Dr. Pap's smear: The test and its times

The important role of the screening test created by Dr. George N. Papanicolaou is being recast with the advent of HPV vaccines and testing for this virus.

By Victoria Stagg Elliott — Posted Sept. 3, 2007

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With new technologies that improve cervical cancer screening and reduce the risk of developing this disease, the changing role of the Pap smear in regard to women's preventive health care is being considered more and more.

"Cervical cytology could still have some role indefinitely, but it's getting to be less and less important," said Ruth Shaber, MD, an obstetrician-gynecologist and medical director of the Center for Healthcare Delivery at Kaiser Permanente's Care Management Institute in Oakland, Calif.

The Food and Drug Administration approved a test for human papillomavirus DNA in 2000. A vaccine to protect against several variants of this virus was given the nod in 2006. With improvements to both of these tools expected soon, the question being asked now is how the Pap smear should be used in light of these advances.

"The future as it relates to Pap smear screening is going to play out in a way that is difficult to predict," said Martin Mahoney, MD, PhD, a family physician and associate professor of oncology at Roswell Park Cancer Institute in Buffalo, N.Y.

This test's past achievements are legion, and its value without doubt. It has been credited with slashing the cervical cancer death rate and becoming the tie that binds many women to their doctors' offices for annual checkups. According to data from the Agency for Healthcare Research and Quality, in 2005 slightly more than 86% of women between the ages of 18 and 64 received one within the past three years, making it the most common cancer screening procedure.

"It really has made a significant impact in decreasing the death rate from cervical cancer and allowing the treatment to be done in the premalignant stage," said Robert Knapp, MD, William Baker professor emeritus of gynecology at Harvard Medical School in Boston. He knew Dr. George N. Papanicolaou, the test's inventor, when he was at Cornell University Medical College in New York. "The Pap smear has encouraged women to seek routine medical care. Patients of mine came to me for a Pap smear, and, lo and behold, I found out they were early diabetic. It's been a tremendous medical advance."

The American Cancer Society recommends that women have one annually, although this interval between Paps can be longer if the liquid-based version of the test is used or among women older than 30 who have had three consecutive normal tests. The U.S. Preventive Services Task Force strongly recommends Pap smears, although is not specific about their frequency, and these guidelines are under review. The American Medical Association has long had policy supporting the Pap smear as an effective cervical cancer screen.

"It's been apple pie, the American flag and the annual Pap smear ingrained in the American tradition for so long," said Daron Ferris, MD, professor of family medicine and obstetrics and gynecology at the Medical College of Georgia in Augusta.

A checkered past

Such descriptors are quite auspicious for a test that initially met with little interest. Dr. Papanicolaou first proposed that cancer cells found in a vaginal smear could be indicative of the early stages of this disease in a study presented at the 1928 meeting of the Third Race Betterment Conference, a gathering of eugenicists. The paper was full of typos -- such as "conscious" instead of "cancerous" cells -- and reception was so indifferent that Dr. Papanicolaou didn't return to this line of research until a decade later.

In 1941 he published what would become the landmark paper on this subject in the American Journal of Obstetrics and Gynecology. This time the idea was embraced by ob-gyns but reviled by pathologists, who were particularly skeptical that this approach would be an improvement on biopsy.

"When the Pap smear was first proposed, the pathologists were generally opposed to it, because it was an extremely complicated, very time-consuming test with uncertain results," said Leopold G. Koss, MD, a pathologist and chair emeritus of Montefiore Medical Center and Albert Einstein College of Medicine in the Bronx, N.Y. He worked with Dr. Papanicolaou and carried out the first studies suggesting that the Pap smear could detect cervical cancer early.

But while this caused controversy, it attracted financing for more research from the Commonwealth Fund. In 1945, the American Cancer Society started promoting Pap smears as part of an effort to encourage early cancer detection.

"The American Cancer Society promoted it relentlessly," said Adele Clarke, PhD, author of several papers on Pap smear history and professor of sociology and history of health sciences at the University of California, San Francisco.

But these efforts were not enough to push the Pap smear quickly into the medical mainstream. According to a story from the Oct. 24, 1952, New York Times, ACS's medical director, Charles S. Cameron, MD, complained that most physicians were not willing to cooperate with his organization's efforts to promote cancer checkups that included the Pap smear. Similarly, an Oct. 23, 1961, NYT story reported that, according to ACS research, 40% of women had never even heard of the Pap smear.

"You had to convince people that there was, in fact, a precancerous state," said Ralph Richart, MD, professor emeritus of pathology at Columbia University College of Physicians and Surgeons. He was instrumental in establishing the first classification systems for the Pap smear in the 1960s. "As surprising as it may be today when this is universally accepted, it was not accepted then at all."

Still important after all these years

Despite these hiccups, cervical cancer deaths declined precipitously, and, to more and more women, an annual checkup became synonymous with this screening. But science supporting this interval always has been lacking, and historians say the timing was adopted to mirror the rhythm of refilling annual birth control prescriptions and other checkup requirements.

But over time, data began to suggest that this frequency may not be necessary. In 1980, the ACS first changed its recommendation from yearly to once every three years for women with at least two negative tests. A National Institutes of Health panel that year advocated that all women have a Pap smear every one to three years. Now, with both the HPV vaccine and virus testing available, the possibility of reducing the interval for Pap smears even further is a hot topic, although most doctors agree that, for the moment, the Pap smear's position is secure.

And most physicians expect the Pap smear to be refined further rather than eliminated.

"The Pap smear is going to become even more exquisitely particular," said Nancy Church, MD, an ob-gyn with the Wellness Connection in Chicago.

The true impact of the HPV vaccine also will not be known for decades, and the difference it may make on cervical cancer deaths may be muted by the fact that current formulations do not protect against all strains. It's also unknown how long protection lasts.

It's going to be "at least a generation before we really see a difference in the way we will conduct business," said Dina R. Mody, MD, president-elect of the American Society of Cytopathology and director of cytopathology at Methodist Hospital in Houston. "There's a whole bunch of answers that we don't have about the HPV vaccine. They think the immunity will last, but we know what happened with pertussis. I had whooping cough a couple years ago."

The potential impact of HPV testing could be more immediate. Some physicians are advocating this step as the first screen and then following with the Pap smear.

"Particularly for women above 30, that makes very good sense," Dr. Ferris said. "I tell women that, if you're above 30 and ... the third-party payer told you that they're only going to pay for one of those two tests, the one you want is the HPV test."

This concept, however, is extremely controversial. The most common practice is to carry out HPV testing either in conjunction with a Pap smear or in response to an uncertain result. Those who argue against putting HPV testing first question how meaningful the results would be because the virus is so prevalent, particularly among some age groups. Evidence supporting this strategy is also lacking.

"A huge number of patients have HPV. If you tell the patient, 'You've got oncogenic-grade HPV,' and then you do a Pap smear on that woman and the Pap smear comes back negative or normal, that woman is still terrified. You're going to actually increase unnecessary investigations or interventions," said Paul Callaway, MD, clinical associate professor of family and community medicine at the University of Kansas School of Medicine in Wichita.

But what is clear is that many physicians and patients may not be quick to give up the annual Pap smear. Most physicians say the recommendations to increase the interval have not been very popular. Also, there is a fear that because the Pap smear is such an anchor service, some women have confused not needing a Pap smear with not needing to come in at all.

"We've come so far with educating women about the need for annual health screenings. We need to be very careful, very measured in our attempts to undo that learned health behavior," Dr. Mahoney said.

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Measuring the impact

[download pdf]

The Pap smear is credited with significantly decreasing the death rate from cervical cancer. Mortality rates for this disease alone are not available for all years, but the combined rates for this carcinoma along with uterine cancer went down by 82% from 1931 to 2004.

Source: American Cancer Society, Centers for Disease Control and Prevention

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Dr. George N. Papanicolaou

Born: May 13, 1883, in Kimi, Greece

Died: February 19, 1962; heart attack

Education: Medical degree, University of Athens, Greece, 1904; doctorate in zoology, University of Munich, Germany, 1910

Career highlights: He was a second lieutenant in the Greek army medical corps during the Balkan War of 1912-13. In 1913 he took a position as an assistant in the pathology department at New York Hospital and worked his way up to professor of clinical anatomy at what then was Cornell University Medical College, an affiliated institution. He continued in this position until a few months before his death.

Crowning achievement: He recognized that the detection of exfoliated abnormal cells could indicate early-stage cancer.

How he did it: While developing a vaginal smear intended to track the reproductive cycle he noticed cancerous cells as well.

Colleague comments: "[He] shares with Jonas Salk the distinction of being perhaps the most widely known name in American medicine. ... It can be said that his work represents the most significant, practically useful discovery in the great field of cancer in our time," Charles S. Cameron, MD, former medical director of the American Cancer Society, said in 1958.

Source: New York Times, Feb. 20, 1962; Papanicolaou Society of Cytopathology

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External links

"Screening for Cervical Cancer," U.S. Preventive Services Task Force, January 2003 (link)

"American Cancer Society Guideline for the Early Detection of Cervical Neoplasia and Cancer," abstract, CA: A Cancer Journal for Clinicians, November/December 2002 (link)

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