A population-based prospective study of carcinogenic human papillomavirus variant lineages, viral persistence, and cervical neoplasia.
A population-based prospective study of carcinogenic human papillomavirus variant lineages, viral persistence, and cervical neoplasia.
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DOI：
10.1158/0008-5472.can-09-4179
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发表时间：
2010-04-15
期刊：
影响因子：
11.2
通讯作者：
Burk RD
中科院分区：
文献类型：
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作者：
Schiffman M;Rodriguez AC;Chen Z;Wacholder S;Herrero R;Hildesheim A;Desalle R;Befano B;Yu K;Safaeian M;Sherman ME;Morales J;Guillen D;Alfaro M;Hutchinson M;Solomon D;Castle PE;Burk RD
HPV 类型在宫颈癌的致癌性方面存在显着差异。对于致癌性最强的类型 HPV16，代表进一步进化分化的变异谱系在癌症风险方面也有所不同。其余 10-15 种致癌 HPV 类型的变体尚未得到充分研究。在第一项基于人群的 HPV 变异前瞻性研究中，我们探讨了平均而言，每种致癌类型中最古老的进化分支是否可以预测 ≥2 年病毒持续存在和/或癌前期和癌症 (CIN3+) 的不同风险。我们使用巢式病例对照设计，在为期 7 年、涉及 10,049 名女性的瓜纳卡斯特队列研究中检查了 HPV 变异的自然史。感染被分配给基于 URR/E6 序列的系统发育简约方法确定的变异谱系。我们使用费舍尔组合检验来评估风险关联的显着性，累积不同类型的证据。在全球范围内，对于包括 HPV16 在内的 HPV 类型，持久性的 p 值为 0.01，CIN3+ 的 p 值为 0.07。排除 HPV16，p 值分别为 0.04 和 0.37。对于 HPV16，非欧洲病毒变种比欧洲变种更有可能导致持续存在（OR = 2.6，p = 0.01）和 CIN3+（OR = 2.4，p = 0.004）。 HPV35 和 HPV51 变异谱系也预测 CIN3+。 HPV 变种的持续风险通常有所不同。对于某些 HPV 类型，尤其是 HPV16，变异谱系的 CIN3+ 风险有所不同。研究结果表明，HPV 类型的持续进化导致了与 HPV 自然史和宫颈癌风险相关的更精细的遗传歧视。需要进行更大规模的病毒基因组研究，特别是为了确定 HPV16 独特致癌性的遗传基础。
HPV types differ profoundly in cervical carcinogenicity. For the most carcinogenic type, HPV16, variant lineages representing further evolutionary divergence also differ in cancer risk. Variants of the remaining 10-15 carcinogenic HPV types have not been well-studied. In the first prospective, population-based study of HPV variants, we explored whether, on average, the oldest evolutionary branches within each carcinogenic type predicted different risks of ≥2-year viral persistence and/or precancer and cancer (CIN3+). We examined the natural history of HPV variants in the 7-year, 10,049-woman Guanacaste Cohort Study, using a nested case-control design. Infections were assigned to a variant lineage determined by phylogenetic parsimony methods based on URR/E6 sequences. We used the Fisher's combination test to evaluate significance of the risk associations, cumulating evidence across types. Globally, for HPV types including HPV16, the p-value was 0.01 for persistence and 0.07 for CIN3+. Excluding HPV16, the p-values were 0.04 and 0.37, respectively. For HPV16, non-European viral variants were significantly more likely than European variants to cause persistence (OR = 2.6, p = 0.01) and CIN3+ (OR = 2.4, p = 0.004). HPV35 and HPV51 variant lineages also predicted CIN3+. HPV variants generally differ in risk of persistence. For some HPV types, especially HPV16, variant lineages differ in risk of CIN3+. The findings indicate that continued evolution of HPV types has led to even finer genetic discrimination linked to HPV natural history and cervical cancer risk. Larger viral genomic studies are warranted, especially to identify the genetic basis for HPV16's unique carcinogenicity.