Please share your oppinion:

请分享你的观点

Recently I noticed this topic in another cytology website in China. Let us have a discussion here.

最近我在另一个中国的细胞学网站中注意到这个主题。让我们一起在这里讨论。

1. Are all cervical carcinoma related to HPV infection?

所有的宫颈癌都是由HPV导致的吗？

2. When the women or who should have high risk HPV (hrHPV) testing?

那些女性需要或者什么时候做高危HPV检测呢？

3. What methods to detect hrHPV do you used in your hospitals?

你们医院用的是那种方法检测高危HPV？

4. What should the women do if she has positive hrHPV result?

如果她的高危HPV的结果是阳性的，她们该怎么办？

5. hrHPV testing should be performed for women with AGC?

细胞学结果为AGC的女性应该进行高危的HPV检测吗？

6. Any question, experience or oppinion you have, please share or discuss.

所有以上问题，就你个人的观点或经验来分享和讨论吧。

We as pathologists should know some basic information about HPV even though HPV testing might not be oerformed in your hospital, or the patients might not be able to pay for the test.

 即使HPV检测在你们医院没有开展或病人没有经济能力支付这项检测。我们做为病理学医生应该知道一些关于HPV的基本知识。 

 1. ThinPrep Pap test is produced by cytyc corporation. The ThinPrep Pap Test is the only liquid-based pap test FDA-approved for HPV. ThinPrep Pap test accounts for 70-80% liquid based Pap cytology marketing in the USA

2. In 2007 Cytyc and Hologic have combined together under the Hologic name.

3. For HPV test: HC2 is only FDA approved test and widely used in the USA. HC2 is the product of DIAGEN.

In 2007 DIAGEN and QIAGEN mergered named QIAGEN.

4. From above news (97 floor) we know now FDA approved Hologic two HPV test products,  Cervista(TM) HPV HR (high risk, 14 types) and the Cervista HPV 16/18 tests.

Hologic wants to eat the pie of HPV testing of QIAGEN

 FDA Approves Two Hologic HPV Tests

BEDFORD, Mass., March 13 /PRNewswire-FirstCall/ -- Hologic, Inc., (Hologic or the Company) (Nasdaq: HOLX - News), a leading women's healthcare company dedicated to serving the healthcare needs of women, today announced that the U.S. Food and Drug Administration (FDA) has approved the Company's premarket approval (PMA) applications for both the Cervista(TM) HPV HR (high risk) and the Cervista HPV 16/18 tests. Cervista HPV HR, designed to detect the 14 high-risk types of human papillomavirus (HPV) known to cause cervical cancer, is the first HPV DNA test approved by the FDA in more than 10 years. Cervista HPV 16/18 is the first HPV test approved for genotyping for HPV types 16 and 18, known to be associated with approximately 70% of all cervical cancers in the United States.

The Cervista HPV HR test has been approved for two uses:

• To screen patients with atypical squamous cells of undetermined significance (ASC-US) cervical cytology results to determine the need for referral to colposcopy.

• Used adjunctively with cervical cytology to screen women 30 years and older to assess the presence or absence of high-risk HPV types.

The Cervista HPV 16/18 test has been approved for two uses:

• In women 30 years and older the test may be used adjunctively with the Cervista HPV HR test in combination with cervical cytology to assess the presence or absence of specific high-risk HPV types.

• Used adjunctively with the Cervista HPV HR test in patients with ASC-US cervical cytology results, to assess the presence or absence of specific high-risk HPV types. The results of this test are not intended to prevent women from proceeding to colposcopy.

It is also noted that for both the Cervista HPV HR test and the Cervista HPV 16/18 test, the test results, along with the physician's assessment of cytology history, other risk factors, and professional guidelines, may be used to guide patient management.

The Cervista HPV HR clinical trial was one of the largest and most demographically diverse conducted in the United States to date, involving 89 sites and enrolling approximately 4,000 women nationwide. The trial met or exceeded all target endpoints: most importantly, the Cervista HPV HR test achieved 100% sensitivity for the detection of CIN3, an immediate precursor to cervical cancer.

The Company believes Cervista HPV HR provides a number of benefits over current products. Cervista HPV HR includes an internal control intended to verify adequate cellularity for testing, thus reducing the potential for false negative results. In addition, because it requires a smaller specimen volume, this technology may minimize inconclusive, or indeterminate results, which may lead to fewer patients being called back for repeat testing. More importantly, Cervista HPV HR is designed to minimize false positive results due to a low-risk HPV strain being mistakenly recognized as a high-risk HPV strain, thereby potentially reducing unnecessary clinical management and patient anxiety.

The additional approval of Cervista HPV 16/18 marks the first FDA approved HPV genotyping test available in the United States. The HPV strains identified by this test represent the two most oncogenic and persistent types of HPV, together believed to cause approximately 70% of cervical cancer. Previous studies have shown HPV 16 and 18 are respectively 5.5 times and 4.5 times more likely to cause cancer than all other high-risk HPV types combined.

"We are extremely excited to enter this market with such a unique and strong portfolio of FDA approved molecular tests for HPV DNA," said Jack Cumming, chairman and chief executive officer of Hologic. "Our state-of-the-art Cervista HPV tests individually and in combination are designed to provide significant advantages over the existing technology and should help solidify our leadership in cervical cancer screening."

The Cervista HPV HR and Cervista HPV 16/18 tests are based on Invader® chemistry, a patented technology owned by Hologic and well established in other areas of molecular testing. Both tests are approved for use utilizing the sample collected with the ThinPrep® Pap Test, offering additional convenience for the healthcare provider.

About Human Papillomavirus and Cervical Cancer

HPV is the most common sexually transmitted disease (STD) in the United States and is recognized as the cause of most cervical cancers. To help prevent the onset of disease, the American College of Obstetrics and Gynecology (ACOG) suggests routine Pap and HPV testing for women over the age of 30 to identify women most likely to develop cervical cancer.

About Hologic, Inc.

Hologic, Inc. is a leading developer, manufacturer and supplier of premium diagnostics products, medical imaging systems and surgical products dedicated to serving the healthcare needs of women. Hologic's core business units are focused on breast health, diagnostics, GYN surgical, and skeletal health. Hologic provides a comprehensive suite of technologies with products for mammography and breast biopsy, radiation treatment for early-stage breast cancer, cervical cancer screening, treatment for menorrhagia, osteoporosis assessment, preterm birth risk assessment, mini C-arm for extremity imaging and molecular diagnostic products including reagents for a variety of DNA and RNA analysis applications. For more information, visit www.hologic.com.

Hologic, Cervista, ThinPrep and Invader are trademarks and/or registered trademarks of Hologic, Inc. and/or its subsidiaries in the United States and/or other countries.

 Just feel interested in the new careHPV trial in China and did some literature search and pasted above.

Hope our news or scentific research papers can report study results and significance more objectively. Otherwise they can mislead the readers and geneal people.

 What is careHPV

I copied the method description from the Lancer oncolgy paper:

CareHPV and HC2

The careHPV test is broadly based on the HC2 test with some important differences. The assay time is 2·5 h or less, compared with up to 6 h for HC2. The careHPV collection medium, unlike other collection media, contains no toxic chaotropic salts, but rather contains non-toxic surfactants and is specifically formulated for solubilisation of cervical specimens from the collection brush without any requirement for extended mechanical shaking. The capture microplates in HC2 are replaced by magnetic beads coated by a monoclonal antibody with high affinity to RNA-DNA hybrids. Furthermore, the temperatures of some steps in the careHPV assay are increased to decrease the overall assay time by more than 2 h. The principle of the assay is as follows: target HPV DNA from lysed cells is denatured and hybridised to full-length complementary RNA, then captured by monoclonal antibodies coated on paramagnetic beads. The captured hybrids on the beads are detected by antihybrid monoclonal antibody conjugated to calf intestine alkaline phosphatase, which reacts with an added chemiluminescent substrate to produce light in proportion to the number of bound alkaline phosphatase molecules along the hundreds of antigenic binding sites per target molecule. Specimen test findings are expressed in relative light units (RLU) and compared with the mean RLU from a minimum positive control set at 1 pg/mL of HPV-16 DNA (expressed numerically as the cutoff) resulting in a ratio, the RLU/cut-off, the proportion of which is indicative of clinical positivity. Because the output signals of both HC2 and the new careHPV test are quite linear over a broad range around the cut-off-point ratio (RLU/cutoff) of 1·0, there is the possibility to vary the cut-point by adjusting the calculations to indicate specimen positives at lower or higher values than the value of positive controls, thus a cut-point of 0·5 reflects an assay that can score 0·5 pg/mL of HPV-16 DNA as positive.

 I think this is great we can do the cooperation with some companies or experts from other countries, or founding to do basic search or clinical trials to develpe or confirm the new, low price HPV detection method for the people in China and the world.

英国《柳叶刀—肿瘤学》（The Lancet Oncology）杂志9月22日在线发表中国医学科学院肿瘤研究所、中国癌症基金会、江西省妇幼保健院等单位共同完成的一项最新研究成果。研究人员第一次在世界上验证了人乳头瘤病毒快速检测技术（care HPV）能够准确、快速地发现子宫颈癌及癌前病变，

From the Chinese News  (floor 67).

If you read above story about the study in China and if you are a true medical doctor or scentific researcher, you know 1) this study is not a true Chinese new research achievement  2) HPV testing (careHPV ,even HC2) cannot (能够)准确、快速地发现子宫颈癌及癌前病变.

 Today i read the full paper careHPV in China

 In India they had very large numbers of women for study, 161845. HC2 was used foe HPV testing. The results indicated the HPV testing was more senstive for detecting high grade dysplasia and cancer than visual inspection with acetic acid (VIA). I can not see HPV testing is better than LBC even though the paper mentioned yes (New Egl J Med april 2009). See above floor 39-40.

Now we see the study in China. I have not the time to read the entire paper yet (paper in hospital computer). We know about 2000 women detected with care HPV, HC2, VIA, LBC, colposcopy.

from the abstract:

 the careHPV test was done locally by use of self-obtained vaginal and provider-obtained cervical specimens from a screening population-based set of 2530 women aged 30 to 54 years in Shanxi province, China. All women were assessed by visual inspection with acetic acid (VIA), Digene High-Risk HPV HC2 DNA Test (HC2), liquid-based cytology, and colposcopy with directed biopsy and endocervical curettage as necessary.

Do you think the normal women will agree to have colposcopy for these kinds of trials  in the USA?

the sensitivities and specificities of care HPV to detect cin2+  was better than VIA. I can not see care HPV is better than LBC in the study. Of cause we know care HPV will not be or cannot be more sensitiv and specific than HC2.

 In fact I never pay attention to care HPV until today.

Now we know HC2 and care HPV are the products from the same company, Qiagen.

HC2 testing is widely used in the USA and other western countries for women with abnormal Pap and is recommended for women age 30 and old along with Pap test by FDA (see above 77).

Qiagen has not had care HPV in marketing yet. The compay had  the first clinical trial  for about 2000 Chinese women in two county hospitals rural areas in Shanxi, China.

HC2 detrect 13 high risk HPV and care HPV detecte 14 high risk HPV. I do not know the detailed priniciple for care HPV testing. However we know it is easy, cheap, and fast (mentioned by the paper). The purpose of the new product is mainly for use in the rural areas in other words for the people who do not have enough money for medical care. Logically we will know the sensitivity, and specificity of care HPV will be lower than HC2 (remmber the products of the same company). Otherwise this care HPV can be used in the USA or other western countries, in stead of current HC2. If you do the ggogle serach for care HPv, only very few reports can be found (I pasted above).

 Ok, I want to finish the discussion today.

A few mian points

1. Care HPV is still in the testing stage. No product commercially is available.

2. Care HPV may be cheaper, fast and easy to be used baed on the paper.

3. Purpose of this product is for rural areas, in other words for people who cannot have enough money for medical care or not rich people ( I do not like to use the word poor).

4. Both care HPV and HC2 are the products of QIAGEN. Care HPV cannot be or will not be more sensitive or specific than HC2.

5. Some companies are trying to produce kit for detecting HPV16/18, main types of HPV for cervical cancer. 6. In term of my knowledge I do not know any  HPV detecting method can detect cervical cancer.

Ok, Thank you for reading.

 Now we can see a few points in the news from China (floor 67 from o164) I do not know where was the news published.

子宫颈癌快速筛查技术----care HPV技术有望极大减轻发展中国家子宫颈癌疾病负担

研究人员第一次在世界上验证了人乳头瘤病毒快速检测技术（care HPV）能够准确、快速地发现子宫颈癌及癌前病变.

夸大，吓人: It is just kind of cheaper HPV testing. We know almost cervical squamoust ca and most adenocarcinoma are caused by HPV or related to HPV. High risk HPV infection does not mean cancer. Most women with HPV infection will not develope high grade dysplasia or cancer.

HC2 has been used for many years.

英国《柳叶刀—肿瘤学》（The Lancet Oncology）杂志9月22日在线发表中国医学科学院肿瘤研究所、中国癌症基金会、江西省妇幼保健院等单位共同完成的一项最新研究成果。研究人员第一次在世界上验证了人乳头瘤病毒快速检测技术（care HPV）能够准确、快速地发现子宫颈癌及癌前病变，这一检测技术不仅只需两个多小时就能得出结果，而且费用也只有目前高收入发达国家与地区所使用检测方法的1/10。

You read the paper carefully you will know the senior author is not Chinese.

Check 82 floor:

Attila Lorincz, PhD, senior author of the study and a professor of molecular epidemiology at Barts and the London School of Medicine, as well as London's Queen Mary College.

The first published study of patient outcomes with Qiagen's Care HPV test, developed with support from Path, appears in the October issue of Lancet Oncology (82 floor).

From abroad news you will see no people will think this is a great search study  or breaking news done by Chinese researchers or scientistis. People know that the truth is that some companies, 基金会 cooperated with Chinese medical people, researchers, pathologists to do some clinical trials in rural areas in China or India.

The News abroad only mentioned that QIAGEN companony with Path had the first trial about care HPV in rural areas in China.No one mentioned that this was a trial by Chinese researchers.

It is good some companies or institute can help our Chinese people or do some clinical trials in China.

If some effective and cheaper HPV detection methods can be used in rural areas in China, I am very happy to see it. I am not against HPV testing. In fact we use a lot of HPV testing testing in our clincal practice.

More news about careHPV test in China.

HPV Test For Rural Areas Major Breakthrough

The news provided by Qiagen:

HPV test provides accurate front-line screening

A Qiagen product story

 http://www.thehpvtest.com/About-the-digene-HPV-Test/HPV-Testing-in-the-News.html

Diagen or Qiagen HPVtest.com

They listed the large good news for HPV testing. I did not notice the study in China.

 March 2000:

FDA approved HC2 test for women with abnormal Pap test.

March 2003:

FDA approved to allow HC2 test to be used for screening, in conjunction with the Pap test, of women over age 30 for HPV infection. It should be used along with the Pap test, a complete medical history and an evaluation of other risk factors to help physicians determine what kind of follow-up is necessary.

Below for detailded FDA news.

FDA News

FDA Approves Expanded Use of HPV Test

The Food and Drug Administration (FDA) today approved expanded use of a laboratory test to detect the presence in women of human papillomavirus (HPV), one of the most common sexually transmitted infections.

There are more than 100 types of HPVs. The test, the HC2 High-Risk HPV DNA Test, manufactured by Digene Corp., of Gaithersburg, Md., can identify 13 of the high-risk types associated with the development of cervical cancer. The HPV DNA test does not test for cancer, but for the HPV viruses that can cause cell changes in the cervix. If left untreated, these changes can eventually lead to cancer in some women.

FDA initially approved the HPV DNA test in March 2000 for testing women who had abnormal Pap test results to determine whether they needed to be referred for further examination. The new indication allows the test to be used for screening, in conjunction with the Pap test, of women over age 30 for HPV infection. It should be used along with the Pap test, a complete medical history and an evaluation of other risk factors to help physicians determine what kind of follow-up is necessary.

“Knowing whether or not a woman is infected with high-risk HPV is added information that will help physicians detect and treat early cell changes that might eventually lead to cervical cancer,” said FDA Commissioner Mark B. McClellan, M.D., Ph.D. “FDA is committed to bringing safe and effective new technologies to the market quickly.”

Up to 20 percent of the sexually active U.S. population is believed to be infected with HPV at any one time. Most women who become infected with HPV are able to eradicate the virus and suffer no apparent long-term consequences to their health. But a few women develop a persistent infection that can eventually lead to pre-cancerous changes in the cervix.

The HPV DNA test, like the Pap test, is performed by collecting cells from the cervix and then sending them to a laboratory for analysis. The test detects high-risk types of HPV in cell DNA even before there are any conclusive visible changes to the cervical cells.

Women who have normal Pap test results and no HPV infection are at very low risk (0.2%) for developing cervical cancer. Women who have an abnormal Pap test and a positive HPV test are at higher risk (6%-7% or greater) of developing cervical cancer if not treated.

FDA approved the expanded use of the test based on published literature describing studies of a cross section of women with normal and abnormal Pap test results who tested positive or negative for high-risk types of HPV. FDA also took into account additional input from professional societies, FDA advisory panel members and other interested parties in arriving at a decision.

The HPV DNA test is not intended to substitute for regular Pap screening. Nor is it intended to screen women under 30 who have normal Pap tests. Although the rate of HPV infection in this group is high, most infections are short-lived and not associated with cervical cancer.

Some 50 million women get Pap tests annually in the United States. According to the American Cancer Society, in 2003, 12,200 women will be diagnosed with cervical cancer and 4,100 will die from the disease. With proper screening, cervical cancer is avoidable and, if caught early, curable.