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ORIGINAL RESEARCH |
From the Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Division of Cancer Prevention and Control, Atlanta, Georgia; and Information Management Services, Inc, Silver Spring, Maryland.
Address reprint requests to: Vicki B. Benard, PhD, Epidemiology and Health Services Research Branch, Division of Cancer Prevention and Control, Mailstop K-55, NCCDPHP, CDC, 4770 Buford Highway NE, Atlanta, GA 30341; e-mail: vdb9{at}cdc.gov.
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ABSTRACT |
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 ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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METHODS: We analyzed data from 750,591 women who received their first Papanicolaou (Pap) test in the program between July 1995 and March 2001.
RESULTS: Nearly 85% of the women were aged 40 years or older. Almost half were members of racial or ethnic minority groups. Overall, the percentage of abnormal Pap test results decreased with increasing age. The rates of cervical intraepithelial neoplasia (CIN) were highest in the younger age groups but the rate of invasive cancer increased with age. White women had the highest age-adjusted percentage of abnormal Pap test results and the highest rate of biopsy-confirmed CIN 2 or worse.
CONCLUSIONS: In this nationwide screening program, only 7% of all biopsy-confirmed high-grade cervical lesions (CIN 2 or worse) were invasive cancer. This underscores the success of Pap screening in identifying preinvasive disease and preventing cancer.
LEVEL OF EVIDENCE: II-3
Cervical cancer typically develops over many years after initial infection with oncogenic types of the human papillomavirus (HPV).10 The peak incidence of HPV infection is usually soon after initiation of sexual activity and is closely followed by a peak in the incidence of low-grade cervical lesions.10 Most HPV infections and associated low-grade lesions regress without treatment, but for some women they ultimately progress to high-grade lesions.11 The incidence of high-grade lesions occurs among women in their late 20s and early 30s, a median of 5–10 years after the peak of HPV infection and occurrence of low-grade cervical intraepithelial neoplasia (CIN).10 On average, cases of invasive cancer occur a decade or more later, and most invasive cervical tumors are diagnosed after the age of 45 years.10 Correspondingly, the risk of dying and death rates are greatest for those aged 45 years and older, notwithstanding the widespread perception that cervical cancer is a disease of younger women.
In response to federal health objectives on cervical cancer screening, the U.S. Congress passed the Breast and Cervical Cancer Mortality Prevention Act of 1990 (Public Law 101–354),12 which led to the establishment of the National Breast and Cervical Cancer Early Detection Program in 1991. To be eligible for the program, women must have a low income and not have insurance coverage for cancer screening. Because of the eligibility criteria of the program, racial and ethnic minorities and older women are overrepresented. In 2003, the Centers for Disease Control and Prevention (CDC) supported breast and cervical cancer screening services in all 50 states, the District of Columbia, 6 U.S. territories, and 14 American Indian and Alaskan Native programs.
Several reports on screening outcomes from the National Breast and Cervical Cancer Early Detection Program have been published since the program’s inception.13–17 This report describes the percentage of abnormalities and rates of biopsy-detected CIN and invasive cancer by age and race or ethnicity for the period of July 1995 through March 2001. Because the program has been screening women for more than a decade, we were interested in evaluating results from the program over time and comparing the results with other screening programs. Updated results for breast cancer will be the subject of a separate report.
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MATERIALS AND METHODS |
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ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Programs report Pap test results by using the 1991 Bethesda System categories18 (normal, infection/reaction, atypical squamous cells of undetermined significance [ASCUS], low-grade squamous intraepithelial lesion [LSIL], high-grade squamous intraepithelial lesion [HSIL], squamous cell carcinoma, and other). Cancer stage is reported by using the International Federation of Gynecology and Obstetrics definitions19 or the Surveillance, Epidemiology, and End Results Summary Staging System.20
For the present study, we calculated age based on the birth date reported at enrollment and used 5 age classifications: 18–29, 30–39, 40–49, 50–64, and 65 years or older. The age groups were selected after consideration of age-related influences on screening rates, such as Medicare benefits primarily for those aged 65 years and older. If a woman said she was Hispanic, she was classified as Hispanic regardless of any racial classifications she indicated. Other women were classified by self-report as white, black, Asian-Pacific Islander, or American Indian/Alaskan Native. Women not claiming any racial classification or Hispanic ethnicity were classified as "other."
We examined Pap test and biopsy results for women whose first screen in the program ("first round") occurred between July 1995 and March 2001. For women who received more than 1 Pap test within this time frame, results from all tests after the first are reported as "subsequent rounds." In reporting subsequent Pap tests, we excluded women whose initial examination led to a diagnosis of cancer. We also excluded Pap test results obtained less than 90 days after the first program Pap test result because these examinations are conducted as surveillance after an abnormal result is obtained.
For this analysis, data from the program were available for all Pap test results reported to CDC through September 2001, and thus the selection of March 2001 as a cutoff date allowed at least 6 months for diagnostic workups to be completed after abnormal findings were obtained. Complete follow-up information was available for 97% of Pap tests that required a workup (in calculating rates for this report we included those with incomplete follow-up). Of 1,135,484 Pap tests performed during the time frame, we eliminated the results of 11,283 (1%) from the analysis, 2,495 first-round tests and 8,788 subsequent-round tests. Of the first-round exclusions, the age was younger than 18 years for almost all (2,490) and unknown in the remaining 5 women. In the subsequent-round tests that were excluded, in most cases (6,601) the test occurred less than 90 days after the initial program test; the remaining exclusions (2,187) were for women younger than 18 years at program entry, women of unknown age, or women with a diagnosis of cervical cancer as a result of their first-round test. Results for 312,858 women who received Pap tests in the program from 1991 through June 1995 were presented by age by Lawson et al14 in an earlier analysis.
Pap test results were considered abnormal if they were reported as LSIL, HSIL, or squamous cell carcinoma. The program follows the Consensus Guidelines for the Management of Abnormal Cervical Cytological Abnormalities developed by the American Society for Colposcopy and Cervical Pathology.21 The guidelines state that all results of HSIL or squamous cell carcinoma should be followed up with a colposcopy-directed biopsy to detect any precancerous or cancerous conditions. For patients whose smears are interpreted as ASCUS or LSIL, there are several management options, including a repeat Pap test or colposcopy, depending on clinical circumstances.
We calculated the percentages of all Pap test results interpreted as abnormal by screening round. We computed detection rates for each grade of CIN and invasive cancer as the number of cases with a final histologic diagnosis of CIN (CIN 1, CIN 2, CIN 3/carcinoma in situ [CIS]) or invasive cancer per 1,000 Pap tests performed, by first and subsequent screening rounds; to estimate the detection rate of high-grade lesions, we combined biopsy results of CIN 2, CIN 3/CIS, and invasive cancer (ie, CIN 2 or worse).
We computed the positive predictive value of a high-grade test result by dividing the number of tests with results of HSIL or squamous cell carcinoma that led to a histologic diagnosis of CIN 2 or worse by the total number of tests read as HSIL or squamous cell carcinoma. Positive predictive values were calculated by age, race or ethnicity, and screening round.
Rates were adjusted by the direct method22 by using the distribution of the population receiving a Pap test through the program in 2000. We computed multiplicative risk models to test for trends by fitting the log of the risk of an abnormal Pap test result as a function of age in years (as a continuous variable) using the GENMOD procedure in SAS (SAS. The GENMOD procedure. In: SAS/STAT user’s guide, version 8, volume 2. Cary, NC: SAS Publishing; 1999:1365–462).23 The trend for the risk of CIN 2 or worse with increasing age was also computed using this log-linear model.
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RESULTS |
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). Nearly 85% of these women were aged 40 years or older, with a mean age of 49 years. Slightly less than half were members of racial or ethnic minorities, with blacks and Hispanics representing 14.4% and 19.3% of the study population. Seventy-six percent of the women reported having had a Pap test before enrollment.
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. In the first round, the overall percentage of abnormal test results was 1.8%, with the percentage declining with increasing age, from 10.3% in the youngest group (18–28 years) to 0.8% among women aged 65 years and older. Overall, the percentage of abnormal tests was lower in the subsequent rounds, but little or no difference was seen for women older than 40 years of age.
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Age-specific detection rates per 1,000 Pap tests for all grades of biopsy-diagnosed CIN and invasive cancer are presented in Table 3 by screening round. Overall and for all age groups except 65 years and older in the first round, CIN 1 was the most common histologic abnormality. Even so, in both the first and subsequent rounds, CIN 3/CIS was more common than CIN 2 in all age groups except the youngest one. In the first round, the rate of invasive disease increased slightly with greater age, peaking at 50–64 years.
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). Overall, the rate decreased as age increased, dropping in the first round from 30.9 per 1,000 among women aged 18–29 years to 2.5 per 1,000 for those aged 65 years or older.
Age-adjusted results of Pap tests and rates per 1,000 tests of biopsy-diagnosed CIN 2 or worse are presented by race or ethnicity in Table 4 for the first and subsequent rounds. In both rounds, white women had the highest percentage of abnormal Pap test results and the highest rate of CIN 2 or worse. There are considerable differences in risk between the screening rounds, which suggest that prior screening offers some additional level of protection. In Table 5, the positive predictive values of a high-grade Pap test for CIN 2 or worse are reported. In the first round, the positive predictive value was 59.9% overall; consistent with the relationship between positive predictive values and disease prevalence, the positive predictive value was lower (47.7%). In both rounds, positive predictive values were highest for women in their 30s and for white women.
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). Fifty-one percent of the cancers were classified as local disease (either stage I [International Federation of Gynecology and Obstetrics] or local [Surveillance, Epidemiology, and End Results]). Fifty-seven percent of the invasive cancers were diagnosed among women aged 50 years or older. Of the 465 women with invasive disease, 69% reported a prior Pap test before program entry (results not shown). Age was a factor, as of the women with invasive cancer, 75% of those aged 18–29 years reported a prior Pap test versus 68% of those aged 50–64 years and just 58% of those aged 65 years or older.
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DISCUSSION |
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As noted earlier, Lawson et al reported results form the National Breast and Cervical Cancer Early Detection Program for 1991–1995 by age; in addition, Benard and colleagues17 reported results for the program for 1991–1998 by race or ethnicity. Although the goals and objectives of the program have remained the same, many changes have occurred since its inception. Women who entered the program during its early years were younger (42.2% were younger than 40 years in 1991–1995 versus 15.6% in 1995–2001) and less likely to report a prior Pap test than women in our analysis (61.1% versus 75.9%). These population changes explain some but not all of the differences between our results and those reported previously.
In the results reported by Lawson et al14 the percent of abnormal Pap tests was about 2 times as high than that found in our analysis; this higher percentage is probably a reflection of differences in the age distribution and screening history of the women screened. In contrast, the detection rate of CIN 2 or worse reported by Lawson et al14 was lower than what we found (7.4 versus 9.6 per 1,000 Pap tests, age adjusted to the 1995 National Breast and Cervical Cancer Early Detection Program population). This increase in high-grade lesions may be a consequence of the program restrictions on the number of younger women screened. When the first article was published, the program targeted all women for recruitment, but as the program grew, the emphasis shifted to rescreening and to reaching those women never or rarely screened. Because most women in their reproductive years have some access to medical care and screening, the program concentrated its outreach efforts on women older than 40 years. Thus, younger women (younger than 30 years) screened in 1995–2001 may have been referred to the program because of an abnormal Pap test result. Our finding for women less than age 30 of an HSIL percentage that was twice that reported by Lawson et al supports this explanation. Women with a diagnosis of HSIL have approximately a 70–75% chance of having biopsy-confirmed CIN 2 or CIN 3 and a 1–2% chance of having invasive cervical cancer26; thus, an increased percentage of HSIL would increase the rate of CIN 2 or worse.
The report by Benard et al17 for 1991–1998 illustrates the effect of population changes in the program. Before 1998, 26.7% of American Indian/Alaskan Native participants were younger than 30 years; in our analysis only 13.4% were this young. In addition, in the study by Benard et al,17 just 30.5% of American Indian/Alaskan Native women reported a prior Pap test, compared with 61.6% in our analysis. Correspondingly, both the age-adjusted percentages of abnormal Pap test results and biopsy-detected rates of CIN 2 or worse were higher for American Indian/Alaskan Native women in the Benard et al17 study than in the present analysis. In the current analysis, the American Indian/Alaskan Native women are similar to the overall population in terms of age and percentage with a prior Pap test. In addition, the percentage of abnormal Pap tests and the rate of biopsy-detected CIN 2 or worse for the American Indian/Alaskan Native women in this analysis were among the lowest.
The National Breast and Cervical Cancer Early Detection Program is one of the largest cervical cancer screening programs to use the Bethesda system in reporting results. Difficulties exist in comparing our data directly with reports using other taxonomic systems, but where comparisons can be made, our results are comparable with those of previous studies among screened populations. We reviewed results for programs that screened women with ages ranging from 20 to 69 years, but the results are neither age specific nor age adjusted, which is a limitation when making comparisons. In the European Union countries with a screening program (Belgium, Denmark, Finland, France, Germany, Ireland, Italy, Netherlands, Sweden, and the United Kingdom), the percentage of abnormal Pap test results reported, which included ASCUS, varied from 1.5% to 8%.27 When we include ASCUS as abnormal in our study, our percentage of abnormal test results rose from 2.0% to 6.3% (unadjusted percentages). Our figure of 2.0% (LSIL, HSIL, and squamous cell carcinoma) is consistent with the findings of a study conducted in Spain28 that found 2.2% of 324,196 Pap test results to be abnormal by the same standard. In the same Spanish population, CIN was diagnosed in 1.6%28 of the Pap tests versus 1.1% in the program (includes first and subsequent rounds of CIN 1, CIN 2, CIN 3/CIS, unadjusted). In Taiwan, 1.0% of screened women were diagnosed with CIN.29 Reports from Victoria, Australia, indicated an overall prevalence of CIN of 3.6%, whereas for aboriginal Australian women, the rate was 1.6%.30 Analysis of Canadian data indicated patterns similar to those in our program, with younger women having the highest proportion of abnormal smears and biopsy-detected lesions.31
In conclusion, the National Breast and Cervical Cancer Early Detection Program represents the only national organized screening program in the United States for cervical cancer and precancerous lesions. The CDC funds a network of programs to develop interventions that increase access to and use of screening services among underserved women. Because the program targets women aged more than 40 years who are shown to be at a greater risk for never or rarely having Pap tests for cervical cancer, we have an opportunity to identify and treat precancerous lesions and reduce the burden of cervical cancer in the United States.
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Footnotes |
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Received July 23, 2003. Received in revised form October 14, 2003. Accepted November 25, 2003.
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REFERENCES |
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