD4 T cells in lesion responders; in contrast, non-responders (persistent VIN by histology) showed an increased density of T regulatory cells. After vaccination, only lesion responders had significantly increased lympho-proliferation to the HPV vaccine antigens. CONCLUSION: The therapeutic effect of treatment depends on the differential immune response of responders and non-responders with affect locally and systemically. | |
dc.language.iso | en | en |
dc.subject | Anticancerous Combined Chemotherapy Protocols | en |
dc.subject | Vulvar Cancer | en |
dc.subject.mesh | Adolescent | |
dc.subject.mesh | Adult | |
dc.subject.mesh | Aged | |
dc.subject.mesh | Aminoquinolines | |
dc.subject.mesh | Antigens, Viral | |
dc.subject.mesh | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject.mesh | Cancer Vaccines | |
dc.subject.mesh | Carcinoma in Situ | |
dc.subject.mesh | Drug Tolerance | |
dc.subject.mesh | Female | |
dc.subject.mesh | Human papillomavirus 16 | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Middle Aged | |
dc.subject.mesh | Papillomavirus Vaccines | |
dc.subject.mesh | Vulvar Neoplasms | |
dc.subject.mesh | Young Adult | |
dc.title | Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia. | en |
dc.type | Article | en |
dc.contributor.department | Academic Unit of Obstetrics and Gynaecology, University of Manchester, St Mary's Hospital, Whitworth Park, Manchester M13 0JH, UK. | en |
dc.identifier.journal | British Journal of Cancer | en |
html.description.abstract | BACKGROUND: Vulval intraepithelial neoplasia (VIN) is a premalignant condition, which is frequently associated with type HPV16 infection, and multifocal disease has high rates of surgical treatment failure. METHODS: We report a phase II clinical trial of the topical immunomodulator, imiquimod, for 8 weeks, followed by 3 doses (weeks 10, 14 and 18) of therapeutic human papillomavirus (HPV) vaccination (TA-CIN, fusion protein HPV16 E6E7L2) in 19 women with VIN grades 2 and 3. Histology and HPV testing of biopsies were performed at weeks 0, 10, 20 and 52. Intralesional infiltration of T-cell subsets and lymphocyte proliferation for HPV systemic immune responses were also assessed. RESULTS: Lesion response (complete regression of VIN on histology) was observed in 32% (6 out of 19) of women at week 10, increasing to 58% (11 out of 19) at week 20 and 63% (12 out of 19) at week 52. At this time, 36% (5 out of 14) of lesions showed HPV16 clearance and 79% (15 out of 19) of women were symptom free. At week 20, after treatment with imiquimod and vaccination, there was significantly increased local infiltration of CD8 and CD4 T cells in lesion responders; in contrast, non-responders (persistent VIN by histology) showed an increased density of T regulatory cells. After vaccination, only lesion responders had significantly increased lympho-proliferation to the HPV vaccine antigens. CONCLUSION: The therapeutic effect of treatment depends on the differential immune response of responders and non-responders with affect locally and systemically. |