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Immunological and viral factors assiciated with the response of vulval intraepithelial neoplasia to photodynamic therapy.

Abdel-Haidy, El-Said and Martin-Hirsch, Pierre L. and Duggan-Keen, Maggie and Stern, Peter L. and Moore, James V. and Corbitt, Gerald and Kitchener, Henry C. and Hampson, Ian N. (2001) Immunological and viral factors assiciated with the response of vulval intraepithelial neoplasia to photodynamic therapy. Cancer Research, 61 (1). pp. 192-196. ISSN 0008-5472

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Abstract

Topical 5-aminolevulinic acid-based photodynamic therapy (PDT) has produced complete response rates of >90% for nonmelanoma skin carcinomas, which are mostly human papillomavirus (HPV) negative. Using a similar treatment protocol, we observed a short-term response in only one third (10 of 32) of high-grade vulval intraepithelial neoplasia (VIN 2–3) lesions. Unifocal lesions were found more responsive than multifocal and pigmented lesions. Animal model studies have suggested that long-term PDT response involves an immune reaction in which CTLs play a crucial role. In this study, we have assessed: (a) HPV infection; (b) HLA expression; and (c) immune infiltrating cells in VIN biopsies from responders and nonresponders to determine whether these factors may limit response to topical 5-aminolevulinic acid-based PDT. Tissues from normal vulva (n = 9), vulval carcinoma (n = 11), and VIN (32 patients from which 19 pre- and 43 post-PDT biopsies were taken) were investigated for immune cell infiltration and HLA class I expression by immunohistochemistry and HPV infection by PCR. There was a greater likelihood of HPV positivity associated with a lack of response of VIN to PDT (P = 0.002), and VIN nonresponders were more likely to show HLA class I loss compared with responders (P = 0.030). HLA class I down-regulation was significantly greater in the carcinomas (82%, total loss) than the VIN (28%, 19%, total loss; and 9%, allele loss; P = 0.004). None of the cases with class I down-regulation responded to PDT, whereas 3 of 6 (50%) of cases that showed total class I loss subsequently developed superficial invasion. Compared with normal vulval skin, VIN lesions showed increased infiltration by CD4 (T-helper) and CD68 (macrophages) but not CD1a (Langerhans cells) or CD8 (CTLs). There was, however, a significant increase of CD8 infiltration in posttreatment VIN responders compared with nonresponders (P = 0.0001). These data clearly support the contention that high-risk HPV infection and lack of cell-mediated immunity may play a role in the observed poor response of lower genital lesions to topical PDT.

Item Type: Article
Journal or Publication Title: Cancer Research
Additional Information: RAE_import_type : Journal article RAE_uoa_type : Allied Health Professions and Studies
Subjects: R Medicine > R Medicine (General)
Departments: Faculty of Science and Technology > Lancaster Environment Centre
Faculty of Health and Medicine
Faculty of Arts & Social Sciences > History
ID Code: 2029
Deposited By: ep_importer
Deposited On: 05 Feb 2010 14:05
Refereed?: Yes
Published?: Published
Last Modified: 26 Jul 2012 15:38
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/2029

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