头颈部鳞癌人乳头瘤病毒感染与p16和表皮生长因子受体表达及患者预后的关系

Relationship between human papilloma virus infection and expression of p16 and EGFR in head andneck squamous cell carcinoma and their prognostic significance

目的探讨人乳头瘤病毒（HPV）感染与p16、表皮生长因子受体（EGFR）表达和头颈部鳞癌患者预后的关系。方法采用原位杂交技术和免疫组化法检测HPV感染、p16和EGFR的表达情况。采用Kaplan-Meier法计算生存率，采用Cox比例风险模型分析影响患者预后的独立因素。结果本组43例患者中，HPV感染11例，感染率为25．6％，均为汉族。其中HPV16/18感染率为63．6％，HPV31/33感染率为27．3％，HPV16/18和HPV31/33共同感染率为9．1％。p16阳性表达率为53．5％，EGFR阳性表达率为69．8％。HPV阳性患者的民族、吸烟、饮酒情况与HPV阴性组患者比较，差异均有统计学意义（均P〈0．05）。HPV感染与p16和EGFR表达均有关（均P〈0．05）。p16表达与EGFR表达呈负相关（r=-0．447，P=0．003）。HPV阳性组和阴性组患者的3年生存率分别为60．0％和59．7％，差异无统计学意义（P=0．789）。p16阳性组和阴性组患者的3年生存率分别为72．2％和43．9％，差异有统计学意义（P=0．012），EGFR阳性组和阴性组患者的3年生存率分别为48．8％和81．8％，差异有统计学意义（P=0．037）。结论维吾尔族和汉族头颈部鳞癌患者HPV的感染率可能存在差异。HPV感染与p16和EGFR表达有关。p16表达是影响头颈部鳞癌患者预后的独立因素。

Objective To detect the infection of human papillomavirus （HPV） 6/11, 16/18, 31/33 in patients with head and neck squamous cell carcinoma and explore the relationship between HPV infection and expression of p16 and EGFR in the tumor tissue and their clinical significance. Methods The infection of HPV6/ll, 16/18, 31/33 was detected by in situ hybridization （ISH）, and expression of p16 and EGFR was assessed by immunohistochemistry in biopsy or surgical specimens of 43 cases of head and neck squamous cell carcinoma, and analyzed its impact on the prognosis. Spearman rank correlation method was used for analysis of the relationship. Overall survival rate of the patients was estimated by Kaplan-Meier analysis. Cox regression model was used for multivariate analysis. Results HPV6/ll, 16/18, 31/33 were detected in 25.6% （ 11/43 ） of this group of patients, among them, HPV16/18 accounted for 63.6% , HPV31/33 accounted for 27.3% , and HPV6/ll accounted for 0. EGFR was expressed in 69.8% and p16 was expressed in 53.5% of the patients. The difference was statistically significant between the HPV-positive and HPV-negative groups in ethnicity, smoking, alcohol consumption （ P = 0. 045, 0. 040, 0. 011, respectively）. HPV infection was found to be positively correlated with p16 expression and inversely correlated with EGFR expression （ P = O. 029, P = 0. 009 ）. The expression of p16 protein was negatively correlated with EGFR protein expression （ r = - 0. 447, P = 0. 003 ）. The 3-year overall survival rate was 60.0% in the HPV-positive group and 59.7% in the negative group （P =0. 789）; 72.2% in the p16positive patients and 43.9% in the pl6-negative patients （ P = 0. 012） ; 48.8% in the EGFR-positive patients and 81.8% in the EGFR-negative patients （ P = 0. 037）. Conclusions The results of our study suggest that the HPV infection rate, HPV subtypes and clinicopathological features of HPV-positive SCCHN are in accordance with those reported in Western literatures. There may be differences between the HPV infections in Uygur and Han nationalities. HPV infection is positively correlated with p16 and negatively correlated with EGFR expressions. The prognosis of pl6-positive patients is significantly better than that of negative cases, and p16 is an independent prognostic factor for head and neck squamous cell carcinoma.