口咽鳞癌HPV感染与p16表达及放疗预后相关性研究

Relationship between HPV infection/p16 expression and radiotherapy prognosis in oropharyngeal squamous cell carcinoma

目的 探讨口咽鳞癌HPV感染与p16表达及放疗预后相关性,以及p16是否有预测放疗预后的价值.方法 对1999-2008年间本院42例初治口咽鳞癌组织标本采用PCR检测HPV-DNA,采用免疫组织化学法检测p16表达情况.对HPV、p16不同状态肿瘤根治性放疗后局部区域CR及HPV感染与p16表达相关性比较行x2检验,Kaplan-Meier法计算OS并Logrank法检验.结果 随访率100％.HPV感染率为19％,p16阳性率为43％.接受根治性放疗者HPV（＋）与HPV（-）的局部CR分别为100％与54％（P=0.026）,p16（＋）与p16（-）的局部CR分别为92％与44％（P=0.006）,p16（＋）与p16（-）的局部加区域CR为69％与22％ （P =0.009）.高危型HPV感染与p16表达明显相关（P =0.000）.p16（＋）与p16（-）的3年OS分别为91％与26％ （P =0.001）.结论 p16表达与HPV感染的口咽鳞癌密切相关,有望成为预测口咽鳞癌放疗预后的标志物之一.

Objective To investigate the relationship between human papillomavirus （HPV） infection/pl6 expression and radiotherapy prognosis in oropharyngeal squamous cell carcinoma （OSCC） and the prognostic value of p16 in OSCC patients treated with radiotherapy. Methods Tissue samples were collected from 42 patients newly diagnosed with OSCC in our hospital from January 1999 to December 2008. PCR was performed to detect HPV DNA, and p16 expression was measured by immunohistoehemistry. The chi-square test was used to compare the local/regional control rate （CR） between HPV （ ＋ ）/p16 （ ＋ ） patients and HPV （ - ）/p16 （ - ） patients after radical radiotherapy and evaluate the association between HPV infection and p16 expression; the Kaplan-Meier method was used to calculate overall survival （OS）, and the log-rank test was used for survival difference analysis. Results The follow-up rate was 100%. The HPV infection rate was 19%, and the positive rate of p16 was 43%. In patients who received radical radiotherapy, the local CR for HPV （ ＋ ） patients was 100%, versus 54% for HPV （ - ） patients （P = 0. 026） ;the local CR for p16（ ＋ ） patients was 92%, versus 44% for p16（ - ） patients （P =0. 006） ;the loeoregional CR for p16（ ＋ ） patients was 69%, versus 22% for p16（ - ） patients （P =0. 009）. For high- risk patients, HPV infection was significantly associated with p16 expression （P = 0. 000）. The 3-year OS rates for p 16 （ ＋ ） and p 1 6 （ - ） patients were 9 1% and 2 6 % , respectively （ P = 0. 0 01 ） . Conclusions The p16 expression is closely associated with HPV infection in OSCC patients, and it is expected to become one of the prognostic markers in OSCC patients treated with radiotherapy.