title: Human papillomavirus type 16-specific T cell responses and their association with recurrence of cervical disease following treatment.
abstract: Human papillomavirus type 16 (HPV-16) L1- and E7-specific T cell responses were measured in 58 women with abnormal cervical cytology in a prospective study. On recruitment, patients responded most frequently and with the highest numbers of responding cells to the L1 region aa 311-345 and this response was significantly associated with the presence of cervical disease (P=0.041). Responses to the L1 peptide aa 281-295 were significantly higher in patients with CIN III than in those with HPV/CIN I or CIN II lesions (P=0.027). The E7 region aa 70-98 was the most immunogenic in patients with squamous intraepithelial lesions of the cervix (SIL) but the responses detected were not significantly higher than in patients without SIL. Following treatment, the T cell response profiles of patient groups did not change significantly. However, on analysis of the responses of individual patients with and without recurrent disease on follow-up, significant differences were found. Recurrence of disease was associated with T cell responses to the E7 region aa 70-98 at the patient's first clinic visit (P=0.017). Recurrence of disease was also accompanied by an increase in the total number of L1-specific short-term T cell lines (STLs) at follow-up, whereas absence of disease was accompanied by a decrease in L1-specific STLs. The data also suggested a possible link between E7 70-98-specific responses and acquisition of disease by patients who were previously disease-free. Further studies are warranted to determine whether this response could be useful as a marker of recurrent disease in some patients.
authors.affiliation: Peter Gorer Department of Immunobiology, GKT, 3rd Floor New Guy's House, Guy's Hospital, London SE1 9RT, UK.
authors.forename: Jenny C
authors.initials: JC
authors.lastname: Luxton
authors.affiliation: Department of Obstetrics and Gynaecology, Birmingham Women's Hospital, Metchley Park Road, Edgbaston, Birmingham B15 2TG, UK.
authors.forename: Rahul
authors.initials: R
authors.lastname: Nath
authors.affiliation: Department of Histopathology, St Thomas' Hospital, London SE1 7EH, UK.
authors.forename: Nawal
authors.initials: N
authors.lastname: Derias
authors.affiliation: Department of Histopathology, St Thomas' Hospital, London SE1 7EH, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Herbert
authors.affiliation: Peter Gorer Department of Immunobiology, GKT, 3rd Floor New Guy's House, Guy's Hospital, London SE1 9RT, UK.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Shepherd
mesh_terms: D036022:Capsid Proteins; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D009856:Oncogene Proteins, Viral / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011446:Prospective Studies; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D002577:Uterine Cervical Diseases / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000503:physiopathology* / Q000821:virology
chemical_list: D036022:Capsid Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010455:Peptides; C059731:oncogene protein E7, Human papillomavirus type 16; C063317:L1 protein, Human papillomavirus type 16