Janusicova Veronika, Mendelova Andrea, Zubor Pavol, Kapustova Ivana, Svecova Iveta, Kudela Erik, Burjanivova Tatiana, Lasabova Zora, Danko Jan
Departments of 1Obstetrics and Gynecology and 2Molecular Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovak Republic.
J Low Genit Tract Dis. 2014 Jul;18(3):273-80. doi: 10.1097/LGT.0000000000000000.
The objective of current study was to determine the p16 mRNA level in cervical cells by relative quantification (RQ) and to test viral E6 expression in human papillomavirus (HPV) -16 or -18-positive specimens by widely used methods. We targeted the pivotal mRNA level associated with severe dysplasia or worse.
Cervical specimens were taken from 134 women with cervical disease and 132 women with normal cytologic results. The presence of HPV was analyzed by sequencing. The results of p16 and E6 analyses were statistically processed in receiver operating characteristic curve analysis to predict severe dysplasia or worse.
The HPV DNA was detected in 81.4% (109/134) of women with cervical disease and in 27.3% (36/132) of women with normal cytologic results. HPV-16 or -18 were present in 59.7% (80/134) of abnormal specimens. p16 and E6 mRNA expression was increasing with severity of cervical dysplasia. p16 mRNA expression was found 4.35-fold and 13.15-fold increased in high-grade squamous intraepithelial lesions and squamous cell carcinomas, respectively. E6 mRNA expression was significantly increased (p = .0038) in severe dysplasias or worse. The RQ method achieved better sensitivity (82.6%), and E6 mRNA got better specificity (80.6%) for the prediction of severe dysplasia or worse.
An increasing level of p16 and E6 mRNA transcripts could mean the potential of cervical dysplasia progression to cancer, but further studies should be done to confirm this proposition. Nevertheless, we consider using both tests to improve the sensitivity and specificity for prediction of severe dysplasia or worse.
本研究的目的是通过相对定量（RQ）测定宫颈细胞中的p16 mRNA水平，并通过广泛使用的方法检测人乳头瘤病毒（HPV）-16或-18阳性标本中的病毒E6表达。我们针对与严重发育异常或更严重情况相关的关键mRNA水平。
从134例患有宫颈疾病的女性和132例细胞学结果正常的女性中采集宫颈标本。通过测序分析HPV的存在情况。在接受者操作特征曲线分析中对p16和E6分析结果进行统计学处理，以预测严重发育异常或更严重情况。
在81.4%（109/134）患有宫颈疾病的女性和27.3%（36/132）细胞学结果正常的女性中检测到HPV DNA。59.7%（80/134）的异常标本中存在HPV-16或-18。p16和E6 mRNA表达随宫颈发育异常的严重程度增加而升高。在高级别鳞状上皮内病变和鳞状细胞癌中，p16 mRNA表达分别增加了4.35倍和13.15倍。在严重发育异常或更严重情况中，E6 mRNA表达显著增加（p = 0.0038）。RQ方法在预测严重发育异常或更严重情况时具有更好的敏感性（82.6%），而E6 mRNA具有更好的特异性（80.6%）。
p16和E6 mRNA转录水平的升高可能意味着宫颈发育异常进展为癌症的可能性，但需要进一步研究来证实这一观点。尽管如此，我们认为同时使用这两种检测方法可以提高预测严重发育异常或更严重情况的敏感性和特异性。
