For decades, the Pap smear — a test in which cervical cells are examined under a microscope — has been the mainstay of cervical-cancer prevention in the United States.

However, it is a process that requires expensive supplies and trained technicians, making it inaccessible for women in developing countries. Now, UW scientists are developing a potentially more accurate and less costly screening for cervical cancer that could be accessible for women in Third World countries.

Widespread Pap testing has reduced occurrences of cervical cancer — which doctors now know is caused by high-risk Human Papilloma Virus (HPV) infections — by 70 percent in the United States, said Constance Mao, professor of obstetrics and gynecology. In developing countries, however, the need for expensive equipment and trained pathologists and cytotechnologists has prevented most women from being tested regularly. According to the World Health Organization, 260,000 women died of the disease in 2005.

Because a single Pap smear test has only a 50-percent chance of finding precancerous changes, women need a Pap smear every year to catch problems that may have been missed in the last Pap smear, said professor of pathology, Nancy Kiviat.

"Everyone knows that Pap smears — although they've done a terrific job of decreasing cervical cancer in any country where there's regular Pap screening — have lots of problems," Kiviat said. "They're very labor intensive, and they're insensitive, so you have to be tested every year. A single Pap smear only has a 50-percent chance of detecting abnormal cells."

Pap smears also give many false positives, forcing women with non-problematic HPV infections to come back for invasive procedures like biopsies, Mao said. Most people will have an HPV infection at some point in their life, but the immune system usually clears the HPV virus on its own. Only women with persistent infection are more likely to develop cervical cancer, Kiviat said.

"There are a lot of women who are referred for colposcopy and biopsy who really have self-limited infection and don't need to be worked up," Kiviat said. "We need to find markers that tell us who is at real risk of developing cancer."

To that end, the researchers looked at a protein called P16 as a potential marker for these precancerous changes. P16 was considered a good candidate because HPV-related cancer cells have much higher levels of P16 production, according to the June 1 article in the International Journal of Cancer.

"Because you're testing for a protein that is further down the chain of events after an HPV infection, potentially we will find more women who have true disease compared to HPV tests. That's the theory," Kiviat said.

In addition, the P16 test does not require trained pathologists or expensive equipment to analyze.

"It's very quick — you can get the results right away — and it's a very cheap technology," Mao said.

In a preliminary study, 319 women with abnormal Pap smear results were sent for further evaluation. The women were tested with traditional methods like colposcopy and biopsy. Cell samples were also tested for the presence of HPV DNA and for the P16 protein. The P16 test caught about 90 percent of the precancerous cell changes.

Before a cervical-cancer screening test like the P16 test could replace the Pap smear, the number of false positive test results would have to be dramatically reduced, and whether that's possible for P16 remains unclear, Kiviat said.

Still, the results are promising enough that the researchers are currently enrolling women in a large-scale study to see how the P16 test works in a population of women who haven't had abnormal Pap smears, Mao said.

"The Pap works for us, but it's hugely expensive — everybody has to go in every year," Mao said. "Wouldn't it be nice if it was easier, quicker, cheaper and maybe you didn't have to go in as often?"

Reach columnist Tia Ghose at news@thedaily.washington.edu.