With the prospect of vaccines eliminating most cases of cervical cancer, the status of the Pap smear is uncertain. Two gynecologists address the issue.

Ever since women began getting Pap tests more than 50 years ago, the number of cervical-cancer deaths has dropped dramatically. Once the leading cause of cancer mortality among women in the United States, cervical cancer now ranks 15th. With this sterling record, you’d expect the Pap smear’s position within preventive care to be secure. But technologic innovation eventually catches up with all things medical, and thanks to the introduction of the human papillomavirus (HPV) vaccine and genetic tests that detect the virus, the Pap test may be threatened.

To better understand what the new technology means for cervical-cancer screening, The Clinical Advisor spoke with Alan G. Waxman, MD, professor of obstetrics and gynecology at the University of New Mexico School of Medicine in Albuquerque, and Constance Young, MD, senior attending physician in the department of obstetrics and gynecology at Phelps Memorial Hospital in Sleepy Hollow, N.Y.

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Q: As the HPV vaccine and HPV DNA tests gain traction, there’s speculation that Pap tests may be on their way out. What is your view?

Dr. Waxman: Maybe in the distant future, but I suspect it will be 20 years before HPV vaccines have a measurable impact on the incidence of invasive cervical cancer. Until then, regular Pap testing remains a woman’s best protection against the disease. One HPV vaccine, Merck’s Gardasil, just hit the market and a second, Cervarix, is expected from GlaxoSmithKline sometime this year. Nevertheless, it will be a long time before the entire reproductive-age population is vaccinated. Also, while the HPV vaccines cover viruses responsible for two thirds of cervical-cancer cases, one third remain.

Dr. Young: Even when both vaccines are widely used, Pap testing will make sense, but at greater intervals. We will see less frequent Pap tests for women older than 30 who are either monogamous or not sexually active. However, Pap tests will remain an important adjunct to HPV testing. The current recommendation for women older than 30 is to screen with both the HPV and Pap tests every three years as long as all previous testing has been normal to that point.

Q: Since Pap tests are so deeply embedded in primary care, won’t there be resistance to dropping this form of screening, even if it no longer makes as much sense?

Dr. Waxman: Of course. Providers and patients are reluctant to change. The American Cancer Society (ACS) has recommended discontinuing Pap tests in well-screened women at age 70 (see “American Cancer Society cervical-cancer screening guidelines”), yet some older patients still request them and providers still do them. The ACS has also recommended that women who have had hysterectomies for nonmalignant indications refrain from Pap tests, yet 60% of these women are still getting them. This is actually a testimony to public-health practice; we did a good job of making women aware of the importance of cervical-cancer screening.

Dr. Young: It’s an educational process. We now have enough information to screen some patients less often, and at least 80% of my patients are perfectly comfortable having Pap tests at greater intervals. However, I still do annual screening if women want it. Peace of mind is important.

Q: The HPV test was introduced in 1999, and about 7 million American women receive it annually. How does this test work, and how effective is it?

Dr. Waxman: In this test, cells are scraped off the cervix to see if HPV is present. The test, which is very sensitive, is recommended for women whose Pap tests indicate the presence of atypical squamous cells of undetermined significance (ASCUS), which is quite common. It is important to note that the HPV test should not be used to triage atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion; patients with this indication should be referred immediately for colposcopy. Currently, the HPV test is being used for screening in conjunction with Pap tests for women over 30. If both tests are negative in these women, the HPV test should not be repeated more than once every three years.

Dr. Young: The HPV test is very accurate and allows clinicians to stratify patients into low- and high-risk groups. Women with positive test results are at risk for cervical cancer and should be screened annually with both Pap and HPV tests. Women with negative test results can be screened less frequently.

Q: Who should be tested for HPV at this point?

Dr. Waxman: In addition to patients with ASCUS, there are also selective scenarios in which HPV tests may be used to follow up colposcopy or treatment for high-grade dysplasia to make sure the cells have returned to normal. A woman’s risk of developing precancerous cell changes is significantly higher if she has been exposed to HPV strains 16 or 18 than if she has been exposed to other cancer-causing virus types. Other products will look specifically at HPV 16 and 18. So in addition to an initial triage test for HPV, there may soon be a second test to determine whether HPV 16 or 18 is present. This may be of particular value for women who are HPV-positive but have negative Pap tests. If we know they have been exposed to HPV 16 or 18, we can examine more closely with colposcopy.

Q: Some experts say that because the HPV test detects more lesions than the Pap, stand-alone HPV testing for cervical cancer is the next step. Do you agree?

Dr. Waxman: That may very well be the next step. A reasonable approach might be to screen with HPV and follow up positive results with Pap tests. However, I would not recommend this strategy in women under 30 because the rate of HPV positivity in this population is so high, and younger women will usually clear the HPV on their own.

Dr. Young: At this point, I would be uneasy screening with HPV testing only. The combination of Pap and HPV testing is the most accurate strategy.

Q: Are there any downsides to HPV testing?

Dr. Waxman: In addition to being overused in some cases, the HPV test leaves many women feeling stigmatized because HPV is a sexually transmitted infection. (There is little risk for the male partner because cancer of the penis is very rare.) In counseling patients, we try to take away the stigma by pointing out how common HPV infection is—fully 75%-80% of sexually active women will have an HPV infection at some point. There is frequently a latent period of years to decades after becoming infected before a woman becomes HPV-positive or has an abnormal Pap test. A positive HPV test should not be considered a sign of infidelity.

Dr. Young: The HPV test is not perfect. There are probably some false positives and false negatives. It is also fairly expensive. But any additional cost will be more than offset by less frequent Pap testing.

Q: Who should be getting Merck’s HPV Gardasil vaccine?

Dr. Waxman: The highest priority is to vaccinate women who are not yet sexually active, although I recommend it for all young women up to age 26. The vaccine is effective against four viral types—HPV types 16 and 18, which together cause approximately 70% of cervical cancers, and HPV types 6 and 11, which together cause approximately 90% of genital warts. Even if a woman has been exposed to one strain of HPV, it is still reasonable to give her the vaccine because it will protect her against the other types. Many health insurance plans are paying all or most of the cost for the three-part series ($300-$500). The American Academy of Pediatrics has proposed that children come in for a regular preadolescent visit, but that’s not yet ingrained in pediatric practice. Also, this vaccine requires three visits, which could limit its use as well.

Dr. Young: Gardasil is recommended for girls and women aged 9-26, regardless of sexual activity. As with any vaccine, the more people vaccinated the better, and the younger they are vaccinated the better.

Q: What do you think of liquid cytology, which spreads cells more evenly on slides?

Dr. Waxman: Liquid cytology is a very effective system. Its ease of use with reflexive HPV testing makes it convenient and cost-effective because you can get one sample of cells for both the Pap and HPV tests. In the past, women had to come back for a second visit to get an HPV test. But with the ability to perform the HPV test using residual material from the liquid Pap, clinicians are getting a much higher compliance rate.

Dr. Young: I have not done a traditional Pap for at least seven years. Liquid cytology is a great improvement. It’s much more accurate and easier to interpret because mucus and WBCs are siphoned off during the centrifuging process.

Q: Are the ACS Pap test guidelines still appropriate for liquid cytology? Are there any exceptions?

Dr. Young: The ACS Pap test guidelines are good, but there are always exceptions and gray areas. In women who are HIV-positive or undergoing cancer treatment, I suggest yearly Pap tests plus annual HPV testing. And we’ll have to watch for changes to the ACS guidelines in the future.

Q: If Pap testing becomes less widespread, will it dampen women’s motivation to come to primary-care providers for annual checkups?

Dr. Waxman: It’s very important for primary-care providers to educate patients about the difference between a Pap test and the rest of the primary-care visit. Providers should tell their patients, “Even when I’m not testing for cervical cancer, it is still important for you to come back each year so we can check your ovaries, lipid profile, and BP, and evaluate for possible diabetes, and also so we can talk about family planning or menopausal changes.”

Dr. Young: Hopefully, patients will still come in regularly. Even if they’re not having Pap tests, women should have their ovaries and uterus checked. They should also come in for breast exams and to discuss other things that may come up.

Q: What will cervical cancer screening guidelines be five or 10 years from now?

Dr. Waxman: I don’t think we’ll see a dramatic change in the next five years. However, our understanding of what causes cervical cancer has changed over the past decade or so, the technology has exploded, and the cervical-cancer screening industry is moving in some remarkable ways. For example, the FDA has approved a spectroscopy device that measures the way light is reflected off the cervix as a means of detecting the presence of precancerous cells. So 10 years from now, it may be a whole new ballgame.

Ms. Edmondson Gupta is a senior editor with The Clinical Advisor.