High-risk HPV is causally linked to the development of cervical intraepithelial neoplasia and cancer. The low grade lesions may prevent the progression to cancer. Importantly, the majority of HPV-induced low grade cervical intraepithelial neoplasia (CIN1) regresses spontaneously and this is likely to be mediated by cellular immune responses comparable to those seen in naturally resolving genital warts. Our previous studies suggested that the E2 and E6 proteins are the most probable target antigens for protective T-cell responses in women with spontaneously regressing CIN. The aim of this longitudinal study is to demonstrate that HPV16 E2- and E6-specific T-cell responses are important for the regression of CIN and that failure to make such a response is associated with persistence/progression of low grade CIN. We plan to follow a cohort of women with CIN1 over a one year period, with disease status assessed by histology, HPV DNA presence and activity by molecular assays in biopsy tissue. Immunity will be evaluated by testing systemic lymphocyte activity using well established ELISPOT and proliferation assays as well as by immunohistochemistry on biopsy sections. This study is relevant in view of the further development of vaccination strategies against HPV and HPV-induced cancers.