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利用配对的脱落宫颈阴道细胞和石蜡包埋组织进行人乳头瘤病毒(HPV)基因分型,以突显将HPV类型归因于特定病变的困难。

Human papillomavirus (HPV) genotyping using paired exfoliated cervicovaginal cells and paraffin-embedded tissues to highlight difficulties in attributing HPV types to specific lesions.

作者信息

Gravitt Patti E, van Doorn Leen Jan, Quint Wim, Schiffman Mark, Hildesheim Allan, Glass Andrew G, Rush Brenda B, Hellman Jared, Sherman Mark E, Burk Robert D, Wang Sophia S

机构信息

Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Room E6535, Baltimore, MD 21205, USA.

出版信息

J Clin Microbiol. 2007 Oct;45(10):3245-50. doi: 10.1128/JCM.00216-07. Epub 2007 Aug 15.

Abstract

Defining type-specific human papillomavirus (HPV) infections within cervical tissues is important for understanding the pathogenesis of cervical neoplasia and assessing the effectiveness of prophylactic vaccines with limited type-specific spectra. We compared HPV DNA-testing results from 146 matched exfoliated-cell and formalin-fixed-tissue specimens collected by cervicovaginal lavage (CVL) within 90 days of each other from women with histologically confirmed cervical intraepithelial lesions (CIN). The CVL specimens were HPV typed using a MY09/11 L1 consensus primer PCR method followed by dot blot hybridization. The tissue specimens were HPV typed using an SPF(10) line probe assay HPV detection system. Of the 146 specimen pairs with evidence of CIN in the tissue, 91.8% were positive for one or more HPV types in both the tissue and cellular specimens. Tissue sections were more likely to be HPV negative (P < 0.01). Typing directly from tissue sections resolved multiple infections detected in exfoliated cells to a single HPV type in only 46.9% of cases. Combined use of both specimen types to attribute lesions to HPV type 16 (HPV-16) and/or -18 led to 43.1% attributed to HPV-16 and/or -18 by both specimen types and 19.9% attributed to HPV-16 and/or -18 by one, but not both, specimen types. Unambiguous attribution of cervical lesions to a single, specific HPV type remains a difficult proposition. Use of multiple specimen types or the development of highly sensitive and robust in situ hybridization HPV-testing methods to evaluate the certainty of attribution of lesions to HPV types might provide insights in future efforts, including HPV vaccine trials.

摘要

确定宫颈组织中特定类型的人乳头瘤病毒(HPV)感染,对于理解宫颈肿瘤的发病机制以及评估具有有限特定类型谱的预防性疫苗的有效性至关重要。我们比较了146对匹配的脱落细胞和福尔马林固定组织标本的HPV DNA检测结果,这些标本是通过宫颈阴道灌洗(CVL)在90天内从组织学确诊为宫颈上皮内瘤变(CIN)的女性中采集的。CVL标本采用MY09/11 L1共识引物PCR方法进行HPV分型,随后进行斑点杂交。组织标本采用SPF(10)线性探针分析HPV检测系统进行HPV分型。在146对组织中有CIN证据的标本对中,91.8%的组织和细胞标本中一种或多种HPV类型呈阳性。组织切片更可能为HPV阴性(P < 0.01)。直接从组织切片进行分型仅在46.9%的病例中将脱落细胞中检测到的多种感染解析为单一HPV类型。联合使用两种标本类型将病变归因于HPV 16型(HPV-16)和/或-18型,导致43.1%的病例两种标本类型均归因于HPV-16和/或-18型,19.9%的病例一种标本类型(而非两种)归因于HPV-16和/或-18型。将宫颈病变明确归因于单一特定HPV类型仍然是一个难题。使用多种标本类型或开发高度敏感且可靠的原位杂交HPV检测方法来评估病变归因于HPV类型的确定性,可能会为未来的研究工作提供见解,包括HPV疫苗试验。

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