高危型人乳头瘤病毒 DNA 检测和 p16(INK4a)在低度鳞状上皮内病变（LSIL）中的分流作用：一项前瞻性诊断研究。

High-risk human papillomavirus DNA test and p16(INK4a) in the triage of LSIL: a prospective diagnostic study.

机构信息

Department of Obstetrics and Gynecology, University Hospitals of South Manchester, Manchester, UK.

出版信息

Gynecol Oncol. 2011 Apr;121(1):49-53. doi: 10.1016/j.ygyno.2010.12.002. Epub 2010 Dec 30.

DOI:10.1016/j.ygyno.2010.12.002

PMID:21194734

Abstract

OBJECTIVE

The detection of high-grade cervical intraepithelial neoplasia (CIN) amongst patients with low-grade cytology (LSIL) is challenging. This study evaluated the role of high-risk HPV (HR-HPV) DNA test and p16(INK4a) immunostaining in identifying women with LSIL cytology at risk of harboring CIN2 or worse (CIN2+) and the role of p16(INK4a) in the triage of a population of HR-HPV positive LSIL.

METHODS

We conducted a prospective study including women with LSIL cytology. Detection of HR-HPV was carried out by means of a polymerase chain reaction based assay. p16(INK4a) immunostaining was performed using the Dako CINtec cytology kit. All patients had colposcopically directed punch biopsies or large loop excision of the transformation zone of the cervix. The endpoint was detection of a biopsy-confirmed CIN2+.

RESULTS

A series of 126 women with LSIL cytology were included. HR-HPV test had sensitivity 75% and specificity 64% for an endpoint of CIN2+. p16(INK4a) had significantly higher specificity of 89% (p=0.0000) but low sensitivity of 42%. The role of p16(INK4a) immunostaining in the triage of LSIL positive for HR-HPV was also evaluated. p16(INK4a) triage had 70% positive predictive value (PPV); however, this was not significantly higher than the PPV (56%) of HR-HPV test alone (p=0.4).

CONCLUSIONS

The results indicate that HR-HPV or p16(INK4a) cannot be used as solitary markers for the assessment of LSIL. The addition of p16(INK4a) immunostaining led to an increase in HR-HPV specificity; however, the biomarker needs to be assessed further to establish its role as an adjunct test in the triage of LSIL.

摘要

目的

在低级别细胞学（LSIL）患者中检测高级别宫颈上皮内瘤变（CIN）具有挑战性。本研究评估了高危型 HPV（HR-HPV）DNA 检测和 p16（INK4a）免疫染色在识别 LSIL 细胞学患者中存在 CIN2 或更高级别病变（CIN2+）的风险，以及 p16（INK4a）在 HR-HPV 阳性 LSIL 人群中的分流作用。

方法

我们进行了一项前瞻性研究，纳入了 LSIL 细胞学患者。通过聚合酶链反应（PCR）检测 HR-HPV。使用 Dako CINtec 细胞学试剂盒进行 p16（INK4a）免疫染色。所有患者均行阴道镜引导下活检或宫颈转化区大圈切除术。终点是检测活检证实的 CIN2+。

结果

共纳入 126 例 LSIL 细胞学患者。HR-HPV 检测对 CIN2+的敏感性为 75%，特异性为 64%。p16（INK4a）的特异性显著更高（89%，p=0.0000），但敏感性较低（42%）。还评估了 p16（INK4a）免疫染色在 HR-HPV 阳性 LSIL 患者中的分流作用。p16（INK4a）分流的阳性预测值（PPV）为 70%；然而，与 HR-HPV 检测单独的 PPV（56%）相比，这并没有显著更高（p=0.4）。