Hu X, Guo Z, Tianyun P, Pontén F, Wilander E, Andersson S, Pontén J
Department of Genetics and Pathology, University Hospital, Uppsala University, Uppsala, Sweden.
Int J Cancer. 1999 Sep 24;83(1):34-7. doi: 10.1002/(sici)1097-0215(19990924)83:1<34::aid-ijc7>3.0.co;2-q.
We microdissected 15 specimens of invasive cervical cancer co-existing with some of its precursors. Out of 15 cases, 10 carried HPV16, 2 HPV31, 1 HPV18 and 2 were HPV-negative. We found 3 HPV16 E6 variants among the 10 cases; one was A --> G in nt 131 (one case) and a second was A --> G in nt 276. The third, T;--> G in nt 350, was common, and was found in 5 of the 10 patients infected by HPV16. The type of HPV and the E6 variant were identical in all lesions within the same patient. Viral DNA present in normal epithelium was identical in type and E6 variant to HPV in the same patient's lesions. Multiple samples from invasive cancers with HPV were consistently positive. The data suggest that the originally infecting HPV, including its variant type in the E6 gene, persists unaltered in the whole series of CIN that precedes invasive cancer. Our data are compatible with an essential role of HPV manifested by persistence of the viral genome during the entire natural life history of cervical cancer. We did not confirm previous data on the specific association of invasive cancer with an HPV E6 variant (G at nt 350 rather than T). The discrepancy may depend on the relatively few cases investigated or selection of a special sub-set with progression from CIN to invasive cancer already manifest.
我们对15例浸润性宫颈癌及其一些前驱病变共存的标本进行了显微切割。在这15例病例中，10例携带HPV16，2例携带HPV31，1例携带HPV18，2例HPV阴性。我们在10例病例中发现了3种HPV16 E6变异体；一种是第131位核苷酸处A→G（1例），另一种是第276位核苷酸处A→G。第三种是第350位核苷酸处T→G，较为常见，在10例HPV16感染患者中有5例发现。同一患者所有病变中的HPV类型和E6变异体均相同。正常上皮中存在的病毒DNA在类型和E6变异体方面与同一患者病变中的HPV相同。来自HPV阳性浸润性癌的多个样本始终呈阳性。数据表明，最初感染的HPV，包括其E6基因中的变异类型，在浸润性癌之前的整个CIN系列中持续不变。我们的数据与HPV在宫颈癌整个自然生命史中通过病毒基因组持续存在所表现出的重要作用相一致。我们没有证实先前关于浸润性癌与HPV E6变异体（第350位核苷酸处为G而非T）特定关联的数据。这种差异可能取决于所研究的病例相对较少，或者选择了已经表现出从CIN进展为浸润性癌的特殊子集。
