T cell epitopes are polypeptide fragments presented to T cell receptors by MHC molecules encoded by human leukocyte antigen (HLA) genes after antigen-presenting cell processing, which is the basis for the study of antigen immune mechanism and multi-epitope vaccine. This study investigated T cell response to HPV16 E6 and E7 in patients with cervical squamous cell carcinoma (CSCC). Also, the HLA-A allele distribution was compared among patients and evaluated as a factor to predict prognosis in these patients. This study recruited a total of 76 patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IIB–IIIB CSCC. Mononuclear cells were isolated from the peripheral blood before any treatment and then enzyme-linked immunosorbent spot (ELISpot) assay was employed to measure the E6 and E7-specific T cell response. HLA‐A alleles were typed using Sanger sequencing‐based typing techniques with DNA extracted from the peripheral blood. The correlation between the T cell responses, HLA‐A allele distribution and patient prognosis were analysed using the Kaplan–Meier method, univariate and multivariate Cox proportional hazard models. The frequency of HPV E6-specific T cell responses in patients with pelvic lymph node metastasis was lower than that in patients without metastasis (P = 0.022). The 5-year overall survival (OS) rates of patients were 87.5% for those responding to multiple overlapping peptides, 72.7% for those responding to 1–2 overlapping peptides and 47.7% for non-responders (P = 0.032). Cox regression analysis indicated that the presence of HLA*A02:07 was independently associated with worse OS (hazard ratio [HR] 3.042; 95% confidence interval [CI] 1.348–6.862; P = 0.007), while concurrent chemoradiation therapy (CCRT) was independently associated with better OS (HR 0.475; 95% CI 0.232–0.975; P = 0.042). The results of our study demonstrated that the level of HPV16 E6-specific T cell response and HLA*A02:07 were correlated with prognosis in patients with advanced CSCC.

中文翻译：

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HPV16 E6特异性T细胞反应和HLA-A等位基因与宫颈癌患者预后相关

T细胞表位是人类白细胞抗原（HLA）基因编码的MHC分子经抗原呈递细胞加工后呈递给T细胞受体的多肽片段，是研究抗原免疫机制和多表位疫苗的基础。本研究调查了宫颈鳞状细胞癌 (CSCC) 患者对 HPV16 E6 和 E7 的 T 细胞反应。此外，还比较了患者之间的 HLA-A 等位基因分布，并将其作为预测这些患者预后的一个因素进行评估。本研究共招募了 76 名国际妇产科联合会 (FIGO) IIB-IIIB 期 CSCC 患者。在任何处理之前从外周血中分离出单核细胞，然后采用酶联免疫吸附点 (ELISpot) 测定法测量 E6 和 E7 特异性 T 细胞反应。HLA-A 等位基因使用基于 Sanger 测序的分型技术与从外周血中提取的 DNA 进行分型。使用 Kaplan-Meier 方法、单变量和多变量 Cox 比例风险模型分析 T 细胞反应、HLA-A 等位基因分布和患者预后之间的相关性。盆腔淋巴结转移患者HPV E6特异性T细胞反应频率低于无转移患者（P = 0.022）。对多种重叠肽有反应的患者的 5 年总生存 (OS) 率为 87.5%，对 1-2 种重叠肽有反应的患者为 72.7%，无反应者为 47.7%（P = 0.032）。Cox 回归分析表明，HLA*A02:07 的存在与较差的 OS 独立相关（风险比 [HR] 3.042；95% 置信区间 [CI] 1。348–6.862；P = 0.007)，而同步放化疗 (CCRT) 与更好的 OS 独立相关（HR 0.475；95% CI 0.232–0.975；P = 0.042）。我们的研究结果表明，HPV16 E6 特异性 T 细胞反应和 HLA*A02:07 的水平与晚期 CSCC 患者的预后相关。