EPIDEMIOLOGIC EVIDENCE SHOWING THAT HUMAN PAPILLOMAVIRUS INFECTION CAUSES MOST CERVICAL INTRAEPITHELIAL NEOPLASIA
EPIDEMIOLOGIC EVIDENCE SHOWING THAT HUMAN PAPILLOMAVIRUS INFECTION CAUSES MOST CERVICAL INTRAEPITHELIAL NEOPLASIA
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DOI：
10.1093/jnci/85.12.958
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发表时间：
1993-06-16
影响因子：
10.3
通讯作者：
MANOS, MM
中科院分区：
文献类型：
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作者：
SCHIFFMAN, MH;BAUER, HM;MANOS, MM
背景：实验研究已经提供了强有力的证据表明，人乳头瘤病毒(HPV)是长期寻求的宫颈肿瘤的性病因，但流行病学证据一直不一致。目的：鉴于HPV检测的进步揭示了性行为史与宫颈HPV感染之间的密切联系，我们对HPV和宫颈上皮内瘤变(CIN)进行了一项大型病例对照研究，以评估性行为和其他已确定的CIN危险因素是否主要通过HPV感染影响风险。方法：我们研究了500名患有CIN的妇女和500名对照受试者，他们在俄勒冈州波特兰的Kaiser Permanente接受细胞学筛查，Kaiser Permanente是一家大型预付费健康计划。通过电话访谈对已建立的CIN流行病学危险因素进行评估。我们对宫颈阴道灌洗液标本进行了HPV检测，通过聚合酶链式反应对HPV的L1基因区进行了基因扩增。使用非条件Logistic回归分析来估计CIN的相对风险，并调整与HPV检测结果的流行病学相关性，以证明这些相关性是否由HPV介导。结果：病例对象表现出典型的CIN流行病学特征：性伴较多，吸烟较多，首次性行为年龄较早，社会经济地位较低。对HPV感染的统计调整大大减少了这些病例对照差异的大小。76%的病例可归因于HPV感染；细胞学检查结果表明，真实比例更高。一旦将HPV感染考虑在内，在HPV阴性和HPV阳性的妇女中，观察到产次与CIN风险的相关性。结论：绝大多数CIN的发生与HPV感染有关，尤其是与癌相关类型的HPV感染。根据这一结论，对人乳头瘤病毒自然史的调查具有预防和病因学的重要性。
Background: Experimental studies have provided strong evidence that human papillomavirus (HPV) is the long-sought venereal cause of cervical neoplasia, but the epidemiologic evidence has been inconsistent. Purpose: Given improvements in HPV testing that have revealed a strong link between sexual activity history and cervical HPV infection, we conducted a large case-control study of HPV and cervical intraepithelial neoplasia (CIN) to evaluate whether sexual behavior and the other established risk factors for CIN influence risk primarily via HPV infection. Methods: We studied 500 women with CIN and 500 control subjects receiving cytologic screening at Kaiser Permanente, a large prepaid health plan, in Portland, Ore. The established epidemiologic risk factors for CIN were assessed by telephone interview. We performed HPV testing of cervicovaginal lavage specimens by gene amplification using polymerase chain reaction with a consensus primer to target the L1 gene region of HPV. Unconditional logistic regression analysis was used to estimate relative risk of CIN and to adjust the epidemiologic associations for HPV test results to demonstrate whether the associations were mediated by HPV. Results: The case subjects demonstrated the typical epidemiologic profile of CIN: They had more sex partners, more cigarette smoking, earlier ages at first sexual intercourse, and lower socioeconomic status. Statistical adjustment for HPV infection substantially reduced the size of each of these case-control differences. Seventy-six percent of cases could be attributed to HPV infection; the results of cytologic review suggested that the true percentage was even higher. Once HPV infection was taken into account, an association of parity with risk of CIN was observed in both HPV-negative and HPV-positive women. Conclusion: The data show that the great majority of all grades of CIN can be attributed to HPV infection, particularly with the cancer-associated types of HPV. Implications: In light of this conclusion, the investigation of the natural history of HPV has preventive as well as etiologic importance.