Sindos Michael, Ndisang Daniel, Pisal Narendra, Chow Carl, Singer Albert, Latchman David S
Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
Gynecol Oncol. 2003 Aug;90(2):366-71. doi: 10.1016/s0090-8258(03)00261-0.
We have previously demonstrated that Brn-3a cellular transcription factor activates transcription of the human papillomavirus (HPV) E6 and E7 oncogenes in human cervical cancer cells and that Brn-3a levels are dramatically elevated in biopsies from women with high-grade cervical neoplasia. The aim of this study was to establish the relationship between Brn-3a levels in Pap smears and the histological diagnoses. We also analysed whether Brn-3a levels can be used in combination with Pap smear to predict the presence of cervical intraepithelial lesion.
Two hundred thirty-eight women who were referred with abnormal Pap smear underwent a diagnostic colposcopy, repeat in-study Pap smear, colposcopically directed biopsy, and assessment of Brn-3a and HPV-16 E6 m-RNA levels. Data were analysed to assess the association between Brn-3a levels and the histological diagnosis.
Brn-3a was readily measured in smears and showed a statistically significant correlation with the grade of cervical abnormality. Positive Brn-3a is associated with increased relative risk of higher-grade lesion. Moreover, measurement of Brn-3a levels in smears can be used to detect a significant proportion of cervical lesions that were missed by Pap smear.
Measurement of Brn-3a levels in routinely taken Pap smears is a feasible technique that correlates with the severity of the epithelial abnormality and is a useful adjunct to cytology. Brn-3a appears to have great promise since it detects activation of oncogenic HPVs rather than simply detecting their presence, as is currently being done.
我们之前已经证明，Brn-3a细胞转录因子可激活人乳头瘤病毒（HPV）E6和E7致癌基因在人宫颈癌细胞中的转录，且在高级别宫颈瘤变女性的活检样本中，Brn-3a水平显著升高。本研究的目的是确定巴氏涂片检查中Brn-3a水平与组织学诊断之间的关系。我们还分析了Brn-3a水平是否可与巴氏涂片联合使用，以预测宫颈上皮内病变的存在。
238名因巴氏涂片异常而前来就诊的女性接受了诊断性阴道镜检查、重复的研究期巴氏涂片检查、阴道镜引导下活检，以及Brn-3a和HPV-16 E6 mRNA水平评估。对数据进行分析，以评估Brn-3a水平与组织学诊断之间的关联。
在涂片样本中可轻松检测到Brn-3a，且其与宫颈异常程度具有统计学意义上的相关性。Brn-3a呈阳性与高级别病变的相对风险增加相关。此外，检测涂片样本中的Brn-3a水平可用于发现巴氏涂片漏诊的相当一部分宫颈病变。
在常规采集的巴氏涂片中检测Brn-3a水平是一种可行的技术，它与上皮异常的严重程度相关，是细胞学检查的有用辅助手段。Brn-3a似乎很有前景，因为它检测的是致癌性HPV的激活情况，而不是像目前这样仅仅检测其存在情况。
