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Interleukin 2 Production in Vitro by Peripheral Lymphocytes in Response to Human Papillomavirus-derived Peptides: Correlation with Cervical Pathology

Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch [T. T., D. C., M. A. M., J. A. B.], Environmental Epidemiology Branch [A. H., M. H. S.], and Experimental Immunology Branch [M. Cl., G. M. S.], National Cancer Institute, Bethesda, Maryland 20892; University of Texas Southwestern Medical School, Dallas, Texas 75235 [J. L., D. P. C.]; Kaiser Permanente, Portland, Oregon 97227 [P. L., B. B. R., D. R. S.]; Digene Diagnostics, Silver Spring, Maryland 20904 [A. C., A. T. L.]; Albert Einstein College of Medicine, Bronx, New York 10461 [R. D. B., W. Q.]; Laboratory of Viral Carcinogenesis [D. M.] and Intramural Research Support Program, Science Applications International Corporation, Frederick [M. Ca.]. National Cancer Institute, Frederick Cancer Research and Developmental Center, Frederick, Maryland 21702; and Torrey Pines Institute for Molecular Studies, San Diego, California 92121 [R. A. H.]

Human papillomavirus (HPV) is believed to be the major cause of cervical cancer. To investigate whether a cellular immune response, especially a T helper type 1 response, is related to the natural defense against HPV-related cervical lesions, the interleukin 2 response of peripheral blood lymphocytes in vitro to overlapping peptides from HPV-16 E6 and E7 oncoproteins was compared with the degree of cervical cytological abnormality among 140 women in a cross-sectional study. We compared 66 women diagnosed with low-grade squamous intraepithelial lesions (LSIL), 21 with high-grade squamous intraepithelial lesions (HSIL), and 28 with invasive cervical cancer with 25 women who were cytologically normal but previously HPV-16 DNA positive. The fraction showing strong interleukin 2 production against HPV-16 peptides was greatest among cytologically normal women (35%) and declined with increasing disease severity [LSIL] (20%), HSIL (17%), and cancer patients (7%); X² test P for the trend = 0.02], whereas the responses against a recall influenza antigen were not significantly different among groups. Our finding suggests that a T helper lymphocyte type 1 response to HPV antigens is associated with disease status. This result may reflect a targeted effect of the disease on immune function or a protective effect of the immune response against disease progression.

¹ Present address: Third Department of Internal Medicine, Nippon Medical School. 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113, Japan.

² To whom requests for reprints should be addressed. at Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, Building 10, Room 6B-12 (MSC#1578), NIH, Bethesda, MD 20892-1578. Phone: (301) 496-6874; Fax: (301) 496-9956; E-mail: berzofsk@helix.nih.gov.

Received 2/14/96. Accepted 7/ 1/96.

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