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

2.50
Hdl Handle:
http://hdl.handle.net/10541/85568
Title:
Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy.
Authors:
Abdel-Hady, El-Said; Martin-Hirsch, Pierre; Duggan-Keen, Margaret F; Stern, Peter L; Moore, James V; Corbitt, Gerald; Kitchener, Henry C; Hampson, Ian N
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.
Affiliation:
University of Manchester, Academic Department of Obstetrics and Gynaecology and Reproductive Health Care, St. Mary's Hospital, United Kingdom.
Citation:
Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy. 2001, 61 (1):192-6 Cancer Res.
Journal:
Cancer Research
Issue Date:
1-Jan-2001
URI:
http://hdl.handle.net/10541/85568
PubMed ID:
11196160
Type:
Article
Language:
en
ISSN:
0008-5472
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorAbdel-Hady, El-Saiden
dc.contributor.authorMartin-Hirsch, Pierreen
dc.contributor.authorDuggan-Keen, Margaret Fen
dc.contributor.authorStern, Peter Len
dc.contributor.authorMoore, James Ven
dc.contributor.authorCorbitt, Geralden
dc.contributor.authorKitchener, Henry Cen
dc.contributor.authorHampson, Ian Nen
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.en
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

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.