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目的探讨高危型人乳头瘤病毒(HR-HPV)核酸定量、P16、HPV L1壳蛋白在女性宫颈病变中的关系。方法选取2012年6月-2016年6月山西省中西医结合医院妇科收治的宫颈癌患者68例,低级别鳞状上皮病变(LSIL)54例,高级别鳞状上皮病变(HSIL)79例。另选取同期35例正常宫颈组织进行对照。采用免疫组化SP法检测P16蛋白、采用原位杂交检测HPV L1壳蛋白,采用第二代杂交捕获法(HC-2)检测HR-HPV,PCR体外扩增法测定HPV DNA核酸定量。分析3者在宫颈病变不同阶段中的相关性。结果随着宫颈病变的进展,P16蛋白的阳性率逐渐增加,各组间差异有统计学意义(P<0.01)。在LSIL中L1壳蛋白阳性表达率最高,随着宫颈病变进展,其阳性率下降,差异有统计学意义(P<0.05)。随着宫颈病变级别增高,HR-HPV阳性率及核酸定量增加,差异有统计学意义(P<0.01)。在慢性宫颈炎中,P16蛋白的阳性表达与HR-HPV核酸定量呈正相关(P<0.05);L1壳蛋白与HR-HPV核酸定量及P16蛋白均无相关性(P>0.05)。在LSIL中,P16蛋白、HPV L1壳蛋白的表达均与HR-HPV核酸定量呈正相关(P<0.01);P16与L1壳蛋白也呈正相关(P<0.01)。在HSIL中,P16蛋白、HR-HPV核酸定量呈正相关(P<0.05),L1壳蛋白与HR-HPV核酸定量及P16蛋白均无相关性(P>0.05)。在宫颈癌中P16蛋白阳性表达与HPV核酸定量呈正相关(P<0.01),L1壳蛋白与P16及HR-HPV核酸定量无相关性(P>0.05)。结论联合P16蛋白、L1壳蛋白分析HPV感染宿主后的状态,可有效判断宫颈病变的发展阶段,对宫颈病变的诊断及判断预后有重要意义。
Objective To investigate the relationship between nucleic acid quantification of high-risk human papillomavirus (HR-HPV), P16 and HPV L1 capsid protein in female patients with cervical lesions. Methods Sixty-eight cases of cervical cancer, 54 cases of low grade squamous cell carcinoma (LSIL) and 79 cases of high grade squamous cell carcinoma (HSIL) were selected from June 2012 to June 2016 in Shanxi Provincial Hospital of Integrated Traditional Chinese and Western Medicine. Another 35 cases of normal cervical tissue selected for control. Immunohistochemical SP method was used to detect P16 protein. HPV L1 capsid protein was detected by in situ hybridization. HR-HPV was detected by second-generation hybridization capture method (HC-2). To analyze the correlation between the three stages in different stages of cervical lesions. Results With the progress of cervical lesions, the positive rate of P16 protein gradually increased, with significant difference between the groups (P <0.01). The positive expression rate of L1 capsid protein in LSIL was the highest, with the progression of cervical lesions, the positive rate decreased, the difference was statistically significant (P <0.05). With the increase of cervical lesions, the positive rate of HR-HPV and the quantity of nucleic acid increased, the difference was statistically significant (P <0.01). In chronic cervicitis, positive expression of P16 protein was positively correlated with HR-HPV nucleic acid (P <0.05). There was no correlation between L1 capsid protein and HR-HPV DNA and P16 protein (P> 0.05). In LSIL, the expression of P16 protein and HPV L1 capsid protein were positively correlated with HR-HPV nucleic acid (P <0.01), and P16 was positively correlated with L1 capsid protein (P <0.01). In HSIL, there was a positive correlation between P16 protein and HR-HPV nucleic acid (P <0.05). There was no correlation between L1 capsid protein and HR-HPV DNA and P16 protein (P> 0.05). There was a positive correlation between the expression of P16 protein and HPV DNA in cervical cancer (P <0.01). There was no correlation between L1 protein and P16 and HR-HPV nucleic acid (P> 0.05). Conclusion The combination of P16 protein and L1 capsid protein in analyzing the status of HPV infected host can effectively judge the developmental stage of cervical lesions and is of great significance for diagnosis and prognosis of cervical lesions.