Screening for cervical cancer
Burden of Suffering
Approximately 13,000 new cases of cervical cancer are diagnosed each year, and about 7, 000 women die of this disease annually.(1 ) Although the five-year survival rate is about 90 percent for women with localized cervical cancer, it is considerably lower (about 40 percent) for women with advanced disease. (1 ) The incidence of invasive cervical cancer has decreased significantly over the past 40 years, in large part because of organized early detection programs.(2 )
Although all sexually active women are at risk for cervical cancer, the disease is more common among women of low socioeconomic status and those with a history of multiple sexual partners or early onset of sexual intercourse. (3-5)
Efficacy of Screening Test
The principal screening test for cervical cancer is the Pap smear. Precise data on the sensitivity and specificity of this test are lacking, because of methodologic problems. Depending on study design, false-negative rates of 1 to 80 percent have been reported,( 7) ; a range of 20 to 45 percent has been quoted most frequently, primarily in studies comparing normal test results with subsequent smears.(8-12) Although reliable data are lacking, specificity is probably greater than 90 percent(7 ) and may be as high as 99 percent. (12)
The test-retest reliability of Pap smears is also influenced by variations in the expertise and procedures of cytopathology laboratories. A significant proportion of diagnostic errors may be attributable to laboratory error. In one study of more than 300 laboratories given slides with known cytologic diagnoses,(6 ) false-negative diagnoses were made in 7.5 percent of smears with moderate dysplasia or frank malignancy, and false-positive diagnoses were made in 8.9 percent of smears with no more than benign atypia.
Important potential adverse effects are associated with errors in the interpretation of Pap smears. False-negative results are of significance because carcinoma in situ or more invasive lesions may escape detection and progress to more advanced disease during the period between tests. The potential adverse effects of false-positive results include patient anxiety regarding the risk of cervical cancer, as well as the unnecessary inconvenience, discomfort and expense of follow-up diagnostic procedures.
Effectiveness of Early Detection
Early detection of cervical neoplasia provides an opportunity for the physician to prevent or delay progression to invasive cancer by performing clinical interventions such as colposcopy, conization, localized excision and, when necessary, hysterectomy.(13) Evidence suggests that early detection (through routine Pap testing) and treatment of precursor cervical intraepithelial neoplasia can lower mortality from cervical cancer. Correlational studies in the United States, Canada and several European countries comparing cervical cancer data over time have shown dramatic reductions in the incidence of invasive disease following the implementation of cervical screening programs. (14-19)
Case-control studies, which have shown a strong negative association between screening and invasive disease, also suggest that screening is protective.(20-23) These observational studies do not constitute direct evidence that screening is responsible for the findings,(24) and randomized controlled trials to provide such evidence have not been performed. Nonetheless, the large body of supportive evidence accumulated to date has prompted the adoption of routine cervical cancer screening in many countries and makes performance of a controlled trial of Pap smears unlikely for ethical reasons.
The effectiveness of cervical cancer screening increases when Pap testing is performed more frequently.(2,21) Aggressive dysplastic and premalignant lesions are less likely to escape detection when the interval between smears is short. There are, however, diminishing returns as frequency is increased.(2,20,25) Although studies have shown that reducing the interval between Pap smears from ten to five years is likely to achieve a significant reduction in the risk of invasive cervical cancer, case-control studies and mathematical modeling have demonstrated that reducing the interval even further, to two to three years, offers only a slight added benefit.(2-5,20) There is little evidence that women who receive annual screening are at significantly lower risk for invasive cervical cancer than are women who are tested every three to five years.
These findings were confirmed in a major study(26) of eight cervical cancer screening programs in Europe and Canada that involved over 1.8 million women. According to this report, the cumulative incidence of invasive cervical cancer was reduced 64.1 percent when the interval between Pap tests was ten years, 83.6 percent at five years, 90.8 percent at three years, 92.5 percent at two years and 93.5 percent at one year These estimates were for women aged 35 to 64 who had at least one screen before age 35, and they are based on the assumption of 100 percent compliance.
Recommendations of Others
Although inconsistent guidelines on Pap testing have been issued in the past, a general consensus recommendation was adopted recently by the American Cancer Society, the National Cancer Institute, the American College of Obstetricians and Gynecologists, the American Medical Association, the American Nurses Association, the American Academy of Family Physicians and the American Medical Women’s Association.(27)
The consensus guideline recommends annual Pap smears for all women who are or have been sexually active or who have reached age 18. The recommendation permits less frequent Pap testing once three or more annual smears have been normal and if recommended by the physician. These organizations did not recommend an age at which to discontinue Pap testing.
The 1980 National Institutes of Health Consensus Development Conference on Cervical Cancer Screening(3 ) and the 1982 Canadian Task Force on Cervical Cancer Screening Programs(28) recommended that Pap testing begin when a woman becomes sexually active or reaches age 18, and that it be discontinued at age 60 if previous screening has been adequate and Pap smears have been consistently negative. The consensus conference recommended an interval of one to three years after two normal annual smears. The Canadian Task Force recommended annual Pap testing until age 35, followed by rescreening every five years.
Performing Pap tests every year rather than every two to three years has important economic implications, since a policy of annual screening could double or triple the total number of smears taken for more than 77 million American women at risk.(29) Although at least some epidemiologic data support Pap testing as frequently as every two to three years,(5,20) annual testing appears to be of limited additional benefit in lowering mortality. (26) It has been estimated that screening women aged 20 to 64 every three years reduces the cumulative incidence of invasive cervical cancer by 91 percent, requires about 15 tests per woman, and yields 96 cases of cervical cancer for every 100,000 Pap smears. Annual screening reduces incidence by 93 percent but requires 45 tests per woman and yields only 33 cases of cervical cancer for every 100,000 tests.(26)
Annual testing, however, is common. A survey of recently trained gynecologists found that 97 percent recommend that women have Pap tests at least once a year. The preference of many clinicians for annual Pap smears is based on concerns that less frequent testing may result in more harm than good, but reliable scientific data to support these concerns are lacking. Specifically, advocates of annual testing have expressed concerns that data demonstrating little added value in annual tests are based on retrospective studies and mathematical models that are subject to biases and invalid assumptions; that an interval longer than one year may permit aggressive, rapidly growing cancers to escape early detection; that women may obtain Pap smears at an even lower frequency than that publicized in recommendations; that a longer interval might affect compliance among high-risk women, a group with poor coverage even with an annual testing policy; that repeated testing may offset the false-negative rate of the Pap smear; that the test is inexpensive and safe, and that a large proportion of women believe it is important to have an annual Pap test and, while visiting the clinician, may receive other preventive interventions.(31) Definitive evidence to support these concerns is lacking.
Women who do not engage in sexual intercourse are not at risk for cervical cancer and therefore do not require screening.(3,4,28) In addition, screening of women who have only recently become sexually active (e.g., adolescents) is likely to have low yield. The incidence of invasive cancer in women under age 25 is only about one to three per 100,000, a rate much lower than that for older age groups.(12) One study (4 ) found that most women with cervical intraepithelial neoplasia who had become sexually active at age 18 were not diagnosed as having severe dysplasia or carcinoma in situ until age 30.
Although invasive cervical cancer is uncommon at young ages, a number of authorities advocate initiating screening with the onset of sexual activity.(3,27,28) This policy is based in part on the concern that a proportion of young women with cervical intraepithelial neoplasia may have an aggressive cell type that can progress rapidly and undetected if screening is delayed. The exact incidence and natural history of aggressive disease in young women remains uncertain, however.
Another reason given for early screening is the concern that the incidence of cervical dysplasia in young women appears to be on the rise, coincident with the increasing sexual activity of adolescents. On these grounds, testing should begin by age 18, since about 60 percent of American teenagers are sexually active by this age.(32) Screening in the absence of a history of sexual intercourse may be justified if the credibility of the sexual history is in question.
When screening is initiated, it is frequently recommended that the first two to three smears be obtained one year apart as a means of detecting aggressive tumors at a young age. There is little evidence to suggest, however, that young women whose first two tests are separated by two or three years, rather than one year, have a greater mortality or person-years life lost.(2 ) Recommendations to perform these first tests annually are based primarily on expert opinion.
Elderly women do not appear to benefit from Pap testing if repeated cervical smears have consistently been normal.(2,4,28) Many older women have had inadequate screening, however; nearly half of women over age 65 have never received a Pap test and 75 percent have not received regular screening.(33,34) Screening beyond age 65 in this group of older women is important (2,34) and has been shown to be cost-effective.(35)
The effectiveness of cervical cancer screening is more likely to be improved by extending testing to women who are not currently being screened and by improving the accuracy of Pap smears than by increasing the frequency of testing. Studies suggest that those at greatest risk for cervical cancer are the very women least likely to have access to testing.(33,36) Inadequate Pap testing is most common among blacks, the poor and the uninsured, the elderly and those living in rural areas. In addition, many women who are tested receive inaccurate results because of interpretive or reporting errors made by cytopathology laboratories or specimen collection errors made by clinicians. (37) The failure of some physicians to provide adequate follow-up for abnormal Pap smears is another source of delay in the management of cervical dysplasia.(37)
Regular Pap smears are recommended for all women who are or have been sexually active. Testing should begin when the woman first engages in sexual intercourse. Adolescents whose sexual history is thought to be unreliable should be presumed to be sexually active at age 18. Pap tests are appropriately performed at an interval of one to three years, to be recommended by the physician on the basis of risk factors (e.g., early onset of sexual intercourse, history of multiple sexual partners, low socioeconomic status). Pap smears may be discontinued at age 65, but only if the physician can document previous Pap screening in which smears have been consistently normal. Physicians should submit specimens to laboratories that have adequate quality control measures, to ensure optimal accuracy in the interpretation and reporting of results. Thorough follow-up of test results should also be ensured.
Information about this report may be obtained from the Office of disease Prevention and Health Promotion National Health Information Center, R 0. Box 1133, Washington, DC20013-1133. Phone: (800) 336-4797; in Maryland, (301) 565-416%
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