The Expression Of HPV E6/E7mRNA And P16Protein And P53Protein In Head And Neck Squamous Cell Carcinomas

BackgroundHead and neck squamous cell carcinoma (HNSCC) is induced by many riskfactors such as tobacco and alcohol, long-term chronic stimulation, viral infection andgenetic mutation.In recent years, the strongest correlation between humanpapillomavirus and the development of HNSCC has been found, particularly inoropharyngeal squamous cell carcinoma (OPSCC), HPV DNA present in up to70%of patients studied.HPV-infection tumors have special biological characteristic, HPV-positivepatients are more sensitive to radiation/chemotherapy and have a better prognosis than patientswith classi risk factors such as tobacco and alcohol. Indeed, detection of HPV is emerging as avalid biomarker to select specific treatments and to post-treatment tumor surveillance. The mostwidely used techniques include polymerase chain reaction (PCR) or In Situ Hybridization (ISH)for viral DNA detection, but no optimal sensitivity and specificity levels are offered. E6and E7oncoprotein coding by HPV, by inhibiting p53and pRb respectively, play a key role in thedevelopment of cancer. Detection of E6/E7mRNA is considered as the gold standard for HPVdetection.P16serves as a marker of HPV E7-mediated functional inactivation of pRb. The loss ofpRb and function leads to p16protein overexpression. P16protein overexpression is found inHPV positive tumor.Is there difference between HPV infection and classical factors in HNSCC?And whether it can predict the prognosis by HPV and its associated tumor molecular indicatorsh?This is the most important issue about HPV infection.Objective(1) To detect the expression of HPV infection in HNSCC.(2) To investigate the correlation between HPV E6/E7mRNA and the expression ofp16protein and p53protein.(3) To evaluate the effect of HPV infection,the expression of p16protein and p53protein on the prognosis of HNSCC.Methods30HNSCCpatients included in the standard in henan province tumor hospitalfrom January2010to June2012were inrolled. The clinical data were retrospectively analyzed, and the survival time was followed up. HPV E6/E7mRNA would bedetected using branch–DNA(b-DNA) technology, while p16protein and p53protein would be detected using immunohistochemical (IHC) methods.Thecorrelation between HPV E6/E7mRNA, the expression of p16protein and p53protein and clinical indicators and the prognostic factors would be analyzed bySPSS17.0.Results(1) Tthe incidence rate of HPV E6/E7mRNA is26.7%by b-DNA amplificationtechnology.(2) p16protein is overexpression in20.0%of the tumor tissues with HNSCC, whilep53protein is lower expression in43.3%.(3) Detection of HPV E6/E7mRNA is no associated with clinical data such assmoking, alcohol, gender and age.(4) We find a positive correlation between HPV-positive and p16（r=0.829，p=0.000）,and a negative correlation between HPV-positive and p53（r=-0.472，p=0.008）.75.0%of HPV-positive patients are alive in2years whereas only45%of HPV-negative patients are alive in2years,and there is statisticallysignificant difference between the two groups.83.30%of p16-positive patientsare alive in2years whereas only45%of p16-negative patients are alive in2years,and there is statistically significant difference between the twogroups.37.5%of p53-positive patients are alive in2years whereas only75.0%ofp53-negative patients are alive in2years,and there is statistically significantdifference between the two groups.(5) The median survival time of follow-up was24months.In Kaplan-Meier analysis,HPV infection status and p16protein influence on prognosis of patients wasstatistically significant (p <0.05). there is statistically significan differencebetween HPV infection status, p16protein, p53protein and the prognosis ofpatients（p＜0.05）.With multiariable COX multivariate regression analysis, p16protein is a major risk factor for prognosis of patientsConclusion(1) HNSCC may be initiated by HPV infection. (2) HPV E6/E7m RNA has relationship with the expression of p16protein and p53protein in HNSCC;(3) p16protein can be used as one of the important molecular indicators to predict theprognostic of HNSCC...