口咽鳞癌组织中HPV16感染和p16蛋白表达的临床意义

目的:检测口咽鳞癌中HPV16感染及p16表达率，并分析临床意义。方法:采用原位杂交法检测60例口咽鳞癌组织中HPV16的表达，免疫组化法检测95例口咽鳞癌组织p16的表达情况，分析HPV16与p16的相关性，总结上述两种蛋白在口咽癌中的临床意义。结果:口咽鳞癌组织中HPV16感染率为48.3%（29/60），p16阳性表达率为52.6%（50/95），60例标本中HPV16感染与p16表达显著相关（P<0.001），用p16表达预测HPV16感染的正确率可达90%（54/60），跟国内外报道一致。p16阳性组相比p16阴性组，吸烟、饮酒、非嚼槟榔、T3+T4、有淋巴结转移、III-IV临床分期和高分化者所占比例更低，但不具有统计学差异(P>0.05)。平均随访时间38个月,随访率65.3%（62/95）,62例口咽鳞癌病人中p16阳性组和p16阴性组的3年总体生存率和无瘤生存率分别为70.4%对比40.0%（P=0.008）和63.0%对比25.7%（P=0.004）。总体生存率多因素分析提示，p16阴性病人死亡风险是p16阳性病人的2.12倍(HR 0.471，95%CI 0.201-1.103，P=0.083)，无瘤生存率多因素分析提示，p16阴性病人死亡风险是p16阳性病人的2.36倍(HR 0.432，95%CI 0.201-0.891，P=0.024)，p16与口咽癌的预后密切相关。结论:p16表达和HPV16表达存在紧密相关性，p16可以替代HPV16来预测预后，p16蛋白阳性口咽癌患者具有非吸烟、非饮酒、嚼槟榔和肿瘤分化程度低的趋势，检测p16表达对口咽癌病人预后判断有重要的提示意义。

HPV16 infection and p16 protein expression in oropharyngeal squamous cell carcinoma and their clinical significance

Objective:To investigate the infection rate of human papillomavirus16 (HPV16) and p16 protein expression in oropharyngeal squamous cell carcinoma (OPSCC) and their clinical significance.Methods:HPV16 DNA was measured by in situ hybridization in 60 specimens of OPSCC.p16 protein was evaluated by immunohistochemistry in 95 specimens.We assessed mutual correlation of the HPV16 and p16,and summarized their clinical significance in oropharyngeal cancer.Results:The incidence rate of HPV infection was 48.3%（29/60）.p16 was expressed in 52.6%（50/95） of the tumor tissues.The p16 protein expression was highly correlated with the presence of HPV16 in 60 specimens （P<0.001).We can use the p16 expression instead of HPV16 infection to predict prognosis alternative in our specimens as the correct prediction rate was 90%（54/60).This was consistent with domestic and international coverage.Compared p16 positive group to the negative group，there was a lower proportion in smokers，drinkers，non-chewing betelers，T3+T4，lymph node metastasis and III-IV clinical stage patients，though the difference was not statistically (P>0.05).The mean follow-up time was 38 months and the follow-up rate was 65.3%（62/95).Both OS and DFS were increased in p16 positive group （70.4% and 63.0%) compared with the p16 negative group (40.0% and 25.7%,P=0.008 and 0.004，respectively) in 62 patients.When multivariable analysis was performed in DFS,patients with p16 protein negative tumors had a higher risk of death than patients with p16 protein positive tumors (HR 0.423，95%CI 0.201-0.891，P=0.024).p16 was closely related to the prognosis of oropharyngeal cancer.Conclusion:The p16 protein expression was highly correlated with the presence of HPV16,and might be a surrogate marker for HPV16 to predict the prognosis.There was a trend that p16 protein positive oropharyngeal cancer patients might be non-smokers，non-drinkers，chewing betelers and low degree of tumor differentiation.Detecting the p16 protein expression has important prognostic significance for OPSCC patients.