Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study
Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study
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DOI：
10.1016/s1470-2045(10)70230-8
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发表时间：
2010-11-01
期刊：
影响因子：
51.1
通讯作者：
Xavier Bosch, F.
中科院分区：
文献类型：
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作者：
de Sanjose, Silvia;Quint, Wim G. V.;Xavier Bosch, F.
背景了解人乳头状瘤病毒(HPV)基因在浸润性宫颈癌中的分布对于指导预防性疫苗的引入至关重要。方法收集来自欧洲、北美、中南美洲、非洲、亚洲和大洋洲38个国家的浸润性宫颈癌石蜡标本。纳入标准是组织样本中选择用于HPV DNA分析的原发上皮源性浸润性宫颈癌的病理确认，以及诊断年份的信息。HPV检测采用SPF-10广谱引物聚合酶链式反应、DNA酶免疫分析和反向杂交线探针基因分型方法。对未知HPV类型的HPV阳性样本进行了序列分析。数据分析包括多重感染的算法，以估计特定类型的相对贡献。结果从14249名妇女中获得了22661份石蜡包埋样本。10575例浸润性宫颈癌中，8977例(85%)HPVDNA阳性。最常见的HPV类型是16、18、31、33、35、45、52和58，全球范围内的相对贡献率为8196/8977(91%，95%可信区间90-92)。在8977例浸润性宫颈癌中，6357例(71%，70-72)检出HPV16、18型。470例(94%，92~96)宫颈鳞癌中，443例检出HPV16型、18型和45型。在8977例浸润性宫颈癌中，103例(1%)经序列分析确定未知HPV型分别为26、30、61、67、69、82和91。与HPV16、18或45型相关的浸润性宫颈癌患者的平均年龄比其他HPV型患者年轻(分别为50.0岁[49.6-50.4]岁、48.2岁[47.3-49.2]岁、46.8岁[46.6-48.1]岁和55.5岁[54.9-56.1]岁)。据我们所知，这项研究是迄今为止对HPV基因型别的最大评估。在评估当前疫苗的交叉保护效果以及制定使用第二代多价HPV疫苗的建议时，应优先考虑16、18、31、33、35、45、52和58型HPV16、18、31、33、35、45、52和58型。我们的结果还建议，基于HPV-DNA的特定类型的高危HPV筛查测试和方案应侧重于HPV16、18和45型。
Background Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer.Methods Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions.Findings 22 661 paraffin-embedded samples were obtained from 14 249 women. 10 575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90-92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70-72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92-96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50.0 years [49.6-50.4], 48.2 years [47.3-49.2], 46.8 years [46.6-48.1], and 55.5 years [54.9-56.1], respectively).Interpretation To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45.