e6e7检查结果10.6正常吗(e6e7检查结果是9.27厉害吗?)

文献摘要

题目

RNA (E6 and E7) Assays versus DNA (E6 and E7) Assays for Risk Evaluation for Women Infected with Human Papillomavirus.

E6/E7 RNA检测与E6/E7 DNA检测对HPV感染妇女的风险评估。

文献信息

Paola Cattani,1* Alessia Siddu,1 Sara D’Onghia,1 Simona Marchetti,1 Rosaria Santangelo,1Valerio G. Vellone,2 Gian Franco Zannoni,2 and Giovanni Fadda1Institute of Microbiology1 and Institute of Pathology,2 Universita` Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy.JOURNAL OF CLINICAL MICROBIOLOGY, July 2009, p. 2136–2141

材料和方法

MATERIALS AND METHODS

Patients and sampling. This study was conducted on cervical specimens from 400 Italian women (age range, 21 to 59 years) undergoing tests for HPV detection at the Outpatient Department of the Institute of Microbiology (UniversitaCattolica del Sacro Cuore, Rome, Italy). Specimens were collected in the period from May 2006 to September 2007. All of the patients in the study had previously tested positive for HR HPV, in tests carried out at our own institution, 8 to 10 months before samples were taken. Patients who had tested positive only for LR HPV or who did not undergo concurrent cytological tests were not included in the study.

Patients were grouped based on cytological findings, as follows: 108 women showed normal cytology, in 84 we detected atypical squamous cells of undetermined significance (ASCUS), in 136 we found low-grade squamous intraepithelial lesions (LSIL), and in 72 we found HSIL. Three identical aliquots were prepared, including one for DNA detection by the Hybrid Capture II HPV DNA test and two for DNA and RNA extractions.

材料和方法

患者和抽样。这项研究是在400名意大利女性（年龄在21至59岁）的宫颈标本进行的，这些妇女在微生物学研究所门诊部（意大利罗马大学医学院）进行HPV检测。在2006年5月至2007年9月期间收集样本。所有研究中的患者以前在本组织进行的测试中，在采集样本前8至10个月进行了HPV检测阳性。仅测试LR-HPV阳性或未同时进行细胞学检查的患者未被纳入研究中。

患者根据细胞学检查结果分组如下：108例女性显示正常的细胞学检查，84例检测到不确定意义的非典型鳞状细胞（ASCUS），136例发现低度鳞状上皮内病变（LSIL），72例发现HSIL。制备了三个相同的等分试样，包括用于HC2 HPV DNA检测，另外两个用于DNA和RNA提取。

内容

Ninety percent of HPV infections clear spontaneously over a period of 6 to 24 months (33). Generally speaking, only persistent infections lead to cancer. This implies that although DNA testing has a high negative predictive value, its positive predictive value is relatively low, and tests need to be repeated periodically, with a negative impact on health service costs and patient comfort.

Research in recent years has found that histologically proven cases of cervical intraepithelial neoplasia 3 (CIN3) and invasive cervical carcinoma are associated with the presence of transcripts from the E6 and E7 oncogenes. It has been suggested that tests for these transcripts or for other biomarkers, such as p16, could be more effective than DNA detection in predicting disease progression.

In this study, therefore, we compared the two approaches (DNA and RNA testing) with clinical specimens from patients previously diagnosed with HR-HPV.

在6-24个月，90%的HPV感染会自发清除。一般来说，只有持续感染才会导致癌症。这意味着尽管HPV DNA测试具有较高的阴性预测值，但其阳性预测值相对较低，需要定期重复测试，这会对健康服务成本和患者舒适度产生负面影响。

近年来的研究发现，组织学证实的子宫颈上皮内瘤变3（CIN3）和浸润性宫颈癌的病例与E6和E7致癌基因的转录物的存在有关。对于这些转录物或其他生物标志物（如p16）的检测在预测疾病进展中可能比DNA检测更有效。

因此，在本研究中，我们将两种方法（DNA和RNA检测）对以前诊断为HR-HPV阳性患者的临床标本进行了比较。

结果

Among 223 HPV DNA-positive samples, only 118 were positive in the RNA test. Among HPV DNA-positive patients with normal cytology, we detected E6 and E7 RNA transcripts in two cases (18.2%). The rate of detection increased gradually with the grade of the observed lesions, rising from 20% for patients with atypical squamous cells of undetermined significance to 48.1% for women with low-grade squamous intraepithelial lesions and 86.3% for those with high-grade squamous intraepithelial lesions. These results suggest that testing for HPV E6 and E7 transcripts could be a useful tool for screening and patient management, providing more accurate predictions of risk than those obtained by DNA testing.

在223例HPV DNA阳性标本中，RNA检测阳性患者为118。在正常细胞学且HPV阳性的患者中，我们检测到2例E6/E7 RNA转录（18.2%）。检出率随病变程度逐渐上升，其检出率从意义不明的不典型鳞状细胞患者（ASCUS）20%上升到低度鳞状上皮内病变患者（LSIL）48.1%，高级别鳞状上皮内病变的妇女检出率达到86.3%。这些结果表明，HPV E6/E7 RNA比HPV DNA提供更准确的风险预测，可作为一个对于患者筛查和管理的有用工具。

Compared to the DNA test, the RNA assay produced fewer positive results. E6 and E7 transcripts were detected in just 52.9% of patients who tested positive for HR-HPV. The lack of RNA transcripts possibly reflects an episomal state of the virus in which regulation of the transcription process is still effective, creating a higher probability that the infection will clear spontaneously. Negative test results were common for women with normal cytology, ASCUS, and LSIL. In contrast, 86.3% of patients with HSIL tested positive. The high frequency of E6 and E7 transcripts in high-grade dysplasia confirms that the integration of HR HPV into the host genome, loss of control over oncogene transcription, and consequent expression of E6 and E7 gene products are necessary conditions for the development and maintenance of malignant phenotypes

与DNA测试相比，RNA检测的阳性结果较少。 在仅有52.9％的HR-HPV检测为阳性的患者中检测到E6和E7转录物。 RNA转录物的缺失可能反映了病毒处于游离状态，提示病毒自发清除的可能性更高。对于具有正常细胞学，ASCUS和LSIL的妇女其阴性检测结果是常见的。 相比之下，86.3％的HSIL患者呈阳性。 E6和E7转录物在高级别病变中大量存在可证实，HR HPV整合到宿主基因组中，便失去对癌基因转录的控制，随之发生的E6和E7基因产物的大量表达是宫颈病变开始和进展的必要条件。

结论

In sum, the findings from our study support the hypothesis that, especially for patients with normal cytology or low-grade lesions, E6 and E7 mRNA detection may be a more specific diagnostic tool and a better predictor of disease progression than DNA-based assays.

总之，我们研究的结果支持这样的假设，尤其是对于具有正常细胞学或低度病变的患者，E6和E7 mRNA检测可能是比DNA的检测更具有特异性和更好的预测疾病的进展作用。

1、联合筛查（包括30岁以下女性）：关注高危人群，评估进展风险，有 效提高宫颈病变检出率。

2、辅助诊断：分流低级别宫颈病变患者，有效减少一过性HPV感染导致 的过诊。

3、术后随访：准确评估宫颈术后患者的复发风险，提高宫颈术后人群随访的特异性。