人乳头瘤病毒基因亚型与宫颈病变的关系

Relationship between human papillomavirus types and cervical diseases

目的研究不同程度的子宫颈癌前病变者感染HPV的基因亚型,以探讨不同基因型HPV感染的致癌性。方法研究对象系356例宫颈HPV感染的患者。以第二代杂交捕获(HCⅡ)试验检测13种HPV-H,同时采用核酸分子快速杂交基因分型技术进行21种HPV-DNA亚型分析;所有研究对象均行宫颈薄层液基细胞学检测(LCT)及阴道镜下宫颈多点活检。根据细胞与病理学诊断有无宫颈病变及其病变程度分组。①宫颈癌与高度鳞状上皮内瘤变(HSIL)组:包括宫颈浸润癌9例、CINⅢ57例、CINⅡ53例;②低度鳞状上皮内瘤变(LSIL)组:包括CINⅠ112例、HPV感染52例;③正常或炎症组:宫颈细胞与组织学正常或炎症者73例。通过HPV-DNA亚型分布,分析HPV感染基因型与宫颈病变程度的关系。结果HPV-H与宫颈癌变密切相关,本组高度病变以上患者中HPV-H阳性率达98·4%;随着宫颈病变程度加重,HPV-H双重与多重感染有增加趋势,在正常与炎症组、LSIL组与HSIL组中两种以上HPV-H基因型感染者分别占13·7%、17·7%和36·6%,HSIL组明显高于其他两组,差异有显著性(P<0·01);本组HPV亚型感染频度由高到低依次为HPV-16(32·9%)、58(18·8%)、52(16·9%)、18(9·0%)、33(8·2%)、68(7·3%)、11(低危型,6·5%)、31(6·2%)、53(5·6%)、39(5·3%)、CP8304(5·1%)、66(3·9%)、6(2·5%)和51、56、45、35、59、43、44、82等少见型;HPV-16、58、33、52与18型在高度鳞状上皮内瘤样病变(HSIL)中感染率分别为56·4%、19·3%、16·0%、12·6%和8·4%,说明这些亚型致癌性更强;两种HPV-DNA检测技术所获结果,具有很高的一致性。结论本组宫颈病变患者感染HPV型别以16、58、52、18、33较为多见,HPV-16、58、33、52与18型致癌性较强;HPV-DNA分型检测在临床诊断与判断预后上具有重要意义。

Objective To investigate the human papillomavirus （HPV） types detected in patients with non - cancer, pre - cancer and cancer lesions at cervix and to analyze the oneogenesis of the various HPV types. Methods the cervical specimens from 356 patients with HPV infection were collected, Hybrid Capture Ⅱ （HCⅡ） assay was used to detect the 13 HPV-H types, and DNA flow - through hybridization genotyping technique was applied to determine the 21 HPV - DNA types. All of the patients received liquid- based cytology test （LCT） and colposcopy with multiple biopsy. According to the cytological and pathological diagnosis, the patients were. divided into three groups： ① cervical cancer and high - grade squamous intraepithelial lesions （HSIL） group, including 9 cases of invasive cervical cancer, 57 CINⅢ and 53 CINⅡ ; ② low - grade squamous intraepithelial lesions （LSIL） group, including 112 CIN Ⅰ and 52 mere HPV infection; ③ 73 in normal or inflammatory group. 1he relationship between HPV types and different cervical diseases was analyzed. Results HPV - H was tested positive in 98.4% of HSIL patients. In normal or inflammatory, LSIL and HSIL groups, double or multiple HPV- H type infection occurred at 13.7%, 17.7 % and 36.6% respectively, with HSIL group noticeably higher than the other two groups, P 〈 0.01. In this study, the prevalence of HPV types from highest to lowest order were as follow： HPV - 16 （32.9%）, 58 （18.8%）, 52 （16.9%）, 18 （9.0%）, 33 （8.2%）, 68 （7.3%）, 11 （low risk type, 6.5%）, 31 （6.2%）, 53 （low risk .type, 5.6%）, 39 （5.3%）, CP8304 （5.1%）, 66 （low risktype, 3.9%）, 6 （2.5%）, and other rare types 51, 56, 45, 35, 59, 43, 44, 82, etc. The infection rates of HPV types 16, 58, 33, 52 and 18 in HSIL were 56.4%, 19.3%, 16.0%, 12.6% and 8.4% respectively. The data from HCⅡ and HPV-DNA genotyping were consistent. Conelusiorm HPV - H is closely associated with cervical cancer. HPV types 16, 58, 52, 18, 33 are more common in cervical disease more oncogenic than other HPV types. HPV - DNA genotyping is of great importance in diagnosis and prognosis of cervical disease.