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关于癌前病变、宫颈癌及HPV的关系

今天在罗氏网站中看到了这样一段话，有很大的疑问，不知哪位大神能解答下，以下是原文：

HPV是一种极为常见的病毒，高达75%的女性在一生的某一阶段会感染HPV。HPV持续感染是宫颈癌及其癌前病变——宫颈上皮内瘤变（CIN）——的主要病因，且宫颈病变程度越重，高危HPV 感染率越高。在CIN 1、CIN 2 、CIN 3患者中，HPV感染率分别为30 %、55 %和65 %，而99.8%以上的宫颈癌患者体内能检测到HPV感染，HPV阴性者几乎不会发生宫颈癌２,３。

最新的cobas HPV基因检测，则检测宫颈位置是否存有HPV，并不需要主观分析或诠释，具有更高的灵敏度和可重复性，已被美国临床广泛接受。ATHENA研究发现，在年龄30岁及以上的妇女中，每10位HPV 16和/或18阳性的女性中就有1位为宫颈癌前病变，而她们的巴氏涂片检查结果是正常的。此外，许多文献报道发现，单纯使用HPV基因检测CIN2或CIN3的灵敏度达94.6%，而细胞学方法的灵敏度仅有一半左右，但两者结合的灵敏度可以达到100%９。

大家请注意看大字黑体中的数据，我的疑问是：CIN2、CIN3的HPV感染系分别为30%、55%和65%，文中却说使用HPV检测CIN2或CIN3的灵敏度却为94.6%，大家觉得有没有问题。

我猜大家可能会提出HPV感染率与灵敏度是两个概念，两个是没必然的联系的。这就关系到灵敏度的定义了，在HPV基因检测中，灵敏度是否指能检测HPV基因的概率呢？但CIN2中HPV感染率为55%，为何HPV基因试剂能检测94.6呢？举个例子：100例，CIN2患者中，有55位有HPV感染，但HPV基因检测却为94位。

哪位老师能为我解答下，谢谢！

标签：癌前病变宫颈癌 HPV

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4 楼发表于2015-01-29 16:36:57举报|引用
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还有个问题：HPV感染、癌前病变和癌是什么关系？？第一种关系：HPV持续感染导致癌前病变，最终导致癌吗？第二种关系：癌前病变，加重引发HPV感染，最终导致癌？第三中：癌前病变导致癌，加重引发HPV呢？还是他们的关系是其中的两种或三种呢？不都说HPV是导致宫颈癌的元凶吗？为什么是：在CIN 1、CIN 2 、CIN 3患者中，HPV感染率分别为30 %、55 %和65 %，而99.8%以上的宫颈癌患者体内能检测到HPV感染

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5 楼发表于2015-01-29 16:45:42举报|引用
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你是跟掌心同学类似的研究型人才，鉴定完毕。

空了再继续唠。别急啊。。。。。。

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10 楼发表于2015-02-11 13:44:12举报|引用
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引用 8 楼 jtprli 在 2015-02-02 10:39:04 的发言:

宫颈病变程度越重，高危HPV型感染率越高。

这句话对

在CIN 1、CIN 2 、CIN 3患者中，HPV感染率分别为30 %、55 %和65 %

这个数据有问题，这个数据应该也是指的高危型HPV感染，在CIN2以上，感染率比这高

这篇文章就是想强调HPV检测敏感度高，但其实它的特异性低，加之国外的检测耗材价格又高，根本不可能替代细胞检测。

agree above

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11 楼发表于2015-02-11 13:48:17举报|引用
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在CIN 1、CIN 2 、CIN 3患者中，HPV感染率分别为30 %、55 %和65 %.

Not right. In Pap cytology sample, HR HPV positive rate is 70-80% in LSIL cases, >90% in HSIL cases.

Not sure where they got the percentage.

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12 楼发表于2015-02-11 13:54:36举报|引用
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而99.8%以上的宫颈癌患者体内能检测到HPV感染，HPV阴性者几乎不会发生宫颈癌２,３。

Not correct. Relative percentage of cervical cancers are negative in HPV detection both in Pap cytology and tissue samples.

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13 楼发表于2015-02-11 13:54:54举报|引用
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2010 Nov;11(11):1048-56. doi: 10.1016/S1470-2045(10)70230-8. Epub 2010 Oct 15.

Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study.

Author information

Abstract

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.

2010 Nov;11(11):1048-56. doi: 10.1016/S1470-2045(10)70230-8. Epub 2010 Oct 15.

Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study.

Author information

Abstract

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.

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14 楼发表于2015-02-11 13:56:49举报|引用
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2015 Feb;139(2):184-8. doi: 10.5858/arpa.2014-0028-OA. Epub 2014 Apr 2.

Prior high-risk human papillomavirus testing and papanicolaou test results of 70 invasive cervical carcinomas diagnosed in 2012: results of a retrospective multicenter study.

Zhao C¹, Li Z, Nayar R, Levi AW, Winkler BA, Moriarty AT, Barkan GA, Rao J, Miller F, Fan F, Zhou Z, Si Q, Fischer AH, Sturgis CD, Jing X, Marshall CB, Witt BL, Birdsong GG, Crothers BA.

Author information

¹From the Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Drs Zhao and Li); the Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (Dr Nayar); the Department of Pathology, Yale School of Medicine, New Haven, Connecticut (Dr Levi); the Department of Pathology, Mount Kisco Medical Group PC, Mount Kisco, New York (Dr Winkler); the Department of Esoteric Testing, AmeriPath, Indianapolis, Indiana (Dr Moriarty); the Department of Pathology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois (Dr Barkan); the Department of Pathology & Laboratory Medicine, University of California, Los Angeles (Dr Rao); the Department of Pathology, Metropolitan Pathologists PC, Lakewood, Colorado (Ms Miller); the Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City (Dr Fan); the Department of Pathology and Laboratory Medicine, University Rochester Medical Center, Rochester, New York (Dr Zhou); the Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York (Dr Si); the Department of Pathology, University of Massachusetts Memorial Medical Center, Inc, Worcester (Dr Fischer); Providence Regional Medical Center, Everett, Washington (Dr Sturgis); the Department of Pathology, University of Michigan, Ann Arbor (Dr Jing); the Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora (Dr Marshall); the Department of Pathology, University of Utah, Salt Lake City (Dr Witt); the Department of Pathology & Laboratory Medicine, Emory University School Medicine, Atlanta, Georgia (Dr Birdsong); and the Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Maryland (Dr Crothers).

Abstract

Context .- Persistent high-risk human papillomavirus (hrHPV) infection is essential for the development of cervical cancer and its precursor lesions. High-risk HPV testing has a higher sensitivity than cytology does for detecting cervical epithelial lesions. However, a large study from a single institution showed 31% of patients with invasive cervical cancer had negative baseline hrHPV testing within 5 years preceding the diagnosis. Objective .- To investigate the limitation of hrHPV testing in detecting invasive cervical cancer. Design .- Cases from 2012 with a histologic diagnosis of invasive cervical carcinoma were retrieved from multiple institutions. From those records, prior hrHPV testing and Papanicolaou test results in the 5 years before the cancer diagnosis were recorded. Results .- Seventy patients with cervical carcinoma were included in the study. Negative HPV test result rates were 9% (5 of 53), 23% (6 of 26), and 25% (2 of 8) during the periods of less than 1 year, 1 to 3 years, and 3 to 5 years before the histologic diagnoses, respectively. Negative Papanicolaou testing results in the same time intervals were 3.4% (2 of 59), 33% (10 of 30), and 40% (6 of 15). Although the HPV(-) rate seemed to be different among different HPV test methods, no statistical significance was detected because of small sample size. Negative hrHPV rates in patients with adenocarcinoma were similar to those in patients with squamous cell carcinoma. Conclusions .- These data expose limitations for the potential use of primary HPV testing. In addition, current screening guidelines recommending cotesting at 5-year intervals should be evaluated further with additional historic data collection because there are women with negative results for both Papanicolaou tests and hrHPV testing within the period of 3 to 5 years before an invasive carcinoma diagnosis.

2015 Feb;139(2):184-8. doi: 10.5858/arpa.2014-0028-OA. Epub 2014 Apr 2.

Prior high-risk human papillomavirus testing and papanicolaou test results of 70 invasive cervical carcinomas diagnosed in 2012: results of a retrospective multicenter study.

Zhao C¹, Li Z, Nayar R, Levi AW, Winkler BA, Moriarty AT, Barkan GA, Rao J, Miller F, Fan F, Zhou Z, Si Q, Fischer AH, Sturgis CD, Jing X, Marshall CB, Witt BL, Birdsong GG, Crothers BA.

Author information

¹From the Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Drs Zhao and Li); the Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (Dr Nayar); the Department of Pathology, Yale School of Medicine, New Haven, Connecticut (Dr Levi); the Department of Pathology, Mount Kisco Medical Group PC, Mount Kisco, New York (Dr Winkler); the Department of Esoteric Testing, AmeriPath, Indianapolis, Indiana (Dr Moriarty); the Department of Pathology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois (Dr Barkan); the Department of Pathology & Laboratory Medicine, University of California, Los Angeles (Dr Rao); the Department of Pathology, Metropolitan Pathologists PC, Lakewood, Colorado (Ms Miller); the Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City (Dr Fan); the Department of Pathology and Laboratory Medicine, University Rochester Medical Center, Rochester, New York (Dr Zhou); the Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York (Dr Si); the Department of Pathology, University of Massachusetts Memorial Medical Center, Inc, Worcester (Dr Fischer); Providence Regional Medical Center, Everett, Washington (Dr Sturgis); the Department of Pathology, University of Michigan, Ann Arbor (Dr Jing); the Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora (Dr Marshall); the Department of Pathology, University of Utah, Salt Lake City (Dr Witt); the Department of Pathology & Laboratory Medicine, Emory University School Medicine, Atlanta, Georgia (Dr Birdsong); and the Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Maryland (Dr Crothers).

Abstract

Context .- Persistent high-risk human papillomavirus (hrHPV) infection is essential for the development of cervical cancer and its precursor lesions. High-risk HPV testing has a higher sensitivity than cytology does for detecting cervical epithelial lesions. However, a large study from a single institution showed 31% of patients with invasive cervical cancer had negative baseline hrHPV testing within 5 years preceding the diagnosis. Objective .- To investigate the limitation of hrHPV testing in detecting invasive cervical cancer. Design .- Cases from 2012 with a histologic diagnosis of invasive cervical carcinoma were retrieved from multiple institutions. From those records, prior hrHPV testing and Papanicolaou test results in the 5 years before the cancer diagnosis were recorded. Results .- Seventy patients with cervical carcinoma were included in the study. Negative HPV test result rates were 9% (5 of 53), 23% (6 of 26), and 25% (2 of 8) during the periods of less than 1 year, 1 to 3 years, and 3 to 5 years before the histologic diagnoses, respectively. Negative Papanicolaou testing results in the same time intervals were 3.4% (2 of 59), 33% (10 of 30), and 40% (6 of 15). Although the HPV(-) rate seemed to be different among different HPV test methods, no statistical significance was detected because of small sample size. Negative hrHPV rates in patients with adenocarcinoma were similar to those in patients with squamous cell carcinoma. Conclusions .- These data expose limitations for the potential use of primary HPV testing. In addition, current screening guidelines recommending cotesting at 5-year intervals should be evaluated further with additional historic data collection because there are women with negative results for both Papanicolaou tests and hrHPV testing within the period of 3 to 5 years before an invasive carcinoma diagnosis.

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8 楼发表于2015-02-02 10:39:04举报|引用
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宫颈病变程度越重，高危HPV型感染率越高。

这句话对

在CIN 1、CIN 2 、CIN 3患者中，HPV感染率分别为30 %、55 %和65 %

这个数据有问题，这个数据应该也是指的高危型HPV感染，在CIN2以上，感染率比这高

这篇文章就是想强调HPV检测敏感度高，但其实它的特异性低，加之国外的检测耗材价格又高，根本不可能替代细胞检测。

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6 楼发表于2015-01-29 21:53:17举报|引用
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本帖最后由笨YAZI 于 2015-01-29 21:58:13 编辑

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9 楼发表于2015-02-02 14:41:22举报|引用
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学习

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2 楼发表于2015-01-29 14:51:15举报|引用
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你没弄清楚概念。我通俗地讲一下，不一定专业。请谅。

感染率：100例受检者中，检出50例阳性，即感染率为50%。

灵敏度：100例阳性者中，某方法或试剂最多能检出94例阳性，别有6例却是阴性的，即灵敏度为94%。

一般地，这些数据，属于抽样调查，能在“一定程度上”说明问题。

在感染率的概念中，实际上也涉及到了灵敏度，特异性，可靠性等概念。挺复杂的。100例受检者中，检出50例阳性，即感染率为50%。请问，你这50例阳性可靠吗，有没有假阳性呢？另50例阴性中有没有假阴性而未检出呢？如果有5例假阳性，那感染率实际不是50%，而是45%。如果有5例假阴性，那感染率是55%，也不是50%。然而，某一方法或试剂或许可以研究出其灵敏度，特异性，但是，实验是以数据说话的，能想当然在检测数据中加入“非灵敏”那一部分吗？能想当然在检测数据中减去“非特异”那一部分吗？不可以。

在CIN 1、CIN 2 、CIN 3患者中，HPV感染率分别为30 %、55 %和65 %，而99.8%以上的宫颈癌患者体内能检测到HPV感染。这是指的高危HPV感染率，不含低危。100例宫颈癌中，检测结果是99.8例高危HPV阳性。

单纯使用HPV基因检测CIN2或CIN3的灵敏度达94.6% 是指100例HPV阳性的CIN2或CIN3中，单纯使用HPV基因检测这种方法，最高能测出94.6例阳性。

稀里糊涂讲完了。布置个思考题：100阳性，这个数字是如何来的？

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金易龙: 抽样来的

2015-01-29 16:09

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Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study.

Author information

Abstract

BACKGROUND:

METHODS:

FINDINGS:

INTERPRETATION:

Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study.

Author information

Abstract

BACKGROUND:

METHODS:

FINDINGS:

INTERPRETATION:

Prior high-risk human papillomavirus testing and papanicolaou test results of 70 invasive cervical carcinomas diagnosed in 2012: results of a retrospective multicenter study.

Author information

Abstract

Prior high-risk human papillomavirus testing and papanicolaou test results of 70 invasive cervical carcinomas diagnosed in 2012: results of a retrospective multicenter study.

Author information

Abstract

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