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dc.contributor.authorDaayana, Sai*
dc.contributor.authorElkord, Eyad*
dc.contributor.authorWinters, U*
dc.contributor.authorPawlita, M*
dc.contributor.authorRoden, R*
dc.contributor.authorStern, Peter L*
dc.contributor.authorKitchener, Henry C*
dc.date.accessioned2010-08-10T15:28:23Z
dc.date.available2010-08-10T15:28:23Z
dc.date.issued2010-03-30
dc.identifier.citationPhase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia. 2010, 102 (7):1129-36 Br J Canceren
dc.identifier.issn1532-1827
dc.identifier.pmid20234368
dc.identifier.doi10.1038/sj.bjc.6605611
dc.identifier.urihttp://hdl.handle.net/10541/109412
dc.description.abstractBACKGROUND: 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.isoenen
dc.subjectAnticancerous Combined Chemotherapy Protocolsen
dc.subjectVulvar Canceren
dc.subject.meshAdolescent
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAminoquinolines
dc.subject.meshAntigens, Viral
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols
dc.subject.meshCancer Vaccines
dc.subject.meshCarcinoma in Situ
dc.subject.meshDrug Tolerance
dc.subject.meshFemale
dc.subject.meshHuman papillomavirus 16
dc.subject.meshHumans
dc.subject.meshMiddle Aged
dc.subject.meshPapillomavirus Vaccines
dc.subject.meshVulvar Neoplasms
dc.subject.meshYoung Adult
dc.titlePhase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia.en
dc.typeArticleen
dc.contributor.departmentAcademic Unit of Obstetrics and Gynaecology, University of Manchester, St Mary's Hospital, Whitworth Park, Manchester M13 0JH, UK.en
dc.identifier.journalBritish Journal of Canceren
html.description.abstractBACKGROUND: 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.


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