Papillomaviruses in human cancers.

H zur Hausen
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Abstract

Papillomaviruses have proved to be the most complex group of human pathogenic viruses. Eighty-five genotypes have been fully characterized; approximately 120 additional isolates represent only partially characterized putative novel genotypes. Specific types, most notably human papillomavirus (HPV) types 16, 18, and a few others, have been shown to cause the majority of cervical cancers and their high-grade precursor lesions. The viral oncogenes E6 and E7 are required for the initiation and maintenance of the malignant phenotype in HPV-positive cancers. Proteins coded by these genes are multifunctional and interfere with important cell cycle regulatory proteins. Expression of viral oncogenes is tightly controlled in nondifferentiated keratinocytes by at least two signaling cascades, one operative at the functional level, the other at the transcriptional level. The latter has been partially characterized. Papillomaviruses are also suspected of playing a role in a subset of oropharyngeal cancers, in squamous cell cancers of the skin, and possibly also in esophageal cancers. Clinical trials are being conducted to test the preventive and therapeutic efficacy of HPV vaccines, directed particularly against HPV 16 and 18. If proven to be effective, their global application should have a measurable effect on the worldwide incidence of cancer.

人类癌症中的乳头瘤病毒。
乳头瘤病毒已被证明是人类致病性病毒中最复杂的一类。85个基因型已被完全鉴定;大约120个额外的分离株仅部分表征了假定的新基因型。特定类型,最明显的是人乳头瘤病毒(HPV) 16、18型和其他一些类型,已被证明是大多数宫颈癌及其高级前体病变的病因。在hpv阳性癌症中,病毒致癌基因E6和E7是恶性表型的起始和维持所必需的。这些基因编码的蛋白质是多功能的,并干扰重要的细胞周期调节蛋白。在未分化的角质形成细胞中,病毒癌基因的表达受到至少两个信号级联的严格控制,一个在功能水平上起作用,另一个在转录水平上起作用。后者已被部分描述。乳头状瘤病毒也被怀疑在口咽癌的一个亚群、皮肤鳞状细胞癌以及可能在食管癌中发挥作用。正在进行临床试验,以测试人类乳头瘤病毒疫苗的预防和治疗效果,特别是针对人类乳头瘤病毒16和18。如果证明是有效的,它们的全球应用应该对全球癌症发病率产生可衡量的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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