新疆妇女宫颈癌组织中HPV-16E1/dup突变体分布的研究

摘要

目的 检测HPV-16 1311～1773位63bp重复序列插入突变的E1基因(E1/dup)在宫颈炎、宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及宫颈癌病变组织中的分布及病毒的整合状态,探讨该突变对病毒致癌活性的影响.方法 收集维吾尔族和汉族宫颈炎、CIN和宫颈癌临床组织标本215例,提取组织DNA,PCR检测E1/dup突变体以及病毒E1/E2基因的完整性.结果新疆地区215例宫颈病变组织中HPV-16 E1检出率为60.00％(129/215),宫颈炎、CIN及宫颈癌病样中HPV-16 E1的检出率分别为31.15％(19/61)、49.21％ (31/63)和86.81％(79/91).在HPV-16E1阳性病样中,HPV-16 E1/dup突变率为37.21％ (48/129),宫颈炎、CIN和宫颈癌病样中E1/dup突变率分别为15.79％、22.58％和48.10％,E1/dup突变率在宫颈癌中显著高于宫颈炎(P＜0.05)和CIN(P＜0.05).E1/dup突变率在汉族和维吾尔族宫颈癌病样中分别为40.00％(6/15)和50.00％(32/64),两者无显著性差异(P＞0.05).在HPV-16 E1阳性病样中病毒整合率为51.72％(60/116),E1/dup突变病样中HPV16整合率[69.05％(29/42)]明显高于未发生E1/dup突变的病样[41.89％(31/74)] (P＜0.05).结论新疆地区E1/dup突变率在宫颈癌中显著高于宫颈炎及CIN,E1/dup与病毒致癌活性及病毒整合相关.%Objective To detect the distribution of HPV-16 El gene mutant with the insertion of 63bp nucleotide duplication sequences at position 1311-1373 (E1/dup) from clinical tissue specimens of cervicitis, cervical intraepithelial neoplasia (CIN) and cervical cancer, and define the integrated status of HPV-16, then research into the carciongenic potency of El/dup. Methods 215 clinical tissue specimens of cervicitis, CIN and cervical cancer from Uygur and Han patients were collected, the tissue DNAs were extracted. Then E1/dup mutant and integral E1/E2 were detected by PCR. Results The positive rate of HPV-16 El in the 215 specimens was 60.00% (129/215), and the rates in cervicitis, CIN and cervical cancer were 31.15% (19/61), 49.21% (31/63) and 86.81% (79/91) respectively. In the HPV-16 E1 positive specimens, the rates of E1/dup mutant were 37.21%(48/129), and the rate of E1/dup mutant from the cervical cancer (48.10%) was significantly higher than that from the cervicitis (15.79%) (P<0.05) and CIN(22.58%) (P<0.05). The rates of E1/dup mutant from Han cervical cancer and Uygur cervical cancer specimens were 40.00% (6/15) and 50.00% (32/64) respectively, there were no significant differences between of them (P>0.05). The rate of integrated HPV-16 from the E1 positive specimens was 51.72%(60/119), and the rate[69.05%(29/42)] from the E1/dup Specimens was significantly higher than the rate [41.89%(31/74)] from no-E1/dup Specimens. Conclusion The rate of E1/dup mutant from the cervical cancer was significantly higher than that from the cervicitis and CIN, and E1/dup mutant was associated with the carciongenic potency and integrated status of HPV-16.