Improve cervical cancer screening: Review new terminology, guidelines

Use information for better reporting and treatment of cervical abnormalities

Information in two just-published articles is expected to improve care for women with abnormal Pap test results.1,2 The two articles, published in the April 24, 2002, issue of the Journal of the American Medical Association (JAMA) include the overview of the revised system for reporting the results of Pap tests, known as the 2001 Bethesda System, as well as new national consensus guidelines designed to better evaluate women whose Pap tests suggest they may have abnormal cells that may lead to cervical cancer. (Both articles may be viewed free of charge at the JAMA web site, Click on "past issues," "April 24, 2002," then the article titles to read the articles on-line.)

The new reporting system is designed to decrease the number of ambiguous results, so providers will need to recommend follow-up testing for a smaller percentage of women. The guidelines give clinicians options to use new technologies to clarify ambiguous cytology results, including liquid-based cytology and DNA testing for human papillomavirus (HPV).

Cervical cancer is the second-leading cause of cancer-related death among women worldwide; in the United States, about 13,000 new cases are reported each year, resulting in 4,100 deaths.3 Pap tests represent an important tool in cancer screening and detection; some 50 to 60 million U.S. women are screened each year with the method.3

The 2001 Bethesda System and the management guidelines represent the best way for women to be reassured that they are receiving management and care based on the best available evidence, says Diane Solomon, MD, senior investigator at the Bethesda, MD-based National Cancer Institute. Solomon served as coordinator of the Bethesda System and as an investigator in the Atypical Squamous Cells of Undetermined Significance/ Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS) Trial, which examined options in managing treatment of women with abnormal Pap tests.

The Bethesda terminology and the management guidelines provide more uniform and evidence-based care of women with abnormal Pap tests, says Solomon.

"That is why it is important for clinicians taking care of women to understand the terminology, as well as how that fits in with the guidelines," she notes. "I think the fact that the terminology and the guidelines have been developed in concert with one another actually provides a more seamless management strategy for clinicians to follow."

It is critical that clinicians understand the changes incorporated in the 2001 Bethesda System so that the clinician and the cytopathologist are speaking the same language, maintains Michael Policar, MD, MPH, associate clinical professor of obstetrics, gynecology, and reproductive sciences at the school of medicine at the University of California, San Francisco, and vice president for medical affairs at NorthBay Healthcare System in Fairfield, CA. Policar addressed the changes in his lecture, "New Developments in Cervical Cancer Screening and Abnormal Pap Smear Management: Bethesda III and ALTS Trial," at the 2002 Contraceptive Technology conferences.

"One of the main purposes for maintaining the Bethesda System is to improve consistency in both the interpretation and management of cervical cancer screening tests," reflects Policar. "Use of the system has helped to reduce variation in interpretation between cytopathology labs as well as in clinician management, and the 2001 modifications should lead to further improvements."

Until now, there have not been uniform standards defining the best way to manage women with abnormal Pap tests, observes Thomas Wright Jr., MD, lead author of the consensus guidelines and associate professor of pathology at the New York City-based Columbia University College of Physicians and Surgeons. As a result, women with abnormal Pap tests may be managed quite differently depending on whom and where they are seen.

"This can lead to inequities in health care such that poor women receive different care than do women with access to the newest technologies," says Wright. "It can also lead to confusion and anxiety; to overtreatment, placing women at risk for injury, and to undertreatment, placing women at risk for the development of cervical cancer."

New technology included

One important change in the 2001 Bethesda System is its recognition of "liquid-based" collection technology. Two companies manufacture liquid-based cytology test kits: Cytyc Corp. of Boxborough, MA, and TriPath Imaging of Burlington, NC. (See resource box on p. 75 for contact info. Contraceptive Technology Update reviewed information on Cytyc Corp.’s ThinPrep Pap Test in its article, "More effective Pap test now available" in its March 1997 issue, p. 35.)

Previous versions of the Bethesda System required an evaluation of whether the specimen was considered adequate, but the criteria were based on the conventional smear and did not address the new technology. The 2001 Bethesda System incorporates criteria that are specific to the new cell collection method.

The consensus guidelines offer precise management strategies based on liquid-based cytology. One of the most important recommendations addresses care of women with the most common type of abnormal Pap test, an inconclusive result referred to as ASC-US or atypical squamous cells of undetermined significance.

Before the guidelines were issued, clinicians would follow women with several repeat Pap tests or with colposcopy. The new guidelines say that while these approaches still may be used, HPV testing is preferred whenever liquid-based Pap tests are used.

If liquid-based cytology is used, the laboratory can test the same sample used for the original Pap test for HPV, eliminating the need for a repeat provider visit. Known as "reflex" testing, this form of testing quickly reassures women who are HPV-negative they are unlikely to have a high-grade lesion and that they simply need regular Pap tests. Women who are HPV-positive are identified and scheduled for further evaluation. Just-published research indicates that reflex HPV DNA testing provides the same or greater life-expectancy benefits and is more cost-effective than other management strategies for women diagnosed as having ASC-US.4 (HPV testing kits are manufactured by Digene Corp. of Gaithersburg, MD; see resource box, above. Review HPV DNA test information in the article, "HPV DNA tests: Studies target use for cancer screening," included in the May 2000 STD Quarterly inserted in CTU.)

The approach of using reflex HPV DNA testing allows 50% of women with ASC-US who are found to be HPV DNA negative to return for annual cytological screening without having to return for additional testing, says Wright.

More than 60% of all Pap tests in the United States are liquid-based, and this number is considerably higher in the private sector, says Wright. He predicts an almost complete conversion to liquid-based cytology within the next two years.

New term flags cases

The older Bethesda System grouped all cells considered equivocal — atypical but not clearly precancerous — into the ASCUS category. The 2001 Bethesda System adds a new category for atypical cells at higher risk of association with precancer: atypical squamous cells — cannot exclude a high-grade lesion (ASC-H). By highlighting such cases, the new system should help providers detect and treat precancerous lesions more rapidly. In addition, the term "atypical squamous cells favor reactive" has been eliminated to focus attention on women at higher risk of having an abnormality.

The ASC-H category is useful because it highlights a group of women who are at increased risk for underlying high-grade lesions, says Solomon. The need for such a category was demonstrated in the findings of the ALTS trial, she notes.5

"The addition of the ASC-H category hopefully will simplify the management of women with ASC smears, in addition to prompting colposcopy referral for women with ASC findings who are most likely to have high-grade SIL [squamous intraepithelial lesion]," says Policar.

The 2001 Bethesda System also includes changes in how specimens are categorized. The new terminology uses three streamlined categories — "negative," "epithelial cell abnormality," and "other" — to depict whether a result is negative or positive. Whenever a report indicates either "epithelial cell abnormality" or "other," it will offer additional interpretations and diagnoses.

While the new terminology and management guidelines represent important strides in medical care, the emphasis should remain on screening women for cervical cancer, says Solomon.

"We focus on new technologies in screening and management of the abnormal Pap test, but what we can never forget is that in order to have the greatest impact on decreasing mortality from cervical cancer, we need to screen women who aren’t currently being screened," she notes. "[Providers who work in clinic settings] need to be given a pat on the back and an extra note of congratulations because they are really on the forefront of trying to reduce cervical cancer mortality by screening women who may otherwise fall through the cracks."


1. Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda System: Terminology for reporting results of cervical cytology. JAMA 2002; 287:2,114-2,119.

2. Wright Jr. TC, Cox JT, Massad LS, et al. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities. JAMA 2002; 287:2,120-2,129.

3. American Society for Colposcopy and Cervical Pathology. Frequently Asked Questions. Accessed at:

4. Kim JJ, Wright Jr. TC, Goldie SJ. Cost-effectiveness of Alternative Triage Strategies for Atypical Squamous Cells of Undetermined Significance. JAMA 2002; 287:2,382-2,390.

5. Sherman ME, Solomon D, Schiffman M. Qualification of ASCUS. A comparison of equivocal LSIL and equivocal HSIL cervical cytology in the ASCUS LSIL Triage Study. Am J Clin Pathol 2001; 116:386-394.


For information on liquid-based cytology test kits, contact:

For information on HPV testing kits, contact:

  • Digene Corp., 1201 Clopper Road, Gaithersburg, MD 20878. Telephone: (800) 344-3631 or (301) 944-7000. Fax: (301) 944-7121. E-mail: Web: