Ma Miaomiao, Feng Yaning, Fan Peiwen, Yao Xuan, Peng Yanchun, Dong Tao, Wang Ruozheng
1Department of Radiation Oncology, The Affiliated Tumor Hospital of Xinjiang Medical University, Ürümqi, China.
Key Laboratory of Cancer Immunotherapy and Radiotherapy, Chinese Academy of Medical Sciences, Ürümqi, China.
Infect Agent Cancer. 2018 Nov 16;13:35. doi: 10.1186/s13027-018-0206-5. eCollection 2018.
Cervical 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).
A 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.
The 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 PBMCs. The frequency and intensity of HPV E1-specific T cell response in patients were higher than healthy controls( < 0.001; = 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 ( = 0.038; = 0.044). Univariate analysis showed that HPV E1 specific T cell response was associated with progression-free survival (PFS) and overall survival (OS) (PFS: = 0.021; OS: = 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: = 7.252, 95% = 1.690-31.126, = 0.008; OS: = 7.499, 95% = 1.661-33.856, = 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.
Our 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.
在大多数情况下，宫颈癌归因于人乳头瘤病毒（HPV）感染。E1是一种源自HPV的蛋白，在宫颈癌的发生和发展中起重要作用。我们的研究旨在调查宫颈鳞状细胞癌（CSCC）患者中HPV E1特异性T细胞反应。
共纳入66例FIGO分期为IIB-IIIB期的CSCC患者和60例健康对照。采用酶联免疫斑点（ELISPOT）试验检测这些患者治疗前外周血中HPV E1特异性T细胞反应。患者接受化疗和/或放疗，并进行三年的临床随访。采用单因素分析、多因素分析和生存曲线分析研究T细胞反应、各种临床特征与预后之间的关系。
宫颈癌患者外周血中HPV E1特异性T细胞反应频率为59.09%，平均反应强度为24.56 SFC/10 PBMCs。患者中HPV E1特异性T细胞反应的频率和强度高于健康对照（<0.001；=0.009）。IIB期患者和无盆腔淋巴结转移患者的HPV E1特异性T细胞反应强度较高（=0.038；=0.044）。单因素分析显示，HPV E1特异性T细胞反应与无进展生存期（PFS）和总生存期（OS）相关（PFS：=0.021；OS：=0.004）。多因素分析显示，在我们研究纳入的所有因素中，HPV E1特异性T细胞反应是影响PFS和OS的独立预后因素（PFS：=7.252，95%=1.690-31.126，=0.008；OS：=7.499，95%=1.661-33.856，=0.009）。生存曲线显示，有HPV E1特异性T细胞反应的患者的PFS和OS率显著高于无反应的患者。
我们的研究表明HPV E1特异性T细胞反应水平与晚期CSCC患者的生存相关。未表现出HPV E1特异性T细胞反应的患者更可能是预后较差的患者。
