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HPV16 E6-specific T cell response and HLA-A alleles are related to the prognosis of patients with cervical cancer

  • Cai, Hongchao1, 2
  • Feng, Yaning1, 2, 3
  • Fan, Peiwen1, 2, 3
  • Guo, Yuping1, 2
  • Kuerban, Gulina1, 2
  • Chang, Cheng1, 2
  • Yao, Xuan4
  • Peng, Yanchun4
  • Wang, Ruozheng1, 2, 3
  • 1 Chinese Academy of Medical Sciences,
  • 2 Key Laboratory of Oncology of Xinjiang Uyghur Autonomous Region, Urumqi, China
  • 3 State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, China
  • 4 Chinese Academy of Medical Sciences Oxford Institute (CAMS Oxford Institute), Oxford, UK
Published Article
Infectious Agents and Cancer
Springer (Biomed Central Ltd.)
Publication Date
Sep 16, 2021
DOI: 10.1186/s13027-021-00395-y
PMID: 34530896
PMCID: PMC8447512
PubMed Central
  • Research Article


Background 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. Materials and methods 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. Results 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). Conclusion 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. Supplementary Information The online version contains supplementary material available at 10.1186/s13027-021-00395-y.

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