Approval of new HPV DNA tests prompts update to guidelines for appropriate use

The first test provides information similar to another test that has been on the market for the past ten years. It detects all 14 HPV subtypes (including subtypes 16 and 18) associated with cervical cancer. It is intended to be used to screen women with certain abnormal results on a Pap smear known as "atypical squamous cells of undetermined significance" (ASC-US) to determine the need for colposcopy, a procedure that allows a doctor to visually inspect the vagina and cervix under magnification for the presence of abnormal cells. The HPV test is also recommended for screening women over age 30 for the types of HPV infections that are linked to cancer. It is not recommended for use in younger women because infections with HPV are relatively common in this age group and often resolve without treatment or complications. The second test is the first the FDA has approved for specifically detecting the HPV subtypes 16 and 18. These two types of HPV cause about 70 percent of all cervical cancers in the United States.

The new tests aim to give health care providers more information on a woman's risk of developing cervical cancer. The director of the FDA's Center for Devices and Radiological Health, Daniel Schultz, MD, said that "results from these two tests, when considered with a physician's assessment of the patient's history, other risk factors, and professional guidelines, can help physicians better determine risk [for cervical cancer] and could lead to better patient management."

Soon after the test for types 16 and 18 was approved, the American Society for Colposcopy and Cervical Pathology (ASCCP) published a decision aid for health care providers to give guidance and promote proper use. Several other organizations weighed in on the subject in a statement that was published in the June 2009 issue of the American Journal of Clinical Pathology. The statement, based in part on the decision aid developed by the ASCCP, was released by the Cytopathology Education and Technology Consortium (CETC) and was endorsed by several health care groups and professional societies, including the American Cancer Society, the American Society for Clinical Pathology, and the College of American Pathologists, to name a few.

The flowchart from ASCCP and the CETC statement outline the situations in which testing for high-risk types of HPV are appropriate. In general, some of these include:

• In women over 30, routine screening for cervical cancer in conjunction with a Pap smear is recommended. For those with negative results on both a Pap and an HPV test, repeat screening with both tests should only be done after 3 years.
• If a woman over 30 years old has a normal Pap smear result but tests positive for any high-risk type of HPV, then the test for HPV types 16 and 18 may be suggested as follow up. Women who test positive for type 16 or 18 should be examined with a colposcope. According to the guidelines, those whose test for types 16 and 18 is negative can wait 12 months and have another sample of cervical cells analyzed (via Pap test and DNA test for high-risk HPV). They also recommend actions based on the follow-up test results a year later.
• In women over 21 who have atypical cells (ASC-US) on a Pap smear, HPV DNA testing can be done to help decide how to manage the patient. If the test is positive for high-risk types, additional procedures such as colposcopy may be done to determine if the positive results are due to the presence of cancer.

HPV DNA tests are not appropriate and should not be part of patient management in many instances, notes the ASCCP and CETC; for example, not for any woman 20 years old or younger, even if her Pap test results are abnormal, women thinking of getting an HPV vaccine, or women 21 years old or older with specific cellular abnormalities or lesions that may indicate precancerous or cancerous changes in cells from the cervix. (These include "atypical squamous cells with high-grade changes" (ASC-H), "low-grade squamous intraepithelial lesion" (LSIL), and "high grade squamous intraepithelial lesion (HSIL)." See the Pap Smear article for more on these). Testing for low-risk types of HPV, the types that can cause genital warts but do not increase the risk of cancer, should not be used for routine screening or in the evaluation of women with abnormal Pap smear results, say the guidelines.

One stumbling block in using the new test for types 16 and 18 is that many labs have invested and become experienced in using other commercial or in-house tests for high-risk HPV. Yet the FDA only approved the HPV 16 and 18 test as an adjunct to the high-risk HPV test made by the same company. A comment in Journal Watch Women's Health noted another concern, both medical and economic: many experts wonder whether the additional step of testing for HPV subtypes before performing colposcopy as outlined by the ASCCP is necessary.

At present, it is not clear if the new test for HPV subtypes 16 and 18 will become widely available or if doctors will begin to order the new test as an adjunct to a positive screening test. While use of HPV DNA testing expands and evolves, women should continue having Pap smears and pelvic exams on a yearly basis or as recommended by their health care provider.

Sources

Davis, A. J. 2009 May 28. Clinical usefulness of HPV DNA testing and genotyping. Journal Watch Women's Health.

FDA approved first DNA test for two types of human papillomavirus; agency also approved second DNA test for wider range of HPV types. 2009 Mar 13. US Food and Drug Administration. Available online at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149544.htm through http://www.fda.gov. Accessed 9 Jun 2009.

FDA approves two DNA tests to detect HPV. 2009 Mar 17. Infectious Disease News. Available online at http://www.infectiousdiseasenews.com/article/37896.aspx through http://www.infectiousdiseasenews.com. Accessed 9 Jun 2009.

FDA approves two Hologic HPV tests (press release). 2009 Mar 13. Hologic, Inc. Available online at http://www.hologic.com/news-releases/view/173-year.2009_173-id.234881444.html through http://www.hologic.com. Accessed 9 Jun 2009.

Descriptions of new FDA-approved HPV DNA tests (clinical update). American Society for Colposcopy and Cervical Pathology. PDF available for download at http://www.asccp.org/pdfs/consensus/clinical_update_20090408.pdf through http://www.asccp.org. Accessed 11 Jun 2009.

Solomon D, Papillo J, Davey D, on behalf of the Cytopathology Education and Technology Consortium. Statement on HPV DNA Test Utilization. Am J Clin Pathol 2009;131:768-769.

Human papillomaviruses and cancer: questions and answers (fact sheet). National Cancer Institute. Available online at http://www.cancer.gov/cancertopics/factsheet/Risk/HPV through http://www.cancer.gov. Accessed 9 Jun 2009.