【摘要】 目的从基因组突变角度探讨人乳头瘤病毒(human papillomavirus,HPV)与宫颈癌发生及病变程度的相关性,为宫颈癌的筛查和早期诊断提供新思路。方法选择正常宫颈组织、慢性宫颈炎组织、宫颈癌前病变组织以及宫颈癌组织,采用PCR法检测HPV18及其载量,测序分析E1-E4基因突变情况。结果宫颈癌组HPV18阳性率为95.1%,病毒载量为(280.14±54.89)pg/ml,宫颈癌前病变组和慢性宫颈炎组HPV18阳性率分别为92.0%和51.9%,病毒载量分别为(246.26±78.31)pg/ml和(253.51±58.63)pg/ml,与正常宫颈组HPV18阳性率4.5%和病毒载量(13.48±32.65)pg/ml比较差异均有统计学意义(P<0.05);宫颈癌组、宫颈癌前病变组及慢性宫颈炎组病毒载量差异无统计学意义(P>0.05)。宫颈癌组HPV18无突变和17/18突变率分别为54.3%和24.1%,与慢性宫颈炎组30.4%和12.2%比较差异有统计学意义(P<0.05)。慢性宫颈炎组54突变率为23.2%,与宫颈癌前病变组13.8%和宫颈癌组12.1%比较差异有统计学意义(P<0.05);34突变率为28.0%,与宫颈癌组4.3%比较差异有统计学意义(P<0.05)。慢性宫颈炎、宫颈癌前病变以及宫颈癌组63/67突变率差异无统计学意义(P>0.05)。结论宫颈病变程度与HPV18载量无明显相关性,而与HPV18E1-E4基因突变相关。发生17/18突变的HPV18毒力基本保持不变,而34突变和54突变会导致病毒毒力下降,使宫颈病变进程减缓。更多还原

【Abstract】 Objective To investigate the relationship between human papillomavirus(HPV)and the development and severity of cervical carcinoma from the perspective of genetic mutations and to provide new avenues for screening and early diagnosis of cervical carcinoma. Methods Materials were pathology specimens of normal cervical tissue,tissue displaying chronic cervicitis,precancerous cervical lesions,and cervical carcinoma.The rate of HPV18 detection,viral loads,and E1-E4 gene mutations were detected. Results The rate of HPV18 detection was 95.1%in cervical carcinoma,92.0%in precancerous cervical lesions,and 51.9%in tissue displaying chronic cervicitis.The viral load was 280.14±54.89 pg/ml in cervical carcinoma,246.26±78.31 pg/ml in precancerous cervical lesions,and 253.51±58.63 pg/ml in tissue displaying chronic cervicitis.The rate of HPV18 detection and the viral load in the three groups differed significantly(P<0.05)from the rate of detection(4.5%)and the viral load(13.48±32.65 pg/ml)in normal cervical tissue.The viral titer did not differ in cervical carcinoma,precancerous cervical lesions,and tissue displaying chronic cervicitis(P>0.05).A mutation was not found in 54.3% of HPV18 in cervical carcinoma,though a mutation was found in 24.1% of HPV17 or HPV18.The rate at which a mutation was found or not found differed significantly from the rate in tissue displaying chronic cervicitis(30.4% and 12.2%,respectively,P<0.05).A mutation at codon 54 was found in 23.2% of tissue displaying chronic cervicitis,which was significantly higher than the rate in cervical carcinoma(12.1%)and the rate in precancerous cervical lesions(13.8%,P<0.05 for both).A mutation at codon 34 was significantly more frequent in tissue displaying chronic cervicitis than in cervical carcinoma(28.0% vs.4.3%,P<0.05).The frequency of a mutation at codon 63 or 67 did not differ significantly among tissue displaying chronic cervicitis,precancerous cervical lesions,and cervical carcinoma group. Conclusion The severity of cervical lesions was not correlated with the viral titer of HPV18 but it was correlated with mutations in the E1-E4 genes.The virulence of HPV18 remained the same when mutations occurred at codons 17 and 18,while mutations at codons 34 and 54 led to a decrease in virulence and slowed down the progression of cervical lesions.更多还原