人乳头瘤病毒基因型在宫颈癌中的分布：一项回顾性、全球性的横断面研究。
Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study.
机构信息
IDIBELL, Institut Català d'Oncologia-Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain.
出版信息
Lancet Oncol. 2010 Nov;11(11):1048-56. doi: 10.1016/S1470-2045(10)70230-8. Epub 2010 Oct 15.
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.
背景
了解人乳头瘤病毒（HPV）基因型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。我们旨在提供关于全球范围内浸润性宫颈癌患者 HPV 基因型分布的新的和全面的数据。
方法
从欧洲、北美、中南美、非洲、亚洲和大洋洲的 38 个国家收集了经组织学证实的浸润性宫颈癌石蜡包埋样本。纳入标准为组织样本中 HPV DNA 分析所选择的原发性上皮来源浸润性宫颈癌的病理证实，以及关于诊断年份的信息。HPV 检测使用 SPF-10 广谱引物进行 PCR，然后进行 DNA 酶免疫测定和反向杂交线探针测定进行基因分型。对 HPV 阳性但 HPV 类型未知的样本进行序列分析以确定 HPV 类型。数据分析包括多重感染算法，以估计特定类型的相对贡献。
结果
共获得 22661 个石蜡包埋样本，来自 14249 名女性。研究纳入了 10575 例浸润性宫颈癌病例，其中 8977 例（85%）HPV DNA 阳性。最常见的 HPV 类型是 16、18、31、33、35、45、52 和 58，其全球相对贡献率为 8977 例中的 8196 例（81%，95%CI 90-92）。在 8977 例浸润性宫颈癌病例中，6357 例（71%，70-72）检测到 HPV 类型 16 和 18。在 470 例宫颈腺癌病例中，443 例（94%，92-96）检测到 HPV 类型 16、18 和 45。在 8977 例浸润性宫颈癌病例中，通过序列分析确定的未知 HPV 类型为 26、30、61、67、69、82 和 91。与 HPV 类型 16、18 或 45 相关的浸润性宫颈癌患者的平均发病年龄低于其他 HPV 类型（分别为 50.0 岁[49.6-50.4]、48.2 岁[47.3-49.2]、46.8 岁[46.6-48.1]和 55.5 岁[54.9-56.1]）。
解释
据我们所知，这是迄今为止对 HPV 基因型的最大评估。在评估当前疫苗的交叉保护作用以及制定第二代多价 HPV 疫苗使用建议时，应优先考虑 HPV 类型 16、18、31、33、35、45、52 和 58。我们的结果还表明，基于 HPV 高危型 DNA 的特定类型的筛查试验和方案应侧重于 HPV 类型 16、18 和 45。
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