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Study Supports Use of Pap and HPV Co-Tests

NEW YORK (GenomeWeb News) – Routine testing for the presence of carcinogenic human papillomavirus strains in women over the age of 30 years old does not lead to excessive positive tests, according to a paper appearing in this month's issue of the journal Obstetrics & Gynecology.

A team of researchers from Kaiser Permanente and the National Cancer Institute conducted a five-year study aimed at determining how many positive tests they'd find by routinely co-testing women who were 30-years-old or older using both traditional Pap tests and a molecular test sold by Qiagen, which looks for more than a dozen high-risk HPV genotypes. Though women between the ages of 30 and 39 years old were most likely to test HPV positive, the team's results suggest that, in general, HPV testing does not lead to a preponderance of positive tests in women over 30.

Pap tests are designed to detect suspicious looking or pre-cancerous cells that may lead to cervical cancer. Even so, such tests are not perfect and need to be done relatively frequently.

"Although it has successfully reduced the burden of cervical cancer by 75 percent or more in the United States, Pap test/cervical cytology is insensitive for the detection of precancer and cancer of the cervix and must be repeated frequently to achieve programmatic effectiveness," senior author Walter Kinney, a gynecological oncologist with the Kaiser Permanente Medical Group, and his colleagues wrote. "A more efficient and accurate screen could greatly reduce the billions of dollars spent annually on the US cytology-based system."

The human papillomavirus is the best-known cervical cancer culprit. And in 1999, the US Food and Drug Administration approved a test — which at the time was sold by Digene, who was acquired last year by Qiagen — that identifies 13 HPV genotypes thought to contribute most to increase cervical cancer risk.

For women over 30 years old, Kinney and his colleagues noted, research suggests women who have both normal Pap tests and are HPV negative are at "extremely low risk for incipient precancer and cancer of the cervix for the subsequent ten years or more." As a result, these women can usually forego yearly screening and opt for co-testing every three years or so instead.

But some physicians have expressed concern that routinely implementing carcinogenic HPV testing could identify a wave of women over 30 years old with normal Pap results but HPV positive tests, leading to lengthy follow-up and surveillance times in a large group of women at indeterminate risk.

In an effort to understand how many positive tests they would get using a combination of conventional Pap testing and HPV testing using Qiagen's Hybrid Capture 2 High-Risk HPV DNA Test, Kinney and his team evaluated 580,289 women who had been co-tested between early 2003 and the spring of 2008 at the Kaiser Permanente Northern California, which introduced co-testing for women over 30 in 2003. Altogether, the women had had 797,927 co-tests that provided sufficient data for inclusion in the study.

Overall, the team found that 6.27 percent of the HPV tests were positive — 2.28 percent were HPV positive and had abnormal Pap tests while 3.99 percent were HPV positive with normal Pap results.

Women between the ages of 30 and 34 were most likely to test positive with the Hybrid Capture 2 test and nearly 11 percent of women in that age group had positive HPV tests. Within that group, HPV positive and cytology negative tests were also most common, occurring in nearly seven percent of those tested. On the other hand, just 3.67 percent of women between the ages of 60 and 64 had positive HPV tests, with 2.56 percent turning up HPV positive and cytology negative.

Meanwhile, the researchers reported that 5.18 percent of those tested had suspicious Pap test results, with 2.87 percent testing HPV negative.

Based on these results, the team concluded that HPV testing turns up fewer positive tests than previously reported. They speculated that this may be due to an over-representation of women between the ages of 30 and 39 years old — the age group that is most likely to be HPV positive — in earlier studies, such as the HPV Sentinel Surveillance project.

Though they cautioned that the results may not necessarily apply to all populations, the researchers argued that "the concerns raised about introduction of HPV testing into clinical practice may be seen to have been overstated when population screening data are considered."

In particular, the team noted that co-testing provides peace of mind for women who test negative both by Pap and HPV tests. That, in turn, appears to have helped many low-risk women move from annual cytology screening to a co-testing every three years. Even so, the researchers suggested additional research is needed and urged the development of a consistent and effective plan for dealing with women who are Pap negative and HPV positive.

Qiagen's Senior Vice President of Research and Development for North America, Jim Godsey, said in a statement today that the study by Kinney and his team dispels the notion that HPV testing leads to excessive monitoring based on the HPV test alone.

"This is good news to the clinical community who may have been overly anxious about the management of a large number of HPV positive, Pap normal test results," Godsey said. "[B]y identifying the women who test positive for infection with one of the cancer-causing types of HPV — and who are hence at greater risk of developing cervical diseases — clinicians can more effectively direct treatment and follow-up, potentially detecting more early stage diseases and saving lives."

Up until very recently Qiagen had the only molecular HPV test cleared for clinical diagnostic use by the US Food and Drug Administration. But two weeks ago, Hologic received the FDA's nod to sell two HPV genotyping tests.