It is clear that HPV, the human papilloma virus, is the principal cause of cervical cancer.
But what is the best way to identify women who are at risk from the common virus: using the traditional method of looking for cell abnormalities on the cervix, or testing for the presence of high-risk strains of HPV?
Canadian researchers yesterday announced a massive study to try to answer that bedevilling question, a project that will enroll more than 33,000 women 25 to 65 years old in the Vancouver area.
Janet Abe, a 38-year-old production manager at a Vancouver magazine, has enrolled as a student participant, motivated to do so because both her parents have endured bouts of cancer in recent years.
"My family has been touched by cancer and the care was great so I wanted to give something back," she said. "This is one of the simplest things a woman can do because you don't even have to change your routine."
Ms. Abe and the other women in the study will undergo routine testing - in which cells are scraped from the cervix using a small paddle - but the samples will be processed differently in the laboratory.
The study participants will be divided into three groups:
One will undergo a traditional, annual Pap test, in which cells are analyzed by a laboratory technologist looking for cellular changes;
another group will receive an HPV test, repeated after two years if no HPV is found;
the third group will get an HPV test, repeated after four years if no HPV is found.
Andy Coldman, vice-president of population oncology at the B.C. Cancer Agency and the study's principal investigator, said the research is expected to identify which testing method is better and which time interval is better for testing.
"The goal here is to do a better job of controlling the disease - to prevent as many women as possible from developing cervical cancer," he said.
Biologically, Dr. Coldman said, there is little doubt the HPV test is more accurate than Pap testing for detecting cervical cancer, but there are complicating factors in determining the ideal screening approach.
The Pap test generates a lot false negatives, meaning it misses some cases of cancer.
The HPV test, meanwhile, generates some false positives, meaning it might point to cancer where there is none. Earlier research done in Canada found that the HPV test gave a false reading 6 per cent of the time, compared to 3 per cent for the Pap test.
There are also cost issues: The Pap test costs about $15, compared with $30 for HPV.
"It's a balancing act, and we want to figure out how to get the balance right," Dr. Coldman said.
The research is also expected to help determine whether cervical cancer screening is best done annually, every two years or every four years.
Ms. Abe said she hopes the research will help improve cervical cancer detection, but, she said, regardless of the findings, she will continue to go for annual gynecological exams.
"It doesn't matter which test is most effective. It's not replacing the need to go to the doctor. That's part of my routine for being healthy," she said.
Dr. Coldman said that is exactly the kind of issue that needs to be explored. "Not all the answers can be found in pure biology. There is a public health piece here that isn't clear."
Bhagi Singh, scientific director of the Institute of Infection and Immunity of the Canadian Institutes of Health Research, which is funding the study, said that while many experts already believe HPV testing is far superior to Pap testing, the issue needs to be probed thoroughly.
"For women, this is a very important question - in some cases, a matter of life or death," he said. "What seems obvious may not be."
For example, Dr. Singh said, the research will help determine whether the ideal testing method varies depending on age or ethnicity.
A study published in today's edition of the Journal of the National Cancer Institute suggests that HPV testing produces many more false positives in women under 35.
The research team, led by Guglielmo Ronco of the Centre for Cancer Prevention in Turin, Italy, recommends that, if HPV testing is done in younger women, that a "watchful waiting approach" be used - essentially that no action be taken for 12 months and that women be retested. This is because most HPV infections clear naturally.
In most of Canada, screening for cervical cancer is done using the Pap test, and only when results are unclear is the HPV test used. Another test, a colposcopy, is required to confirm a cancer diagnosis.
About 1,350 women were diagnosed with cervical cancer in Canada in 2007 and an estimated 390 died of the disease, according to the Canadian Cancer Society.
There is a vaccine available that protects against four strains of HPV that are responsible for the bulk of cervical cancer. But it is recommended that women who receive the vaccine - along with those who have not - undergo Pap testing once they are sexually active.