Lymphoid follicles are generated in high-grade cervical dysplasia and have differing characteristics depending on HIV status.
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.
Kobayashi
Akiko
A
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco, California 94143-0128, USA.
Darragh
Teresa
T
Herndier
Brian
B
Anastos
Kathryn
K
Minkoff
Howard
H
Cohen
Mardge
M
Young
Mary
M
Levine
Alexandra
A
Grant
Linda Ahdieh
LA
Hyun
William
W
Weinberg
Vivian
V
Greenblatt
Ruth
R
Smith-McCune
Karen
K
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*