中国和澳大利亚妇女子宫颈上皮内瘤变人乳头瘤病毒感染和相关危险因素的病例对照研究

Study on cervical intraepithelial neoplasia in relation to human papillomavirus and co-factors:a casecontrol study in China and Australia

目的研究不同型别人乳头瘤病毒(HPV)感染及相关危险因素与子宫颈上皮内瘤变(CIN)发生的关系。方法对来自中国(中组)、澳大利亚(澳组)的212例CIN和427名正常妇女,进行相关危险因素的问卷调查,并采集相应的子宫颈标本,PCR方法检测HPV DNA,用直接测序法及条型反向杂交法鉴定HPV型别。运用logistic回归方法分析HPV感染及其他辅助因素对宫颈病变发生的相对危险度。结果中、澳对照组妇女的HPV感染检出率分别为11%和15%(P>0.05)。常见型别为HPV16、58、66、18、31、33、53和MM8等,10%为混合感染。澳组CIN患者的HPV感染检出率高于中组,分别为99%和85%(P<0.001);HPV16型最为常见。中、澳组HPV感染致CIN的OR值分别为43.3和541.6。HPV16的致瘤危险性最强;中组HPV58和59型次之;澳组HPV 31型次之,且该组中HPV混合感染的相对危险度较高。多因素分析显示,在考虑了HPV感染之后,受教育程度(OR 3.88)、子宫颈癌家族史(OR 4.98)分别是中、澳两组妇女发生CIN的辅助危险因素。两组合并后,受教育程度(OR 4.02～5.15)和经常服用维生素(OR 0.40)是相关因素。结论HPV感染是中、澳两组妇女CIN发生的主要致病因素,不同HPV型别的危险性在两组妇女的子宫颈病变发生中存在一定差异,辅助危险因素也略有不同,提示在子宫颈病变防治中应有所侧重。

Objective This study was to elucidate the role of human papillomavirus （HPV） types and cofactors in the development of cervical intraepithelial neoplasia （CIN）. Methods Two hundred and twelve women with CIN and 427 women with normal cervical cytology （control group） were recruited from China and Australia. A questionnaire was administered to each participant to obtain the demographic and risk factor information. Cervical biopsies or smears were taken to detect HPV DNA by PCR and to identify HPV types by direct sequencing and/or Amplicor hybridisation. Data were analyzed by logistic regression. Results HPV prevalence rates of specimens from Chinese and Australian were 11% and 15% among controls（P〉0.05）, with 99% and 85% of CINs（P〈0.001）, respectively. The presence of any type of HPV DNA was strongly associated with CIN with OR 43.3 for Chinese and OR 541.6 for Australian women. The strongest risk was for HPV16, followed by HPV31 in Australians, but HPV58,59 in Chinese women. The risk for multiple HPV infection was stronger in the Australians than that in the Chinese cohort. Except for HPV infection, educational attainment was unexpectedly associated with an increased risk for CIN in Chinese, and cancer history in family was a risk factor for Australians. For the combined cohorts, educational attainment, and frequency of vitamin consumption were identified to be risk factors for CIN. Conclusion Cervical HPV DNA was a major risk factor, with the highest relative risk for type 16 HPV infection for CIN. There were variations in the distribution of HPV genotypes and cofactors in China versus Australia and in CIN.