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Lab Industry Reacts to USPSTF Recommendation Against Cervical Cancer Co-testing

New York (GenomeWeb) – Lab industry stakeholders are expressing concerns over new draft recommendations for cervical cancer screening, saying they may be difficult to implement.

Recently, the US Preventive Services Task Force issued draft recommendations saying women aged 30 to 65 can be screened for cervical cancer either every three years using a Pap smear, or every five years with high risk human papillomavirus testing alone. Previously the USPSTF had recommended that HPV testing at five year intervals should be done as part of a co-test that included a combination of cytology and hrHPV testing.

Recommendations for women in other age groups remain unchanged. The comment period on the recommendations ends Oct. 9.

For some, a major concern is that only one hrHPV test is FDA-approved to be used alone for primary screening, Roche's Cobas hrHPV. This, detractors of the draft recommendations said, could have major implications for the hrHPV test manufacturers and the labs that offer them.

"At present, there is only one HPV test approved by the FDA for Primary HPV screening that is available in a limited number of laboratories," wrote members of the Cytopathology Education and Technology Consortium to the USPSTF in a comment letter, suggesting challenges with implementation. The consortium is made up of four industry groups, the College of American Pathologists, the American Society for Cytotechnology, the American Society of Cytopathology, and the American Society for Clinical Pathology.

There are currently five HPV tests available for use in co-testing, including the Roche test, explained Debbie Saslow, senior director HPV-related and women's cancers at the American Cancer Society. The USPSTF proposed guideline have raised questions as to which HPV tests can be used going forward.

"Is it just the one test? Is it any of the five? Is there any preference? There are significant differences between the tests, so I think that is an area that can create confusion," Saslow said. The American Cancer Society has not yet commented on the recommendations, Saslow said, noting that her comments reflected her own observations.

The Cytopathology Education and Testing Consortium questioned whether the USPSTF draft recommendation suggested several existing HPV tests could be used for primary screening.

"We strongly recommend that only methds approved by the FDA or vigorously validated for a primary screening indication be used [independent of the co-testing model]," the consortium wrote.

One issue may lie in how USPSTF words its recommendations. While final recommendations are being created, the American Cancer Society and many professional organizations generally suggest a "preferred" screening method. In contrast, the USPSTF has so far simply recommended HPV testing for primary screening, Saslow noted. This can leave questions about whether the recommendation effectively eliminates co-testing.

This issue was raised by Hologic, a maker of one of the HPV tests available for use with co-testing.

"We are concerned that lives will be lost if women are denied access to co-testing if these draft recommendations are implemented," said Steve MacMillan, Hologic's chairman, president and CEO in a statement.

Roche, maker of Cobas hrHPV, approved by the FDA for primary screening, noted that the USPSTF's recommendations follow a growing consensus among other nations to cervical cancer screening.

"While most medical societies in the US still recommend a co-testing model with both high-risk HPV testing and cytology for this age group, the USPSTF approach is more aligned with the growing global trend of countries adopting screening protocols that utilize high-risk HPV testing as primary screening method, due to its superior sensitivity," said Alan Wright, chief medical officer of Roche Diagnostics in a emailed statement.

Impact on labs

The recommendation has the potential to affect which testing methods patients can receive if guidelines affect reimbursements.

"Guidelines often drive reimbursements, so as much as a doctor might want to offer co-testing, his or her hand may be tied," said Harvey Kaufman, senior medical director at Quest Diagnostics.

The use of HPV testing has not increased as quickly as expected, noted Saslow. The American Cancer Society has supported its use in co-testing since 2002; however recent estimates suggest that in the US about half of the women who are screened for cervical cancer receive co-testing and the other half receive Pap smears. Still, while it's unclear how quickly guidelines can affect patient care, if a large group of women transition from two co-tests to one test, the number of cervical cancer screening tests could be sharply reduced.

Some labs that offer only one type of test may also bear the expense for switching to a new test, Saslow added.

"I have heard concerns that eliminating co-testing fairly abruptly might be too soon for the system to handle," she said.

Meanwhile, Quest's Kaufman questioned the studies upon which USPSTF based its draft recommendation. As primary testing is gaining acceptance in Europe, most of the tests the USPSTF considered were European. The US is far more diverse in terms of the number of African-Americans and Hispanic non-whites here, compared to Europe, Kaufman noted. African-American and Hispanic non-white women are more likely to progress to cervical disease, he added. Four of the studies that USPSTF used also relied on conventional cytology, not the newer liquid cytology methods used in the US.

Much of the data in the studies that USPSTF used as the basis for its draft recommendation also showed co-testing to be more effective, he said.

"Starting with data used in their models, the sensitivity for [primary screening] HPV is 90.1 percent. That means, of women who have significant pathology, 90.1 percent are detected with HPV," Kaufman said. "With co-testing, that number is 95.2 percent."

Another issue that both Kaufman and Saslow noted was that because studies of cervical cancer screening have generally been three years in length, USPSTF's data projecting the effectiveness of testing at five-year intervals was largely based on modeling.

"I happen to put a lot of weight into modeling, but it's not perfect, so there are questions," Saslow said. "There are other countries that are recommending five years, but the US isn't like other countries."

When the current five-year interval for screening was introduced in 2012, the medical community pushed back, and many continue to express concerns about it, Saslow noted.

Quest's Kaufman said that a certain percentage of women will progress to cancer within five years. He noted data used by USPSTF in forming its proposal showed that 0.7 percent of women with a precancerous lesion known as CIN2 will progress to cancer within five years, and 2.7 percent of women with a more severe lesion, known as CIN3, will progress to cancer within five years.

"If you want to catch speeders, you could put police officers every mile, but that isn't realistic, so the questions is what is the ideal frequency?" he said. "If you are paranoid about cervical cancer, it probably would be every six months, but that is not something we collectively as a society want to pay for. We started with models that said once every year, and now particularly with better technology, we can make those intervals longer. The intervals they chose, every five years, is strange to me."

The harm of screening

In the end, USPSTF's decision to move to one test instead of two, may have been influenced by perceived potential harms of screening or for cervical cancer. In issuing its draft proposal, USPSTF noted that screening with cytology or hrHPV can lead to harms that include more frequent follow-up testing and invasive diagnostic procedures, as well as unnecessary testing for women with false-positive results. Certain treatments for precancerous lesions are associated with preterm births and related complications, according to the task force.

But Kaufman questioned the assumption that co-testing is more harmful than primary hrHPV screening.

"One of the incorrect assumptions in the model used by USPSTF is that they consider each test [in co-testing] separately, but from the woman's perspective it's the same swab. It's one swab going into one container, so from that standpoint it's one test," he said.

Colposcopies, Saslow noted, are basically magnified views of the cervix.

"A colposcopy in itself is not harmful, but it is what all of us use as a marker," she said. "The number of colposcopies is what is measured and what is reported. So the real harm might be, for example, particularly for younger women who are still going to be having children. A colposcopy can lead to a biopsy. A biopsy, and more likely multiple biopsies, can lead to problems with carrying a fetus to term, and low birthweight babies, bleeding, and other issues."

That balancing act of deciding how much testing is needed to identify the most possible cases of cancer is the balancing act of cancer guidelines, according to Saslow.

"A lot of people would say 'I would be happy if a million people got a biopsy if it saved one life.' To me that's worth it," she said. "Others might say that's horrible."