Department Genome Modifications and Carcinogenesis (F020), Research Program Infection and Cancer, German Cancer Research Center, Heidelberg, Germany.
J Clin Microbiol. 2013 May;51(5):1458-64. doi: 10.1128/JCM.00087-13. Epub 2013 Feb 27.
Multiple human papillomavirus (HPV) genotypes often coexist within cervical epithelia and are frequently detected together in smears of different grades of cervical neoplasia. Describing the association between multiple infections and cervical disease is important in generating hypotheses regarding its pathogenesis. We analyzed the prevalence of multiple HPV infections and their attribution to cervical disease in a screening population of 999 consecutive BD SurePath liquid-based cervical cytology samples enriched with atypical squamous cells of undetermined significance (ASCUS) (n = 100), low-grade squamous intraepithelial lesions (LSIL) (n = 100), and high-grade squamous intraepithelial lesions (HSIL) (n = 97). HPV genotyping was performed only on cytology specimens using a broad-spectrum GP5(+)/6(+)-PCR/multiplex HPV genotyping (BSGP5(+)/6(+)-PCR/MPG) assay that detects and quantifies 51 HPV genotypes and 3 subtypes. Using a recently defined high viral load cutoff, the quantitative data were scored as high or low viral load. In the 36-month follow-up, 79 histologically confirmed cervical intraepithelial neoplasia grade 2 or greater (CIN2+) cases were identified. In the screening population, there was a trend of having more multiple infections at a younger age. Multiple HPV infections were common. Multiple HPV types were most prevalent in LSIL (75.9% of HPV positives), followed by HSIL (65.5%), ASCUS (64.6%), and negative for intraepithelial lesion or malignancy (NILM) (36.8%). On average, 3.2 and 2.5 HPV types were detected per LSIL and HSIL sample, respectively. Multiple HPV types with high viral loads were most prevalent in LSIL (62.6% of high viral load positives), followed by HSIL (51.9%), ASCUS (40.7%), and NILM (19.3%). Patients with multiple high viral loads showed a 4- to 6-fold-higher risk of having cervical precancerous cytological lesions than did patients with single high viral loads. Compared to NILM, multiple infections, especially with multiple high viral loads, were significantly associated with cytological precancerous lesions. However, the presence of multiple infections did not distinguish low-grade from high-grade cytological lesions.
多种人乳头瘤病毒（HPV）基因型通常在宫颈上皮内共存，并经常在不同级别宫颈癌涂片中共检出。描述多重感染与宫颈疾病之间的关联对于探讨其发病机制具有重要意义。我们分析了 999 例连续的 BD SurePath 液基细胞学标本中多重 HPV 感染的流行率及其与宫颈疾病的关系，这些标本均为不典型鳞状细胞意义不明（ASCUS）（n=100）、低度鳞状上皮内病变（LSIL）（n=100）和高度鳞状上皮内病变（HSIL）（n=97）。仅对细胞学标本进行 HPV 基因分型，使用广谱 GP5(+)/6(+)-PCR/多重 HPV 基因分型（BSGP5(+)/6(+)-PCR/MPG）检测方法进行检测，该方法可检测和定量 51 种 HPV 基因型和 3 种亚型。使用最近定义的高病毒载量临界值，定量数据被评为高或低病毒载量。在 36 个月的随访中，发现了 79 例经组织学证实的宫颈上皮内瘤变 2 级或更高级别（CIN2+）病例。在筛查人群中，年龄越小，多重感染的趋势越明显。多重 HPV 感染很常见。多重 HPV 类型在 LSIL 中最为常见（HPV 阳性者的 75.9%），其次是 HSIL（65.5%）、ASCUS（64.6%）和非上皮内病变或恶性肿瘤（NILM）（36.8%）。平均而言，LSIL 和 HSIL 样本中分别检测到 3.2 和 2.5 种 HPV 类型。高病毒载量的多重 HPV 类型在 LSIL 中最为常见（高病毒载量阳性者的 62.6%），其次是 HSIL（51.9%）、ASCUS（40.7%）和 NILM（19.3%）。与单一高病毒载量患者相比，多重高病毒载量患者发生宫颈癌前细胞学病变的风险高 4-6 倍。与 NILM 相比，多重感染，尤其是多重高病毒载量感染，与细胞学癌前病变显著相关。然而，多重感染的存在并不能区分低级别和高级别细胞学病变。
