International Agency for Research on Cancer, Lyon, France.
Int J Cancer. 2012 Nov 15;131(10):2349-59. doi: 10.1002/ijc.27485. Epub 2012 Mar 20.
Genotyping may improve risk stratification of high-risk (HR) human papillomavirus (HPV)-positive women in cervical screening programs; however, prospective data comparing the natural history and carcinogenic potential of individual HR types remain limited. A meta-analysis of cross-sectional HR HPV-type distribution in 115,789 HPV-positive women was performed, including 33,154 normal cytology, 6,810 atypical squamous cells of undetermined significance (ASCUS), 13,480 low-grade squamous intraepithelial lesions (LSIL) and 6,616 high-grade SIL (HSIL) diagnosed cytologically, 8,106 cervical intraepithelial neoplasia grade 1 (CIN1), 4,068 CIN2 and 10,753 CIN3 diagnosed histologically and 36,374 invasive cervical cancers (ICCs) from 423 PCR-based studies worldwide. No strong differences in HPV-type distribution were apparent between normal cytology, ASCUS, LSIL or CIN1. However, HPV16 positivity increased steeply from normal/ASCUS/LSIL/CIN1 (20-28%), through CIN2/HSIL (40/47%) to CIN3/ICC (58/63%). HPV16, 18 and 45 accounted for a greater or equal proportion of HPV infections in ICC compared to normal cytology (ICC:normal ratios = 3.07, 1.87 and 1.10, respectively) and to CIN3 (ICC:CIN3 ratios = 1.08, 2.11 and 1.47, respectively). Other HR types accounted for important proportions of HPV-positive CIN2 and CIN3, but their contribution dropped in ICC, with ICC:normal ratios ranging from 0.94 for HPV33 down to 0.16 for HPV51. ICC:normal ratios were particularly high for HPV45 in Africa (1.85) and South/Central America (1.79) and for HPV58 in Eastern Asia (1.36). ASCUS and LSIL appear proxies of HPV infection rather than cancer precursors, and even CIN3 is not entirely representative of the types causing ICC. HPV16 in particular, but also HPV18 and 45, warrant special attention in HPV-based screening programs.
基因分型可能会改善宫颈癌筛查计划中高危(HR)人乳头瘤病毒(HPV)阳性女性的风险分层;然而,比较个别 HR 型的自然史和致癌潜力的前瞻性数据仍然有限。对 115789 例 HPV 阳性妇女的 HR HPV 型分布进行了荟萃分析,包括 33154 例正常细胞学、6810 例非典型鳞状细胞意义不明(ASCUS)、13480 例低度鳞状上皮内病变(LSIL)和 6616 例高级别鳞状上皮内病变(HSIL)细胞学诊断、8106 例宫颈上皮内瘤变 1 级(CIN1)、4068 例 CIN2 和 10753 例 CIN3 组织学诊断和 36374 例来自全球 423 项基于 PCR 的研究的浸润性宫颈癌(ICC)。在正常细胞学、ASCUS、LSIL 或 CIN1 之间,HPV 型分布没有明显差异。然而,HPV16 的阳性率从正常/ASCUS/LSIL/CIN1(20-28%),通过 CIN2/HSIL(40/47%),增加到 CIN3/ICC(58/63%)。HPV16、18 和 45 在 ICC 中占 HPV 感染的比例大于或等于正常细胞学(ICC:正常比值分别为 3.07、1.87 和 1.10)和 CIN3(ICC:CIN3 比值分别为 1.08、2.11 和 1.47)。其他 HR 型在 HPV 阳性的 CIN2 和 CIN3 中也占重要比例,但在 ICC 中所占比例下降,ICC:正常比值范围从 HPV33 的 0.94 下降到 HPV51 的 0.16。HPV45 在非洲(1.85)和南美/中美(1.79)以及 HPV58 在东亚(1.36)的 ICC 中比值特别高。ASCUS 和 LSIL 似乎是 HPV 感染的代表,而不是癌症前体,甚至 CIN3 也不完全代表引起 ICC 的类型。HPV16 特别是 HPV18 和 45,在 HPV 为基础的筛查计划中需要特别关注。