Presented at the American Association for Cancer Research 10th International Conference on Frontiers in Cancer Prevention Research; Boston, MA; October 22-25, 2011.
The authors thank Dr. Jiaquan Xu from the Centers for Disease Control and Prevention, National Center for Health Statistics, Mortality Statistics Branch, for provision of mortality rates by educational attainment.
Despite substantial declines in cervical cancer mortality because of widespread screening, socioeconomic status (SES) disparities persist. The authors examined trends in cervical cancer mortality rates and the risk of late-stage diagnoses by SES.
Using data from the National Vital Statistics System, trends in age-standardized mortality rates among women ages 25 to 64 years (1993-2007) by education level (≤12 years, 13-15 years, and ≥16 years) and race/ethnicity for non-Hispanic white (NHW) women and non-Hispanic black (NHB) women in 26 states were assessed using log-linear regression. Rate ratios (RRs) and 95% confidence intervals (CIs) were used to assess disparities between those with ≤12 years versus ≥16 years of education during 1993 to 1995 and 2005 to 2007. Avertable deaths were calculated by applying mortality rates from the most educated women to others in 48 states. Trends in the risk of late-stage diagnosis by race/ethnicity and insurance status were evaluated in the National Cancer Data Base.
Declines in mortality were steepest for those with the highest education levels (3.2% per year among NHW women and 6.8% per year among NHB women). Consequently, the education disparity widened between the periods 1993 to 1995 and 2005 to 2007 from 3.1 (95% CI, 2.4-3.9) to 4.4 (95% CI, 3.5-5.6) for NHW women and from 3.8 (95% CI, 2.0-7.0) to 5.6 (95% CI, 3.1-10.0) for NHB women. The risk of late-stage diagnosis increased for uninsured versus privately insured women over time. During 2007, 74% of cervical cancer deaths in the United States may have been averted by eliminating SES disparities.
Cervical cancer mortality has declined substantially in the United States since the 1950s because of the widespread use of Papanicolaou (Pap) testing, which results in the detection of precancerous lesions and early stage cancers that are amenable to treatment.1 However, progress in reducing the cervical cancer burden has been stymied among those with low versus high socioeconomic status (SES) and among blacks versus whites.2-4 SES influences cancer risk factors, such as persistent human papillomavirus (HPV) infection,5 a necessary cause of cervical cancer, as well as access to the health care system (eg, cancer prevention, screening, and treatment).2 In addition, advanced disease stage, insurance status, and older age at diagnosis are associated with poorer outcomes.6-8
Previous evaluations of SES disparities in cervical cancer incidence and mortality were limited because they were based on area-level, rather than individual-level, SES measures,6, 9, 10 or they were restricted to small geographic areas.11 Herein, we examine recent trends in cervical cancer mortality among non-Hispanic whites, non-Hispanic blacks, and Hispanics using individual-level education as a marker of SES as well as trends in the risk of late-stage disease at diagnosis by race/ethnicity and insurance status.
MATERIALS AND METHODS
We obtained cervical cancer mortality data (1993-2007) from the National Vital Statistics System administered by the Centers for Disease Control and Prevention, National Center for Health Statistics, for non-Hispanic white, non-Hispanic black, and Hispanic women, the 3 largest racial/ethnic groups, to provide stable rates. Cervical cancer deaths were classified according to the coding rules of the ninth revision of the International Classification of Diseases (ICD-9) (code 180) for deaths that occurred during the period from 1993 to 1998,12 and according to the 10th revision of the International Classification of Diseases (ICD-10) (code C53) for deaths that occurred from 1999 onward.13
We considered education level noted on a death certificate as a marker of SES, because education is associated with health, wealth, and access to the health care system.14-16 Educational attainment (based on years of schooling recorded on death certificates reported by next of kin) was classified into 3 categories: ≤12 years (high school graduate or less), 13 to 15 years (some college education), and ≥16 years (college graduate or postgraduate). Analyses were limited to deaths among women ages 25 to 64 years, because those who died before age 25 years may not have completed their education and because educational attainment predicts SES better for individuals aged <65 years than for older individuals.17 An additional reason for evaluating mortality among women aged <65 years is the possible impact of near universal access to health care afforded by Medicare (which begins at age 65 years) in attenuating mortality disparities.
Although educational attainment has been included on the US standard death certificate since 1989, most states did not routinely collect such information until 1993. In 2003, classifications were modified to report the highest degree received.18 The gradual adoption of this new system complicates the interpretation of long-term trends. Therefore, we restricted our analyses to the 26 states (Alabama, Alaska, Arizona, Arkansas, Colorado, Hawaii, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Minnesota, Mississippi, Missouri, Nevada, North Carolina, North Dakota, Pennsylvania, Tennessee, Vermont, Virginia, Wes Virginia, and Wisconsin) that had not yet implemented the new death certificate as of 2007. The majority of cervical cancer deaths during 1993 to 2007 occurred among women ages 25 to 64 years (62%), and cervical cancer deaths in the 26 states that were included in the current study (n = 16,421) represent 42% of cervical cancer deaths among women ages 25 to 64 years in the United States.
Population estimates for the corresponding age, education, state, and time intervals were obtained in a custom tabulation from the US Bureau of Census (Victor Valdisera, Housing and Household Economic Statistics Division, personal communication, 2010) of data based on the Annual Social and Economic Supplement to the Current Population Survey, an ongoing, nationally representative household survey. Mortality rates per 100,000 population were standardized to the 2000 US population in 10-year age increments (ages 25-34 years, 35-44 years, 45-54 years, and 55-64 years)19 and are reported by education and race/ethnicity strata. Standard errors and 95% confidence intervals (CIs) for rates were computed by accounting for the sampling variability of population estimates according to educational attainment.20
Temporal trends in annual mortality rates (1993-2007) by race/ethnicity and education level were assessed by fitting a weighted least-squares regression model to the log-transformed, annual, age-standardized rates, weighted by the inverse of their variance.21 The annual percent change, or slope of the line segment, was considered statistically significant if the 2-sided P value for the parameter was <.05. We also calculated weighted average age-adjusted rates during the periods 1993 to 1995 and 2005 to 2007 to assess changes in educational disparities between the 2 periods. On the absolute scale, we calculated the rate difference (as the difference in rates between women with ≤12 vs ≥16 years of education) to demonstrate the actual risk of cervical cancer death associated with low levels of educational attainment. Next, on the relative scale, we calculated the rate ratio (RR) (as the ratio of rates in women with ≤12 vs ≥16 years of education) to assess the relative effect of low versus high educational attainment on cervical cancer death rates. Large-sample 95% CIs were calculated for RRs.22
To determine the impact of reducing SES disparities on cervical cancer deaths, we also calculated the proportion of deaths that would have been averted in 2007 had all population segments experienced the same cervical cancer mortality as the most educated non-Hispanic white women in 48 states (excluding Georgia and Rhode Island, because neither state routinely obtained educational attainment information) and the District of Columbia, regardless of how education was reported. Averted deaths are calculated as the difference between the observed deaths by race/ethnicity and age group, and the expected number of deaths had all women experienced the same mortality as the reference group with the lowest death rate (ie, non-Hispanic white women with ≥16 years of education according to the old version of the death certificate and a college degree or greater according to the new version of the death certificate). Expected deaths were calculated by applying the 2007 death rate for the most educated non-Hispanic whites to non-Hispanic whites in the 2 least educated groups and to non-Hispanic blacks and Hispanics of any education level. We summed the numbers of expected deaths by race/ethnicity and age group to obtain expected deaths according to each educational classification system for national estimates. The fraction of avertable deaths also is presented as the number of deaths averted divided by the total number of deaths observed in 2007.
We also used data from the National Cancer Data Base (NCDB) to assess trends in the risk of late-stage cervical cancer (a proximal outcome associated with poor survival) by insurance status (assessed at cancer diagnosis as private, uninsured, or Medicare/Medicaid) as a marker of SES and race/ethnicity over time. Although the 2 government insurance programs (Medicare and Medicaid) are different, they were combined because of sparse data. Eligibility for Medicaid is based on a poverty threshold, whereas eligibility for Medicare before age 65 years is based on long-term disability status. The NCDB is a hospital-based cancer registry that collects data from all Commission on Cancer (CoC)-accredited facilities, is sponsored by the American Cancer Society and the American College of Surgeons, and covers approximately 85% of cervical cancers diagnosed in the United States from 2004 to 2008.7 Late stage was defined as American Joint Commission on Cancer (AJCC) (sixth edition) clinical stage III or IV tumors.23, 24 If clinical stage was missing, then the pathologic stage was used as a proxy. Initially, women ages 25 to 64 years in the aforementioned 26 states with their first invasive primary tumor who were diagnosed or treated at a CoC facility during 1998 to 2007 (n = 33,446) were selected from the NCDB. Women who were missing information on disease stage (n = 1945) or insurance status (n = 1234) and those who had other forms of insurance (n = 81) or were not reported by a continuously CoC-accredited facility (n = 2078) were excluded. Women with Asian, other, or unknown race/ethnicity were excluded (n = 4488) to focus on similar groups in the main analysis. Hispanics were excluded because of sparse data (n = 1494), resulting in a cohort of 22,126 women. RRs for late stage at diagnosis by race/ethnicity and calendar period (1998-2004 and 2005-2007) were obtained from log-binomial regression that was adjusted for geographic region, age group, and histologic type, because these characteristics are associated with disease stage at diagnosis.7, 25 Geographic region was classified as South, Midwest, Northeast, and West according to census regions26; and age was categorized into 7 groups (ages 18-34 years, 35-39 years, 40-44 years, 45-49 years, 50-54 years, 55-59 years, and 60-64 years). Histology was categorized as squamous cell carcinoma, adenocarcinoma, adenosquamous/glassy cell carcinoma, other specified, and other unspecified tumors.27
Table 1 and Figure 1 indicate the trends in cervical cancer mortality rates among women ages 25 to 64 years by race/ethnicity and education level in the 26 states that were included in this analysis. Among non-Hispanic white women (n = 11,577 deaths; 70.5%), cervical cancer mortality declined from 3.6 per 100,000 during 1993 to 1995 down to 2.7 per 100,000 women during 2005 to 2007, a 2.5% annual decline (P < .05). The largest decline was observed among non-Hispanic white women who had ≥16 years of education (3.2% per year) compared with no significant change among those with ≤12 years of education. Consequently, the educational disparity in cervical cancer mortality among non-Hispanic whites increased over time (comparing mortality rates among women with ≤12 years vs ≥16 years of education on the relative scale) from an RR of 3.1 (95% CI, 2.4-3.9) during 1993 to 1995 to an RR of 4.4 (95% CI, 3.5-5.6) during 2005 to 2007. The rate difference (absolute scale) suggested that as many as 3.3 deaths per 100,000 (during 1993-1995) and 3.7 deaths per 100,000 (during 2005-2007) were associated with factors related to low levels of educational attainment.
Table 1. Age-Standardized Cervical Cancer Death Rates Among Women Ages 25 to 64 Years in 26 States by Race/Ethnicity and Educational Attainment: 1993-2007
Level of Educational Attainment
Abbreviations: APC, annual percent change; CI, confidence interval; NA, estimate not available because of sparse data; RD, rate difference; RR, rate ratio.
Indicates that the APC from the log-linear regression is significantly different from zero at P < .05.
The model for this subgroup demonstrated a significant trend during 1996 to 2006 only.
Cervical cancer mortality rates were highest among non-Hispanic blacks (n = 3657 deaths; 22.2%) and declined 3.8% per year during the study period. It is noteworthy that declines in the rates within each level of education were greater for non-Hispanic blacks versus non-Hispanic whites, although mortality remained higher among non-Hispanic black women relative to non-Hispanic white women across education levels (Fig. 1). Similar to non-Hispanic whites, the greatest declines among non-Hispanic blacks were among those with ≥16 years of education (annual percent change, 6.8%), and the declines increased with increasing levels of education (Table 1). In absolute terms, 8.2 and 6.6 deaths per 100,000 women were due to factors associated with low education levels during the 1993 to 1995 and 2005 to 2007 periods, respectively. The disparity in mortality according to education level among non-Hispanic black women increased from almost 4-fold (RR, 3.8; 95% CI, 2.0-7.0) during 1993 to 1995 to more than 5-fold (RR, 5.6; 95% CI, 3.1-10.0) during 2005 to 2007.
Among Hispanics overall (n = 648 deaths; 3.9%), mortality declined 4.2% per year during 1993 to 2007 (Table 1). Although the small number of deaths in the most educated group during 1993 to 1995 limited comparisons between subgroups, there was an almost 3-fold disparity in death rates between Hispanic women with ≤12 years of education versus those with 13 to 15 years of education during that period. During 2005 to 2007, there was an excess of cervical mortality among Hispanics with ≤12 years versus ≥16 years of education on the both the absolute (rate difference, 2.0) and relative scales (RR, 2.5; 95% CI, 0.8-8.5).
We also calculated the proportion of actual cervical cancer deaths in 2007 that would have been averted if all women experienced the same mortality of the most educated non-Hispanic whites. Of 2349 deaths among women ages 25 to 64 years in 48 states and the District of Columbia with educational attainment reported on death certificates, 74% of all cervical cancer deaths would have been averted had no educational disparities existed.
In addition, we evaluated the risk of late-stage cervical cancer diagnosis in the NCDB, because this is generally associated with poorer survival. The analysis revealed that the risk of late-stage diagnosis increased for women who were uninsured versus privately insured women during 1998 to 2004 and 2005 to 2007, for non-Hispanic whites, from an RR of 1.4 (95% CI, 1.3-1.6) to a RR of 1.7 (95% CI, 1.6-1.9) and, for non-Hispanic blacks, from a RR of 1.4 (95% CI, 1.2-1.6) to a RR of 1.5 (95% CI, 1.2-1.8) (Table 2).
Table 2. The Relationship Between Late-Stage Cervical Cancer Diagnosis, Race/Ethnicity, and Insurance Status Among Women Ages 25 to 64 Years in 26 States in the National Cancer Data Base: 1998-2007a
To our knowledge, this is the first study to evaluate temporal trends in age-adjusted cervical cancer mortality rates by individual level education in the United States. We observed that overall mortality declined during the 1993 to 2007 period but that decreases were smaller for women with lower versus higher levels of education, leading to a widening of SES disparities. Between the periods 1993 to 1995 and 2005 to 2007, the education disparity increased to more than 4-fold for non-Hispanic white women and to more than 5-fold for non-Hispanic black women. In addition, the risk of late-stage diagnosis increased for uninsured non-Hispanic whites and non-Hispanic blacks. These results may plausibly be explained by differences in screening, early detection, and treatment.
We considered individual educational attainment as a marker of SES, because it is associated with access to the health care system, including regular Pap screenings that identify precancerous lesions for removal or early stage cancers for treatment. Women with low SES are less likely to receive regular Pap testing: data from a nationally representative sample of women in 2008 (who had not undergone a hysterectomy) revealed that, among those ages 25 to 44 years with <12 years of education, 76.5% had a Pap smear in the previous 3 years versus 89.8% of women with some college-level education or greater. Findings were similar for women ages 45 to 64 years.28 Furthermore, among women ages 18 to 64 years who had insurance, 85.9% had received a screening test in the previous 3 years versus 68.1% among uninsured women.28 These findings also likely are reflected in the results of our analysis of NCDB data. Relative to privately insured women, those who were uninsured had a significantly increased risk of late-stage diagnosis that increased over time, perhaps reflecting the importance of lower screening rates in this population.
By race/ethnicity, cervical cancer screening rates in 2008 were similar among women ages 18 to 44 years (78.4% among Hispanics, 83.9% among non-Hispanic whites, and 83.5% among non-Hispanic blacks).28 A similar pattern was observed for women ages 45 to 64 years. Despite these similarities, our results and the findings of others suggest that black women are more likely to be diagnosed with advanced-stage cervical cancer,29 which we posit may be because of critical delays in follow-up after abnormal screening results, although additional research is needed to determine the factors associated with late-stage diagnosis. Black women also are less likely to receive timely and adequate cervical cancer treatment, underscoring the need for future interventions.30 Our findings suggest that increased rates of screening and follow-up are needed to decrease cervical cancer deaths among all women who were evaluated in the current study.
The current analysis of trends in cervical cancer mortality rates by individual educational attainment through 2007 compliments previous reports using area-level SES measures. Singh and colleagues examined data from the Surveillance, Epidemiology, and End Result Program (1975-2000) and observed greater declines in incidence and mortality among women in areas with higher versus lower levels of overall education.9 A more recent study revealed elevated mortality among women in urban areas, highlighting the complex relation between geographic location and individual health.31 Another study revealed excess mortality among non-Hispanic blacks and Hispanics relative to whites in New York City, but those investigators did not evaluate trends or the role of education.11
The nadir of cervical cancer mortality (1.1 per 100,000 population during 2005-2007) was among the most educated non-Hispanic white women. This may be considered the best-case scenario among women with the greatest access to the health care system and resources. Relative to non-Hispanic whites, the most educated non-Hispanic blacks (1.5 per 100,000) and Hispanics (1.3 per 100,000) still had excess mortality. We observed that mortality among non-Hispanic blacks and Hispanics declined significantly, but their higher baseline rates reflect population-level lags in screening, prevention, and treatment. Although there were differences in mortality by race/ethnicity, they were much smaller in magnitude than the education disparities: During 2005 to 2007, mortality among non-Hispanic blacks versus non-Hispanic whites was 1.9-fold higher, and the rates were almost identical for Hispanics versus non-Hispanic whites, much smaller than the 4-fold to 5-fold education disparities observed by race/ethnicity. It is noteworthy that, if all segments of the population had experienced the same mortality rates as the most educated non-Hispanic white women during 2007, then an estimated 74% of deaths may have been averted, underscoring the need for programs that focus on the role of SES and access to the health care system.
Primary prevention of cervical cancer is achieved through HPV vaccination, and girls ages 11 and 12 years are recommended to receive 3 doses of the quadrivalent HPV vaccine.32 Vaccination can be started as young as age 9 years, with catch-up vaccination at ages 13 to 26 years before sexual debut. Widely recommended since 2007, ≥1 dose coverage among adolescent girls (ages 13-17 years) during 2009 was similar across racial/ethnic groups (43.9% for non-Hispanic whites, 44.6% for non-Hispanic blacks, and 45.5% for Hispanics).33 Coverage was greater among girls living below the poverty threshold, suggesting the success of targeted programs for low-resource families.33 Such programs should continue to ensure increases in equitable coverage among all eligible girls and women and may help ameliorate future disparities in cervical cancer mortality rates.
Strengths of our analysis include its large, population-based nature, providing stable estimates of mortality rates. A unique contribution is the use of individual-level education data as a marker of SES, which were 97% complete. Although underlying causes of deaths were coded differently during the study period using ICD-9 and ICD-10, a previous study indicated that changes in coding had little impact on the attribution of deaths to cervical cancer.34 In addition, our analysis focused on women ages 25 to 64 years, in which educational attainment is a reliable proxy for SES and clinical and public health interventions may occur well before advanced cervical cancer to favorably impact survival.
These findings also have limitations. We note that SES is a complex construct with both individual and societal-level determinants. When possible, it is desirable to consider multiple indices of SES in analyzing the association between SES and health outcomes.14 The analysis of mortality rates was unable to account for insurance status and stage at diagnosis, because neither variable is available on death certificates. Also, consistent education information was reported from only 26 states, precluding inference to the rest of the country, although cervical cancer death rates among women ages 25 to 64 years in the 26 states evaluated generally were similar to national rates (data not shown). The generalizability of the NCDB stage and insurance analyses also may be limited to patients who are seen at CoC-accredited facilities, which are more likely to be in urban areas and larger in size than non-CoC facilities.35 There has been no formal validation of insurance status in the NCDB, which is another potential limitation that has been described elsewhere36; however, it is the only national registry with insurance data. In addition, trends in increasing disparities should be interpreted cautiously, because the CIs overlapped for non-Hispanic whites and non-Hispanic blacks across the various periods. However, the increasing point estimates support our conclusions of widening disparities. Continued monitoring of cervical cancer mortality by SES levels is warranted and may utilize the databases used in the current study and other administrative health record systems.3
The major impact of HPV vaccination will take decades to manifest as vaccination coverage increases and as girls age into periods when cervical cancer risk is highest. The disparities noted in the current study may be partly addressed by clinicians through enhanced screening and continuity of care for low-resource women to facilitate treatment.37 Screening also may be expanded through programs that target low-resource women, such as the National Breast and Cervical Cancer Early Detection Program, and also through the Affordable Care Act of 2010, which is likely to increase access to clinical preventive services in the future.
Cervical cancer is a preventable cause of death among women; and in this analysis of trends in mortality rates using the most recently available data, we demonstrated declines in death rates during the period from 1993 to 2007 and widening SES disparities over time for non-Hispanic black and non-Hispanic white women. Although the causes of the observed mortality disparities are multifactorial, our findings suggest that approximately 74% of cervical cancer deaths in 2007 could have been averted if all segments of the population had experienced the same mortality rates as non-Hispanic white women.
This study was funded by the Intramural Research Program of the American Cancer Society.