First there was just one. In 2003, the Food and Drug Administration approved Digene's Hybrid Capture 2 High Risk HPV DNA Test. (Digene would later be acquired by QIAGEN in 2007).
And that's all there was for several years. Then, in 2009, Hologic received FDA clearance for two HPV assays. In 2011, Roche received FDA approval, and so did Gen-Probe (which will formally be acquired by Hologic later this year).
So now there are five FDA-approved HPV assays. And for clinical laboratory decision makers, the question naturally comes up: as HPV testing for women becomes increasingly widespread, which of these tests fits my lab's needs the best?
As editor of MLO, I can't answer that question. But I can provide you with the FDA “overviews” (very lightly edited for consistency) that were published on its site when the approvals were granted, along with the relevant links to more detailed information.
You can still find all of these overviews on the FDA site?but MLO has put them in one package for you. See at a glance: How are they similar to one another? How are they different?
By the way, if you have had any experiences with using any of the HPV assays that are described below, please feel free to share them with MLO by writing me at [email protected].
—Alan Lenhoff
Digene Hybrid Capture 2 High-Risk HPV DNA Test – P890064 S009 A004
This is a brief overview of information related to FDA's approval to market this product. See the links below to the Summary of Safety and Effectiveness and product labeling for more complete information on this product, its indications for use, and the basis for FDA's approval.
Product Name: Digene Hybrid Capture 2 High-Risk HPV DNA Test
Manufacturer: Digene Corporation
Address: 1201 Clopper Road, Gaithersburg, MD 20878
Approval Date: March 31, 2003
Approval Letter: http://www.accessdata.fda.gov/cdrh_docs/pdf/p890064s009a.pdf
What is it? The Digene HC2 High-Risk HPV DNA Test is a laboratory test used to show the presence or absence of the genetic (DNA) material from the Human Papilloma Virus (HPV), in cells from a woman's cervix. (The cervix is the lower part of the uterus or womb.) When HPV genetic material is found in these cells, it sometimes indicates the potential or the presence of disease. The cervical cells are usually obtained during a Pap Test (“pap smear”), when cells are obtained by gently scraping the surface of the cervix.
How does it work? The test causes the release of DNA from the cervical cells: Normal DNA and, if present, HPV DNA. Probe molecules are added that combine with the DNA to form what is called DNA-Probe-Hybrid. This Hybrid recognizes many types of high-risk HPVs.
Then, light-producing antibodies are added and combine with the DNA-Probe Hybrid. The amount of light produced above a certain level indicates the presence of HPV. Anything below that level indicates either the absence of HPV or HPV levels that are too low to detect.
When is it used? The HPV-DNA Test is used only in conjunction with Pap Testing. The test is used:
- When a woman's Pap Test results are mildly abnormal. The HPV-DNA Test is then used to tell whether or not HPV is present at high enough levels to indicate that an HPV infection exists. If she has an HPV infection, she may be tested further to be sure that she does not have serious cervical abnormalities.
- When women over age 30 have HPV infections that do not disappear over time.These women may be at greater risk for developing cervical disease. Women over 30 with a positive Pap Test and a positive HPV-DNA Test have a higher than average risk of cervical cancer and may need to be tested more frequently. Only a small percentage of HPV infections, however, lead to cancer.
Note: Women with normal Pap test results and an absence of HPV infection are at very low risk for developing cervical cancer but should be tested at regular intervals, as prescribed by a doctor. There is not enough information currently to tell us how long women with normal Pap Test results remain at low risk. There is also not enough information to decide how frequently an HPV-infected woman should be tested.
Additional information: Summary of Safety and Effectiveness and labeling are available at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cftopic/pma/pma.cfm?num=p890064s009
Cervista™ HPV HR and Genfind™ DNA Extraction Kit – P080014
This is a brief overview of information related to FDA's approval to market this product. See the links below to the Summary of Safety and Effectiveness Data (SSED) and product labeling for more complete information on this product, its indications for use, and the basis for FDA's approval.
Product Name: Cervista™ HPV HR and Genfind™ DNA Extraction Kit
PMA Applicant: Third Wave Technologies
Address: Third Wave Technologies, Hologic, Inc., 502 South Rosa Road, Madison , WI 53719
Approval Date: March 12, 2009
Approval Letter: http://www.accessdata.fda.gov/cdrh_docs/pdf8/P080014a.pdf
What is it? These reagents are used with the Invader Call Reporter™ software to identify human papillomavirus (HPV) DNA from 14 high-risk genital HPV types that are commonly associated with cervical cancer. If test results are positive, the patient is likely to be infected with HPV.
How does it work? DNA is isolated from a scrape of cells from a woman's cervix and is subsequently mixed in reaction wells with probes that specifically recognize HPV DNA. This reaction is detected by another substance that produces light, which is then measured to determine the presence of HPV in the cervical sample.
When is it used? Test results may be used in women 30 and over, or women of any age with borderline cytology results, to determine the need for additional follow-up and diagnostic procedures. Test results should be used together with the physician's assessment of cytology history, other risk factors, and professional guidelines.
What will it accomplish? The test provides information to clinicians on a patient's risk for developing cervical cancer. Although HPV infection is very common, and usually self-resolving, if HPV DNA is present, the patient is in a higher risk category for developing cervical cancer than if HPV is not detected.
When should it not be used? There are no known contraindications for use.
Additional information: Summary of Safety and Effectiveness and Labeling is available online at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTopic/pma/pma.cfm?num=P080014
Cervista™ HPV 16/18 – P080015
This is a brief overview of information related to FDA's approval to market this product. See the links below to the Summary of Safety and Effectiveness Data (SSED) and product labeling for more complete information on this product, its indications for use, and the basis for FDA's approval.Product Name: Cervista™ HPV 16/18
PMA Applicant: Third Wave Technologies
Address: Third Wave Technologies, Hologic, Inc., 502 South Rosa Road, Madison , WI 53719
Approval Date: March 12, 2009
Approval Letter: http://www.accessdata.fda.gov/cdrh_docs/pdf8/P080015a.pdf
What is it? These reagents are used with the Invader Call Reporter™ software to identify DNA from human papillomavirus (HPV) types 16 and 18 in cervical samples. If test results are positive, the patient is likely to be infected with HPV type 16, 18 or both 16 and 18.
How does it work? DNA is isolated from a scrape of cells from a woman's cervix and is subsequently mixed in reaction wells with probes that specifically recognize HPV type 16 and 18 DNA. This reaction is detected by another substance that produces light, which is then measured to determine the presence of HPV type 16 and/or 18 in the cervical sample.
When is it used? Test results may be used alongside, or as a follow-up to, the Cervista HPV HR test in women 30 and over, or women of any age with borderline cytology results, to determine the need for additional follow-up and diagnostic procedures. Test results should be used together with the physician's assessment of cytology history, other risk factors, and professional guidelines.
What will it accomplish? The test provides information to clinicians on a patient's risk for developing cervical cancer. HPV 16 and 18 are the two HPV types that are most commonly associated with cervical cancer in the United States. Although HPV 16 and/or 18 infection is very common, and usually self-resolving, if HPV 16 and/or 18 DNA is present, the patient is in a higher risk category for developing cervical cancer than if HPV 16 and/or 18 are not detected, or if other high-risk genital HPV types are detected.
When should it not be used? The Cervista HPV 16/18 test should not be used as a stand-alone assay. Cervista HPV 16/18 test results should be interpreted alongside, or as a follow-up to, a Cervista HPV HR test result, adjunctively with cytology.
The Cervista HPV 16/18 test is not intended for use as a screening device for Pap normal women under age 30 and is not intended to substitute for regular Pap screening.
The use of this test has not been evaluated for the management of women with prior cytologic or histologic abnormalities, hysterectomy, who are postmenopausal, or who have other risk factors (e.g., HIV+, immunocompromised, DES exposure, history of STI).
Additional information: Summary of Safety and Effectiveness and Labeling is available online at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTopic/pma/pma.cfm?num=P080015
cobas HPV Test — P100020
This is a brief overview of information related to FDA's approval to market this product. See the links below to the Summary of Safety and Effectiveness Data (SSED) and product labeling for more complete information on this product, its indications for use, and the basis for FDA's approval.
Product Name: cobas HPV Test
PMA Applicant: Roche Molecular Systems, Inc.
Address: 4300 Hacienda Drive, PO Box 9002, Pleasanton, CA 94588-0900
Approval Date: April 19, 2011
Approval Letter: http://www.accessdata.fda.gov/cdrh_docs/pdf10/p100020a.pdf
What is it? The cobas HPV Test is an automated test run on the cobas 4800 system which is used to identify human papillomavirus (HPV) DNA from 14 high-risk genital HPV types that are commonly associated with cervical cancer. The test specifically identifies types HPV 16 and HPV 18 while concurrently detecting the rest of the high risk types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68). If test results are positive, the patient is likely infected with HPV.
How does it work? DNA is isolated from a scrape of cells from a woman's cervix and is subsequently mixed in reaction wells with primers and probes that specifically recognize and amplify HPV DNA. This reaction produces fluorescence, which is then measured to determine the presence of HPV in the cervical sample.
When is it used? Test results may be used in women age 30 and over, or women age 21 and older with borderline cellular (cytology) results to determine the need for additional follow-up and diagnostic procedures. Test results should be used together with the physician's assessment of cytology history, other risk factors, and professional guidelines.
What will it accomplish? The test provides information to physicians on a patient's risk for developing cervical cancer. Although HPV infection is very common, and usually self-resolving, if HPV DNA is present, the patient is in a higher risk category for developing cervical cancer than if HPV is not detected.
When should it not be used? The cobas HPV Test is not intended:
- for use as a screening device for women under age 30 with normal cervical cytology.
- to substitute for regular cervical cytology screening.
- for use in determining the need for treatment of the cervix in the absence of high-grade cervical dysplasia.
Patients who are HPV 16/18 positive should be monitored carefully for the development of high-grade cervical dysplasia according to current practice guidelines. The use of this test has not been evaluated for the management of women with prior treatment of the cervix, those who had a hysterectomy, or who are pregnant, or who have other risk factors (such as, HIV positive, immunocompromised, history of Sexually Transmitted Infection (STI)).
Additional information: Summary of Safety and Effectiveness and labeling are available at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTopic/pma/pma.cfm?num=P100020
APTIMA® HPV Assay – P100042
This is a brief overview of information related to FDA's approval to market this product. See the links below to the Summary of Safety and Effectiveness Data (SSED) and product labeling for more complete information on this product, its indications for use, and the basis for FDA's approval.
Product Name: APTIMA HPV Assay
PMA Applicant: Gen-Probe Incorporated
Address: 10210 Genetic Center Drive, San Diego, CA 92121-4362
Approval Date: October 28, 2011
Approval Letter: http://www.accessdata.fda.gov/cdrh_docs/ pdf10/p100042a.pdf
What is it? The APTIMA HPV Assay reagents are used with the TIGRIS DTS System to identify human papillomavirus (HPV) RNA from 14 high-risk genital HPV types that are commonly associated with cervical cancer. All currently approved HPV assays detect HPV genomic DNA. This is the first FDA approved assay that detects the messenger RNA of two HPV viral oncogenes, E6 and E7. If test results are positive, the patient is likely to be infected with HPV.
How does it work? RNA is isolated from a scrape of cells from a woman's cervix and is mixed in reaction tubes with reagents that specifically capture and amplify HPV RNA. This reaction is detected by another substance that produces light, which is then measured to determine the presence of HPV in the cervical sample.
When is it used? Test results may be used in women 30 and over, or women 21 and over with borderline cervical cytology results, to determine the need for additional follow-up and diagnostic procedures. Test results should be used together with the physician's assessment of cytology history, other risk factors, and professional guidelines.
What will it accomplish? The test provides information to clinicians on a patient's risk for developing cervical cancer. Although HPV infection is very common, and usually self-resolving, if HPV RNA is present, the patient is in a higher risk category for developing cervical cancer than if HPV is not detected.
When should it not be used? There are no known contraindications.
Additional information: Summary of Safety and Effectiveness and labeling are available online at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cftopic/pma/pma.cfm?num=p100042
