title: Alterations of T-cell surface markers in older women with persistent human papillomavirus infection.
abstract: We previously reported decreased lymphocyte proliferative responses among older women with persistent human papillomavirus (HPV) infection. To characterize the phenotype of peripheral lymphocytes associated with persistent HPV infection, we evaluated the expression of different cell surface markers in peripheral blood mononuclear cells (PBMCs) from a case-control study within a 10,049 woman population-based cohort study in Guanacaste, Costa Rica. Women in the cohort aged 46-74 and with HPV results at their 5th year anniversary visit were considered, and all women (n = 87) with persistent HPV infections, all women (n = 196) with transient HPV infections and a random sample of HPV DNA-negative women (n = 261) frequency-matched to cases on age were selected for this study. A median of 3 years after the case-control matching visit, cervical cells were collected for liquid-based cytology and repeat HPV DNA genotyping. Blood was obtained from which PBMCs were extracted and cryopreserved for immunological phenotyping via flow cytometry. Significant increases in risk of HPV persistence were observed for 3 marker subsets indicative of immune cell activation/differentiation. Relative risk estimates were 5.4 (95% CI = 2.2-13.3) for CD69(+)CD4(+), 2.6 (95% CI = 1.2-5.9) for HLADR(+)CD3(+)CD4(+) and 2.3 (95% CI = 1.1-4.7) for CD45RO(+)CD27(-)CD8(+). A significant decrease in HPV persistence was observed for a subset marker indicative of an immature, undifferentiated memory state CD45RO(+)CD27(+)CD4(+) (OR = 0.36; 95% CI = 0.17-0.76). Adjustment for these markers only partially explained the previously reported association between decreased lymphoproliferative responses and persistent HPV infection. Whether phenotypic alterations observed predispose to HPV persistence or result from it should be the focus of future studies.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. acrodriguez@racsa.co.cr
authors.forename: Ana Cecilia
authors.initials: AC
authors.lastname: Rodríguez
authors.forename: Alfonso J
authors.initials: AJ
authors.lastname: García-Piñeres
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.forename: Matthew
authors.initials: M
authors.lastname: Trivett
authors.forename: Marcus
authors.initials: M
authors.lastname: Williams
authors.forename: Ivannia
authors.initials: I
authors.lastname: Atmella
authors.forename: Margarita
authors.initials: M
authors.lastname: Ramírez
authors.forename: Maricela
authors.initials: M
authors.lastname: Villegas
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Robert
authors.initials: R
authors.lastname: Burk
authors.forename: Enrique
authors.initials: E
authors.lastname: Freer
authors.forename: José
authors.initials: J
authors.lastname: Bonilla
authors.forename: Concepción
authors.initials: C
authors.lastname: Bratti
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
mesh_terms: D000328:Adult; D000368:Aged; D052685:Alphapapillomavirus / Q000235:genetics / Q000302:isolation & purification; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D002908:Chronic Disease; D015331:Cohort Studies; D003127:Colposcopy; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000276:immunology*; D016133:Polymerase Chain Reaction / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology*; D014412:Tumor Virus Infections / Q000235:genetics; D002578:Uterine Cervical Dysplasia / Q000150:complications / Q000235:genetics
chemical_list: D015703:Antigens, CD; D004279:DNA, Viral
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