CD44v6与人乳头状瘤病毒L1衣壳蛋白在宫颈鳞癌及癌前病变中的诊断价值

Diagnostic value of CD44v6 and HPV L1 capsid protein in cervical squamous cell carcinoma and precancerous lesions

摘要:

目的 探讨CD44v6与人乳头状瘤病毒（HPV）L1衣壳蛋白在宫颈鳞癌及癌前病变中的诊断价值。方法 收集2017年1月—2022年1月江南大学附属医院102例手术切除的宫颈鳞癌及癌前病变组织石蜡标本，其中宫颈鳞癌组织石蜡标本41例，癌前病变组织石蜡标本61例［宫颈低级别上皮内病变（LSIL）标本30例，宫颈高级别上皮内病变（HSIL）组织31例］，另选取同期49例因子宫肌瘤行子宫切除的正常宫颈组织石蜡标本为对照。采用免疫组织化学法检测不同组织中CD44v6与HPV L1衣壳蛋白表达，绘制受试者工作特征（ROC）曲线分析CD44v6、HPV L1衣壳蛋白在宫颈鳞癌及癌前病变中的诊断价值。结果 正常宫颈组织、LSIL组织、HSIL组织、宫颈鳞癌组织中CD44v6阳性表达率比较，差异有统计学意义（P <0.05），宫颈鳞癌组织高于正常宫颈组织、LSIL组织及HSIL组织（P <0.05），HSIL组织高于正常宫颈组织和LSIL组织（P <0.05）。正常宫颈组织、LSIL组织、HSIL组织、宫颈鳞癌组织中HPV L1衣壳蛋白阳性表达率比较，差异有统计学意义（P <0.05），宫颈鳞癌组织低于HSIL组织、LSIL组织、正常宫颈组织（P <0.05），HSIL组织低于LSIL组织、正常宫颈组织（P <0.05）。ROC曲线分析结果显示，宫颈鳞癌组织中CD44v6、HPV L1衣壳蛋白及两者联合诊断宫颈鳞癌的敏感性分别为70.73%（95% CI：0.543，0.834）、75.61%（95% CI：0.594，0.871）、70.73%（95% CI：0.543，0.834），特异性分别为77.05%（95% CI：0.642，0.865）、73.77%（95% CI：0.607，0.838）、90.16%（95% CI：0.792，0.959），AUC分别为0.746（95% CI：0.648，0.844）、0.742（95% CI：0.638，0.846）、0.907（95% CI：0.848，0.966）。ROC曲线分析结果显示，癌前病变组织中CD44v6、HPV L1衣壳蛋白及两者联合诊断HSIL的敏感性分别为74.19%（95% CI：0.551，0.875）、70.96%（95% CI：0.518，0.851）、70.96%（95% CI：0.518，0.851），特异性分别为76.67%（95% CI：0.573，0.894）、73.33%（95% CI：0.538，0.870）、90.00%（95% CI：0.723，0.974），AUC分别为0.748（95% CI：0.649，0.847）、0.726（95% CI：0.627，0.825）、0.890（95% CI：0.820，0.959）。结论 CD44v6在宫颈病变组织中异常高表达，且随着宫颈病变程度的加重，CD44v6表达水平呈升高趋势，HPV L1衣壳蛋白的变化与CD44v6相反，两者联合诊断宫颈鳞癌及癌前病变价值较高。

关键词:宫颈鳞癌;癌前病变;CD44v6;人乳头状瘤病毒L1衣壳蛋白;诊断效能

Abstract:

Objective To investigate the diagnostic value of CD44v6 and human papillomavirus (HPV) L1 capsid protein in cervical squamous cell carcinoma and precancerous lesions.Methods A total of 102 cases of paraffin specimens of cervical squamous cell carcinoma and precancerous lesions resected in the hospital from January 2017 to January 2022 were collected. Among them, 41 were paraffin specimens of cervical squamous cell carcinoma, 30 were cervical low-grade intraepithelial lesion (LSIL) specimens in precancerous lesions, and 31 were cervical high-grade intraepithelial lesion (HSIL) specimens. Another 49 cases of normal cervical tissue paraffin specimens that underwent hysterectomy due to uterine fibroids were selected as controls. The expression of CD44v6 and HPV L1 capsid protein in different tissue samples was determined by immunohistochemistry. The diagnostic value of CD44v6 and HPV L1 capsid protein in cervical squamous cell carcinoma and precancerous lesions was analyzed.Results The positive expression rate of CD44v6 in normal cervical tissue, LSIL tissue, HSIL tissue, and cervical squamous cell carcinoma tissue was significantly different (P < 0.05). The positive expression rate of CD44v6 in cervical squamous cell carcinoma was higher than that in LSIL tissue and normal cervical tissue (P <0.05). The positive expression rate of CD44v6 in HSIL tissue was higher than that in normal cervical tissue (P <0.05). The positive expression rate of HPV L1 capsid protein in normal cervical tissue, LSIL tissue, HSIL tissue, and cervical squamous cell carcinoma tissue was significantly different (P < 0.05). The positive expression rate of HPV L1 capsid protein in cervical squamous cell carcinoma tissue was lower than that in HSIL tissue, LSIL tissue and normal cervical tissue (P < 0.05), and the positive expression rate of HPV L1 capsid protein in HSIL tissue was lower than that in LSIL tissue and normal cervical tissue (P < 0.05). The results of ROC curve analysis showed that the sensitivity of CD44v6 and HPV L1 capsid protein in cervical squamous cell carcinoma and precancerous lesion tissue samples for diagnosing cervical squamous cell carcinoma was 70.73% (95% CI: 0.543, 0.834), 75.61% (95% CI: 0.594, 0.871), 70.73% (95% CI: 0.543, 0.834), specificities were 77.05% (95% CI: 0.642, 0.865), 73.77% (95% CI: 0.607, 0.838), 90.16% (95% CI: 0.792, 0.959), AUCs were 0.746 (95% CI: 0.648, 0.844), 0.742 (95% CI: 0.638, 0.846), 0.907 (95% CI: 0.848, 0.966). The results of ROC curve analysis showed that the sensitivities of CD44v6 and HPV L1 capsid proteins in the precancerous lesion tissue samples for the diagnosis of HSIL were 74.19% (95% CI: 0.551, 0.875）, 70.96% (95% CI: 0.518, 0.851), 70.96% (95% CI: 0.518, 0.851), the specificity was 76.67% (95% CI: 0.573, 0.894), 73.33%（95% CI: 0.538, 0.870), 90.00% (95% CI: 0.723, 0.974), AUC were 0.748 (95% CI: 0.649, 0.847）, 0.726 (95% CI: 0.627, 0.825), 0.890 (95% CI: 0.820, 0.959).Conclusion CD44v6 is abnormally highly expressed in cervical lesions, and the expression level of CD44v6 increases with the severity of cervical lesions. The changes of HPV L1 capsid protein are opposite to that of CD44v6. The combined diagnosis of cervical squamous cell carcinoma and precancerous lesions is of high value.

Key words:cervical squamous cell carcinoma;precancerous lesions;CD44v6;human papillomavirus L1 capsid protein;diagnosis