title: Naturally occurring systemic immune responses to HPV antigens do not predict regression of CIN2/3.
abstract: Essentially all squamous cervical cancers and their precursor lesions, high grade cervical intraepithelial neoplasia (CIN2/3), are caused by persistent human papillomavirus (HPV) infection. However, not all CIN2/3 lesions progress to cancer. In a brief, observational study window monitoring subjects with CIN2/3 from protocol entry (biopsy diagnosis) to definitive therapy (cervical conization) at week 15, in a cohort of 50 subjects, we found that 26% of CIN2/3 lesions associated with HPV16, the genotype most commonly associated with disease, underwent complete histologic regression. Nonetheless, HPV16-specific T cell responses measured in peripheral blood obtained at the time of study entry and at the time of conization were marginally detectable directly ex vivo, and did not correlate with lesion regression. This finding suggests that, in the setting of natural infection, immune responses which are involved in elimination of cervical dysplastic epithelium are not represented to any great extent in the systemic circulation.
authors.affiliation: Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. ctrimbl@jhmi.edu
authors.forename: Cornelia L
authors.initials: CL
authors.lastname: Trimble
authors.forename: Shiwen
authors.initials: S
authors.lastname: Peng
authors.forename: Christopher
authors.initials: C
authors.lastname: Thoburn
authors.forename: Ferdynand
authors.initials: F
authors.lastname: Kos
authors.forename: T C
authors.initials: TC
authors.lastname: Wu
mesh_terms: D000956:Antigens, Viral / Q000276:immunology; D018450:Disease Progression; D005260:Female; D052162:Human papillomavirus 16; D006801:Humans; D009365:Neoplasm Regression, Spontaneous / Q000276:immunology* / Q000473:pathology; D009856:Oncogene Proteins, Viral / Q000276:immunology; D050725:Papillomavirus E7 Proteins / Q000276:immunology; D030361:Papillomavirus Infections / Q000276:immunology / Q000473:pathology; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000473:pathology / Q000821:virology*
chemical_list: D000956:Antigens, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16