DNA倍体定量分析联合HR-HPV检测在宫颈病变中的应用价值

目的：探讨DNA倍体定量分析联合高危型人乳头瘤病毒(high risk human papillomavirus,HR-HPV)检测技术在宫颈病变诊断中的应用价值。方法：对94例具有明确病理诊断结果的宫颈病变患者行DNA倍体定量和HR-HPV检测数据分析,分别计算单独和联合检测DNA异倍体、HR-HPV感染预测高级别鳞状上皮内病变(high-grade squamous intraepithelial lesion,HSIL)及以上病变的灵敏度、特异度、阳性预测值、阴性预测值和诊断符合率,绘制相应的ROC曲线;分析DNA倍体定量的结果与HR-HPV检测的结果有无相关关系;比较DNA异倍体阳性的不同宫颈病变组织中>5c和>9c细胞的个数。结果：单独和联合检测DNA异倍体、HR-HPV感染预测HSIL及以上病变的灵敏度、特异度、阳性预测值、阴性预测值、诊断符合率分别为98.03%,94.11%,92.15%、41.86%,53.48%,72.09%、66.66%,70.58%,79.66%、94.73%,88.46%,88.57%、72.34%,75.53%,82.97%。从ROC曲线下面积可以直观地看出联合检测DNA异倍体和HR-HPV感染预测HSIL及以上病变的诊断价值最高。DNA异倍体阳性和阴性、HR-HPV阳性和阴性的不同宫颈病变发生率比较,差异均有统计学意义(P<0.01)。DNA倍体分析结果与HR-HPV检测结果呈正相关趋势(rn=0.281,P<0.01)。DNA异倍体阳性的不同宫颈病变组织每1000个被测细胞中出现>5c的细胞个数,在慢性宫颈炎、低度鳞状上皮内病变(low-grade squamous intraepithelial lesion,LSIL)、HSIL和宫颈癌中分别为0.31±0.14、0.40±0.16、2.08±0.68、2.37±0.81;慢性宫颈炎、LSIL患者分别与HSIL、宫颈癌患者比较,差异均有统计学意义(P<0.01)。慢性宫颈炎、LSIL患者中未见>9c细胞,HSIL、宫颈癌患者中>9c细胞个数分别为1.31±0.65、1.64±0.75,差异无统计学意义(P>0.05)。结论：DNA倍体定量分析联合HR-HPV检测在宫颈病变,特别是宫颈HSIL及以上病变的筛查中具有较高的诊断价值。>9c异倍体细胞的检出很大可能提示宫颈HSIL及以上病变的存在。     

DLG1 polarity protein expression associates with the disease progress of low-grade cervical intraepithelial lesions

Human Discs large tumour suppressor (DLG1) participates in regulating cell polarity and proliferation, suggesting an important connection between epithelial organization and cellular growth control. However, it was demonstrated that DLG1 could acquire oncogenic attributes in some specific contexts. In this work, we evaluated the expression of DLG1 and its contribution to the progress of cervical lesions in order to investigate a potential role of this polarity protein in human oncogenic processes.We analyzed cervical biopsies from women with low-grade squamous intraepithelial lesion (LSIL) diagnosis (n = 30), for DLG1 expression by immunohistochemistry. These results were correlated with the clinical monitoring of the patients during a 24-month follow-up period. Our data indicate that while all LSIL patients with a DLG1 staining pattern similar to normal tissues are significantly more likely to regress (n = 23, Pattern I), all LSIL biopsy specimens showing a diffuse and intense DLG1 staining likely progress to high-grade lesions (n = 4, Pattern II). Finally, all persistent LSIL analyzed showed an undetermined DLG1 staining, with a diffuse distribution without a strong intensity (n = 3, Pattern III). We found a significant association between the expression pattern of DLG1 and the evolution of the lesion (p < 0.00001).This work contributes to the knowledge of DLG1 biological functions, suggesting that its expression may have an important role in the progression of early dysplastic cervical lesions, giving prognostic information.     

Comparison of Abbott RealTime High Risk HPV and Hybrid Capture 2 for the detection of high-risk HPV DNA in a referral population setting

Background

The Abbott RealTime High Risk HPV assay (ART) is an automated multiplex real-time PCR test for detection of DNA from 14 high risk (HR) HPV types in cervical specimens and simultaneous distinction of HPV16 and HPV18 from other HR-HPV.

Objectives

To evaluate the performance of the ART assay in specimens referred for HPV testing to our laboratory (referral population) by comparison with historical data from HC2 and INNO-LiPA as well as histological status, if available.

Study design

412 cervical specimens were collected from women between 18 and 70 years of age: 301 previously tested by HC2 without clinical data and 111 previously tested by HC2 and INNO-LiPA with histological diagnosis of CIN3+.

Results

Our study demonstrated good overall agreement between ART, HC2 and INNO-LiPA. In the group of the CIN3+ specimens HR-HPV was detected by ART in 93.07% (95% CI: 88.12-98.02), while HR-HPV detection rates with HC2 and INNO-LiPA were 91.09% (95% CI: 85.53-96.65) and 95.05% (95% CI: 90.82-99.28), respectively. The typing capability of ART for HPV16, HPV18 and a pool of twelve other HR-HPV types was investigated by comparison with INNO-LiPA demonstrating high overall assay concordance (89.81%; k 0.87).

Conclusions

The Abbott RealTime assay showed similar clinical performance for detection of CIN3+ compared with HC2. The high level of automation and ability to identify HPV16, HPV18 and other HR-HPV make this assay a very attractive option for HR-HPV testing, potentially improving patient management by risk stratification of cytological abnormal populations.