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关于癌前病变、宫颈癌及HPV的关系

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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% 。

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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1 楼    发表于2015-01-29 14:21:28举报|引用
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你要跟数字较劲是不?我现在迷迷糊糊的,也真是醉了。空了我来跟你唠下嗑儿。

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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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3 楼    发表于2015-01-29 16:16:31举报|引用
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 巴山老师,清醒了?!从你说的话来看,我没弄错概念。

 你的这句话是我认可的“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。”但是你有没有好好想一想,如果是这样的话,医院做HPV检测的意义就不大或者没有意义了。根据文献内容可推测:100位CIN2患者中,有55例HPV感染患者,而HPV试剂盒的灵敏度为94.6%,可计算出用HPV试剂盒检测HPV阳性的例数为:100×55%×94.6%=52例,实际上还有48位CIN2的患者未检测。如果是这样的话,HPV作为宫颈癌的筛查标记物,其病理意义就不大了。而家商家这么介绍,给让使用人容易误导。

大家也知道做一次HPV检测价格不便,对中国很多人来说是个不小的负担。我只是想弄清楚,这对我们技术员或患者都是很有必要的。

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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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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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7 楼    发表于2015-01-29 23:30:40举报|引用
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我感觉追究这些没特别的意义,知道是一种辅助诊断, 具有代表性的参考价值。正是因为之间存在联系,所以才有辅助,诊断的意义。数字是前人抽样统计出来的,哪个能做到百分百,光说地域性也有很大差别,有地方发病率可能高,而有的地方可能极少,所以,我个人觉得啊 ,文献之类也是参考,你觉得有不妥,你可以去证实,去改进,至于其中的联系很难说用具体数字来证实,大家最实际的是一个病例一个病例的最有利的检查  筛查  到确诊  , 。。。当然你们要研究疫苗之类的,那的具体找出其中的点滴关系 不然一针下去没抗体产生。  说实话,我搞不通数字,我就只能说这些简单眼前 的问题说 哈哈

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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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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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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.

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.

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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15 楼    发表于2015-02-11 13:57:46举报|引用
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 单纯使用HPV基因检测CIN2或CIN3的灵敏度达94.6%

I do not believe it.

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16 楼    发表于2015-02-11 13:59:17举报|引用
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2014 May 22;11:14. doi: 10.4103/1742-6413.132997. eCollection 2014.

Is 58% sensitivity for detection of cervical intraepithelial neoplasia 3 and invasive cervical cancer optimal for cervical screening?

Abstract

Recent Food and Drug Administration (FDA) approval of a Roche cobas human papillomavirus (HPV) test application as a first line primary cervical screening tool in women 25 and older introduces a new era of complex cervical screening choices. Perhaps the most surprising findings in Roche's supporting ATHENA trial data were the unexpectedly low verification bias-adjusted CIN3+ sensitivities documented by the FDA for both the proposed cobas HPV testing algorithm (58.26%) and Pap testing algorithm (42.63%). These unexpectedly low sensitivity estimates suggest intuitively that there is still considerable room for improvement in cervical screening, and available data from large systems point to routine cytology and HPV co-testing as offering the greatest protection against development of cervical cancer. Observational studies of large populations screened over time remain essential to document actual protection from development of cervical cancer with any new cervical screening options, as natural history studies and available data from large systems indicate that most CIN2/3 cases detected in short term clinical trials would not progress to invasive cervical cancer. Interpretation of ATHENA trial data and its application to routine clinical practice is further limited by published studies which document that a significant proportion of CIN2/3 biopsy diagnoses in the ATHENA trial could not be confirmed as accurate when evaluated with p16 immunohistochemistry and that cytology laboratory performance in the trial was notably suboptimal.

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17 楼    发表于2015-02-11 14:01:58举报|引用
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Human Papillomavirus testing and cytologic/histopathologic “test of cure” follow-up results after excisional treatment for high grade cervical intraepithelial neoplasia

Journal of the American Society of Cytopathology 01/2013; DOI: 10.1016/j.jasc.2013.09.004

ABSTRACT 988 patients with high grade cervical intraepithelial neoplasia (CIN2/3) treated by excision between 2005 and 2009 were identified with available “test of cure” follow-up results over an average of 36 months. Average age was 32 years. CIN2/3 was reported during follow- up in 67 of 988 (6.8%) patients; 45 of 67 (67.2%) follow-up CIN2/3 diagnoses were within 2 years of excision. Post-treatment CIN2/3 was significantly more likely after initial CIN3 grade, positive excision margins, and HPV-positive follow-up results, but not significantly associated in this cohort with age. 514 women had follow-up HPV tests, and 32.3% had at least one HPV- positive result. Post-treatment CIN2/3 was diagnosed in 24 of 165 (14.5%) patients with at least one follow-up HPV-positive result and in 6 of 349 (1.7%) with only follow-up HPV-negative results. No HPV-negative/ cytology-negative follow-up results were documented among 30 postreatment patients later developing recurrent CIN2/3. Recently published guidelines now specifically recommend cytology and HPV cotesting as follow-up after CIN2/3 excision

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18 楼    发表于2015-02-11 14:05:38举报|引用
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 CAP Today  Home » 2014 Issues, November 2014, Regular features

Letters (November 2014)

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HPV primary screening

We read with great interest the two recent articles by William Check, PhD, highlighting primary HPV testing proposals (June and September 2014). Additional related information not covered in the two CAP TODAY articles should be brought to readers’ attention.

The first article focused on the ATHENA trial, in which a primary human papillomavirus screening algorithm based on the Roche Cobas HPV assay was evaluated. Although cervical cancer risk increases significantly with age (Cancer. 2014;120:2032–2038), no mention was made of ATHENA trial data documenting that the proposed Cobas primary HPV screening algorithm had not only limited overall verification-bias–adjusted sensitivity for detection of cervical intraepithelial neoplasia 3 (CIN3) and cervical cancer (CIN3+) but that this limited sensitivity steadily decreased even further among the highest risk older age groups (Table 1). The low documented rates for CIN3+ detection (27 to 58 percent) with the proposed Cobas algorithm intuitively raise questions about the safety of the algorithm and its use with extended screening intervals.
lettersTable-1

The second CAP TODAY article focused on a recent publication analyzing risk for CIN3 and cervical cancer during a lengthy experience with conventional Pap and Hybrid Capture 2 (HC2) HPV cotesting in the Kaiser Permanente Northern California system (Gage JC, et al. J Natl Cancer Inst. 2014;106[8]:pii:dju153). While lead author Julia C. Gage, PhD, MPH, acknowledges in the CAP TODAY article that the statistically significant lowest risks for CIN2 and CIN3 were achieved with Pap and HC2 HPV cotesting, the difference in risk between cotest-negative and HPV-negative patients is dismissed as “small.” The CAP TODAY article goes on to add: “The difference in cancer risk was small and not statistically significant.” Although the JNCI authors have chosen thus far not to allow independent statistical evaluation of their privately held data set or to disclose most P values in the data comparisons,

Dr. Gage clearly said in a public presentation in August at the 29th International Papillomavirus meeting in Seattle that the lowest cancer risk at three years after negative cotest results (0.007 percent) was “statistically significant” when compared with cancer risk after a negative HC2 HPV test (0.011 percent). The P value comparing the lower cancer risk at five years after negative cotest results (0.014 percent) with cancer risks after negative HC2 HPV test results (0.017 percent) is still undisclosed.

When the Pap test was introduced after World War II, the emphasis was on decreasing cervical cancer morbidity and mortality. Later, as new cervical screening technologies emerged in the late 1990s in response to observations on the limitations of screening, the Agency for Health Care Policy and Research noted that the verification-bias–adjusted sensitivity of the conventional Pap smear was only “near 50 percent, much less than generally believed” (AHCPR, Evaluation of Cervical Cytology, 1999), and that decreased cancer incidence and mortality would require some combination of increased recruitment to screening, increased screening test sensitivity, and more frequent screening. Available SEER data through 2011 documents that cervical cancer rates have continued to decline in the new screening technology era. As the new era of screening using HPV testing continues to develop and evolve, it is surprising to observe that a new proposed HPV primary screening algorithm with FDA-documented CIN3+ sensitivity “near 50 percent” is being portrayed as a significant advance and seen as the basis for a shift from a continued focus on further reduction of cervical cancer through screening to a new emphasis on 1) extending screening intervals, 2) achieving only “reasonable” cervical cancer risk (now apparently defined as risk associated with every three-year screening with the conventional Pap test), and 3) decreased testing and associated health care expenditures. As Dr. Gage said somewhat dismissively in Seattle, “You can always get a slightly lower risk of cervical cancer by reducing your interval or adding additional tests.”

R. Marshall Austin, MD, PhD
Chengquan Zhao, MD
Department of Pathology
Gynecologic Pathology Division
Magee-Womens Hospital of University of Pittsburgh Medical Center

Mark Stoler, MD, cytopathologist and professor emeritus of pathology and clinical gynecology, University of Virginia, replies: I thank Dr. Austin and Dr. Zhao for their ongoing interest in the comparison between the potential of an HPV primary screening algorithm and cotesting. In my opinion, CAP TODAY and especially its reporter William Check, PhD, have done a superb job in presenting both sides of the argument in a balanced manner. In response to some of Dr. Austin and Dr. Zhao’s specific comments, I would briefly add the following:

Verification bias adjustments, where any detectable disease in a sample of patients with normal screening tests is then extrapolated to the whole population, always have a larger impact on apparent sensitivity than they do specificity. In the opinion of many epidemiologists, this impact is now understood to potentially be very misleading, but in general the relative rankings of the tests do not change.1,2 Thus in ATHENA, while the verification-bias–adjusted sensitivities “sound” low, the VBA sensitivity of cytology is lower than for HPV in all comparisons. Furthermore, as was pointed out in a prior online exchange,3 the figures quoted in the table in Dr. Austin’s letter are the VBA sensitivity of the algorithm, not the test. Unfortunately, individuals often confuse VBA and non-VBA statistics from different sources and compare apples to oranges, including Drs. Austin and Zhao. In numerous published studies, the unadjusted sensitivity of cytology is on the order of 50 to 60 percent, whereas the unadjusted sensitivity of a clinically validated HPV test is always on the order of 90 to 95 percent. As noted in reference No. 3, the published unadjusted sensitivity of the Cobas HPV test for ≥ CIN3 is 92.0 percent compared with 75.1 percent for liquid-based cytology. The performance of both HPV testing and cytology in ATHENA is similar to what was found in the only other large North American screening study, Mayrand, et al., who reported an unadjusted sensitivity of Hybrid Capture 2 of 82.8 percent and 57.7 percent for cytology for ≥ CIN 2.4

The decrease in sensitivity with age of all cervical cancer screening tests is not a new phenomenon, nor perhaps an unexpected one given the known regression of transition zone up the canal inducing sampling issues confounded by the known problem pathologists have with age-related mimics of HSIL, an issue we discussed in reference No. 5. Still, in head-to-head, apples-to-apples comparisons like ATHENA, HPV testing is superior to cytology in sensitivity with only minimal impact on specificity across all age groups. This fact, together with the data presented to and independently analyzed both by the FDA advisory panel and yet again by the FDA, strongly supports our belief that the time has come to consider seriously the benefits and simplicity of an HPV-based primary screening algorithm for cervical cancer screening. Such an approach is gaining worldwide acceptance and will become increasingly necessary as one considers the need to screen populations that have been vaccinated against HPV, where the performance of cytology will only degrade further.6 I am sure we can all agree that the United States should “only have the problem” of having to address how to screen a properly vaccinated and protected population.

    1. Wright TC Jr., Stoler MH, Behrens CM, Apple R, Derion T, Wright TL. The ATHENA human papillomavirus study: design, methods, and baseline results. Am J Obstet Gynecol. 2012;206:46.e1–46.e11.
    2. Sasieni P. Estimating prevalence when the true disease status is incompletely ascertained. Stat Med. 2001;20:935–949.
    3. http://j.mp/stoler-thomas-athena
    4. Mayrand MH, Duarte-Franco E, Rodrigues I, et al. Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N Engl J Med. 2007; 357:1579–1588.
    5. Stoler MH, Wright TC Jr., Sharma A, et al. The interplay of age stratification and HPV testing on the predictive value of ASC-US cytology. Results from the ATHENA HPV study. Am J Clin Pathol. 2012;137:295–303.
    6. http://j.mp/ncsp-renewal

■ Julia C. Gage, PhD, MPH, research fellow, Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, and Thomas S. Lorey, MD, medical director of TPMG Regional Reference Laboratory, Kaiser Permanente Northern California Region, reply:

We have some clarifications in response to the letter written by Drs. Austin and Zhao.

If a study is large enough, even small differences between very low risks can be statistically significant as seen in our findings from KPNC. When comparing the cancer risks after an HPV-negative result with cancer risks after a cotest-negative result at the same time point (i.e. three or five years), the risks have overlapping 95 percent confidence intervals. The three-year cancer risk after an HPV-negative versus cotest-negative result is statistically significant (0.011 versus 0.007, P=.03) while the five-year cancer risk after an HPV-negative versus cotest-negative result is not (0.017 versus 0.014, P=.11).

Importantly, statistical significance should not be conflated with identifying the optimal screening strategy. The decision of how often to screen with what tests is increasingly more complicated and there will always be opportunities to push further toward greater reassurance by using more screening tests or shortening intervals or both. At an extreme, women could be screened every six months with cotesting, but we all realize this would result in excessive identification of benign transient infections and associated changes. A balance must be struck between greater reassurance and the associated costs and harms. We turn to professional guidelines committees, which are best suited to such an endeavor.

Use HPV test in conjunction with Pap

Published data show that an HPV test can fail to detect nine percent to 20 percent of cervical cancers (Zhao C, et al. Evidence emerging for HPV-negative cervical cancer. CAP TODAY, January 2014). At BioReference Laboratories, a national clinical laboratory with specialized expertise in women’s health, cancer, and genetics, we examined relevant data over a one-year period. Our review disclosed that 66 of 733 (nine percent) Pap tests interpreted as suspicious for cancer (high-grade lesions, or HSIL) had a negative Roche Cobas HPV test. If these women had been tested only with the Roche Cobas HPV assay, their potentially precancerous condition (HSIL) would have been missed. In addition, a number of the women who had HSIL Pap results accompanied by a negative Roche Cobas HPV test had the more definitive test for cancer—a cervical biopsy. Of the abnormal biopsies, 10 percent showed squamous cell carcinoma of the cervix, 40 percent showed other precancerous high-grade lesions (CIN 2/CIN 3), and 50 percent had endometrial cancer. These cancers were detected based on a positive Pap test.

In these times of rising health care costs where findings based on population studies may change recommended medical practice guidelines for individual patients, any such changes must be fully vetted and appropriately balanced before they are implemented. For this reason we strongly believe that rather than replace the Pap test, the HPV test should be used in conjunction with the Pap test to assess a woman’s true risk of cervical cancer. While we welcome new advances in medicine, we should learn from previous data and gather additional information before changing our cervical cancer screening behaviors. In light of Pap testing having been enormously successful in reducing deaths from cervical cancer and the cervical cancer screening guidelines having been changed as recently as 2012, we believe more caution and research are warranted before additional changes are made to a screening algorithm.

James Weisberger, MD
Chief Medical Officer

James W. Sharp, MD
Clinical and Anatomical Pathologist
Vassar Brothers Medical Center

Jeffrey Gilbert, MD
Medical Director, STIs

Frank Buccini, MS
Director of Molecular Diagnostics
BioReference Laboratories
Elmwood Park, NJ

Genomic testing and the LIS

In “Why LIS limitations shouldn’t inhibit genomic testing” (Newsbytes, September 2014), Lynn Bry, MD, PhD, said “outside of the upfront sample handling and getting results out the door and billing for it, you probably aren’t going to be able to handle the intermediate steps with current lab information systems.” This continues to be true for many vendors, but in December 2013 Sunquest Information Systems released a complex testing workflow application, completely integrated with the core laboratory information system, that supports genotyping and is well suited to handle the wet bench work of sequencing applications.

This year, Sunquest made a strategic investment in GeneInsight, an IT platform company that streamlines the analysis, interpretation, and reporting of complex genetic test results. Sunquest and GeneInsight are teaming up to offer clients a complete genetics workflow, with integration enabling the exchange of structured information.

It is the case that “Some companies have developed laboratory information management systems to support complex sequencing in a research setting, ‘but what they often lack is the capacity to operate effectively in a CLIA laboratory.’” Sunquest and GeneInsight have been operating in a clinical setting for years and are both registered class I exempt medical devices. Let Sunquest be the first to say, “Here’s a solution that’s going to help you with your complex genomic testing.”

Megan Schmidt
Director, Product Strategy
Sunquest Information Systems

■ Lynn Bry, MD, PhD, medical director and associate pathologist at Brigham and Women’s Hospital, Harvard Medical School, replies: BWH is a founding institution of Partners Healthcare, a majority shareholder in the GeneInsight application. I was aware of the potential partnership between GeneInsight and Sunquest but unable to discuss it at the Pathology Informatics 2014 conference, and later when interviewed by CAP TODAY, as the agreement was still under negotiation. The features offered by GeneInsight cover variant calling from processed sequences, curation of content for evaluating the variants, generation of reports, and data transmission to other clinical systems. Integrating these and earlier stages of bioinformatic processing with clinical information systems will further support genomic analyses in clinical laboratories.

TRALI

Your article on TRALI (October 2014) reported that the BloodCenter of Wisconsin is one of a few laboratories that do most of the human neutrophil antigen testing through their own laboratory-developed tests. As the manager of one of the laboratories that does this HNA testing, I was surprised you named only the BloodCenter of Wisconsin. Our laboratory at the American Red Cross deserved mention also for the following reasons, among others.

The Neutrophil Laboratory at the American Red Cross was developed by Jeffrey McCullough, MD, in 1985. Dr. McCullough along with Dave Stroncek, MD, also a former laboratory director, have been world leaders in the research of neutrophil testing and TRALI investigations for decades. Dr. McCullough was the primary author of Granulocyte Serology: A Clinical and Laboratory Guide (ASCP Press, 1988), which is still used today as a source for laboratory methods linked with HNA laboratory analysis.

Our laboratory and the lab at the BloodCenter of Wisconsin are the only two neutrophil laboratory members in the U.S. associated with the International Society of Blood Transfusion Working Party on Granulocyte Immunobiology. Both of the labs participate in the quality assurance exercises distributed by the International Granulocyte Immunology Workshops (IGIW). The American Red Cross Neutrophil Laboratory is one of four reference laboratories in the IGIW that organize and distribute these QA samples. (The others are in Bristol, U.K., Hagen, Germany, and Amsterdam, the Netherlands.)

The IGIW has recommended a combination of the granulocyte immunofluorescence test (GIFT) and the granulocyte agglutination test (GAT) when detecting and identifying HNA antibodies (Transfusion. 1997;37:977–983; Transfusion. 2002;42:462–468; Vox Sang. 2013;105:259–269). The American Red Cross is the only neutrophil lab in the U.S. that routinely tests all donors and patients for both GAT and GIFT. All other neutrophil laboratories in the U.S. routinely screen samples for HNA antibody by GIFT.

Your article referred to the four-year prospective study led by Pearl Toy, MD, as the seminal investigation in TRALI (Blood. 2012;119[7]:1757–1767). Dr. Toy named our laboratory the neutrophil laboratory to perform all HNA antibody testing for this National Heart, Lung and Blood Institute
SCCOR study.

Randy M. Schuller
Neutrophil and Platelet
Immunology Laboratory Manager
Mid-America Blood Services Division
American Red Cross
Saint Paul, Minn.

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19 楼    发表于2015-02-11 14:10:12举报|引用
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 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。


It is true that FDA approved cobas HPV can be used as primary screening for cervical cancer in April 2014. But in term of my knowledge, HPV as primary screening has not be used by any hospital in the USA.

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2014 Dec 1. [Epub ahead of print]

Human Papillomavirus Testing and Reporting Rates in 2012: Results of a College of American Pathologists' National Survey.

Abstract

Context .- College of American Pathologists (CAP) surveys are used to establish national benchmarks for laboratory parameters. Objective .- To evaluate changes in laboratory human papillomavirus (HPV) testing patterns in laboratories incorporating HPV testing with Papanicolaou tests in 2012. Design .- Data were analyzed from the CAP HPV Supplemental Questionnaire distributed to 1771 laboratories participating in either CAP HPV or CAP Papanicolaou proficiency testing in 2013. Results .- A total of 1022 laboratories (58%) responded. There were more high-risk (HR) HPV tests performed per institution as compared to previous surveys. There were more HPV tests performed within an institution as compared to previous surveys. Hybrid Capture 2 (HC2) remains the most common method (42.4%, 239 of 564); Cervista and cobas methods are used in 37.2% (210 of 564) and 14.9% (84 of 564) of laboratories, respectively. Human papillomavirus testing is offered as a reflex testing after a Papanicolaou test result of atypical squamous cells of undetermined significance (ASC-US) in 89.6% of laboratories (476 of 531); as a cotest for women aged 30 years and older in 60.3% (404 of 531); as reflex testing after atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) in 42.7% (320 of 531); and as reflex testing after atypical glandular cells (AGC) in 27.3% (145 of 531). The HPV-positive rates for ASC-US and ASC-H were similar in 2012 and 2006. Cervista (49.2%, 88 of 179) and Roche cobas (27.4%, 49 of 179) are the most common methods used for genotyping. Most laboratories use CAP Human Papillomavirus for Cytology Program for proficiency test. Conclusions .- There was an increase in annual volume of HR-HPV testing with a shift toward in-house HR-HPV testing. Genotyping volumes also increased. HC2 and Cervista are most commonly used, with an increasing volume of Roche cobas testing. The most common indication for HPV testing among all laboratories was ASC-US reflex testing, but an increase in HPV cotesting was observed. The data provide an update into persisting and newer trends in HPV testing practices.

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