First in a series of monthly stories on the latest in cancer research and treatment.
Last month, the Food and Drug Administration approved a DNA test as an alternative, not just an add-on, to the venerable Pap smear for cervical cancer screening.
The cobas test, made by Roche, detects the DNA of certain types of human papillomavirus (HPV), which causes the disease. Based on a study of more than 47,000 women, using cobas as a primary screening test in women 25 and older could improve detection while reducing invasive diagnostic procedures.
It could also add to confusion over which women should get what screening test when.
"Our biggest concern had less to do with the scientific merit of the test," said Gerald Joseph, a vice president of the American College of Obstetricians and Gynecologists. "Our concern was basically the confusion that it would cause practitioners and the women of America. We've gone from a Pap test once a year, to every few years, to 'co-testing' with an HPV test, to our latest guidelines," which advise certain women to go five years between checkups.
Cervical cancer screening guidelines have become increasingly complex over the last decade to keep pace with the evolving science and technology.
Now, medical groups will consider whether, and how, to incorporate the cobas option into the guidelines, a process that could take about a year, Joseph said.
Meanwhile, experts agree, women (and doctors) need to understand why the one-size-fits-all Pap smear is outmoded and often inaccurate. Here's an overview:
What is HPV? This ubiquitous virus has more than 140 strains. While most are harmless, some cause warts or, as researchers found in the 1980s, harmful changes in the cervix, the opening to the uterus. The cobas test detects HPV 16 and 18, which cause about 70 percent of cervical cancer, plus another 12 types that occasionally induce cancer.
The tricky thing about HPV is that 80 percent of sexually active people are infected at some point, but most infections clear up without treatment, particularly in women in their 20s.
How does the cancer develop? It arises after many years of progressive, precancerous cell changes. When screening flags an abnormality, the woman is sent for a colposcopy, a procedure to examine the cervix and cut, freeze, or burn away the bad tissue, thus preventing full-blown cancer.
Studies suggest care can harm a woman's ability to carry a pregnancy, so it is usually reserved for the most severe precancers.
How does the Pap smear work compared to DNA tests? More than 70 years ago, the man for whom the Pap smear is named, pathologist George Papanicolaou, showed that a scraping of cervical cells could be examined under the microscope to detect precancerous changes.
A single Pap test has about a 50-50 chance of missing warning signs, either because of an inadequate cell sample or misinterpretation by the analyst.
DNA tests - three are on the market - also start with a cervical cell sample, but then use molecular technology to detect harmful HPV types. The detection rate is high, but it reveals the presence of infection, which does not always result in disease.
"We can't separate transient infection from infection that will do real harm," said Wendy Brewster, a University of North Carolina gynecological oncologist who has helped develop screening guidelines.
How have screening guidelines evolved? For decades, experts recommended getting a Pap test each year. The frequency made up for low accuracy, and over time, cervical cancer - once the leading cancer killer of U.S. women - became relatively uncommon. It now claims about 4,000 lives a year, mostly women who don't get screened or follow up with care.
But with new insights and better detection technology, experts realized screening should be less often, and tailored to the woman's age and risk factors.
The 2012 guidelines say:
From age 21 to 29, Pap smears should be done every three years for women with normal results. HPV tests should not be done because infection is common and cancer is rare.
From age 30 to 65, women may have "co-testing" - Pap and HPV tests - every five years if they have normal results.
After 65, screening is unnecessary unless the woman has a history of precancerous cell changes. (Screening is also not needed after a total hysterectomy.)
Women with ambiguous Pap results - a common problem - can use the HPV test to decide whether colposcopy is needed. "With a negative HPV test, the risk of a precancerous lesion is extremely low," the guide says.
Women vaccinated against HPV (two vaccines are on the market) should still get screened because the vaccine does not protect against all harmful strains.
How effective is the cobas HPV test? Cobas is the only HPV test that specifically identifies infection with HPV 16 and 18, the highest risk types, and gives a pooled result for 12 other types linked to cancer. It was first approved in 2011 for co-testing or clarifying ambiguous Pap results.
The new approval is as a primary screening test every three years for women over 24 who have normal results.
The study that led to approval followed 47,000 women for three years to compare cobas with the Pap smear alone and current guidelines.
The bottom line?
The FDA summarized it in a letter to a health group coalition that opposed the approval: For every 10,000 women age 25 or older, cobas screening is expected to detect 61 cases of severe precancers, compared with 41 cases with the Pap alone and 52 cases with current guidelines.
Cobas would also refer fewer women to colposcopy - 4.6 percent, compared with 9.9 percent with the Pap alone, and 4.7 percent with current guidelines.
What does testing cost? Consumer groups say HPV tests cost between $80 and $100, about twice as much as a Pap test.