The carcinogenicity of human papillornavirus types reflects viral evolution
The carcinogenicity of human papillornavirus types reflects viral evolution
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DOI：
10.1016/j.virol.2005.04.002
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发表时间：
2005-06-20
期刊：
影响因子：
3.7
通讯作者：
Burk, RD
中科院分区：
文献类型：
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作者：
Schiffman, M;Herrero, R;Burk, RD
持续感染致癌的人类乳头瘤病毒(HPV)几乎会导致所有的宫颈癌。宫颈HPV型(n>；40)也是最常见的性传播病原体，大多数感染在1-2年内就消失了。宫颈上皮内瘤变3级(CIN3)是癌及其组织学前驱物，其持续性和肿瘤进展的风险因HPV类型而明显不同。为了研究特定类型的HPV自然历史，我们在哥斯达黎加瓜纳卡斯特对HPV感染和CIN3/癌症进行了一项基于人群的10,000名妇女的前瞻性研究。通过对大量女性的研究，我们希望将病毒持久性与肿瘤进展分开。我们观察到，新修订的HPV进化分组与持续和进展为CIN3/癌症的独立风险有很强的一致性。HPV16独一无二地可能持续存在，并在持续存在时导致肿瘤进展，使其成为一种非常强大的人类致癌物，值得单独临床考虑。具体地说，19.9%的感染HPV16的妇女在登记时或在五年的随访期间被诊断为CIN3/癌症。其他致癌类型，许多与HPV16有关，并不是特别持久，但如果它们确实存在，可能会导致肿瘤进展，其发生率低于HPV16。一些低风险类型是持续性的，但实际上从未引起过CIN3。因此，致癌性并不是严格意义上的持久性函数。另外，我们注意到致癌的HPV类型编码E5蛋白，而大多数低风险类型要么缺乏可定义的同源E5 ORF和/或E5的翻译起始密码子。这些结果为我们正在进行的了解HPV癌变的努力提供了几个明确的线索和研究方向。由爱思唯尔公司出版。
Persistent infections with carcinogenic human papillomaviruses (HPV) cause virtually all cervical cancers. Cervical HPV types (n > 40) also represent the most common sexually transmitted agents, and most infections clear in 1-2 years. The risks of persistence and neoplastic progression to cancer and its histologic precursor, cervical intraepithelial neoplasia grade 3 (CIN3), differ markedly by HPV type. To study type-specific HPV natural history, we conducted a 10,000-woman, population-based prospective study of HPV infections and CIN3/cancer in Guanacaste, Costa Rica. By studying large numbers of women, we wished to separate viral persistence from neoplastic progression. We observed a strong concordance of newly-revised HPV evolutionary groupings with the separate risks of persistence and progression to CIN3/cancer. HPV16 was uniquely likely both to persist and to cause neoplastic progression when it persisted, making it a remarkably powerful human carcinogen that merits separate clinical consideration. Specifically, 19.9% of HPV16-infected women were diagnosed with CIN3/cancer at enrollment or during the five-year follow-up. Other carcinogenic types, many related to HPV16, were not particularly persistent but could cause neoplastic progression, at lower rates than HPV16, if they did persist. Some low-risk types were persistent but, nevertheless, virtually never caused CIN3. Therefore, carcinogenicity is not strictly a function of persistence. Separately, we noted that the carcinogenic HPV types code for an E5 protein, whereas most low-risk types either lack a definable homologous E5 ORF and/or a translation start codon for E5. These results present several clear clues and research directions in our ongoing efforts to understand HPV carcinogenesis. Published by Elsevier Inc.