National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
May 31, 2011 • Volume 8 / Number 11

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Special Report

HPV and Pap Co-Testing Safely Extend Cervical Cancer Screening Intervals

For many women, the yearly visit to their gynecologist or primary care physician includes a Pap test to screen for cervical cancer or lesions that are precursors to the disease. A growing body of evidence, however, has shown that for many women, annual cervical screening—particularly if it also includes a test that detects the presence of cancer-causing types of human papillomavirus (HPV)—is unnecessary.

Several gynecologic health and oncology groups have recommended 3-year intervals for cervical cancer screening in women age 30 and older who have a normal Pap test and negative HPV test. The recommendations, however, have not been widely implemented in common clinical practice.

A reconstruction of a papillomavirus (Image courtesy of Dr. Benes Trus, NIH Center for Information Technology) The HPV test used for cervical cancer screening detects the presence of high-risk HPV types, similar to the papillomavirus pictured above. (Image courtesy of Dr. Benes Trus, NIH Center for Information Technology)

Results from a large study of routine clinical practice at Kaiser Permanente Northern California, presented May 18 during a press briefing for the upcoming American Society of Clinical Oncology (ASCO) annual meeting, provide perhaps the strongest confirmation yet that an annual Pap test is no longer a necessity. In women 30 years of age or older who had a normal Pap test and a negative HPV DNA test result, very few cancers or precancerous changes were detected in the following 3-year period, the study found.

“To the extent that there is fear about cancer risk in a 3-year screening interval, our study reassures clinicians and their patients that this interval is safe,” said the study’s lead investigator, Dr. Hormuzd Katki of NCI’s Division of Cancer Epidemiology and Genetics (DCEG).

The study found that the Pap test did not substantially modify the extremely low cancer risk for HPV-negative women. But for HPV-positive women, the Pap test did help better identify women at high risk of cancer. As such, Dr. Katki said, the findings also “present a strong hypothesis” that the HPV test could be conducted first, and, if it is negative, women could be asked to return in 3 years. If the HPV test is positive, the Pap test could help determine whether a woman should undergo a colposcopy to examine the cervix for signs of cancer.

“But we’ll need more study and evaluation of this possibility in routine clinical practice before we can be sure,” he said.

A Real-World Study

The study is particularly important because it comes from a “real-world experience,” said ASCO President Dr. George Sledge during the press briefing. It involved more than 330,000 women in the Northern California region of Kaiser Permanente, a large managed care organization, making it the largest analysis of its kind to date.

“This study tells us where we’re going with cancer screening,” he continued, with the practice transitioning from “an ancient technique such as cytopathology to more molecularly based techniques that allow us to actually look at the specific cause of cancer in patients with cervical carcinoma.”

The women in the study had voluntarily enrolled in an HPV/Pap co-testing program launched by Kaiser in 2003. Every woman in the program was screened annually. Women with a normal Pap test result and a negative HPV test result had an extremely low 5-year cancer rate, 3.2 cancers per 100,000 women per year. Screening with just the HPV test was nearly as effective, with 3.8 cancers per 100,000 women per year. Risk estimates for women with a normal Pap test alone were nearly double: 7.5 cancers per 100,000 women per year.

Compared with a positive Pap test done alone, a single positive HPV test done alone was associated with a greater likelihood of finding cancer or a precancerous lesion after 5 years, meaning that the HPV test allowed for the earlier detection of cervical cancer or precancers.

However, Dr. Katki stressed, a positive Pap test did provide important information in women who also had a positive HPV test, increasing the likelihood of finding women with established cancer or the types of cervical lesions most likely to become cancer.

Enough to Tip the Balance?

Even with clinical guidelines recommending co-testing and longer screening intervals and the continued accumulation of data in support of these recommendations, changing physician behaviors has been very difficult, said Dr. Howard Jones, director of Gynecologic Oncology at Vanderbilt-Ingram Cancer Center in Nashville, TN. Although there is some evidence to suggest that clinicians have modestly increased their use of HPV testing in concert with the Pap test, studies also indicate that many have been reluctant to stretch screening intervals beyond 1 year.

Both the slow uptake of HPV testing and the failure to expand screening intervals can be attributed to several factors, Dr. Jones continued. One of the most prominent reasons for the latter is that many women have come to expect an annual Pap test.

Physicians can tell their patients who have negative results on both tests that they don't need to be screened again for cervical cancer for 3 years.

—Dr. Howard Jones

Physicians can tell their patients who have negative results on both tests that they don’t need to be screened again for cervical cancer for 3 years, he said, but “when those patients come back the next year, and I tell them we don’t have to do a Pap test, they often say ‘No, I want the test.’” He continued, “As a physician, I can argue with a woman for 10 minutes, but I’ve got 10 more patients to see that morning. Many physicians will just do the test and save the time and frustration.”

Physician reluctance to expanding screening intervals has also been linked to fears that women won’t come in for annual check-ups.

“The problem that many OB/GYNs [obstetrician/gynecologists] have [with longer intervals] is that many women largely think the only reason to go to a doctor is for a Pap test,” said Dr. Ellen Smith, a gynecologic oncologist with Texas Oncology in Austin. “For many women, that’s the only time they get their blood pressure checked, their weight checked, just get a general physical.”

A substantial proportion of women already fail to see a primary care physician or OB/GYN regularly, Dr. Smith continued. “So what will it be like if the [cervical cancer] screening interval is every 3 years?”

In the meantime, Dr. Smith stressed, there also needs to be an intense focus on the other side of the coin: ensuring that girls and young women get the HPV vaccine to help prevent cervical cancer in the first place and increasing the number of women who are screened regularly. More than half of women diagnosed with cervical cancer haven’t been screened in the previous 5 years, she said.

Because the current HPV vaccines will prevent only about 70 percent of cervical cancers, Dr. Katki stressed, current guidelines recommend that women who are vaccinated should still be screened.

On all of these issues, Dr. Jones said, “We really do need to educate the doctors, educate the patients, and keep pushing forward.”

Carmen Phillips

Further Reading: Cervical Cancer Screening Approach Slowly Shifting

Current Cervical Cancer Screening Recommendations  

The three most commonly cited sets of recommendations for cervical cancer screening were developed by the American Cancer Society (ACS), the American Congress of Obstetricians and Gynecologists (ACOG), and the U.S. Preventive Services Task Force (USPSTF). The chart below, adapted from a CDC resource, compares key aspects of all three guidelines.

Screening Method & IntervalsACS
2002
USPSTF
2003
ACOG
2009
Conventional cytologyAnnually; every 2–3 years for women age ≥ 30 years with a history of 3 negative cytology tests.* Sexual history should not be used as a rationale for more frequent screening.At least every 3 yearsEvery 2 years from age 21–29 years; every 3 years for women age ≥ 30 years with a history of 3 negative cytology tests.*
Liquid-based cytologyEvery 2 years; every 2–3 years for women age ≥ 30 years with a history of 3 negative cytology tests.* Sexual history should not be used as a rationale for more frequent screening.Insufficient evidenceEvery 2 years from age 21–29 years; every 3 years for women age ≥ 30 years with a history of 3 negative cytology tests.*
HPV co-test (cytology + HPV test)Not recommended under age 30. Age ≥ 30 years, no more than every 3 years if HPV negative, cytology normal. Sexual history should not be used as a rationale for more frequent screening.Insufficient evidenceAge ≥ 30 years, no more than every 3 years if HPV negative, cytology normal, even with new sexual partners. Not recommended for women younger than 30 years.
Primary HPV testingNot FDA approvedNot FDA approvedNot FDA approved

* Some exceptions apply (e.g., women who are immunocompromised, have a history of prenatal exposure to the synthetic hormone DES, are HIV positive, have previously been treated for CIN 2 or 3, cancer, etc.)

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