T cell responses to human papillomavirus type 16 amongst women with different grades of cervical neoplasia

Jane Steele, Christopher Mann, Susan Rookes, Terence Rollason, D Murphy, MG Freeth, Phillip Gallimore, Sally Roberts

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64 Citations (Scopus)


Infection with high-risk genital human papillomavirus (HPV) types is a major risk factor for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The design of effective immunotherapies requires a greater understanding of how HPV-specific T-cell responses are involved in disease clearance and/or progression. Here, we have investigated T-cell responses to five HPV16 proteins (E6, E7, E4, L1 and L2) in women with CIN or cervical carcinoma directly ex vivo. T-cell responses were observed in the majority (78%) of samples. The frequency of CD4+ responders was far lower among those with progressive disease, indicating that the CD4+ T-cell response might be important in HPV clearance. CD8+ reactivity to E6 peptides was dominant across all disease grades, inferring that E6-specific CD8+ T cells are not vitally involved in disease clearance. T-cell responses were demonstrated in the majority (80%) of cervical cancer patients, but are obviously ineffective. Our study reveals significant differences in HPV16 immunity during progressive CIN. We conclude that the HPV-specific CD4+ T-cell response should be an important consideration in immunotherapy design, which should aim to target preinvasive disease.
Original languageEnglish
Pages (from-to)248-259
Number of pages12
JournalBritish Journal of Cancer
Publication statusPublished - 28 Jun 2005


  • disease grade
  • T cells
  • HPV16
  • CIN


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