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Title: [Relationship between cervical lesions and the type-specific viral load of high risk HPV reflected by the Ct value of Cobas 4800 HPV system].
Author: Duan LF, Du H, Xiao AM, Wang C, Huang X, Zhao MF, Men HJ, Wu RF.
Journal: Zhonghua Fu Chan Ke Za Zhi; 2019 Jul 25; 54(7):458-463. PubMed ID: 31365958.
Abstract:
Objective: To explore the relationship between cervical lesions and high risk HPV (HR-HPV) viral load reflected by the cycle threshold (Ct) values of Cobas 4800 HPV (Cobas 4800) system. Methods: From August 2016 to September 2017, 7 000 women from Shenzhen, were recruited for cervical cancer screening with Cobas 4800 system and cytology co-test. Colposcope biopsies were performed on women who were positive of HPV 16, 18, and positive of HPV types other than 16,18 with cytology [≥ atypical squamous cell of undetermined signification (ASCUS)], or HPV negative but abnormal of cytology [≥ low grade squamous intraepithelial lesion (LSIL)]. The Ct values of HPV 16, 18 and all combined other types coming from Cobas 4800 system were used as an indicator of viral load to analyze the relationship between type-specific HPV load and the cervical lesions. Results: (1) Among the 7 000 screening women, 370 cases were positive for cervical cancer screening, 325 of them underwent colposcope biopsies, and coloposcopy referred rate was 87.8% (325/370). Among 325 women undergoing cervical biopsy, pathological diagnosis was 119 cases of normal cervical cervix, 151 cases of LSIL, and 55 cases of high-grade squamous intraepithelial lesion (HSIL) and above (HSIL(+); including 53 cases of HSIL, 1 case of cervical adenocarcinoma, and 1 case of cervical squamous cell carcinoma). (2) The Ct value of HPV 16 was inversely correlated with the upgrading of the lesions (r=-0.617, P=0.000), and significant different among normal cervix,LSIL and HSIL(+) (35.4±4.5 vs 31.0±6.0 vs 26.5±4.0; F=25.537, P=0.000). There was no correlation between Ct value of HPV 18 and cervical lesions (r=-0.021, P=0.902). The Ct value of other 12 HPV types was statistically difference among normal normal cervix, HSIL(+) and cervicitis (33.0±5.3 vs 29.9±7.2 vs 29.8±5.8; F=5.087, P=0.007). Among them, LSIL and HSIL(+) were significantly lower than normal cervix (P<0.05), but there was no significant difference between LSIL and HSIL(+) (P>0.05). Conclusion: The Ct value of HPV 16 detecting in Cobas 4800 system as an indicator of virus load obviously correlates with different grades of cervical lesions, therefore could be a reference of cervical lesion existence and an indicator of lesion prognosis. 目的： 探讨Cobas 4800 HPV（Cobas 4800）检测的循环阈值（Ct值）反映的型别特异性高危型HPV（HR-HPV）亚型病毒载量与子宫颈病变的关系。 方法： 2016年8月—2017年9月在深圳市龙岗区布吉街道募集有性生活的非妊娠期妇女7 000例，以细胞学检查联合HR-HPV检测进行子宫颈癌筛查，细胞学检查采用液基薄层细胞学检查（TCT），HR-HPV检测采用Cobas 4800检测方法，可检测14种HR-HPV亚型，包括HPV 16、18、31、33、35、39、45、51、52、56、58、59、66、68型，对于筛查阳性者回叫行阴道镜下子宫颈活检病理诊断。将Cobas 4800检测中反映病毒拷贝数的Ct值作为反映HR-HPV病毒载量的指标（Ct值越大则病毒载量越低），分析型别特异性的HR-HPV亚型病毒载量与子宫颈病变程度的关系。 结果： （1）接受子宫颈癌筛查的7 000例妇女中，筛查阳性者370例，回叫后行阴道镜下子宫颈活检325例，回叫率为87.8%（325/370）。325例行阴道镜下子宫颈活检的妇女中，病理诊断为正常子宫颈119例、低级别鳞状上皮内病变（LSIL）151例、高级别鳞状上皮内病变（HSIL）及以上病变（HSIL(+)）55例（包括HSIL 53例、子宫颈原位腺癌1例、子宫颈鳞癌1例）。（2）325例行阴道镜下子宫颈活检妇女中，病理诊断为正常子宫颈、LSIL、HSIL(+)妇女的HPV 16型的Ct值分别为35.4±4.5、31.0±6.0、26.5±4.0，3者比较，差异有统计学意义（F=25.537，P=0.000）；Pearson相关分析显示，HPV 16型的Ct值与子宫颈病变程度呈显著负相关关系（r=-0.617，P=0.000），即HPV 16型病毒载量与子宫颈病变程度呈显著正相关关系。HPV 18型的Ct值与子宫颈病变程度无显著相关性（r=-0.021，P=0.902），即HPV 18型病毒载量与子宫颈病变程度无显著相关性。病理诊断为正常子宫颈、LSIL、HSIL(+)妇女的其他12种HR-HPV亚型的Ct值分别为33.0±5.3、29.9±7.2、29.8±5.8，3者比较，差异有统计学意义（F=5.087，P=0.007）；其中LSIL、HSIL(+)均显著低于正常子宫颈（P<0.05），但LSIL与HSIL(+)比较无显著差异（P>0.05）；Pearson相关分析显示，其他12种HR-HPV亚型的Ct值与子宫颈病变程度呈显著负相关关系（r=-0.194，P=0.007），即其他12种HR-HPV亚型病毒载量与子宫颈病变程度呈显著正相关关系。 结论： 高致瘤亚型HPV 16型病毒载量随着子宫颈病变严重程度的增高而升高，两者呈显著正相关关系。反映型别特异性HR-HPV亚型病毒载量的Cobas 4800检测中的Ct值有望作为HR-HPV筛查阳性者的分流与判断预后的指标。.

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