Bosch F X, Manos M M, Muñoz N, Sherman M, Jansen A M, Peto J, Schiffman M H, Moreno V, Kurman R, Shah K V
Institut Catala d'Oncologia, Hospital Duran i Reynals, CSUB, L'Hospitalet del Llobregat, Barcelona, Spain.
J Natl Cancer Inst. 1995 Jun 7;87(11):796-802. doi: 10.1093/jnci/87.11.796.
Epidemiologic studies have shown that the association of genital human papillomavirus (HPV) with cervical cancer is strong, independent of other risk factors, and consistent in several countries. There are more than 20 different cancer-associated HPV types, but little is known about their geographic variation.
Our aim was to determine whether the association between HPV infection and cervical cancer is consistent worldwide and to investigate geographic variation in the distribution of HPV types.
More than 1000 specimens from sequential patients with invasive cervical cancer were collected and stored frozen at 32 hospitals in 22 countries. Slides from all patients were submitted for central histologic review to confirm the diagnosis and to assess histologic characteristics. We used polymerase chain reaction-based assays capable of detecting more than 25 different HPV types. A generalized linear Poisson model was fitted to the data on viral type and geographic region to assess geographic heterogeneity.
HPV DNA was detected in 93% of the tumors, with no significant variation in HPV positivity among countries. HPV 16 was present in 50% of the specimens, HPV 18 in 14%, HPV 45 in 8%, and HPV 31 in 5%. HPV 16 was the predominant type in all countries except Indonesia, where HPV 18 was more common. There was significant geographic variation in the prevalence of some less common virus types. A clustering of HPV 45 was apparent in western Africa, while HPV 39 and HPV 59 were almost entirely confined to Central and South America. In squamous cell tumors, HPV 16 predominated (51% of such specimens), but HPV 18 predominated in adenocarcinomas (56% of such tumors) and adenosquamous tumors (39% of such tumors).
Our results confirm the role of genital HPVs, which are transmitted sexually, as the central etiologic factor in cervical cancer worldwide. They also suggest that most genital HPVs are associated with cancer, at least occasionally.
The demonstration that more than 20 different genital HPV types are associated with cervical cancer has important implications for cervical cancer-prevention strategies that include the development of vaccines targeted to genital HPVs.
流行病学研究表明，生殖器人乳头瘤病毒（HPV）与宫颈癌之间的关联紧密，独立于其他风险因素，且在多个国家都一致。有20多种不同的与癌症相关的HPV类型，但对其地理变异情况知之甚少。
我们的目的是确定HPV感染与宫颈癌之间的关联在全球范围内是否一致，并调查HPV类型分布的地理变异。
在22个国家的32家医院收集了1000多份来自连续性浸润性宫颈癌患者的标本，并冷冻保存。所有患者的玻片均提交进行中心组织学检查，以确诊并评估组织学特征。我们使用基于聚合酶链反应的检测方法，能够检测25种以上不同的HPV类型。对病毒类型和地理区域的数据拟合广义线性泊松模型，以评估地理异质性。
93%的肿瘤中检测到HPV DNA，各国之间HPV阳性率无显著差异。50%的标本中存在HPV 16，14%中存在HPV 18，8%中存在HPV 45，5%中存在HPV 31。除印度尼西亚外，HPV 16是所有国家的主要类型，在印度尼西亚HPV 18更为常见。一些较不常见病毒类型的患病率存在显著地理变异。HPV 45在西非明显聚集，而HPV 39和HPV 59几乎完全局限于中美洲和南美洲。在鳞状细胞肿瘤中，HPV 16占主导（此类标本的51%），但在腺癌（此类肿瘤的56%）和腺鳞癌（此类肿瘤的39%）中HPV 18占主导。
我们的结果证实了通过性传播的生殖器HPV作为全球宫颈癌主要病因的作用。它们还表明，大多数生殖器HPV至少偶尔与癌症相关。
证明20多种不同的生殖器HPV类型与宫颈癌相关，对包括开发针对生殖器HPV的疫苗在内的宫颈癌预防策略具有重要意义。
