Liu Jianhua, Lu Zhitao, Wang Guili, Wang Wei, Zhou Weiqiang, Yang Lianxia, Liu Chao, Wang Bo, Miao Ye, Sun Zhengrong, Ruan Qiang
Department of Clinical Laboratory, The Affiliated Shengjing Hospital, China Medical University, Shenyang, P.R. China.
Virus Laboratory, The Affiliated Shengjing Hospital, China Medical University, Shenyang, P.R. China.
Jpn J Clin Oncol. 2017 Feb 4;47(2):123-129. doi: 10.1093/jjco/hyw166.
We aimed to evaluate the viral load and integration status of human papillomavirus 58 in women with different grades of cervical lesions to determine whether viral load and integration status are related to malignant transformation in HPV58-infected women.
A total of 212 cervical specimens were collected from women in Northeast China who had undergone human papillomavirus genotyping and were HPV58-positive. The HPV58 viral load was determined using real-time polymerase chain reaction, and the integration status was discriminated using the ratio of HPV58 E2 gene copy number to E6 gene copy number.
The median HPV58 viral load in women with normal cervix or cervicitis, low-grade squamous cell intraepithelial lesion, high-grade squamous cell intraepithelial lesion and cervical cancer was 352.12, 864.21, 1199.75 and 693.04 copies/genome, respectively. High significance was obtained when comparing the viral load of infected women presenting normal/cervicitis with that of the women either with precancerous cervical lesions or cervical cancer (P < 0.05). The HPV58 genome was in the episomal form in 35 samples (16.5%), mixed episomal and integrated forms in 165 (77.8%) samples, and completely integrated into the host genome in 12 (5.7%) samples. The HPV58 E2/E6 copy number ratio in the cervical cancer group was significantly lower than that in the other groups (P < 0.01).
The HPV58 viral load in patients with precancerous cervical lesions or cervical cancer increases significantly with disease progression. The HPV58 E2/E6 copy number ratio in patients with cervical cancer is lower than that for less severe cervical lesions, suggesting a high degree of viral integration may be a considerable risk factor for cervical cancer.
我们旨在评估不同级别宫颈病变女性中人类乳头瘤病毒58型(HPV58)的病毒载量和整合状态,以确定病毒载量和整合状态是否与HPV58感染女性的恶性转化有关。
从中国东北地区接受人类乳头瘤病毒基因分型且HPV58呈阳性的女性中总共收集了212份宫颈标本。使用实时聚合酶链反应测定HPV58病毒载量,并通过HPV58 E2基因拷贝数与E6基因拷贝数的比值来判别整合状态。
宫颈正常或患有宫颈炎、低度鳞状上皮内病变、高度鳞状上皮内病变及宫颈癌的女性中,HPV58病毒载量的中位数分别为352.12、864.21、1199.75和693.04拷贝/基因组。将宫颈正常/患有宫颈炎的感染女性的病毒载量与患有宫颈癌前病变或宫颈癌的女性的病毒载量进行比较时,差异具有高度显著性(P < 0.05)。HPV58基因组以游离形式存在于35份样本中(16.5%),以游离和整合混合形式存在于165份样本中(77.8%),并完全整合到宿主基因组中的有12份样本(5.7%)。宫颈癌组中的HPV58 E2/E6拷贝数比值显著低于其他组(P < 0.01)。
宫颈癌前病变或宫颈癌患者的HPV58病毒载量随疾病进展而显著增加。宫颈癌患者的HPV58 E2/E6拷贝数比值低于病情较轻的宫颈病变患者,这表明高度的病毒整合可能是宫颈癌的一个重要危险因素。