Hu X, Pang T, Guo Z, Mazurenko N, Kisseljov F, Pontén J, Nistér M
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
Br J Cancer. 2001 Mar 23;84(6):791-5. doi: 10.1054/bjoc.2000.1619.
HPV16 is frequently seen in invasive cervical cancer (ICC) and cervical intraepithelial neoplasia (CIN). Its E6 gene has frequent sequence variations. Although some E6 variants have been reported to have different biochemical or biological properties, they do not show geographical identity. Moreover, the definition of 'variant' has been a source of confusion because it has been based on all departures from the 'prototype' once isolated randomly from an ICC case. We amplified the HPV16 E6 gene by PCR from fresh-frozen tissue of 104 cases of ICC and CIN from Russian patients and sequenced it in positive cases. We found that 32 of 55 (58.2%) ICC cases and 18 of 49 (36.7%) CIN cases were HPV 16-positive and we could identify 3 groups of E6 variants: group A was characterized by G at nt 350 where group B had T, and group M was a heterogeneous mixture of unique E6 variants; no significant difference existed in the distribution of the different groups between ICC and CIN; the clinically malignant (as defined by FIGO stage) order between the groups was M > A > B in ICC; in the cases with a single HPV16 E6 sequence, coexisting ICC, CIN and normal epithelium in the same patient shared the E6 variant; and 4 cases of ICC had double/multiple E6 variants. The results did not show any importance of E6 variants for ICC progression in Russian women. The results also indicated that the original HPV16 variant persisted during ICC progression, and that at a low frequency, double infections and/or mutation of variants might occur.
人乳头瘤病毒16型（HPV16）常见于浸润性宫颈癌（ICC）和宫颈上皮内瘤变（CIN）。其E6基因存在频繁的序列变异。尽管一些E6变异体已被报道具有不同的生化或生物学特性，但它们并未表现出地域特征。此外，“变异体”的定义一直是一个令人困惑的源头，因为它是基于一旦从ICC病例中随机分离出的所有与“原型”的差异。我们通过聚合酶链反应（PCR）从104例来自俄罗斯患者的ICC和CIN新鲜冷冻组织中扩增HPV16 E6基因，并对阳性病例进行测序。我们发现，55例ICC病例中有32例（58.2%）、49例CIN病例中有18例（36.7%）为HPV 16阳性，并且我们能够识别出3组E6变异体：A组的特征是核苷酸350处为G，而B组为T，M组是独特E6变异体的异质混合物；ICC和CIN之间不同组的分布没有显著差异；在ICC中，各临床恶性程度（根据国际妇产科联盟（FIGO）分期定义）的顺序为M＞A＞B；在具有单个HPV16 E6序列的病例中，同一患者中共存的ICC、CIN和正常上皮共享E6变异体；4例ICC病例有双重/多重E6变异体。结果未显示E6变异体对俄罗斯女性ICC进展有任何重要性。结果还表明，原始HPV16变异体在ICC进展过程中持续存在，并且可能以低频率发生变异体的双重感染和/或突变。
