Most cervical carcinoma (Cxca) cells constitutively express human papillomavirus type 16 (HPV16) E6 and E7 oncoproteins. These proteins are, therefore, attractive targets for T cell-based immunotherapy. Previously, we identified HPV16 E7-encoded CTL epitopes. In patients with cervical intraepithelial neoplasia or Cxca, little is known concerning T-cell activity against viruses in general and against HPV16 in particular. Here, we have screened the blood of 10 healthy donor controls and of 22 patients with HPV16+ cervical lesions for the presence of CTLs directed against HPV16 E7- and control influenza virus matrix-derived epitopes presented by HLA-A*0201. We detected influenza virus-specific CTLs in all donors and in the majority of patients, indicating that most patients have functioning T-cell responses despite their lesions or therapeutic interventions. Moreover, we show that patients with HPV16+ lesions occasionally have memory CTLs against a HPV16 E7-encoded epitope (sequence YMLD-LQPETT), providing evidence for natural CTL immunity against HPV16 in patients with cervical lesions.

Combined, these findings raise possibilities for vaccination with HPV16 E7-encoded peptides to induce or augment CTL responses for treatment or prevention of Cxca.


This study was supported by NIH Grant R01 CA 57933 (to W. M. K.) and by Dutch Cancer Foundation Grant RUL 95-1089 (to W. M. K. and C. J. M. M.). W. M. K. is a senior fellow of the Royal Netherlands Academy of Arts and Sciences.

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