989 Proliferative T-cell responses to HPV16.L1 in patients with CIN: Correlation with HPV type and cervical biopsy histology

Abstract

We have previously demonstrated that 73% of patients with CIN (n = 17) can mount a proliferative T-cell response to an immunodom-inant region of HPV16.L1 between aa 305–345 using short term cell lines expanded with an L1 fusion protein and mapped with overlapping synthetic peptides(15 mers) to this region. The T-cell responses to HPV16.L1 region 199–409 have now been mapped in a larger group of patients (n = 41) and in 11 healthy controls and the patient data correlated with cervical biopsy histology and the presence of HPV DNA as detected by PCR. 26 patients (63%) and 5 controls (45%) responded to one or more peptides representing HPV16.LI aa 199–409. 19 patients(46%) responded to aa region 311–345 as compared to 2 controls (18%,). The patient responses to this region were significantly associated with peptides 311–325(P= 0.04) and 321–335(P= 0.004) and to the presence of HPV 16 (P = 0.006) in their cervical biopsies. Overall, 30% (n = 12) of patients cervical biopsies were HPV16 positive and 92% (n = 11) of these were CIN III lesions, demonstrating the strong association between the presence of HPV16 and high grade lesions (P = 0.0001). All of the HPV16 positive patients (n = 12) demonstrated proliferative T-cell responses to one or more peptides and this association between T-cell responses and the presence of HPV 16 DNA was found to be highly significant (P = 0.0004). Individuals whose biopsies were HPV negative or contained other HPV types also responded to some of the peptides (HPV X, n = 5/12; HPV 33, n = 1/1; and HPV-ve, n = 8/13) but with a lower number of responding cell lines.