HPV L1壳蛋白联合 HPV 分型、TCT 检测在宫颈病变诊治中的临床应用研究

Study of clinical application of HPV L1 capsid protein combined with HPV typing and TCT detection in diagnosis and treatment of cervical lesion

目的：探讨人乳头瘤病毒L1（HPV L1）壳蛋白在不同宫颈病变及不同HPV亚型中的表达，以指导宫颈病变患者的个体化治疗及分流管理。方法回顾性分析本院妇科门诊行HPV L1壳蛋白联合HPV分型、液基薄层细胞学检测（ TCT）的176例患者的临床资料。结果宫颈TCT结果中不同情况与HPV L1壳蛋白的阳性表达率分布不同[未见异常细胞（ NILM），不明确意义的非典型鳞状上皮细胞（ASCUS），低度鳞状上皮内病变（LSIL），不除外高度病变的非典型鳞状上皮细胞（ ASC－H），高度鳞状上皮内病变（ HSIL）和鳞状细胞癌（ SCC）患者中的阳性表达率分别为28．99％、44．19％、64．44％、22．22％、12．50％、0，χ2＝19．98， P ＜0．01]，NILM与ASCUS中HPV L1壳蛋白阳性率比较，差异无统计学意义（ P ＞0．05），LSIL中HPV L1壳蛋白阳性表达率最高，与ASC－H、HSIL组比较，差异均有统计学意义（χ2＝3．88，5．50， P ＜0．05），SCC中HPV L1壳蛋白阳性表达率为0，随着宫颈细胞学病变级别升高而HPV L1壳蛋白阳性表达率呈下降趋势。宫颈组织病理学不同结果与HPV L1壳蛋白的阳性表达率分布不同[炎症、宫颈上皮内瘤变（ CIN）Ⅰ、CINⅡ、CINⅢ、鳞癌患者中的阳性表达率分别为44．76％、52．94％、23．81％、8．33、0，χ2＝13．29， P ＜0．01]，炎症和CIN Ⅰ的患者的HPV L1壳蛋白阳性率相近（ P ＞0．05），CINⅠ与CINⅡ、CINⅢ比较，差异均有统计学意义（χ2＝4．53，5．56， P ＜0．05），SCC中HPV L1壳蛋白阳性表达率为0，随宫颈组织病变级别升高而HPV L1壳蛋白阳性表达率呈下降趋势。 HPV L1壳蛋白在HPV感染频数前5位：多重感染、16型、52型、58型、18型中的阳性表达率分别为60．78％、17．65％、50％、66．67％、12．5％，16型感染者L1壳蛋白阳性表达率低于52型、58型及多重感染，其差异均有统计学意义（χ2＝4．15， P ＜0．05，χ2＝7．88，15．44， P ＜0．01）；18型感染者L1壳蛋白阳性表达率低于其它三类，但仅与多重感染比较差异有统计学意义（χ2＝4．70， P ＜0．05），其余比较差异无统计学意义（ P ＞0．05）。结论 HPV L1壳蛋白检测评估宫颈病变进展风险有一定临床价值，而HPV L1壳蛋白联合HPV分型、TCT检测有助于对宫颈病变患者进行最佳的分流管理与个体化治疗。

Objective To investigate the expression of human papilloma virus L1 （HPV L1）capsid protein in cervical lesions and different human papillomavirus （ HPV） subtypes, and to guide clinical triage management and best individual treatment.Methods Retrospective analysis of 2012 January to 2014 Janu-ary in Jiaxing Hospital of Traditional Chinese Medicine gynecology clinic for HPV L1 protein combined with HPV type, and liquid-based cytology test （ TCT） of 176 patients data.Results The positive expression rate of HPV L1 protein with TCT examination in the negative for intraepithelial lesion or malignancy （ NILM） , atypical squamous cells of undetermined significance（ ASCUS） , low-grade squamous intraepithe＆amp;nbsp;lial lesion （ LSIL） , atypical squamous cells not except high lesion （ ASC-H） , high-grade squamous intraep-ithelial lesion （ HSIL） , and squamous-cell carcinoma （ SCC） was 28.99%, 44.19%, 64.44%, 22.22%, 12.50%, and 0, respectively.No significant differences were found between the NILM and ASCUS groups （ P 〉0.05） .The positive expression rate of HPV L1 protein in LSIL group was the highest, and it was sta-tistically significantly different from ASC-H and HSIL groups （χ2 =3.88,5.50, P 〈0.05） , and 0 expres-sion in SCC group.It suggests that the positive expression rate of HPV L1 protein decreased with the severi-ty of cervical cytology lesions.The top five diseases with positive expression of HPV L1 protein were inflam-mation （44.76%）, cervical intraepithelial neoplasia （CIN）Ⅰ（52.94%）, CIN Ⅱ（23.81%）, CIN Ⅲ（8.33%）, and squamous cell carcinoma （0）; no significant difference was found between inflammation group and CIN Ⅰ group （ P 〉0.05 ）; and statistically significant difference was found between CIN Ⅰgroup and CINⅡ, CINⅢgroup （χ2 =4.53,5.56, P 〈0.05）, and 0 expression in SCC group.It sug-gests that the positive expression rate of HPV L1 protein increased with the increased level of cervical le-sions.The positive expression rate of HPV L1 protein in top five frequency of HPV infection was 60.78%in multiple infection, 17.65%in type 16, 50%in type 52, 66.67%in type 58, and 12.5%in type 18, re-spectively.The expression rate of HPV L1 protein of Type 16 infection was significantly lower than that of type 52, type 58 infection and multi infection（χ2 =4.15, P 〈0.05, χ2 =7.88,15.44, P 〈0.01）.The positive expression rate of HPV L1 protein of type 18 infection was lower than the other three, but significant differences occurred only compared to multiple infection（χ2 =4.70, P 〈0.05）.The rest had no significant difference（ P 〉0.05） .Conclusions Detection of HPV L1 protein is of clinical value to evaluate the risk of cervical lesions.HPV L1 protein combined with HPV type and TCT detection is helpful for traffic man-agement and personalized treatment, and benefit patients with cervical lesions.