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(American Journal of Pathology. 2002;160:151-164.)
© 2002 American Society for Investigative Pathology

Regular Articles

Lymphoid Follicles Are Generated in High-Grade Cervical Dysplasia and Have Differing Characteristics Depending on HIV Status

Akiko Kobayashi^*, Teresa Darragh, Brian Herndier^¶, Kathryn Anastos^||, Howard Minkoff^**, Mardge Cohen, Mary Young, Alexandra Levine, Linda Ahdieh Grant^¶¶, William Hyun, Vivian Weinberg, Ruth Greenblatt^|||| and Karen Smith-McCune^*

From the Department of Obstetrics, Gynecology, and Reproductive Sciences,^*
the Cancer Research Institute,
the Department of Pathology
and the Department of Medicine,
University of California at San Francisco, San Francisco, California; the Department of Pathology,^¶
at the University of California at San Diego, San Diego, California; Lincoln Medical and Mental Health Center,||
New York City/Bronx Consortium, Bronx, New York; the Department of Obstetrics and Gynecology,^**
Maimonides Medical Center, Brooklyn, New York; the CORE Center,
Chicago, Illinois; the Department of Medicine,
Georgetown University Medical Center, Washington, DC; the School of Medicine,
University of Southern California, Los Angeles County/Southern California Consortium, Los Angeles, California; Bloomberg School of Public Health,^¶¶
the Johns Hopkins University, Baltimore, Maryland; and the Connie Wofsy Study Consortium of Northern California,||||
San Francisco, California

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.

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