Kim C. J., Um S. J., Hwang E. S., Park S. N., Kim S. J., Namkoong S. E., Park J. S.
Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, Catholic University Medical College, Catholic Cancer Center, Seoul, Korea; University of Seoul, Department of Life Science, Seoul, Korea; Virus/Oncology Research Unit, KRIBB, Daejeon, Korea.
Int J Gynecol Cancer. 1999 Jan;9(1):1-11. doi: 10.1046/j.1525-1438.1999.09891.x.
Human papillomavirus (HPV) DNAs are often found to be integrated into the human genome in high-grade cervical intraepithelial neoplasia (CIN) as well as in invasive cervical cancers. Investigation of the relationship between the genomic status of specific HPV genes and their antibody responses to the virus-like particles (VLPs) of HPV-16 L1/L2 proteins and the in vitro translated HPV-16 E6 and E7 proteins may help to illustrate the mechanism of HPV-related cervical carcinogenesis and host immune response. Cervical cancer tissues obtained from 39 patients were studied to evaluate the physical status of HPV genes by Southern blotting, DNA-PCR, and RT-PCR of E2. The antibody response against the HPV-16 L1/L2 VLPs of serum specimens were tested by ELISA and the antibody response against the HPV-16 E6 and E7 proteins were tested by radioimmunoprecipitation assay (RIPA), respectively. Integrated forms of HPV-16 DNA were found in 23 of the 38 patients (60.5%). The HPV-16 positive cervical cancer patients showed a significantly higher prevalence rate (39.5%; 15/38) of antibodies to HPV-16 L1/L2 VLPs than that of the control group (8.7%; 2/28) (P < 0.05). Antibodies to HPV-16 L1/L2 VLPs were more commonly detectable in cervical cancer patients having the episomal form of HPV-16 DNA (pure episomal and mixed forms) (60%; 9/15) than in those who had only the integrated forms of HPV-16 DNA (26.1%; 6/23) (P < 0.05). Antibodies to E6 and E7 proteins were positive in 36.8% (14/38) and 50% (19/38) of the patients with HPV-16 positive cervical cancer, respectively. These were significantly higher than the positive rates for the control group (8.3% and 2.8%) (P < 0.05). The differences between sero-reactivities to E6 and E7 proteins in the patients with episomal forms of HPV-16 DNA and those with integrated forms of HPV-16 DNA were not statistically significant (P > 0.05). Integrated forms of HPV-16 DNA were prevalent in most patients with cervical cancer in Korea. Antibodies to HPV-16 L1/L2 VLPs, in vitro translated HPV-16 E6 and E7 proteins, appeared in a significantly larger proportion of the HPV-associated cervical cancer patients than in the controls. Antibodies to HPV-16 L1/L2 VLPs were more often detected in cervical cancer patients having the episomal form of HPV-16 DNA than in those having only integrated forms of HPV-16 DNA. Antibody responses to HPV-16 E6 and E7 proteins were not influenced by the different viral states.
在高级别宫颈上皮内瘤变（CIN）以及浸润性宫颈癌中，经常发现人乳头瘤病毒（HPV）DNA整合到人类基因组中。研究特定HPV基因的基因组状态与其针对HPV-16 L1/L2蛋白病毒样颗粒（VLP）以及体外翻译的HPV-16 E6和E7蛋白的抗体反应之间的关系，可能有助于阐明HPV相关宫颈癌发生机制及宿主免疫反应。对39例患者的宫颈癌组织进行研究，通过Southern印迹法、DNA-PCR以及E2的RT-PCR评估HPV基因的物理状态。分别采用ELISA检测血清标本针对HPV-16 L1/L2 VLP的抗体反应，采用放射免疫沉淀试验（RIPA）检测针对HPV-16 E6和E7蛋白的抗体反应。38例患者中有23例（60.5%）发现HPV-16 DNA的整合形式。HPV-16阳性的宫颈癌患者中，针对HPV-16 L1/L2 VLP的抗体患病率（39.5%；15/38）显著高于对照组（8.7%；2/28）（P<0.05）。在具有HPV-16 DNA游离形式（纯游离形式和混合形式）的宫颈癌患者中，比仅具有HPV-16 DNA整合形式的患者更常检测到针对HPV-16 L1/L2 VLP的抗体（60%；9/15比26.1%；6/23）（P<0.05）。HPV-16阳性宫颈癌患者中，针对E6和E7蛋白的抗体阳性率分别为36.8%（14/38）和50%（19/38）。这些均显著高于对照组的阳性率（8.3%和2.8%）（P<0.05）。具有HPV-16 DNA游离形式的患者与具有HPV-16 DNA整合形式的患者对E6和E7蛋白的血清反应性差异无统计学意义（P>0.05）。在韩国，大多数宫颈癌患者中HPV-16 DNA的整合形式普遍存在。与对照组相比，HPV相关宫颈癌患者中针对HPV-16 L1/L2 VLP、体外翻译的HPV-16 E6和E7蛋白的抗体出现比例显著更高。在具有HPV-16 DNA游离形式的宫颈癌患者中，比仅具有HPV-16 DNA整合形式的患者更常检测到针对HPV-16 L1/L2 VLP的抗体。对HPV-16 E6和E7蛋白的抗体反应不受不同病毒状态的影响。
