HPV16 E6-specific T Cell Response and HLA-A Alleles Are Related to the Prognosis of Patients With Cervical Cancer 

Abstract Background: It is worthwhile to identify more epitopes as target to design T cell-based therapeutic interventions that can benefit cervical cancer patients whose disease cannot be well controlled with current treatment modalities. This study investigated T cell response to HPV16 E6 and E7 in patients with cervical squamous cell carcinoma (CSCC). Also, the human leukocyte antigen (HLA)-A allele distribution was compared among patients and evaluated as factors 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 sequence‐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 the multiple overlapping peptide group, 72.7% for the 1–2 overlapping peptide group, and 47.7% for the negative group (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.