4.3 Article

Human papilloma virus E1-specific T cell immune response is associated with the prognosis of cervical cancer patients with squamous cell carcinoma

Journal

INFECTIOUS AGENTS AND CANCER
Volume 13, Issue -, Pages -

Publisher

BMC
DOI: 10.1186/s13027-018-0206-5

Keywords

Human papillomavirus 16; Cervical squamous cell carcinoma; Enzyme-linked immunoassay; T cell immune response; PBMC

Funding

  1. National Natural Science Foundation of China [U1603282]
  2. MRC [MC_UU_00008/11, G0600520, G1001046, MR/L018942/1] Funding Source: UKRI

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BackgroundCervical cancer is attributable to human papilloma virus (HPV) infection in the majority cases. E1, an HPV derived-protein, plays an important role in the initiation and development of cervical cancer. Our study aims to investigate the HPV E1-specific T cell response in patients with cervical squamous cell carcinoma (CSCC).MethodsA total of 66 CSCC patients with FIGO stage IIB-IIIB and 60 healthy controls were enrolled. Enzyme-Linked ImmunoSpot (ELISPOT) assays was used to measure the HPV E1-specific T cell response in the peripheral blood of these patients before treatment. The patients were treated with chemotherapy and/or radiotherapy and followed up clinically for three years. The relationship between the T cell response, various clinical characteristics and the prognosis were studied with univariate analysis, multivariate analysis and survival curve analysis.ResultsThe frequency of HPV E1-specific T cell response in peripheral blood of cervical cancer patients was 59.09%, with mean response intensity 24.56 SFC/10(6) PBMCs. The frequency and intensity of HPV E1-specific T cell response in patients were higher than healthy controls(p<0.001; p=0.009). The intensity of HPV E1-specific T cell responses were higher in the stage IIB patients and patients with no pelvic lymph node metastasis (p=0.038; p=0.044). Univariate analysis showed that HPV E1 specific T cell response was associated with progression-free survival (PFS) and overall survival (OS) (PFS: p=0.021; OS: p=0.004). Multivariate analysis showed that HPV E1-specific T cell response was an independent prognostic factor influencing PFS and OS among all the factors included in our study (PFS: HR=7.252, 95%CI=1.690-31.126, p=0.008; OS: HR=7.499, 95%CI=1.661-33.856, p=0.009). The survival curves showed that the rate of PFS and OS in patients with HPV E1 specific T cell response was significantly higher than those who did not response.ConclusionsOur study demonstrated that the level of HPV E1-specific T cell response was correlated with the survival of advanced patients with CSCC. Patients who displayed no HPV E1-specific T cell response were more likely to be those with poor prognosis.

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