HPV16Infection and p16,HSP70Protein Expression in Oropharyngeal Squamous Cell Carcinoma and Their Clinical Significance
|School||Central South University|
|Keywords||oropharyngeal squamous cell carcinoma HPV16 p16 HSP70 prognosis radiosensitivity|
Objectives：We will investigate the infection rate of human papillomavirus16(HPV16) and p16,HSP70protein expression in oropharyngeal squamous cell carcinoma(OPSCC) and their clinical significance.We are aimed to get preliminary study on the molecular mechanisms of radiation-sensitive in HPV associated OPSCCs.Methods:We got95tissue specimens of patients who met the eligibility criteria were obtained from patients diagnosed with oropharyngeal squamous cell carcinomas treated in Xiangya Hospital and collected their clinical data. HPV16DNA was measured by in situ hybridization.P16and HSP70protein were evaluated by immunohistochemistry. We are aimed to assess mutual correlation of the three indicators.HSP70and radiosensitivity were detected by Western blot and single-cell cloning efficiency assay in oropharyngeal cancer cell lines with downregulation of HPV16.SPSS17.0software was used for statistical analysis. We evaluate the differences in patient characteristics and survival with different p16protein status.The primary end point was overall survival(OS) and disease free survival(DFS). Survival data were analyzed by means of the Kaplan-Meier method,and survival curves were compared with the log-rank test in univariate analysis.Cox regression model was used for multivariate analysis.Results:The incidence rate of HPV infection was48.3%. P16was expressed in52.6%of the tumor tissues. The p16protein expression was highly correlated with the presence of HPV16(P<0.001). Based on Kaplan-Meier estimates,both OS and DFS were increased in p16positive group (70.4%and63.0%) compared with the p16negative group(40.0%and25.7%,P=0.008and0.004, respectively). When multivariable analysis was performed in DFS,patients with p16protein negative tumors had a higher risk of death than patients with p16protein positive tumors(HR0.423,95%CI0.201-0.891, P=0.024). The p16might be a reliable prognostic indicator for Oropharyngeal Cancer in DFS. P16negative OPSCC tissue showed strong cytoplasm cell expression of HSP70.While p16positive OPSCC tissue showed strong membrane expression of HSP70. When HPV16was effectively reduced,we found HSP70was upregulated and the radiosensitivity was decline.Conclusions:HPV infection rate of OPSCC in this study was48.3%. P16was expressed in52.6%of the tumor tissues. The p16protein expression was highly correlated with the presence of HPV16,and might be a surrogate marker for HPV16positive OPSCC.Patients with p16positive OPSCCs have a significant survival advantage. The p16might be a reliable prognostic indicator for Oropharyngeal Cancer. HSP70was upregulated when HPV16was effectively reduced. We predict that HSP70might be an important factor to explain the radiosensitivity in patients with HPV associated OPSCCs.