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dc.contributor.authorAbdel-Hady, El-Said
dc.contributor.authorMartin-Hirsch, Pierre
dc.contributor.authorDuggan-Keen, Margaret F
dc.contributor.authorStern, Peter L
dc.contributor.authorMoore, James V
dc.contributor.authorCorbitt, Gerald
dc.contributor.authorKitchener, Henry C
dc.contributor.authorHampson, Ian N
dc.date.accessioned2009-11-06T15:11:47Z
dc.date.available2009-11-06T15:11:47Z
dc.date.issued2001-01-01
dc.identifier.citationImmunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy. 2001, 61 (1):192-6 Cancer Res.en
dc.identifier.issn0008-5472
dc.identifier.pmid11196160
dc.identifier.urihttp://hdl.handle.net/10541/85568
dc.description.abstractTopical 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.
dc.language.isoenen
dc.subjectTumour Virus Infectionsen
dc.subjectVulvar Canceren
dc.subject.meshAdolescent
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAminolevulinic Acid
dc.subject.meshCD4-Positive T-Lymphocytes
dc.subject.meshCD8-Positive T-Lymphocytes
dc.subject.meshDNA, Viral
dc.subject.meshFemale
dc.subject.meshHLA Antigens
dc.subject.meshHistocompatibility Antigens Class I
dc.subject.meshHumans
dc.subject.meshLangerhans Cells
dc.subject.meshMiddle Aged
dc.subject.meshPapillomaviridae
dc.subject.meshPapillomavirus Infections
dc.subject.meshPhotochemotherapy
dc.subject.meshPhotosensitizing Agents
dc.subject.meshTumor Virus Infections
dc.subject.meshVulvar Neoplasms
dc.titleImmunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy.en
dc.typeArticleen
dc.contributor.departmentUniversity of Manchester, Academic Department of Obstetrics and Gynaecology and Reproductive Health Care, St. Mary's Hospital, United Kingdom.en
dc.identifier.journalCancer Researchen
html.description.abstractTopical 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.


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