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dc.contributor.authorWinters, Ursula
dc.contributor.authorDaayana, Sai
dc.contributor.authorLear, John T
dc.contributor.authorTomlinson, Anne E
dc.contributor.authorElkord, Eyad
dc.contributor.authorStern, Peter L
dc.contributor.authorKitchener, Henry C
dc.date.accessioned2009-05-13T16:12:56Z
dc.date.available2009-05-13T16:12:56Z
dc.date.issued2008-08-15
dc.identifier.citationClinical and immunologic results of a phase II trial of sequential imiquimod and photodynamic therapy for vulval intraepithelial neoplasia. 2008, 14 (16):5292-9 Clin. Cancer Res.en
dc.identifier.issn1078-0432
dc.identifier.pmid18698049
dc.identifier.doi10.1158/1078-0432.CCR-07-4760
dc.identifier.urihttp://hdl.handle.net/10541/68066
dc.description.abstractPURPOSE: High-risk human papillomavirus (HPV)-associated vulval intraepithelial neoplasia (VIN) is difficult to treat by excision or ablation because of high recurrence rates. Small studies of photodynamic therapy (PDT) and imiquimod treatments have shown some success and function at least in part through stimulation of local immune responses. Indeed, there is evidence that immunosuppressed individuals have higher rates of VIN, suggesting immune control is relevant. EXPERIMENTAL DESIGN: In the study, 20 women with high-grade VIN were treated with topical imiquimod and the PDT sequentially. Vulval biopsy and blood were taken pretreatment and, after imiquimod and PDT, with follow up for 1 year. Clinical response was assessed by measuring lesion size. Biopsies were analyzed for HPV DNA and tumor-infiltrating lymphocytes including T regulatory cells. RESULTS: The treatment was well-tolerated. There was an overall response rate of 55% by intention treat and 64% per protocol. The 52-week symptom response was 65% asymptomatic, compared with 5% at baseline. The nonresponders showed a significantly higher level of T regulatory cells in the lesions after imiquimod treatment. CONCLUSIONS: The response rates are clinically relevant, and the treatment regimen was feasible for the majority. Initial nonresponders to imiquimod seem to be relatively refractory, and this may derive from their unfavorable local immune environment, in particular, the increased proportions of T regulatory cells, possibly the limiting action and/or development of any HPV T-cell immunity. The potential benefit of this treatment is its ability to treat multifocal disease.
dc.language.isoenen
dc.subjectVulvar Canceren
dc.subject.meshAdministration, Topical
dc.subject.meshAdult
dc.subject.meshAminoquinolines
dc.subject.meshAntigens, CD
dc.subject.meshAntineoplastic Agents
dc.subject.meshCarcinoma in Situ
dc.subject.meshCombined Modality Therapy
dc.subject.meshFemale
dc.subject.meshFluorescent Antibody Technique
dc.subject.meshHumans
dc.subject.meshImmunohistochemistry
dc.subject.meshLymphocytes, Tumor-Infiltrating
dc.subject.meshMiddle Aged
dc.subject.meshPhotochemotherapy
dc.subject.meshT-Lymphocytes, Regulatory
dc.subject.meshVulvar Neoplasms
dc.titleClinical and immunologic results of a phase II trial of sequential imiquimod and photodynamic therapy for vulval intraepithelial neoplasia.en
dc.typeArticleen
dc.contributor.departmentSchool of Cancer and Imaging, University of Manchester, St. Mary's Hospital, Immunology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom.en
dc.identifier.journalClinical Cancer Researchen
html.description.abstractPURPOSE: High-risk human papillomavirus (HPV)-associated vulval intraepithelial neoplasia (VIN) is difficult to treat by excision or ablation because of high recurrence rates. Small studies of photodynamic therapy (PDT) and imiquimod treatments have shown some success and function at least in part through stimulation of local immune responses. Indeed, there is evidence that immunosuppressed individuals have higher rates of VIN, suggesting immune control is relevant. EXPERIMENTAL DESIGN: In the study, 20 women with high-grade VIN were treated with topical imiquimod and the PDT sequentially. Vulval biopsy and blood were taken pretreatment and, after imiquimod and PDT, with follow up for 1 year. Clinical response was assessed by measuring lesion size. Biopsies were analyzed for HPV DNA and tumor-infiltrating lymphocytes including T regulatory cells. RESULTS: The treatment was well-tolerated. There was an overall response rate of 55% by intention treat and 64% per protocol. The 52-week symptom response was 65% asymptomatic, compared with 5% at baseline. The nonresponders showed a significantly higher level of T regulatory cells in the lesions after imiquimod treatment. CONCLUSIONS: The response rates are clinically relevant, and the treatment regimen was feasible for the majority. Initial nonresponders to imiquimod seem to be relatively refractory, and this may derive from their unfavorable local immune environment, in particular, the increased proportions of T regulatory cells, possibly the limiting action and/or development of any HPV T-cell immunity. The potential benefit of this treatment is its ability to treat multifocal disease.


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