RECENT PROGRESS IN DEFINING THE EPIDEMIOLOGY OF HUMAN PAPILLOMAVIRUS INFECTION AND CERVICAL NEOPLASIA
RECENT PROGRESS IN DEFINING THE EPIDEMIOLOGY OF HUMAN PAPILLOMAVIRUS INFECTION AND CERVICAL NEOPLASIA
复制标题
DOI：
10.1093/jnci/84.6.394
复制
发表时间：
1992-03-18
影响因子：
10.3
通讯作者：
SCHIFFMAN, MH
中科院分区：
文献类型：
--
作者：
SCHIFFMAN, MH
长期以来，流行病学资料表明，一种性传播感染因子引起宫颈瘤变（该术语用于包括浸润性宫颈癌及其上皮内前体病变）。特别是，许多研究已经确定，在较早开始性行为和性伴侣较多的妇女中，发生宫颈瘤变的风险增加（/）。在20世纪80年代中期，实验室科学家收集的病例系列表明，宫颈癌活检标本含有HPV DNA序列(2)。随后，支持HPV感染在宫颈肿瘤病因学中的因果作用的实验室证据已大大加强。反复研究表明，大多数宫颈上皮内病变、宫颈癌和衍生细胞系含有HPV DNA（3-5）。HPV基因组E6和E7区域编码的蛋白质的转化活性强烈表明，HPV不仅仅是一种偏爱肿瘤宫颈细胞的“乘客病毒”(6)。最近的研究（7,8）表明，这些转化蛋白与肿瘤抑制基因产物结合，为hpv诱导的宫颈瘤变提供了一种合理的机制。为了证实这些实验室发现，流行病学家试图从他们的角度证实HPV感染是长期寻找的宫颈肿瘤性病传播原因。大多数流行病学研究都集中在几个关键点上。流行病学家研究了细胞学正常的女性中HPV感染的患病率（9-11），并进行了病例对照比较，以解释宫颈瘤变女性中HPV阳性的高患病率（12）。他们研究了HPV感染的危险因素，认为如果HPV是由病毒引起的，那么HPV应该与宫颈肿瘤有许多相同的危险因素（10,12 -14）。最后，他们建立了前瞻性调查，以检查HPV感染是否预测宫颈瘤变的发生、复发或病理进展（15,16）。事实证明，这些努力比预期的要困难得多，部分原因是HPV检测方法存在问题，通常依赖于检测宫颈组织样本中的HPV特异性DNA。结果已被证明明显依赖于宫颈组织取样和DNA检测的方法。目前，至少有四种不同的收集脱落的宫颈细胞用于HPV检测的技术是常用的：拭子、刮、细胞刷和灌洗。试验灵敏度因采集方法而异（17）。采集宫颈样本后，采用多种DNA-DNA或RNA-DNA杂交方法进行HPV检测和分型。大多数流行病学家要么使用市售的RNA-DNA点印迹系统（18），要么使用聚合酶链反应（PCR）技术来扩增20种左右不同类型生殖器hpv中许多人共有的DNA序列（19）。然而，目前还没有建立“黄金标准”。在最近的一次人乳头瘤病毒会议上进行的非正式调查显示，目前使用的20多种不同的技术，许多方法的不可比性是最近几次的主题
Epidemiologic data have long suggested that a venereally transmitted infectious agent causes cervical neoplasia (a term used to include invasive cervical cancer and its intraepithelial precursor lesions). In particular, numerous studies have established that the risk of cervical neoplasia is increased among women who initiate sexual intercourse at earlier ages and who have greater numbers of sexual partners (/). In the mid-1980s, case series assembled by laboratory scientists demonstrated that biopsy specimens of cervical cancer contain HPV DNA sequences (2). Subsequently, laboratory evidence supporting a causal role for HPV infection in the etiology of cervical neoplasia has strengthened considerably. Repeated studies have demonstrated that the majority of cervical intraepithelial lesions, cervical cancers, and derived cell lines contain HPV DNA {3-5). The transforming activities of proteins encoded by the E6 and E7 regions of the HPV genome strongly suggest that HPV is not merely a" passenger virus" with a predilection for neoplastic cervical cells (6). Recent studies (7, 8), demonstrating that these transforming proteins bind to tumor suppressor gene products, provide a plausible mechanism for HPV-induced cervical neoplasia. To corroborate these laboratory findings, epidemiologists have attempted, from their perspective, to confirm that HPV infection is the long-sought, venereally transmissible cause of cervical neoplasia. Most epidemiologic research has focused on a few key points. Epidemiologists have studied the prevalence of HPV infection among cytologically normal women (9-11) and made the case-control comparisons needed for the interpretation of a high prevalence of HPV positivity among women with cervical neoplasia (12). They have investigated the risk factors for HPV infection, reasoning that HPV should share many of the same risk factors as cervical neoplasia if the virus causes the disease (10, 12-14). Finally, they have established prospective investigations to examine whether HPV infection predicts the development, recurrence, or pathologic progression of cervical neoplasia (15, 16).These efforts have proven more difficult than anticipated, partly because of methodologic problems with HPV assays, which generally depend on the detection of HPV-specific DNA in samples of cervical tissue. The results have proven to be strikingly dependent on methods of cervical tissue sampling and DNA detection. At present, at least four different techniques of collecting exfoliated cervical cells for HPV testing are in common use: swab, scrape, cytobrush, and lavage. Test sensitivity has been shown to vary by collection method (17). Once cervical samples are collected, multiple methods of DNA-DNA or RNA-DNA hybridization are used for HPV detection and typing. Most epidemiologists have used either a commercially available RNA-DNA dot blot system (18) or polymerase chain reaction (PCR) techniques developed to amplify DNA sequences shared by many of the 20 or so different types of genital HPVs (19). However, no" gold standard" has yet been established. An informal survey at a recent HPV meeting revealed over 20 discrete techniques in current use, and the noncomparability of the many methods was the topic of several recent