Analysis of human papillomavirus type-16 variants in Italian women with cervical intraepithelial neoplasia and cervical cancer
Analysis of human papillomavirus type-16 variants in Italian women with cervical intraepithelial neoplasia and cervical cancer
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DOI：
10.1002/jmv.20154
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发表时间：
2004-09-01
影响因子：
12.7
通讯作者：
Buonaguro, FM
中科院分区：
文献类型：
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作者：
Tornesello, ML;Duraturo, ML;Buonaguro, FM
人乳头瘤病毒16型(HPV-16)亚型(E、AA、AS、AM AF2)及其变异株地理分布不同，与宫颈病变的关联程度也不同。这项研究旨在检测意大利女性中HPV-16变异及其在病例患者(受浸润性宫颈癌或宫颈上皮内瘤变2-3级和宫颈上皮内瘤变1级影响)中的患病率，并与正常宫颈上皮的对照组(对照组)进行比较。共检测了90例来自意大利高加索血统妇女的HPV-16阳性宫颈样本，包括36例浸润性宫颈癌，21例宫颈上皮内瘤变2-3级，17例宫颈上皮内瘤变1级和16例对照。用E6/E7基因特异性聚合酶链式反应检测HPV-16，并通过对E6和E7癌蛋白编码区、MY09/11扩增的高度保守的L1区和长控制区(LCR)的直接核苷酸测序鉴定HPV-16变异类别和亚类。在90个HPV-16样本中，已确定9个病毒变种属于欧洲分支(EP-T350和E-G350)和非欧洲分支(Aa和Af-1)。在所有分析的不同疾病阶段中，E-G350是普遍存在的变异体，在55.5%的ICC、52.4%的宫颈上皮内瘤变2-3、47.1%的宫颈上皮内瘤变1级和50.0%的对照标本中存在。非欧洲变异体AA和AF1在对照样本中很少检测到，占浸润性宫颈癌HPV-16感染的33.3%(峰值分别为19.4%和13.9%)，在更晚期的病变中频率显著增加(chi(2)趋势=7.2；P<；0.05)。然而，HPV-16EP-T350在对照组(43.7%)和宫颈上皮内瘤变1级(41.2%)中的患病率高于宫颈上皮内瘤变2-3级(28.6%)和浸润性宫颈癌(11.1%)，这强烈表明与这种变异相关的癌前病变没有进展。侵袭性病变中非欧洲变种的频率增加表明它们比欧洲变种更具致癌性。这可能会对未来的诊断和治疗策略产生影响。(C)2004年Wiley-Liss公司
Human papillomavirus type 16 (HPV-16) classes (E, AA, As, AM Af2) and their variants have different geographic distribution and different degrees of association with cervical lesions. This study was designed to examine HPV-16 variants among Italian women and their prevalence in case patients (affected by invasive cervical carcinoma or cervical intraepithelial neoplasia grade 2-3 and cervical intraepithelial neoplasia grade 1), versus control subjects with normal cervical epithelium (controls). A total of 90 HPV-16 positive cervical samples from women of Italian Caucasian descent have been tested, including 36 invasive cervical carcinomas, 21 with cervical intraepithelial neoplasias grade 2-3, 17 with cervical intraepithelial neoplasia grade 1 and 16 controls. HPV-16 was detected with an E6/E7 gene-specific polymerase chain reaction, and variant HPV-16 classes and subclasses were identified by direct nucleotide sequencing of the region coding for the E6 and the E7 oncoproteins, the MY09/11-amplified highly conserved L1 region, and the long control region (LCR). Among the 90 HPV-16 samples, nine viral variants have been identified belonging to the European (Ep-T350 and E-G350) and non-European (AA and Af-1) branches. The E-G350 is the prevalent variant in all analyzed different disease stages being present in 55.5% of ICC, 52.4% of cervical intraepithelial neoplasias 2-3, 47.1% of cervical intraepithelial neoplasia grade 1, and 50.0% of control samples. The non-European variants AA and Af1, rarely detected in control samples, represent 33.3% of all HPV-16 infections in invasive cervical carcinoma (with a peak of 19.4% and 13.9%, respectively), showing a statistically significant increase in frequency in more advanced lesions (chi(2) trend = 7.2; P < 0.05). The prevalence of HPV-16 Ep-T350, however, is higher in controls (43.7%) and in of cervical intraepithelial neoplasia grade 1 (41.2%) than in cervical intraepithelial neoplasia grade 2-3 (28.6%) and in invasive cervical carcinoma (11.1%) cases strongly suggesting lack of progression for pre-neoplastic lesions associated with such variant. The increased frequency of non-European variants in invasive lesions suggests that they are more oncogenic than European variants. This could have implications for future diagnostic and therapeutic strategies. (C) 2004 Wiley-Liss, Inc.