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人乳头瘤病毒基因型及其在意义不明确的非典型鳞状细胞细胞学患者中持续感染的临床进展:统计分析与潜在狄利克雷分配分析

Clinical progress of human papillomavirus genotypes and their persistent infection in subjects with atypical squamous cells of undetermined significance cytology: Statistical and latent Dirichlet allocation analysis.

作者信息

Kim Yee Suk, Lee Sungin, Zong Nansu, Kahng Jimin

机构信息

Department of Anesthesiololgy and Pain Medicine, College of Medicine, The Catholic University of Korea, Bucheon St. Mary's Hospital, Bucheon, Kyunggido 14647, USA.

Biomedical Knowledge Engineering Laboratory, School of Dentistry, Seoul National University, Seoul 08826, USA.

出版信息

Exp Ther Med. 2017 Jun;13(6):3032-3038. doi: 10.3892/etm.2017.4295. Epub 2017 Apr 4.

Abstract

The present study aimed to investigate differences in prognosis based on human papillomavirus (HPV) infection, persistent infection and genotype variations for patients exhibiting atypical squamous cells of undetermined significance (ASCUS) in their initial Papanicolaou (PAP) test results. A latent Dirichlet allocation (LDA)-based tool was developed that may offer a facilitated means of communication to be employed during patient-doctor consultations. The present study assessed 491 patients (139 HPV-positive and 352 HPV-negative cases) with a PAP test result of ASCUS with a follow-up period ≥2 years. Patients underwent PAP and HPV DNA chip tests between January 2006 and January 2009. The HPV-positive subjects were followed up with at least 2 instances of PAP and HPV DNA chip tests. The most common genotypes observed were HPV-16 (25.9%, 36/139), HPV-52 (14.4%, 20/139), HPV-58 (13.7%, 19/139), HPV-56 (11.5%, 16/139), HPV-51 (9.4%, 13/139) and HPV-18 (8.6%, 12/139). A total of 33.3% (12/36) patients positive for HPV-16 had cervical intraepithelial neoplasia (CIN)2 or a worse result, which was significantly higher than the prevalence of CIN2 of 1.8% (8/455) in patients negative for HPV-16 (P<0.001), while no significant association was identified for other genotypes in terms of genotype and clinical progress. There was a significant association between clearance and good prognosis (P<0.001). Persistent infection was higher in patients aged ≥51 years (38.7%) than in those aged ≤50 years (20.4%; P=0.036). Progression from persistent infection to CIN2 or worse (19/34, 55.9%) was higher than clearance (0/105, 0.0%; P<0.001). In the LDA analysis, using symmetric Dirichlet priors α=0.1 and β=0.01, and clusters (k)=5 or 10 provided the most meaningful groupings. Statistical and LDA analyses produced consistent results regarding the association between persistent infection of HPV-16, old age and long infection period with a clinical progression of CIN2 or worse. Therefore, LDA results may be presented as explanatory evidence during time-constrained patient-doctor consultations in order to deliver information regarding the patient's status.

摘要

本研究旨在调查在初次巴氏涂片(PAP)检查结果显示意义不明确的非典型鳞状细胞(ASCUS)的患者中,基于人乳头瘤病毒(HPV)感染、持续感染和基因型变异的预后差异。开发了一种基于潜在狄利克雷分配(LDA)的工具,该工具可为医患咨询提供一种便利的沟通方式。本研究评估了491例PAP检查结果为ASCUS且随访期≥2年的患者(139例HPV阳性和352例HPV阴性病例)。患者在2006年1月至2009年1月期间接受了PAP和HPV DNA芯片检测。HPV阳性受试者至少接受了2次PAP和HPV DNA芯片检测。观察到的最常见基因型为HPV-16(25.9%,36/139)、HPV-52(14.4%,20/139)、HPV-58(13.7%,19/139)、HPV-56(11.5%,16/139)、HPV-51(9.4%,13/139)和HPV-18(8.6%,12/139)。HPV-16阳性的患者中共有33.3%(12/36)患有宫颈上皮内瘤变(CIN)2级或更严重的病变,这显著高于HPV-16阴性患者中CIN2级的患病率1.8%(8/455)(P<0.001),而在基因型与临床进展方面,未发现其他基因型之间存在显著关联。清除与良好预后之间存在显著关联(P<0.001)。年龄≥51岁的患者持续感染率(38.7%)高于年龄≤50岁的患者(20.4%;P=0.036)。从持续感染进展为CIN2级或更严重病变的比例(19/34,55.9%)高于清除率(0/105,0.0%;P<0.001)。在LDA分析中,使用对称狄利克雷先验α=0.1和β=0.01,聚类数(k)=五或十提供了最有意义的分组。关于HPV-16的持续感染、老年和感染期长与CIN2级或更严重临床进展之间的关联,统计分析和LDA分析得出了一致的结果。因此,在时间有限的医患咨询过程中,LDA结果可作为解释性证据呈现,以便提供有关患者状况信息。

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