title: A prospective study on the natural course of low-grade squamous intraepithelial lesions and the presence of HPV16 E2-, E6- and E7-specific T-cell responses.
abstract: This study investigates the clinical course of low grade squamous intraepithelial lesions (LSIL), HPV status and HPV16-specific immune response in a large prospective study of 125 women with LSIL followed cytologically, virologically and histologically. Women with low-grade abnormal smears were recruited and followed-up for one year. Colposcopy, cervical biopsy for histology and brushings for HPV typing was performed at recruitment, 6 months (no biopsy) and upon completion of the study at one year. HPV16-specific T-cell responses were analysed by interferon-gamma ELISPOT at entry, 6 and 12 months. Infection with multiple HPV types was detected in 70% of all patients, HPV16 was found in 42% of the patients. LSIL lesions progressed to HSIL in 24%, persisted in 60% and regressed to normal in 16% of the patients. No difference was observed in the clearance rate of infections with single or multiple HPV types among the groups with a different histological outcome. HPV16-specific type 1 T-cell responses were detected in only half of the patients with an HPV16+ LSIL, and predominantly reactive to HPV16 E2 and E6. Interestingly, the presence of HPV16 E2-specific T-cell responses correlated with absence of progression of HPV16+ lesions (p = 0.005) while the detection of HPV16 E6 specific reactivity was associated with persistence (p = 0.05). This large prospective study showed that the majority of LSIL persisted or progressed within the first year.This was paralleled by immune failure as most of the patients with an HPV16+ LSIL failed to react to peptides of HPV16 E2, E6 or E7.
authors: Department of Pathology, Cambridge University, Cambridge CB2 2QQ, UK.
authors: Yin Ling
authors: YL
authors: Woo
authors: Muriel
authors: M
authors: van den Hende
authors: Jane C
authors: JC
authors: Sterling
authors: Nicholas
authors: N
authors: Coleman
authors: Robin A F
authors: RA
authors: Crawford
authors: Kitty M C
authors: KM
authors: Kwappenberg
authors: Margaret A
authors: MA
authors: Stanley
authors: Sjoerd H
authors: SH
authors: van der Burg
mesh_terms: D000328:Adult; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology* / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000473:pathology* / Q000821:virology