宫颈癌及癌前病变中人乳头瘤病毒16载量与整合频率的研究  

Viral load, genomic integration frequency of human papillomavirus 16 in cervical cancer and precancerous lesions

作　　者：李源[1] 向阳[1] 张瑞芬[2] 蔡玉品[2] 杨毅[1] 程雪梅[1] 朱宝利[2] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院妇产科,100730 [2]中国科学院微生物研究所

出　　处：《中华医学杂志》2011年第13期906-910,共5页National Medical Journal of China

摘　　要：目的 研究人乳头瘤病毒（HPV）16病毒载量、基因组整合状态与癌前病变进展的关系,探讨HPV基因组整合频率作为宫颈病变程度标志物的可行性.方法 收集宫颈脱落细胞标本337例,通过PCR扩增、DNA测序分析筛选出HPV16单一感染的样品40例,利用实时定量PCR检测早期基因E2、E6和β-肌动蛋白的拷贝数,分析病毒载量和整合状态.结果 （1）校正后病毒载量在正常组、低度鳞状上皮内病变（LSIL）组、高度鳞状上皮内病变（HSIL）组和宫颈鳞癌组的中位数分别是0.11拷贝/细胞、18.55拷贝/细胞、44.63拷贝/细胞、7.6拷贝/细胞,正常组低于LSIL与HSIL组,宫颈鳞癌组低于HSIL组.（2）在正常、癌前病变（LSIL-HSIL）和宫颈鳞癌中E2/E6比值的中位数分别是0.93、0.84、0.64,E2/E6比值与病变的严重程度显著相关.（3）随着病变程度的升高,游离型比例逐渐降低：正常4/5、LSIL4/6、HSIL 10/16、宫颈鳞癌5/13,整合型（混合＋整合）比例逐渐升高：正常1/5、LSIL 2/6、HSIL 6/16、宫颈鳞癌8/13.2例完全整合的标本均为宫颈鳞癌.结论 HPV16病毒载量可能不是预测宫颈病变的理想指标.HPV16整合频率与宫颈病变严重程度正相关,可能可作为HPV16感染后宫颈上皮细胞病变发展的预估指标.Objective To investigate the association between viral load, genomic integration frequency of HPV 16 and cervical carcinogenesis and assess the probability that HPV 16 integration frequency may be utilized as a marker for cervical cancer. Methods Forty cases of HPV16 single infection were selected from 337 cervical scrape samples by PCR （polymerase chain reaction） amplification and DNA sequencing. The copy numbers of E2, E6 and β-actin were quantified to evaluate the viral load and integration status by real-time PCR. Results （ 1 ） The median number of adjusted viral load of normal group, LSIL （low-grade squamous intraepithelial lesion） group, HSIL （high-grade squamous intraepithelial lesion） group and squamous cervical cancer group were 0. 11, 18. 55, 44. 63 and 7.6 copies per cell respectively. The viral load was higher in LSIL-HSIL group than that in normal group while lower in squamous cervical cancer group than that in HSIL group. （2） The median number of E2/E6 was 0. 93 in normal group, 0. 84 in precancerous group （LSIL-HSIL） and 0. 64 in squamous cervical cancer group respectively. It showed a descending trend with the progression of cervical disease. （3） With the disease development, the proportion of episomal form decreased （ normal group 4/5, LSIL group 4/6, HSIL group 10/16, cervical squamous cancer group 5/13 ） whereas that of integrated form （ mixed and totally integrated）increased （normal group 1/5, LSIL group 2/6, HSIL group 6/16, cervical squamous cancer group 8/13）.Both totally integrated cases were cervical squamous cancer. Conclusion （ 1 ） HPV 16 viral load may not be an ideal marker to predict cervical carcinogenesis. （2） Due to a positive correlation between HPV16 genomic integration frequency and cervical neoplastic progression, HPV 16 integration frequency may be a potential marker of early diagnosis for cervical lesion progression.

关 键 词：人乳头状瘤病毒16 宫颈肿瘤 病毒载量 病毒整合 

分 类 号：R737[医药卫生—肿瘤]