人乳头状瘤病毒相关扁桃体癌患者临床特征及p16和p53蛋白表达情况

Clinical features and expressions of p16, p53 protein of human papillomavirus-related tonsillar carcinoma

目的总结分析人乳头状瘤病毒（human papillomavirus，HPV）相关扁桃体鳞状细胞癌（鳞癌）患者的临床病理特征、预后特点及分子生物学改变。方法回顾性分析1999年1月至2012年12月期间中国医学科学院肿瘤医院收治的符合人组条件的61例扁桃体鳞癌患者的临床病理资料，应用HPVSPF10PCR／DEIA检测和LiPA分型方法进行HPV-DNA检测及分型；采用免疫组织化学法检测p16及p53蛋白表达情况。采用Kaplan—Meier法计算生存率。结果61例扁桃体鳞癌患者中，男55例，女6例；中位发病年龄57岁。肿瘤临床分期为I期0例，Ⅱ期7例，Ⅲ期10例，Ⅳ期44例。肿瘤的分化程度为高分化2l例，中分化19例，低分化21例。扁桃体鳞癌HPV总感染率为29．5％（18／61），男性14例，女性4例，其中HPV-16亚型占全部感染的72．2％（13／18）。HPV相关扁桃体鳞癌女性患者比例高于非HPV相关扁桃体鳞癌（22．2％比4．7％），且更易发生于非吸烟及非饮酒患者（吸烟：50．0％比79．1％，x2=5．155，P=0．023；酗酒：27．8％比51．2％，x2=4．346，P=0．037）。HPV相关扁桃体鳞癌p16蛋白多为高表达（88．9％比16．3％，x2=28．481，P=0．000），而p53蛋白多为低表达（72．7％比46．5％，x2=5．028，P=0．025）。Kaplan—Meier法计算HPV相关扁桃体鳞癌3年和5年总生存率分别为87．7％和78．9％，明显高于非HPV相关扁桃体鳞癌的3年总生存率49．5％和5年生存率33．0％，差异有统计学意义（X2=9．139，P=0．003）。结论HPV相关扁桃体鳞癌具有特殊的临床病理特征及分子生物学改变，且预后显著好于非HPV相关扁桃体鳞癌。

Objective To analyze the clinical characteristics, prognosis and molecular biological changes of tonsillar squamous cell carcinoma （ TSCC ）. Methods Retrospective analysis of 61 TSCC cases treated from January 1999 to December 2012. Demographic data and clinical charts,including histologic grade of tumor, treatment and outcome of the patients, were reviewed. Human papillomavirus （ HPV ） -DNA were detected using SPF10-DNA enzyme immunoassay and LiPA genotyping method. Expressions of p16 and p53 proteins were examinated by immunohistochemistry. Survival rate was calculated with SPSS 19. 0 software using the Kaplan-Meier method. Results There were 55 males and 6 females, with a median age of 57 years. Of the 61 TSCC ,21 were with well differentiation, 19 with moderate differentiation and 21 with poor differentiation, including 7 patients at stage Ⅱ , 10 at stage Ⅲ and 44 at stage Ⅳ. HPV-positive rate of TSCC was 29. 5% （ 18/61 ） and high-risk HPV-16 subtype aecounted for 72. 2% （ 13/18 ）. The percentage of famel patients in HPV-positive TSCC was higher than HPV-negative TSCC（22. 2% vs 4.7% ）. HPV-positive TSCC was more common in non-smoking patients （50. 0% vs 79. 1% , X2 = 5,155, P = 0. 023 ） and non- drinking patients （27.8% vs 51.2% , X2 = 4. 346, P = 0. 037 ）. HPV-positive TSCC mostly presented with high expression of p16 protein （ 88.9% vs 16. 3% , X2 = 28. 481, P = 0. 000 ） , and low expression of p53 protein（72. 7% vs 46. 5%, X2 =5. 028,P = 0. 025 ）. The prognosis of patients with HPV-associated TSCC was significantly better than non-HPV-associated TSCC, and The 3-year and 5-year overall survival rates of patients with HPV-positive TSCC were higher than those of patients with HPV-negative TSCC （ 87.7% vs 49. 5% and 78.9% vs 33.0%, respectively ） . Conclusion HPV-associated TSCC had unique clinicopathological and molecular biological features, showing better prognosis compared to HPV-negative TSCC.