宫颈肿瘤中细胞学、阴道镜检查、人乳头瘤病毒分型及生物标志物分析的比较

Comparison of cytology, colposcopy, HPV typing and biomarker analysis in cervical neoplasia.

作者信息

Adamopoulou Maria, Kalkani Eleni, Charvalos Ekatherina, Avgoustidis Dimitris, Haidopoulos Dimitris, Yapijakis Christos

机构信息

Department of Medical Laboratories, Molecular Virology Laboratory, Technological Institution of Athens, Athens, Greece.

出版信息

Anticancer Res. 2009 Aug;29(8):3401-9.

PMID:19661364

Abstract

BACKGROUND

Cervical cancer is the leading cause of mortality among women worldwide, despite existing prevention programs. In light of the recent development of anti-HPV vaccines, the aim of this study was to evaluate concurrently the efficacy of four methods for risk assessment (cytology, colposcopy, HPV molecular typing and detection of biomarkers in cervical biopsies) in an attempt to define the most efficient combination.

PATIENTS AND METHODS

The studied group included 62 women with abnormal Pap tests and cervical lesions ranging from cervicitis and condylomas to intraepithelial neoplasias and invasive cancer. All women underwent full colposcopy assessment and colposcopically-taken biopsies were selected for histological examination, immunohistochemical identification of p16, p53, Bcl-2 biomarkers, as well as molecular detection and typing of HPV genomes.

RESULTS

Cytology and colposcopy showed very high sensitivity in detecting CIN and cancer (91.7% and 94.4%, respectively), but low specificity (34.6% and 50%, respectively). The detection of the 3 biomarkers reached an impressive sensitivity (83.3%) and a moderate specificity (65.4%). HPV detection and typing achieved 77.8% sensitivity, and the highest specificity of 80.8% in detecting CIN and cancer cases. HPV DNA testing had the highest positive prognostic value (84.9%; confidence interval, CI: 67.4%- 94.3%) and cytology the lowest (66.0%; CI: 51.2%- 78.4%). Coupled HPV typing and colposcopy proved to be the most efficient combination, increasing sensitivity to 97.2% and negative prognostic value to 92.3%. The estimation of cervical neoplasia or cancer in women with high-risk HPV types increased approximately 15-fold (odds ratio, OR: 14.70; CI: 4.30-50.09, p<0.001), ~23-fold in the case of combined positive biomarkers (OR: 23.18; CI: 4.97- 104.23, p<0.001), and 35-fold in case of colposcopically detected cervical neoplasia (OR: 35.00; CI: 5.16- 225.07, p<0.001).

CONCLUSION

The most efficient combination among all tested methodologies was found to be HPV typing with colposcopy.

摘要

背景

尽管存在预防项目，但宫颈癌仍是全球女性死亡的主要原因。鉴于抗人乳头瘤病毒（HPV）疫苗的最新进展，本研究旨在同时评估四种风险评估方法（细胞学、阴道镜检查、HPV分子分型以及宫颈活检中生物标志物的检测）的疗效，以确定最有效的组合方式。

患者与方法

研究组包括62名巴氏试验异常且患有宫颈病变的女性，病变范围从宫颈炎、尖锐湿疣到上皮内瘤变和浸润癌。所有女性均接受了全面的阴道镜评估，并选取阴道镜下活检组织进行组织学检查、p16、p53、Bcl-2生物标志物的免疫组化鉴定，以及HPV基因组的分子检测和分型。

结果

细胞学和阴道镜检查在检测宫颈上皮内瘤变（CIN）和癌症方面显示出很高的敏感性（分别为91.7%和94.4%），但特异性较低（分别为34.6%和50%）。三种生物标志物的检测达到了令人印象深刻的敏感性（83.3%）和中等特异性（65.4%）。HPV检测和分型在检测CIN和癌症病例时的敏感性为77.8%，特异性最高，为80.8%。HPV DNA检测具有最高的阳性预测值（84.9%；置信区间，CI：67.4%-94.3%），而细胞学检测的阳性预测值最低（66.0%；CI：51.2%-78.4%）。HPV分型与阴道镜检查相结合被证明是最有效的组合方式，可将敏感性提高到97.2%，阴性预测值提高到92.3%。高危HPV类型女性中宫颈瘤变或癌症的估计值增加了约15倍（优势比，OR：14.70；CI：4.30-50.09，p<0.001），生物标志物联合阳性的情况下增加了约23倍（OR：23.18；CI：4.97-104.23，p<0.001），阴道镜检测到宫颈瘤变的情况下增加了35倍（OR：35.00；CI：5.16-225.07，p<0.001）。