first let's take a look at the HPV virus 首先让我们来看看HPV病毒
itself human papilloma viruses are small 本身人乳头状瘤病毒很小
double-stranded DNA viruses more than 双链DNA病毒超过
100 HPV types have been identified and 已经确定了 100种HPV类型
they are differentiated by the genetic 他们通过遗传来区分
sequence of the protective outer shell 保护性外壳的序列
or capsid made of a protein called l1 或由称为l1的蛋白质制成的衣壳
inside this protective sphere is the 在这个保护范围内是
viral DNA about 40 types of HPV infect 病毒DNA 约有40种HPV感染
the mucosal epithelium and are 粘膜上皮和
categorized according to their 根据他们的分类
association with cervical cancer the HPV 与宫颈癌相关的HPV
gene structure or genome is organized 基因结构或基因组是有组织的
into three regions with eight 进入三个区域，八个
overlapping open reading frames six 重叠的开放阅读框六
early genes II 1 to e7 too late genes l1 早期基因II 1到e7基因l1太晚了
and l2 and one non-coding long control 和l2 和一个非编码长控件
region or LC are containing a variety of 区域或LC包含各种各样的
elements which regulate viral 调节病毒的元素
replication and gene expression the l1 复制和基因表达l1
and l2 genes encode the major and minor 和l2基因编码主要和次要
capsid proteins early genes regulate HPV 衣壳蛋白早期基因调节HPV
viral replication now let's look at the 病毒复制现在让我们来看看
HPV infection process that could lead to HPV感染过程可能导致
cervical cancer 宫颈癌
the typical sight of an HPV infection is HPV 感染的典型情况是
the transformation zone of the cervix 子宫颈的转化区
the cervix is the lower end of the 宫颈的下端
uterus that extends into the vagina and 子宫延伸到阴道和
becomes infected with HPV typically 通常会感染HPV
following sexual contact the epithelial 以下性接触上皮
lining of the cervix consists of 子宫颈衬里由
stratified squamous epithelial cells 分层鳞状上皮细胞
which are flatter and more specialized 更平坦， 更专业
or differentiated the farther they are 或者将它们区分得越远
from the basement membrane the basal 从基底膜到基底膜
cell layer houses the stem cells which 细胞层容纳干细胞
replicate and undergo cell division and 复制并进行细胞分裂和
eventually mature into squamous 最终成熟为鳞状
epithelial cells as they migrate to the 上皮细胞迁移到
upper epithelial layers micro abrasions 上皮上层微磨损
or small tears sometimes occur in the 或者有时会出现小眼泪
lining of the server 服务器的衬里
epithelium HPV infectious viral 上皮HPV感染性病毒
particles opportunistically invade the 粒子机会性地侵入
cervical epithelium and infect the basal 宫颈上皮和感染基底
layer cells viral HPV DNA replicates and 层细胞病毒HPV DNA复制和
is maintained in the dividing basal 维持在分裂的基础
cells as low copy episome all DNA in 细胞作为低拷贝附加体的所有DNA
rare instances HPV DNA may incorporate 罕见的HPV DNA可能含有
into the host genome the dividing basal 进入宿主基因组的分裂基础
cells begin to differentiate and viral 细胞开始分化和病毒
genome amplification and synthesis of 基因组扩增和合成
the capsid proteins l1 and l2 occur in 衣壳蛋白l1和l2出现在
the upper layers of the epithelium 上皮的上层
papilloma virus infections are usually 通常是乳头状瘤病毒感染
long-lived and the dividing basal cells 长寿和分裂的基底细胞
provide a reservoir of infected cells 提供一个受感染细胞的库
for the overlaying virus producing 对于覆盖的病毒产生
tissue this strategy requires that the 组织这种策略需要的
papilloma viruses have a faithful and 乳头状瘤病毒有忠实和
robust mechanism to replicate and retain 强大的复制和保留机制
their episome LG gnomes in the nuclei of 他们的附庸LG 侏儒在核心
the dividing cells when the basal cells 分裂细胞时的基底细胞
are programmed to differentiate it 被编程以区分它
activates the HPV virus to initiate 激活HPV病毒以启动
stages of the viral life cycle this 病毒生命周期的这个阶段
includes reactivating cell replication 包括重新激活细胞复制
to produce multiple copies of viral DNA 产生多拷贝的病毒DNA
forming the viral capsid viral assembly 形成病毒衣壳病毒组装
and finally release of the virus let's 最后释放病毒的，让我们
look at the process of viral replication 看看病毒复制的过程
in more detail to initiate this process 更详细地启动此过程
the first step is for the virus to 第一步是病毒来
express a 6 and a 7 viral genes the 表达6个7病毒基因的
protein product from this messenger RNA 来自该信使RNA的蛋白质产物
interferes with normal cell function and 干扰正常细胞功能和
results in non-scheduled cell 导致非预定的细胞
replication these dysregulated cells are 复制这些失调的细胞是
instructed to divide and produce the 指示分裂和产生
multiple copies of the HPV viral DNA as 的HPV病毒DNA作为多拷贝
a result of this non-scheduled 这种不定期的结果
replication there is an accumulation of 复制有一个积累
cells that disrupts the structural 破坏结构的细胞
appearance of the epithelial tissue 上皮组织的外观
what was once very ordered and highly 什么曾经非常有序和高度
structured now begins to look 结构现在开始看起来
disorganized the extension of this 紊乱了这个的延伸
disorganization through the upper layers 通过上层解体
and to the surface of the epithelium is 并且到上皮的表面是
what is used to classify the degree of 什么是用来分类的程度
the lesion abnormal cell growth in the 在病灶中异常细胞生长
lower 1/3 of the basal epithelium is 较低1/3的基底上皮是
categorized as cervical intraepithelial 分类为宫颈上皮内
neoplasia grade 1 or CIN 1 when this 当这个时，肿瘤1级或CIN 1
extends up 2/3 of the way from the 向上延伸的 距离的方式2/3
bottom basal epithelium it is sent to 它被发送到底部基底上皮
ultimately when the abnormally dividing 最终当异常分裂
cells span more than 2/3 of this cell 细胞跨越该细胞的2/3以上
layer it is referred to as CIN 3 this is 层被称为CIN 3，这是
the immediate precursor to cervical 颈椎的直接前兆
cancer invasive cervical cancer ensues 癌症浸润性宫颈癌随之而来
when the abnormal cells break through 当异常细胞突破时
the basal membrane and infect the dermis 基底膜并感染真皮
it is when this process becomes 这个过程变成了
persistent that cervical cancer becomes 持续的宫颈癌变成了
the ultimate consequence so how does the 最终的结果是如何
HPV virus infection cause cervical HPV病毒感染引起宫颈癌
cancer infection is initiated when the 癌症感染发生时
HPV virus penetrates the basal cells HPV病毒穿透基底细胞
once the cell is infected the viral 一旦细胞感染了病毒
capsid is shed and the circular HPV 衣壳脱落和圆形HPV
genome is shuttled into the nucleus of 基因组穿梭于细胞核
the cell as mentioned earlier the DNA 如前所述的细胞DNA
from the HPV virus contains eight 来自HPV病毒包含八个
different genes early genes are 不同的基因早期基因是
designated as E and late genes are 指定为E和晚期基因
designated as L in normally dividing 通常划分为L
cells to gene products carefully 细胞基因产品仔细
regulate the process these are the p53 调节过程这些是p53
and retinal blastoma or PRB proteins 和视网膜母细胞瘤或PRB蛋白
the p53 is responsible for guarding the p53基因是负责保卫
genome by initiating DNA repair cell 基因组通过启动DNA修复细胞
cycle checkpoints and apoptosis the 循环检查点和细胞凋亡
retinoblastoma protein or PRB is 视网膜母细胞瘤蛋白或PRB是
responsible for preventing replication 负责防止复制
of damaged DNA in the cell and 细胞和细胞中受损的DNA
regulating the cell cycle 调节细胞周期
upon e 6 and e 7 expression the proteins 在e 6和e 7表达蛋白质
that are encoded by the m RNA sequences 由m RNA序列编码
interact with p53 and pRb respectively 分别与p53和pRb相互作用
this is what results in the unscheduled 这就是未计划的结果
cell replication and division as these 细胞复制和分裂就像这些
infected cells are forced to replicate 被感染的细胞被迫复制
viral episomes are also replicated 病毒的附加体也被复制
producing more viral particles several 产生更多的病毒颗粒
important facts about HPV disease 有关HPV 疾病的重要事实
progression are worth considering 进展值得考虑
because e 6 e 7 mRNA expression is 因为e 6 e 7 mRNA的表达是
needed at all points along disease 沿着疾病都需要点
progression and test targeting these 针对这些进展和测试
genes cannot differentiate between 基因无法区分
progressing and regressing lesions a 6 e 进展和消退病变6 e
7 mRNA expression produces c6 e 7 7 mRNA表达产生c6 e 7
proteins driving dysregulated cell 蛋白质驱动失调的细胞
replication this results in an 复制这导致了一个
accumulation of HPV DNA plus cells mRNA HPV DNA加上细胞mRNA的积累
levels are difficult to reliably 水平难以可靠
quantify and therefore presents a more 量化，因此呈现更多
challenging diagnostic target on the 具有挑战性的诊断目标
other hand the l1 gene has been used to 另一方面l1基因已被用于
reliably detect HPV DNA and distinguish 可靠地检测HPV DNA并进行区分
one HPV genotype from another for over 一个HPV基因型来自另一个
25 years 25年
only DNA based tests have been shown to 仅基于DNA的测试已经显示出
have a long-term low-risk period after a a。 之后有一个长期的低风险期
negative test with many copies of HPV 带有许多HPV拷贝的阴性测试
within one cell and many infected cells 一个细胞内和许多感染细胞
within every patient sample random and 在每个患者样本中随机和
unpredictable HPV incorporation makes it 不可预知的HPV合并使其成为现实
impossible for the same 200 BP l1 gene 对于相同的200 BP l1基因是不可能的
region to be uniformly deleted research 区域被统一删除研究
indicates that based upon histological 表示基于组织学
status DNA testing yields increasing 状态DNA测试产量增加
positive results for patients across the 跨患者积极成果
spectrum of disease progression 疾病进展谱
thus making DNA the gold standard for a 从而使DNA成为一个金标准
cervical cancer screening assay 宫颈癌筛查试验
you 您