Too much emphasis on screening interval, too little on safety
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 researchers2,3 [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?
- 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.
- Kim JJ,
Wright TC, Goldie SJ. Cost-effectiveness of alternative triage
strategies for atypical squamous cells of undetermined significance.
- 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.
- ACOG Technology
Assessment in Obstetrics and Gynecology. Cervical Cytology Screening.
No. 2, December 2002.
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.
- 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.
- The National
Breast and Cervical Cancer Early Detection Program At-a-Glance.
Washington, DC: U.S. Department of Health and Human Services.
People 2000 Review. Washington, DC.: U.S. Department of Health
and Human Services.
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.
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.