下咽鳞状细胞癌中HPV感染、p16表达及其与患者预后的关系

HPV infection and p16 expression in hypopharyngeal carcinoma and relationship with prognosis

目的探讨下咽鳞状细胞癌中HPV感染、p16表达及其与患者预后的关系。方法收集46例下咽鳞状细胞癌手术标本,应用免疫组化SP法检测p16的表达;采用PCR-DNA反向点杂交技术检测HPV感染情况,收集临床病理资料并进行随访。结果下咽鳞状细胞癌组织中HPV感染率为26.1%(12/46),HPV感染与患者年龄、性别、发病部位、分化程度、TNM分期无关(P>0.05)。下咽鳞状细胞癌患者p16蛋白阳性率为39.1%(18/46),p16蛋白阳性率与患者年龄、性别、发病部位、分化程度、TNM分期无关(P>0.05)。HPV感染与p16蛋白表达呈正相关(r=0.437,P=0.002)。Kaplan-Meier生存分析显示:HPV阳性者比HPV阴性者中位生存期高(P=0.001);HPV阳性者中位无进展生存期亦高于HPV阴性者(P=0.002)。p16蛋白阳性者比p16阴性者中位生存期高(P=0.001);p16蛋白阳性者中位无进展生存期亦高于p16阴性者(P=0.003)。多因素Cox回归模型分析显示:临床分期、HPV感染及p16表达,是影响患者预后的独立因素(RR值分别为1.969、4.324、0.294,P值分别为0.018、0.015、0.013)。结论下咽鳞状细胞癌中HPV感染与p16蛋白表达相关,临床分期早、HPV感染及p16阳性的患者预后较好。

Purpose To investigate the relationship between HPV infection, p16 expression and prognosis in patients with hypopharyn- geal carcinoma. Methods 46 cases of hypopharyngeal carcinoma surgical specimens were selected, PCR-reverse dot blot hybridization was used to detect infection of HPV and SP immunohistoehemical method was adopted to detect p16 expression in hypopharyngeal carci- noma tissues. Clinical data were collected and all the patients were followed up. Results Infection rate of HPV in hypopharyngeal car- cinoma tissues was 26. 1% （12/46）. No significant difference was found between HPV infection and patients＇ age, gender, primary tumor site, histologic differentiation and TNM classification （ P 〉 0. 05 ）. The expression rate of p16 protein in hypopharyngeal carcino- ma tissues was 39. 1% （18/46）. Expression of p16 proteins was not significantly correlated with patients＇ age, gender, primary tumor site, histologic differentiation and TNM classification （ P 〉 0. 05 ）. However, HPV infection was positively correlated with the expres- sion rate of p16 protein in hypopharyngeal carcinoma tissues （ r = 0. 437, P = 0. 002 ）. Kaplan-Meier analysis showed that HPV-positive patients had a higher median overall survival than HPV-negative patients （ P = 0. 001 ）. Median progression-free survival was virtually the same for both HPV-positive and HPV-negative patients （P = 0. 002 ）. pl6-positive patients had a higher median overall survival than p16-negative patients （P = 0. 001 ）. Median progression-free survival was also almost the same for both pl6-positive and pl6-neg- ative patients （P = 0. 003 ）. Cox regression analysis showed that clinical stage, HPV infection and p16 expression were independent prognostic factors （RR = 1. 969, 4. 324, 0. 294, P = 0. 018, 0. 015, 0. 013）. Conclusion There is a positive correlation between HPV infection and expression of p16 protein in hypopharyngeal carcinoma pateints. Patients with early clinical stage, HPV infection and p16 positive have favorable prognosis.