Jakub Kopycinski (United Kingdom)
University of Oxford Nuffield Dept of MedicinePresenter of 1 Presentation
INVESTIGATION OF THE RELATIONSHIP BETWEEN HR-HPV-SPECIFIC T-CELL RESPONSES AND HR-HPV DNA IN HEALTHY WOMEN AND WOMEN WITH CERVICAL ABNORMALITIES IN A LONGITUDINAL STUDY (ID 790)
- Jakub Kopycinski (United Kingdom)
- Gemma Hancock (United Kingdom)
- Ionitiana Evans (United Kingdom)
- Wendy Byrne (United Kingdom)
- Angela Bloss (United Kingdom)
- Kathryn Saunders (United Kingdom)
- Monique Andersson (United Kingdom)
- Mamatha Oduro (United Kingdom)
- Karin Hellner (United Kingdom)
- Lucy Dorrell (United Kingdom)
Abstract
Introduction
Cell-mediated immune responses play a crucial role in regression of HPV lesions and clearance of infections. However, studies evaluating the role of T cell responses to specific proteins have produced conflicting results, likely reflecting the diverse methods used and predominance of cross-sectional analyses.
Methods
We established a prospective longitudinal cohort of women aged 16-55 years to study the relationship between detection of T-cell responses to early proteins and detection of hrHPV DNA. Cohort 1 comprises asymptomatic sexually active women aged 16-24. Cohort 2 comprises women aged 25-55 undergoing colposcopy, with mild, moderate or severe dyskaryosis. Women are followed for 12 months and provide a blood sample and self-taken vaginal swab at 4-monthly (Cohort 1) or 6-monthly (Cohort 2) intervals. T cell responses to all hrHPV early proteins are quantified by IFNγ Elispot and flow cytometry using overlapping 15-mer peptides based on HPV16, HPV52 and selected conserved sequences across 5 hrHPV genotypes.
Results
144 women were enrolled in the study: 107 in Cohort, mean age 21y; 37 in Cohort 2, mean age 32y. Baseline data are reported. Prior prophylactic vaccination was reported in 88% Cohort 1 and 21% Cohort 2. HPV DNA was detected in 27 (25%) Cohort 1 and 31 (91%) Cohort 2. hrHPV isolates were non-16/18 types in 100% Cohort 1 and 82% Cohort 2. HPV16/18 were also detected in 21% Cohort 2. T-cell responses to E1/E2 or E6/E7 peptides (HPV52 > HPV16) were detected in 22/103 (21%) Cohort 1 and 15/31 (48%) Cohort 2. Overall, E1/E2 was most frequently targeted.
Conclusions
There was no consistent relationship between baseline hrHPV DNA prevalence and T-cell reactivity. Our data suggest that transient infections infrequently elicit T-cell responses. Longitudinal analysis is directed at determining the phenotype and duration of T-cell responses that are associated with hrHPV clearance or persistence.