头颈部鳞癌中HPV感染与HIF-1α、VEGF表达的关系及预后意义

Relationship between HPV infection and expression of HIF-1α and VEGF in head and neck squamous cell carcinoma and its prognostic value

目的分析人乳头瘤病毒(HPV)感染与缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)在头颈部鳞癌(HNSCC)组织中的表达,探讨HPV感染与HIF-1α、VEGF表达的关系及临床意义。方法对43例HNSCC标本采用原位杂交法检测HPV 6/11、16/18和31/33的感染情况;免疫组织化学法检测HIF-la和VEGF的表达。采用Spearman法进行等级相关分析,Kaplan-Meier法计算生存率,Cox模型多因素预后分析。结果 43例HNSCC患者中,HPV阳性感染者占25.6%,HIF-1α和VEGF的阳性表达率分别为65.1%和51.2%。HIF-1α的表达与T、N分期及临床分期有关(P<0.05),VEGF表达与N分期和复发有关(P<0.05)。相关分析显示,HNSCC组织中HIF-1α与VEGF表达呈正相关(r=0.359,P<0.05)。HPV阳性感染组与阴性感染组中HIF-1α和VEGF的表达率差异无统计学意义(P<0.05)。HPV阳性感染组和阴性感染组3年生存率分别为60.0%和59.7%(P>0.05),HIF-1α阳性表达组和阴性表达组3年生存率分别为49.9%和80.0%(P=0.060),VEGF阳性表达组和阴性表达组3年生存率分别为41.2%和81.0%(P<0.05)。结论 HIF-1α、VEGF可作为评估HNSCC发展、转移及预后的参考指标之一,尚不能明确HNSCC组织中HPV感染与HIF-1α、VEGF表达存在相关性。

Objective To investigate the relationship between human papillomavirus （HPV） infection and expression of hypoxia inducible factor-1α （ HIF-1α） and vascular endothelial growth factor （VEGF） in tissues of head and neck squamous cell carcinoma （HNSCC）, and explore its clinical significance. Methods The infection of HPV6/ll, 16/18, 31/33 was examined by in situ hybridization in 43 samples of HNSCC, and the expression of HIF-1α and VEGF was determined by immunohistochemistry method. Spearman method was employed for rank correlation analysis, overall survival of patients was calculated by Kaplan-Meier method, and Cox regression model was used for multivariate analysis. Results In the 43 cases of HNSCC, the positive infection rate of HPV was 25.6%, and the positive expression rates of HIF-1α and VEGF were 65.1% and 51.2% respectively. The expression of HIF-1α was related to T stage, N stage and clinical stage （P 〈 0.05）, and the expression of VEGF was related to N stage and recurrence （P 〈 0. 05）. The expression of HIF-1α was positively related with the expression of VEGF （ r = 0. 359, P 〈 0. 05）. There was no significant difference in the expression of HIF-1α and VEGF between HPV positive group and HPV negative group （P 〉 0.05）. The 3-year overall survival rates of HPV positive group and HPV negative group were 60.0% and 59.7% respectively （P 〉 0.05）, those of H1F-1α positive expression group and HIF-1α negative expression group were 49.9% and 80.0% respectively （P = 0.06）, and those of VEGF positive expression group and VEGF negative expression group were 41.2% and 81.0% respectively （ P 〈 0. 05）. Conclusion HIF-1α and VEGF may be considered as parameters in evaluation of progression, metastasis and prognosis of HNSCC, and the correlation between HPV infection and expression of HIF-1α and VEGF in tissues of HNSCC is undetermined.