Department of Cancer Epidemiology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 17 South Panjiayuan Lane, Beijing 100021, China.
Department of Cancer Epidemiology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 17 South Panjiayuan Lane, Beijing 100021, China; Department of Nutrition, Dongfeng Hospital Affiliated to Hubei Medical University, Shiyan 442000, China.
J Clin Virol. 2018 Nov;108:6-11. doi: 10.1016/j.jcv.2018.08.008. Epub 2018 Aug 28.
It has been reported that high HPV DNA load and elevated E6 protein expression correlate with cervical cancer, but no epidemiological study has been performed.
To assess the association between type-specific HPV DNA load and presence of E6 protein in cervical intraepithelial neoplasia and cancer.
This study was a cross-sectional multicenter study performed between 2013 and 2017. A total of 1717 women (normal histopathology: n = 916; CIN1: n = 94; CIN2: n = 63; CIN3: n = 130; SCC: n = 474; adenocarcinoma: n = 40) were included. HPV DNA load and presence of E6 protein were detected. DNA load was measured as log copies/10,000 cells.
The HPV16/18-E6 positivity rates increased from negative for DNA to the highest load grade. Compared to the HPV16 DNA negatives, women with low (RR = 31.5, 95%CI = 18.9-52.5), medium-low (RR = 133.5, 95%CI = 77.3-230.7), medium-high (RR = 247.9, 95%CI = 134.9-455.6) and high DNA loads (RR = 677.9, 95%CI = 301.6-1523.7) had increasingly higher relative ratios of HPV16-E6 expression. The association of HPV18-E6 with its DNA load was also significant for low (RR = 27.9, 95%CI = 10.4-74.9), medium-low (RR = 89.0, 95%CI = 32.8-241.3), medium-high (RR = 276.8, 95%CI = 76.7-998.9) and high grade (RR = 441.2, 95%CI = 97.7-1992.4). The positivity rates of both HPV16 DNA and E6 protein increased consistently with the severity of diseases from normal histopathology to SCC. Unlike HPV16, the trends of HPV18 DNA and E6 protein fluctuated consistently among women from normal histopathology to cancer. DNA load in E6-positive women was significantly higher than E6-negative for both types.
There is a type-dependent association between HPV16/18 DNA load and E6 protein; our study furthers the understanding of the natural history of cervical cancer.
已有报道称 HPV 病毒载量高和 E6 蛋白表达升高与宫颈癌相关，但尚未有流行病学研究对此进行评估。
评估 HPV 病毒载量与 E6 蛋白在宫颈上皮内瘤变和宫颈癌中的存在之间的关联。
这是一项 2013 年至 2017 年期间进行的横断面多中心研究。共纳入 1717 名女性（正常组织病理学：n=916；CIN1：n=94；CIN2：n=63；CIN3：n=130；SCC：n=474；腺癌：n=40）。检测 HPV 病毒载量和 E6 蛋白的存在。病毒载量以每 10,000 个细胞的 log 拷贝数进行测量。
HPV16/18-E6 的阳性率从 DNA 阴性到最高负荷等级逐渐升高。与 HPV16 DNA 阴性相比，低载量（RR=31.5，95%CI=18.9-52.5）、中低载量（RR=133.5，95%CI=77.3-230.7）、中高载量（RR=247.9，95%CI=134.9-455.6）和高载量（RR=677.9，95%CI=301.6-1523.7）的女性 HPV16-E6 表达的相对比值逐渐升高。HPV18-E6 与其 DNA 载量之间的相关性在低载量（RR=27.9，95%CI=10.4-74.9）、中低载量（RR=89.0，95%CI=32.8-241.3）、中高载量（RR=276.8，95%CI=76.7-998.9）和高级别（RR=441.2，95%CI=97.7-1992.4）中也具有统计学意义。HPV16 DNA 和 E6 蛋白的阳性率从正常组织病理学到 SCC 一直随着疾病的严重程度而持续增加。与 HPV16 不同，HPV18 DNA 和 E6 蛋白在从正常组织病理学到癌症的女性中的趋势波动不定。E6 阳性女性的病毒载量明显高于 E6 阴性女性。
HPV16/18 病毒载量与 E6 蛋白之间存在类型依赖性关联；本研究进一步了解了宫颈癌的自然史。
