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目的探讨高危型人乳头瘤病毒感染的宫颈脱落细胞中人乳头瘤病毒(HPV)L1蛋白表达、人类染色体端粒酶RNA(hTERC)基因的表达与宫颈病变的相关性。方法选择宫颈高危型HPV感染阳性的240例妇女的宫颈脱落细胞标本作为研究对象,240例病例按照TBS(the Bethesda system)2001年宫颈细胞学诊断系统分为以下五组:(1)细胞学检查正常及慢性炎即正常宫颈组织(NILM)组(66例);(2)宫颈不典型鳞状细胞(ASCUS)组(27例);(3)宫颈低度病变(LISL)组(13例);(4)宫颈高度病变(HISL)组(86例);(5)宫颈癌(SCC)组(48例);根据阴道镜下活检送病理组织学检查的结果分为以下5组:(1)正常宫颈或慢性宫颈炎组即NILM组(51例);(2)宫颈上皮内瘤变1级(CIN1)组(42例);(3)宫颈上皮内瘤变2级(CIN2)组(28例);(4)宫颈上皮内瘤变3级(CIN3)组(73例);(5)SCC组(46例)。通过免疫细胞化学法检测宫颈脱落细胞中HPVL1蛋白的表达,通过荧光原位杂交(FISH)技术检测hTERC基因的表达,并对HPVL1蛋白及hTERC基因在不同级别病变的宫颈脱落细胞中的表达情况进行统计学分析。结果 240例高危型HPV感染妇女中150例hTERC基因扩增阳性,hTERC基因扩增阳性率为62.5%。NILM组、CIN1组、CIN2、CIN3和SCC组hTERC基因的扩增阳性率分别为7.8%、16.7%、75.0%、98.6%和100%,五组间hTERC基因扩增阳性率之间的差异有统计学意义(χ2=131.9,P<0.001)。此五组hTERC基因扩增阳性率的大小顺序为:SCC组≈CIN3组>CIN2组>CIN1组≈NILM组。通过Spearman等级相关分析,发现随着宫颈病变恶性程度的增加,各组中hTERC基因的扩增阳性率有增加的趋势(相关系数rs=0.71,P<0.001)。240例高危型HPV感染妇女中49例HPV L1壳蛋白表达阳性,HPV L1壳蛋白表达阳性率为20.4%。NILM组、CIN1组、CIN2组、CIN3组和SCC组HPV L1壳蛋白表达的阳性率分别为9.8%、66.7%、32.1%、9.6%和0%,五组间HPV L1壳蛋白表达阳性率之间的差异具有统计学意义(P<0.001)。通过Spearman等级相关分析,我们进一步发现HPV L1壳蛋白表达的阳性率与宫颈病变的恶性程度呈负相关(rs=-0.38,P<0.001)。结论随着宫颈病变恶性程度的增高,hTERC基因的阳性扩增率呈上升的趋势,HPVL1壳蛋白的阳性表达率呈现下降趋势,HPVL1壳蛋白与hTERC基因检测在临床上可以作为宫颈病变诊断及进一步评估进展风险的有效指标。
Objective To investigate the relationship between the expression of human papillomavirus (HPV) L1 and the expression of human telomerase RNA (hTERC) gene in cervical exfoliated cells infected by high-risk human papillomavirus (HPV) and cervical lesions. Methods The cervical exfoliated cells of 240 women with high-risk HPV infection were selected as the study subjects. 240 patients were divided into the following five groups according to the cervical cytology diagnostic system of TBS (the Bethesda system) in 2001: (1) Cytological examination Normal and chronic inflammation, normal cervical tissue (NILM) group (66 cases); (2) cervical atypical squamous cell (ASCUS) group (27 cases); (3) cervical low grade lesion ; (4) cervical hyperplastic lesions (HISL) group (86 cases); (5) cervical cancer group (48 cases); according to colposcopy biopsy sent histopathological examination results are divided into the following 5 groups: (1 ) In normal cervix or chronic cervicitis group (NILM group, 51 cases); (2) CIN1 group (42 cases); (3) cervical intraepithelial neoplasia grade 2 (CIN2) group 28 cases); (4) CIN3 group (73 cases); (5) SCC group (46 cases). The expression of HPV L1 protein in cervical exfoliated cells was detected by immunocytochemistry, the expression of hTERC gene was detected by fluorescence in situ hybridization (FISH), and the expression of HPV L1 protein and hTERC gene in cervical exfoliated cells of different grade lesions Statistical analysis. Results Among the 240 cases of high risk HPV infection, 150 cases of hTERC gene amplification positive, hTERC gene amplification was 62.5%. The positive rates of hTERC gene amplification in NILM, CIN1, CIN2, CIN3 and SCC groups were 7.8%, 16.7%, 75.0%, 98.6% and 100%, respectively Statistical significance (χ2 = 131.9, P <0.001). The positive rates of hTERC gene amplification in these five groups were as follows: SCC group ≈CIN3 group> CIN2 group> CIN1 group ≈NILM group. Spearman rank correlation analysis showed that with the increase of malignant cervical lesions, the positive rate of hTERC gene amplification increased in all groups (correlation coefficient rs = 0.71, P <0.001). In 240 cases of high risk HPV infection, 49 cases of HPV L1 capsid protein expression, HPV L1 capsid protein expression was 20.4%. The positive rates of HPV L1 capsid protein in NILM group, CIN1 group, CIN2 group, CIN3 group and SCC group were 9.8%, 66.7%, 32.1%, 9.6% and 0%, respectively The difference was statistically significant (P <0.001). By Spearman rank correlation analysis, we further found that the positive rate of HPV L1 capsid protein was negatively correlated with the malignancy of cervical lesions (rs = -0.38, P <0.001). Conclusion With the increase of malignant cervical lesions, the positive rate of hTERC gene increases and the positive rate of HPVL1 capsid protein shows a decreasing trend. The detection of HPVL1 capsid protein and hTERC gene can be used as a diagnosis of cervical lesions and further Effective indicators to assess progress risk.