title: Lymphoid follicles are generated in high-grade cervical dysplasia and have differing characteristics depending on HIV status.
abstract: The exact role of the mucosal immune response in the pathogenesis of human papillomavirus (HPV)-related premalignant and malignant diseases of the genital tract is poorly understood. We used immunohistochemical analysis to characterize immune cells in normal cervix (N = 21), HIV-negative high-grade dysplasia (N = 21), and HIV-positive high-grade dysplasia (N = 30). Classical germinal centers were present in 4.7% of normal cervix, 33% of high-grade lesions from HIV-negative women, and 3.3% of high-grade lesions from HIV-positive women (P = 0.003). HPV16 E7 antigen was detected in a subset of germinal centers, indicating that the secondary immune response was directed in part against HPV. Lymphoid follicles were present in 9.5% of normal cervix, 57% of HIV-negative high-grade dysplasia, and 50% of HIV-positive high-grade dysplasia (P = 0.001 normal versus high-grade). A novel type of lymphoid aggregate, consisting predominantly of CD8(+) T cells, was detected in 4.8% of normal cervix, 0% of HIV-negative high-grade dysplasia, and 40% of HIV-positive high-grade dysplasia (P < 0.001). The recurrence rate of high-grade dysplasia within one year was significantly higher in women with such CD8(+) T cell-dominant aggregates (P = 0.02). In summary, the types of lymphoid follicle in lesions from HIV-positive women were significantly different from those from HIV-negative women, and these differences are associated with the worse clinical outcome in HIV-positive women.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco, California 94143-0128, USA.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Teresa
authors.initials: T
authors.lastname: Darragh
authors.forename: Brian
authors.initials: B
authors.lastname: Herndier
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Howard
authors.initials: H
authors.lastname: Minkoff
authors.forename: Mardge
authors.initials: M
authors.lastname: Cohen
authors.forename: Mary
authors.initials: M
authors.lastname: Young
authors.forename: Alexandra
authors.initials: A
authors.lastname: Levine
authors.forename: Linda Ahdieh
authors.initials: LA
authors.lastname: Grant
authors.forename: William
authors.initials: W
authors.lastname: Hyun
authors.forename: Vivian
authors.initials: V
authors.lastname: Weinberg
authors.forename: Ruth
authors.initials: R
authors.lastname: Greenblatt
authors.forename: Karen
authors.initials: K
authors.lastname: Smith-McCune
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002584:Cervix Uteri / Q000473:pathology*; D005260:Female; D018858:Germinal Center / Q000473:pathology; D018023:HIV Seronegativity; D006679:HIV Seropositivity; D006801:Humans; D007150:Immunohistochemistry; D008221:Lymphoid Tissue / Q000473:pathology*; D012016:Reference Values; D002578:Uterine Cervical Dysplasia / Q000473:pathology*