Looking beyond human papillomavirus (HPV) genotype 16 and 18: Defining HPV genotype distribution in cervical cancers in Australia prior to vaccination

Looking beyond human papillomavirus (HPV) genotype 16 and 18: Defining HPV genotype distribution in cervical cancers in Australia prior to vaccination
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DOI:
10.1002/ijc.30871
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发表时间:
2017-10-15
影响因子:
6.4
通讯作者:
Garland, Suzanne M.
Garland, Suzanne M.
中科院分区:
医学1区
文献类型:
--
作者:
Brotherton, Julia M. L.;Tabrizi, Sepehr N.;Garland, Suzanne M.

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澳大利亚实施了高覆盖率的HPV疫苗接种计划,但迄今尚未确定在澳大利亚宫颈癌中发生的HPV类型的分布。这一信息对于确定当前和更广泛谱的HPV疫苗预防宫颈癌的潜力是重要的。我们分析了2005年至2015年在澳大利亚人口最多的三个州的第三中心诊断的847例宫颈癌,并使用激光捕获显微解剖技术解析了含有多种HPV类型的标本。存档的FFPE组织由专家病理学家审查,夹心切片,最初的全组织切片进行HPV基因分型。首先使用SPF10-LiPA25(版本1)对样本进行基因分型。阴性标本用HPV SPF10 DNA酶联免疫吸附试剂盒筛查,阳性标本用SPF1-LIPA进行基因分型。如果仍为阴性,则对样本进行针对HPV16、18、45和33的E6区域的qPCR检测。在847例癌中(鳞癌65.1%,腺癌28.7%,腺鳞癌4.3%,其他2.0%),92.9%的癌组织中检出HPV。在787例HPV阳性癌中,607例(77.1%)HPV16或18阳性,125例(15.9%)HPV31/33/45/52或58阳性,55例(7.0%)另一种HPV型。HPV类型与年龄有很强的相关性,年轻女性最有可能检测到HPV16/18,最不可能HPV阴性。我们的研究结果表明,在澳大利亚确诊的宫颈癌患者中,HPV16/18携带者比国际患者更多。这可能是因为澳大利亚的子宫颈筛查增加了腺癌的比例,由于预防鳞癌,18型和16型腺癌占更大比例。
Australia has implemented a high-coverage HPV vaccination program but has not, to date, established the distribution of HPV types that occur in cervical cancers in Australia. This information is important for determining the potential for cervical cancer prevention with both current and broader spectrum HPV vaccines. We analysed 847 cervical cancers diagnosed 2005 to 2015 in tertiary centres in the three most populous Australian states with resolution of specimens containing multiple HPV types using laser-capture microdissection. Archived FFPE tissue was reviewed by specialist pathologists, sandwich sectioned, and initially whole-tissue sections genotyped for HPV. Samples were first genotyped using SPF10-LiPA25 (version 1). Negative samples were screened with DNA ELISA kit HPV SPF10, followed by genotyping with SPF1 LiPA if ELISA positive. If still negative, samples were tested on a qPCR assay targeting the E6 region of HPV16, 18, 45 and 33. Of the 847 cancers (65.1% squamous, 28.7% adenocarcinoma, 4.3% adenosquamous, 2.0% other), 92.9% had HPV detected. Of the HPV-positive cancers, 607 of 787 (77.1%) contained HPV16 or 18, 125 of 787 (15.9%) contained HPV31/33/45/52 or 58, and 55 (7.0%) another HPV type. There was a strong correlation between HPV type and age, with younger women most likely to have HPV16/18 detected and least likely HPV negative. Our findings indicate that cervical cancers diagnosed in Australia more frequently contain HPV16/18 than in international series. This could be due to cervical screening in Australia increasing the proportion of adenocarcinomas, in which types 18 and 16 more strongly predominate, due to prevention of squamous cancers.