晚期非小细胞肺癌乳头瘤病毒感染状况及其与 P16表达的关联性研究

目的 探讨晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)人乳头瘤病毒(human papillomavirus,HPV)感染状况及其与P16的相关性研究。方法 收集83例临床确诊的晚期NSCLC患者石蜡包埋组织标本,采用Luminex液相芯片技术对所有标本进行HPV基因分型,免疫组化法检测P16表达情况。收集患者临床病理资料,分析HPV感染和P16表达对患者无进展生存期(progression-free survival,PFS)的影响。结果 83例晚期NSCLC患者组织中HPV感染率为24%(20/83),HPV感染主要发生在非吸烟者、淋巴结不转移者和分化程度较差者(P=0.048,P=0.044,P=0.024)。40%的HPV感染肿瘤组织P16表达阳性。多因素分析发现分化程度差(odds ratio=0.163) 是HPV感染的独立预测因子。P16阳性患者较P16阴性患者具有更长的PFS(P<0.023)。结论 研究结果表明P16蛋白表达与HPV感染无相关性,但P16蛋白表达可能是晚期NSCLC具有较长生存期的独立预测因子。

The association between P16 expression and human papillomavirus in advanced non-small cell lung cancer

Objective The present study examined the association between HPV infection and P16 expression in Chinese patients with advanced NSCLC.Methods A total of 83 advanced NSCLC patients were enrolled in the study.The status and genotype of HPV infection were determined by luminex liquid chip and the presence of P16 expression in tumor tissue was determined by immunohistochemistry.Clinical characteristics of these patients were also recorded to investigate the impact of HPV infection and P16 expression on progression-free survival.Results HPV DNA was detected in 20 out of 83 (24%) lung tumors and was observed more frequently in non-smokers,patients with no lymph node metastasis,and patients with poorly differentiated tumors (P=0.048,P=0.044 and P=0.024,respectively).Eight (40%) were positive for P16 expression.Multivariate analysis revealed that poor differentiation alone (odds ratio=0.163) was an independent predictive factor of HPV infection in advanced NSCLC.P16-positive patients had a significantly longer survival time when compared with P16-negative patients(P<0.023,log-rank test).Conclusions Our results suggest that P16 protein expression is not associated with the expression of HPV DNA,but that P16 expression may be an independent prognostic factor of long survival in advanced NSCLC.