中国口腔癌中高危型HPV感染率的Meta分析

High-risk HPV infection and its cancer risk in Chinese patients with oral cancer:a Meta analysis and systematic review

目的高危型人乳头瘤病毒（human papillomavirus，HPV）感染可能与口腔癌的发病有关。迄今为止，中国人群中仍缺少大样本量的研究分析中国口腔癌中的HPV感染率及口腔感染HPV的致癌风险。本研究对中国口腔癌中高危型HPV的感染率以及感染高危型HPV的口腔癌致癌风险进行荟萃分析。方法检索CNKI、VIP、CBM和万方等中文数据库以及PubMed、Embase等外文数据库，检索时间均从建库至2014—10—24。纳入符合条件的文献，采用Stata11．0软件进行荟萃分析口腔癌患者中HPV（未分型）、HPV-16、HPV-18和HPV-6／18重叠感染率，并根据检测方法、标本类型和研究时间进行HPV-16感染率的亚组分析。纳入病例一对照研究，进行高危型HPV-16、HPV-18感染与口腔癌的发病风险的荟萃分析。结果共44篇文献纳入中国口腔癌中HPV感染率的荟萃分析，中国口腔癌中HPV的总感染率、HPV-16感染率、HPV-18感染率、HPV-16／18的重叠感染率分别为52％（95％CI：41％～63％）、42％（95％CI：33％～51％）、22％（95％CI：13％～30％）和11％（95％CI：7％～16％）；口腔鳞癌中HPV-16感染率为42％（95％CI：32％～52％）。亚组比较显示，2000年以后发表的论文中HPV感染率更高，P=0．020；PCR和非PCR检测方法的感染率差异无统计学意义，P：0．500；新鲜冷冻组织组和石蜡保存标本相比，虽然HPV感染率较高，但是差异无统计学意义，P=0．229。共15篇文献纳入口腔癌HPV-16感染风险效应的荟萃分析，0R为5．95（95％CI：3．97～8．93），差异有统计学意义，P〈0．001；共5篇文献纳入口腔癌中HPV-18感染风险效应的荟萃分析，OR=1．55（95％CI：0．77～3．13），差异无统计学意义，P=0．221。结论中国口腔癌患者中HPV感染率保持在较高的水平，其感染以HPV-16为主，并且有随时间增高的趋势。感染HPV-16明显增加了中国口腔癌发生的危险性。

OBJECTIVE Previous studies indicated that oral cancer may be related to human papillomavirus （HPV） infection. However, up to now, there still lacks a large sample study to analyze the HPV prevalence in Chinese oral canc- er patient and the oral cancer risk conferred by oral HPV infection. In the present study, we synthetically research the prevalence of high-risk HPV infection in Chinese patients with oral cancer, and systematically evaluate the cancer risk conferred by the infection of high-risk HPV. METHODS We identified eligible studies in either English or Chinese pub- lished up to 24th October 2014 by searching the Chinese National Knowledge Infrastructure （CNKI）, Wanfang Database,VIP Database, MEDLINE, and Embase, the trails which met the inclusive criteria were enrolled in this research. The prevalence of HPV （all subtypes）, HPV-16, HPV-18, and HPV-16/18 in oral cancers and the prevalence of HPV-16 in the subgroups which were stratified by detection method, sample preservation method and the year of research were all ana- lyzed by the Stata 11.0 software. We further evaluated the oral cancer risk of high-risk HPV-16 and HPV-18 infection by means of odds ratio （OR）, generated by comparisons with the control group in the identified case-control trails using Stata 11.0 software. RESULTS A total of 44 trails were screened out for the meta-analyses assessing HPV prevalence in Chi- nese oral cancer patients, the prevalence of HPV （all subtypes）, HPV-16, HPV-18, and coinfection of HPV-16/18 were 52% （95%CI：41%-63%）, 42% （95%CI：33%-51%）, 22% （95%CI：13%-30%）, and 11% （95%CI：7%-16%）, respectively. The infection rate of HPV-16 was 42 % （95 %CI： 32 %- 52 % ） in oral squamous cell carcinomas. The compar- isons between subgroups indicated that a higher infection rate was found in papers published after the year of 2000 （P= 0. 020）, while no statistical differences in subgroups stratified by detection methods （PCR vs non-PCR, P=0. 500） and sample types （fresh-frozen samples vs. formalin-fixed paraffin-embedded samples, P=0. 029）. Fifteen trails were enrolled in the meta-analysis for evaluation the oral cancer risk of HPV-16 infection, OR= 5.95（95 %CI： 3.97--8.93）, having sta- tistical significance （P〈0. 001）. Five trails were enrolled in the meta-analysis for evaluation the oral cancer risk of HPV-18 infection, OR=I. 55 （95%CI：0. 77--3.13）, with no statistical significance （P=0. 221）. CONCLUSIONS HPV infection rate in oral cancer patients remained a relatively high level in Chinese population. HPV-16 was the most common subtype, and the infection rate tended to increase over time. The infection of HPV-16 significantly increased the oral cancer risk.