Pap Smears Re-examined

Cervical cancer screening is one of the great success stories in preventive medicine. Prior to the advent of Pap smears in the 1950s, cervical cancer was considered one of the most deadly cancers in women and would claim over 35,000 lives a year in the United States alone. Now largely thanks to Pap smears, which can detect cervical precancers and cancers earlier than they would found otherwise, there are less than 4,000 U.S. deaths annually from cervical cancer. One only need go to areas of the world where Pap smears are not routinely used to appreciate the impact: in 2007 I traveled to a local cancer hospital in India where I was shocked to see that cervical cancer accounted for nearly a quarter of the cases.

Despite this remarkable success, the role of Pap smears is now being re-examined. In early April, the New England Journal of Medicine published a groundbreaking clinical trial that showed that a DNA-based screening test for cervical cancer, called HPV testing, was superior to Pap smears for the prevention of cervical cancer.* The study which randomized 130,000 women in rural India to Pap smears, HPV testing, direct visualization (a technique primarily used in low-resource settings), or control showed that HPV testing led a 50 percent reduction in advanced cancers and deaths compared to only 25 percent reduction with Pap smears. The implications of the study cannot be understated: an accompanying editorial in the Journal stated that, “In developed nations, HPV testing at extended screening intervals could eventually replace [Pap smears] as the primary screening method.” Put more bluntly, the NY Times quoted a Stanford gynecologist as saying that the study was “another nail in the coffin” for Pap smears.**

To people outside of medicine this seems to be sudden change in our approach to cervical cancer screening. But the reality is that this development has been a longtime coming. Over the past several years, we have learned that almost all cases of cervical cancer are caused by the HPV virus (or the Human Papillomavirus). This understanding has led to new tests that directly detect HPV DNA in the cervix. Already, HPV testing is being used as an adjunct test to screen for cervical cancer.*** The American College of Obstetricians and Gynecologists (ACOG) recommends three options for screening in women ages 30 and older: 1) annual Pap smears, 2) Pap smears every 2 to 3 years in women who have had three consecutive negative tests, and 3) Pap smears plus HPV testing every 3 years if both tests are negative. In addition, many doctors are routinely using HPV testing as a “tie breaker” to decide how to treat women whose Pap smear results are indeterminate.

Still, using HPV testing as our primary tool for cervical cancer screening would be a significant departure from our current screening strategy, and one that still has kinks to work out. Most experts agree that the screening interval (the time between each screening test) could safely be lengthened to 3, 5 or even 10 years. A negative HPV test would indicate a low risk of cervical cancer over the next 5 to 10 years. A positive HPV test would likely warrant further risk-stratification with Pap smears. There is even some talk that the lower stringency of HPV testing compared to Pap smears would allow women to swab themselves with home test kits instead of having to go to the doctor for pelvic exams.

For the near future it is safe to say that you should still plan on your regular Pap smear. Expect however a flurry of new studies over the next few years to confirm the results of the Indian study and to develop a new, HPV testing-based screening strategy. Expect too opposition from current practitioners who depend on routine Pap smears for annual patient visits and from advocacy groups fearful of new technologies. But inevitably a day will soon come when you won’t have to go in for your annual Pap smear – a day where instead you will go in for your every 5 or 10 year HPV test or better yet, do the test yourself in the comfort of your own home.

- Shantanu Nundy, M.D.

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*  N Engl J Med. 2009 Apr 2;360(14):1385-95.

** http://www.nytimes.com/2009/04/07/health/07virus.html?_r=2&hp

*** The U.S. Preventive Services Task Force (USPSTF), which is the primary reference source for BeyondApples.org, has concluded that there is insufficient evidence to support HPV testing. However, from anecdotal evidence, most providers rely on ACOG and not the USPSTF for the most up-to-date guidelines on cervical cancer screening.