Too much emphasis on screening interval, too little on safety

May 2003
R. Marshall Austin, MD, PhD

The American Cancer Society screening guidelines for the early detection of cervical neoplasia and cancer were updated last year based on recommendations from a formal review and workshop.¹ The new guidelines have raised serious questions about their impact on cervical cancer incidence and death rates in the United States.

The “evidence-based” review process spanned more than a year and consisted of three work groups. Among the several dozen invited experts who were members of the work groups, only six were pathologists, and of those six, only a few were actively practicing cytopathologists. Joan Jones, MD, and Diane Solomon, MD, were the pathologists on the 10-member Gynecologic Cancer Advisory Group. I was the only pathologist among the 15 members of the Work Group on Interval, Older Women, and Hysterectomy. Drs. Solomon and Jones and Diane Davey, MD, Edward Wilkinson, MD, and Thomas Wright, MD, were the pathologists on the 14-member Work Group on Technologies. The vast majority of the reviewers had an epidemiological perspective, and many of them had participated in the recently concluded deliberations of the U.S. Preventive Services Screening Task Force.

I and several of the pathologists found ourselves in a small subgroup that tried to increase the attention paid to individual patient safety and choice. Our small subgroup was referred to in some ACS staff messages as “the advocates.” Early in the work group process we tried repeatedly to emphasize the ACS mission statement: “The American Cancer Society is a nationwide, community-based, voluntary, health organization that is dedicated to eliminating cancer as a major health problem by preventing cancer, saving lives, and diminishing suffering from cancer through research, education, advocacy, and service.”

Although many of the recommendations have raised controversy, the screening-interval recommendation may prove to be the most provocative. That recommendation is as follows: “After initiation of screening, cervical screening should be performed annually with conventional cervical cytology smears or every two years using liquid-based cytology; at or after age 30, women who have had three consecutive, technically satisfactory normal/negative cytology results may be screened every two to three years (unless they have a history of in utero DES exposure, are HIV+, or are immunocompromised by organ transplantation, chemotherapy, or chronic corticosteroid treatment.” Citing an abstract of an oral presentation as evidence, the discussion states: “Further, it is important to note that there is an irreducible risk of cervical cancer in the United States. If all women were screened annually, it is estimated [I presume from older data using conventional Pap smears] that there would be 1.5 cases of cervical cancer per 100,000 women having a negative cytology result within 0 to 18 months and at least three prior consecutive normal/negative results.” No assessment is made of how the new, more sensitive screening technologies could improve the “irreducible risk of cervical cancer.”

Regarding liquid-based cytology, the discussion says: “There are currently no data to support a particular screening interval for LBP [liquid-based Paps]. This recommendation was based on modeling by two independent researchers^2,3 [Evan Myers, MD, MPH, unpublished data] as well as expert opinion based on the existing data.” All currently available FDA-approved liquid-based Pap test formulations have not yet been recognized by the FDA as able to reliably and significantly increase high-grade squamous intraepithelial lesion detection,⁴ but this was not considered in the generic “liquid-based Pap technology” recommendations. Also, two published peer-reviewed manufacturer-funded modeling studies on the population impact of screening with more sensitive technology, one from Harvard⁵ and the other from Johns Hopkins,⁶ were not considered or referenced as evidence in the ACS publication.

Since 1990, there have been concerted federally funded efforts in the National Breast and Cervical Cancer Early Detection Program to increase the proportion of the U.S. population that undergoes regular Pap screening.⁷ Healthy People 2000, a goal-setting white paper published in 1990 by the Department of Health and Human Services, listed as an objective to “increase to at least 95 percent the proportion of women aged 18 and older with a uterine cervix who have ever received a Papanicolaou test, and to at least 85 percent those who received a Papanicolaou test within the preceding 1 to 3 years.”⁸ Despite success in increasing the number of women screened as measured by the behavioral risk factor surveillance system,⁹ the U.S. fell significantly short of meeting the Healthy People 2000 goals for decreasing cervical cancer. The goals have been updated in a still more ambitious Healthy People 2010 plan.

The Harvard model study⁵ employed the known current frequency of cervical screening of U.S. women and therefore assumed that 34.5 percent of the population is screened annually, 25.3 percent is screened biennially, 10.5 percent is screened triennially, 11 percent each is screened about every five years or every 10 years, and 7.5 percent is never screened. The model reflects that the largest group of U.S. women are now screened annually and predicts that annual screening, compared with biennial or triennial screening, can decrease population cervical cancer rates by a substantial relative percentage,⁵ a predicted benefit of annual screening reflected in outcomes data from a recent Northern California Kaiser Permanente study on the impact of screening interval.¹⁰

The Johns Hopkins model study⁶ used the Harvard study model and was led by the late F.J. Montz, MD, head of gynecologic oncology at Johns Hopkins. The study concluded that liquid-based cytology used at current rates of screening has the potential to decrease the incidence of cervical cancer by more than 30 percent and achieve Healthy People 2010 goals. The model also suggests, however, that rates of screening less frequent than current screening rates—as advocated in the new ACS guidelines—
will inevitably impede progress toward these still elusive national cervical cancer goals.

Thus, the ACS guidelines appear to view more sensitive screening methods only as a means to lengthen screening intervals rather than as an opportunity to reach ambitious Healthy People 2010 goals for lowering cervical cancer rates. This lack of focus on the ACS mission, which emphasizes reducing cancer and cancer-related suffering, is of concern to patient safety advocates. In fact, the Johns Hopkins model study concludes that using liquid-based cytology would be cost-effective in improving outcomes from cervical cancer in all populations and particularly cost-effective in high-risk populations.⁶ Many epidemiologic evaluations tend to minimize the significance of substantial percentage decreases in the relative rate of cervical cancer achieved with improved methods as of little consequence in the context of the “low absolute rate” of developing cervical cancer with traditional methods.¹⁰ An implication of this “context” is that either the additional preventable cancers are of little interest to screened women or that preventing the additional cancers is too costly.

The ACS report acknowledges in closing “the importance of flexibility for women and their providers in the context of informed decision-making. Individual patients will have different perceptions of risk and risk tolerance that may affect their choice of screening interval, screening test, and whether to discontinue screening after a certain age.” It remains to be seen whether cost-conscious third-party payers will respect the ACS document’s brief concluding reference to the desirability of patient and physician choice in selecting optimal screening intervals and methods. Or will payers use the more prominent ACS guideline recommendations as justification to remove a woman’s opportunity to choose frequent screening intervals and more sensitive test methods to achieve the lowest possible risk of developing cervical cancer?

References

1. Saslow D, Runowicz CD, Solomon D, et al. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin. 2002;52:342-362.
2. Kim JJ, Wright TC, Goldie SJ. Cost-effectiveness of alternative triage strategies for atypical squamous cells of undetermined significance. JAMA. 2002;287:2382-2390.
3. Goldie SJ, Kim JJ, Wright TC. Decision analytic modeling to inform U.S. national health policy: new guidelines for cervical cancer screening. Oral presentation at national Society for Medical Decision Making meeting 2002. Accessed April 2, 2003.
4. ACOG Technology Assessment in Obstetrics and Gynecology. Cervical Cytology Screening. No. 2, December 2002.
5. Hutchinson ML, Berger BM, Farber FL. Clinical and cost implications of new technologies for cervical cancer screening: the impact of test sensitivity. Am J Manag Care. 2000;6:766-780.
6. Montz FJ, Farber FL, Bristow RE, et al. Impact of increasing Papanicolaou test sensitivity and compliance: a modeled cost and outcomes analysis. Obstet Gynecol. 2001;97:781-788.
7. The National Breast and Cervical Cancer Early Detection Program At-a-Glance. Washington, DC: U.S. Department of Health and Human Services.
8. Healthy People 2000 Review. Washington, DC.: U.S. Department of Health and Human Services.
9. Blackman DK, Bennett EM, Miller DS. Trends in self-reported use of mammograms (1989–1997) and Papanicolaou tests (1991–1997)—Behavioral Risk Factor Surveillance System. MMWR CDC Surveill Summ. 1999;48:1-22.
10. Miller GM, Sung HY, Sawaya GF, et al. Screening interval and risk of invasive squamous cell cervical cancer. Obstet Gynecol. 2003;101:29-37.

Dr. Austin is medical director and director of cytopathology and gynecologic pathology services for Coastal Pathology Laboratories, Charleston, SC.