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Resolution of cervical dysplasia is associated with T-cell proliferative responses to human papillomavirus type 16 E2

¹ Virus Research Unit, Dept Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand
² Faculty of Medicine, Kanazawa University, Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan
³ Student Health Services, University of Otago, PO Box 56, Dunedin, New Zealand

Correspondence
Merilyn Hibma
merilyn.hibma{at}stonebow.otago.ac.nz

The ‘high-risk’ human papillomaviruses (HPVs) cause persistent infections of the anogenital region that may resolve spontaneously following activation of a protective immune response. The aim of this study was to determine whether cell-mediated immunity (CMI) to the early protein E2 was associated with disease regression and to establish whether E2 CMI and antibodies to L1 virus-like particles (VLPs) were associated markers of immunity to HPV. Lymphoproliferative responses to histidine-tagged E2 and antibody responses to VLPs were measured in patients with persistent cervical dysplasia, those whose disease had recently resolved and normal controls. Resolvers had significantly higher E2-specific lymphoproliferative responses when compared with normal controls or persisters, whereas there was no significant difference between the persisters and the normal controls. The T cells stimulated by E2 secreted high levels of gamma interferon (IFN-), consistent with a type 1 helper (Th1) phenotype. VLP IgG responses were associated with current or previous HPV infection, but not with disease regression or a lymphoproliferative response to E2. Major histocompatibility complex class I-restricted T cells secreted IFN- following stimulation with E1, and E2 peptides were detected more frequently in the persister group. The data showed that lymphoproliferative responses to E2 with a cytokine profile indicative of Th1 are associated with disease resolution, supporting the development of a therapeutic vaccine that activates this type of response for the treatment of individuals with pre-existing disease.