HPV16 E6 gene variations in invasive cervical squamous cell carcinoma and cancer in situ from Russian patients.

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. © 2001 Cancer Research Campaign http://www.bjcancer.com

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基因常有序列变异。尽管据报道一些E6变异体具有不同的生化或生物学特性，但它们没有地域特征。此外，“变异体”的定义一直令人困惑，因为它是基于曾经从一个ICC病例中随机分离出的“原型”的所有差异。我们从俄罗斯患者的104例ICC和CIN的新鲜冷冻组织中通过聚合酶链反应（PCR）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%）以及49例CIN病例中有18例（36.7%）HPV16呈阳性，并且我们能够识别出3组E6变异体：A组在第350位核苷酸处为G，B组为T，M组是独特E6变异体的混合体；ICC和CIN之间不同组的分布没有显著差异；在ICC中，各组之间临床恶性程度（按照国际妇产科联合会分期定义）顺序为M > A > B；在具有单一HPV16 E6序列的病例中，同一患者共存的ICC、CIN和正常上皮共享E6变异体；并且有4例ICC具有双/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，原始的HPV16变异体在ICC进展过程中持续存在，并且可能会以较低频率发生双重感染和/或变异体突变。© 2001癌症研究运动 http://www.bjcancer.com