Variation in cervical cancer screening test utilization and results in a United States-based program.

BACKGROUND: Little is known about cervical cancer screening strategy utilization (cytology alone, cytology plus high-risk human papillomavirus [HPV] testing [cotesting], primary HPV testing) and test results in the United States. METHODS: Data from the Centers for Disease Control and Prevention's National Breast and Cervical Cancer Early Detection Program were analyzed for 199,578 persons aged 21-65 years screened from 2019 to 2020. Screening test utilization and results were stratified by demographic characteristics and geographic region. Age-standardized pooled HPV test positivity and genotyping test positivity were estimated within cytology result categories. RESULTS: Primary HPV testing was performed in 592 persons (0.3%). Among the remaining 176,290 persons aged 30-65 years, cotesting was utilized in 72.1% (95% confidence interval [CI] 71.9-72.3%), and cytology alone was utilized in 27.9% (95% CI 27.7-28.1%). Utilization of cytology alone varied by geographic region, ranging from 18.3% (95% CI 17.4-19.1%) to 49.0% (95% CI 48.4-49.6%). HPV genotyping test utilization among those with positive pooled HPV test results was 33.9%. In persons aged ≥30 years, variations in age-adjusted test results by region were observed for pooled HPV-positive test results and for HPV genotyping-positive test results. CONCLUSIONS: Cervical cancer screening strategy utilization and test results vary substantially by geographic region within a national screening program. Variation in utilization may be due to regional differences in screening test availability or the preferences of healthcare systems, screened persons and/or clinicians. Test result variations may reflect differing risk factors for HPV infections by geographic region.

Accelerating Cervical Cancer Screening With Human Papillomavirus Genotyping.

INTRODUCTION: Selective utilization of human papillomavirus (HPV) genotyping in cervical cancer screening can accelerate clinical management, leading to earlier identification and treatment of precancerous lesions and cancer. Specifically, immediate colposcopy (instead of 1-year return) is recommended in persons with normal cytology and HPV genotypes 16 and/or 18, and expedited treatment (instead of colposcopy) is recommended in persons with high-grade squamous intraepithelial lesion (HSIL) cytology and HPV genotype 16. The effects of implementing HPV testing and genotyping into a screening program are largely unknown. METHODS: Average-risk persons aged 30-65 years screened for cervical cancer in the National Breast and Cervical Cancer Early Detection Program from 2019 to 2020 were included (N=104,991). Percentage HPV genotyping test positivity was estimated within cytology result categories. Analyses were performed in 2022. RESULTS: The most common abnormality was positive high-risk HPV testing with normal cytology, representing 40.1% (7,155/17,832) of all abnormal test result categories; HSIL cytology represented 3.0% (530/17,832) of all abnormal test result categories. In high-risk HPV‒positive persons with normal or high-grade cytology, HPV genotyping could accelerate management (immediate colposcopy and expedited treatment) in 5.4% of all persons with abnormal screening test results; if HPV genotyping had been performed in all high-risk HPV‒positive persons with normal or HSIL cytology, approximately 13.1% could have accelerated management. CONCLUSIONS: HPV genotyping in human papillomavirus‒positive persons with normal or HSIL cytology could accelerate management in a sizable percentage of persons with abnormal test results and may be particularly useful in populations with challenges adhering to longitudinal follow-up.

Geographic Examination of COVID-19 Test Percent Positivity and Proportional Change in Cancer Screening Volume, National Breast and Cervical Cancer Early Detection Program.

INTRODUCTION: In 2020, the COVID-19 pandemic led to significant declines in cancer screening, including among women served by the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). This study examined the spatial association between state-based COVID-19 test percent positivity and proportional change in NBCCEDP screening volume. METHODS: Using the COVID-19 Diagnostic Laboratory Testing dataset, we calculated state-based monthly COVID-19 test percent positivity from July through December 2020 and categorized rates into low, medium, and high groups. We used data from 48 NBCCEDP state awardees to calculate the state-based monthly proportional change in screening volume and compared data for July-December 2020 with the previous 5-year average for those months. We categorized changes in screening volume into large decrease, medium decrease, and minimal change and created maps of the associations between variable subgroups by using bivariate mapping in QGIS. RESULTS: Bivariate relationships between COVID-19 test percent positivity and proportional change in cancer screening volume varied over time and geography. In 5 of 6 months, 4 states had high COVID-19 test percent positivity and minimal change in breast or cervical cancer screening volume; 2 states had high COVID-19 test percent positivity and minimal change in breast and cervical cancer screening volume. CONCLUSION: Some states maintained pre-COVID-19 screening volumes despite high COVID-19 test percent positivity. Follow-up research will be conducted to determine how these states differ from those with consistent decreases in screening volume and identify factors that may have contributed to differences. This information could be useful for planning to maximize NBCCEDP awardees' ability to maintain screening volume during future public health emergencies.

An update on the US adult thalassaemia population: a report from the CDC thalassaemia treatment centres.

Thalassaemia is caused by genetic globin defects leading to anaemia, transfusion-dependence and comorbidities. Reduced survival and systemic organ disease affect transfusion-dependent thalassaemia major and thalassaemia intermedia. Recent improvements in clinical management have reduced thalassaemia mortality. The therapeutic landscape of thalassaemia may soon include gene therapies as functional cures. An analysis of the adult US thalassaemia population has not been performed since the Thalassemia Clinical Research Network cohort study from 2000 to 2006. The Centers for Disease Control and Prevention supported US thalassaemia treatment centres (TTCs) to compile longitudinal information on individuals with thalassaemia. This dataset provided an opportunity to evaluate iron balance, chelation, comorbidities and demographics of adults with thalassaemia receiving care at TTCs. Two adult cohorts were compared: those over 40 years old (n = 75) and younger adults ages 18-39 (n = 201). The older adult cohort was characterized by higher numbers of iron-related comorbidities and transfusion-related complications. By contrast, younger adults had excess hepatic and cardiac iron and were receiving combination chelation therapy. The ethnic composition of the younger cohort was predominantly of Asian origin, reflecting the demographics of immigration. These findings demonstrate that comprehensive care and periodic surveys are needed to ensure optimal health and access to emerging therapies.

Risk of cervical precancer and cancer among uninsured and underserved women from 2009 to 2017.

BACKGROUND: New guidelines for managing cervical precancer among women in the United States use risk directly to guide clinical actions for individuals who are being screened. These risk-based management guidelines have previously only been based on risks from a large integrated healthcare system. We present here data representative of women of low income without continuous insurance coverage to inform the 2019 guidelines and ensure applicability. OBJECTIVE: We examined the risks of high-grade precancer after human papillomavirus and cytology tests in underserved women and assessed the applicability of the 2019 guidelines to this population. STUDY DESIGN: We examined cervical cancer screening and follow-up data among 363,546 women enrolled in the Centers for Disease Control and Prevention's National Breast and Cervical Cancer Early Detection Program from 2009 to 2017. We estimated the immediate (prevalent) risks of cervical intraepithelial lesion grade 3 or cancer by using prevalence-incidence mixture models. Risks were estimated for each combination of human papillomavirus and cytology result and were stratified by screening history. We compared these risks with published estimates used in new risk-based management guidelines. RESULTS: Women who were up-to-date with their screening, defined as being screened with cytology within the past 5 years, had immediate risks of cervical intraepithelial neoplasia grade 3 or higher similar to that of women at Kaiser Permanente Northern California, whose data were used to develop the management guidelines. However, women in the Centers for Disease Control and Prevention's National Breast and Cervical Cancer Early Detection Program had greater immediate risks if they were never screened or not up-to-date with their screening. CONCLUSION: New cervical risk-based management guidelines are applicable for underinsured and uninsured women with a low income in the United States who are up-to-date with their screening. The increased risk observed here among women who received human papillomavirus-positive, high-grade cytology results, who were never screened, or who were not up-to-date with their cervical cancer screening, led to a recommendation in the management guidelines for immediate treatment among these women.

Are uninsured women in a national screening program having longer intervals between cervical cancer screening tests?

With increased understanding of the natural history of cervical cancer, cervical cancer screening recommendations have evolved (Schiffman & Wentzensen, 2013). As research better quantified the balance of benefits and harms of screening, new recommendations called for longer intervals between screening tests. Adherence to longer screening intervals detects similar numbers of abnormalities and decreases harms associated with overscreening/overtreatment. In this descriptive study, we examined the cervical cancer screening intervals from 2010 to 2018 in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). There were 1,397,899 women aged 21-64 who were screened for cervical cancer from 2010 to 2018 and 556,743 rescreenings of average risk women were performed. The median cervical screening interval increased from 2.02 years in 2010 to 3.88 years in 2018. Providers serving uninsured women in a national screening program are following the recommendations of longer intervals between cervical cancer screenings.

Using Evidence-Based Interventions to Improve Cancer Screening in the National Breast and Cervical Cancer Early Detection Program.

CONTEXT: The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides cancer screening to low-income, un-, and underinsured women through more than 11 000 primary care clinics. The program is well-positioned to work with health systems to implement evidence-based interventions (EBIs) to increase screening among all women. OBJECTIVE: To collect baseline data on EBI use, evaluation of EBIs, and related training needs among NBCCEDP grantees. DESIGN: The Centers for Disease Control and Prevention conducted a Web-based survey in late 2013 among NBCCEDP grantees for the period July 2012 to June 2013. This was the first systematic assessment of EBIs among NBCCEDP grantees. SETTING: The Centers for Disease Control and Prevention's NBCCEDP. PARTICIPANTS: Primarily program directors/coordinators for all 67 NBCCEDP grantees. MAIN OUTCOME MEASURES: Data captured were used to assess implementation of 5 EBIs, their evaluation, and related training needs. Frequencies and proportions were determined. Cluster analysis identified grantees with similar patterns of EBI use for NBCCEDP clients and providers. RESULTS: On average, 4.1 of 5 EBIs were implemented per grantee for NBCCEDP clients and providers. Four clusters were identified including "high overall EBI users," "high provider EBI users," "high EBI users with no provider assessment and feedback," and "high client EBI users." Only 1.8 EBIs were implemented, on average, with non-NBCCEDP clients and providers. Fewer than half (n = 32, 47.8%) of grantees conducted process or outcome evaluation of 1 or more EBIs. Overall, 47.6% of grantees reported high or medium training needs for client-oriented EBIs and 54.3% for provider-oriented EBIs. CONCLUSIONS: The NBCCEDP grantees are implementing EBIs extensively with clients and providers. Increased EBI use among non-NBCCEDP clients/providers is needed to extend the NBCCEDP's reach and impact. Grantee training and technical assistance is necessary across EBIs. In addition, grantees' use of process and outcome evaluation of EBI implementation must be increased to inform effective program implementation.

Cervical cancer screening of underserved women in the United States: results from the National Breast and Cervical Cancer Early Detection Program, 1997-2012.

OBJECTIVE: The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides breast and cervical cancer screens to low-income, uninsured, and underinsured women. We describe the number and proportion of women eligible for cervical cancer screening services and the proportion of eligible women screened over the period 1997-2012. METHODS: Low-income, uninsured, and underinsured women aged 18-64 years who have not had a hysterectomy are eligible for cervical cancer screening through the NBCCEDP. We estimated the number of low-income, uninsured women using data from the US Census Bureau. We adjusted our estimates for hysterectomy status using the National Health Interview Survey and the Behavioral Risk Factor Surveillance System. We used data from the NBCCEDP to describe the number of women receiving NBCCEDP-funded screening and calculated the proportion of eligible women who received screening through the NBCCEDP at the national level (by age group, race/ethnicity) and at the state level by age group. We used the Medical Expenditure Panel Survey to estimate the proportion of NBCCEDP-eligible women who were screened outside the NBCCEDP and the proportion that are not screened. RESULTS: We estimate that in 2010-2012, 705,970 women aged 18-64 years, 6.5 % (705,970 of 9.8 million) of the eligible population, received NBCCEDP-funded Pap tests. We estimate that 60.2 % of eligible women aged 18-64 years were screened outside the NBCCEDP and 33.3 % were not screened. The NBCCEDP provided 623,603 screens to women aged 40-64 years, an estimated 16.5 % of the eligible population, and 83,660 screens to women aged 18-39 years, representing an estimated 1.2 % of the eligible population. The estimated proportions of eligible women screened in each state ranged from 1.5 to 32.7 % and 5 % to 73.2 % among the 18-64 and 40-64 years age groups, respectively. Changes in the proportion of eligible women screened over the study period were nonsignificant. CONCLUSIONS: Although the program provided cervical screening to over 700,000 women between 2010 and 2012, it served a small percent of those eligible. The proportion of women screened varied substantially across age groups, racial/ethnic groups, and states. Many low-income, uninsured women are not being screened.

Breast cancer screening of underserved women in the USA: results from the National Breast and Cervical Cancer Early Detection Program, 1998-2012.

OBJECTIVE: To describe the number and proportion of eligible women receiving mammograms funded by the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). METHODS: Low-income, uninsured, and underinsured women aged 40-64 are eligible for mammography screening through the NBCCEDP. We used data from the NBCCEDP, the Current Population Survey, and Medical Expenditure Panel Survey to describe the number and proportion of women screened by the NBCCEDP and overall. RESULTS: In 2011 and 2012, the NBCCEDP screened 549,043 women aged 40-64, an estimated 10.6 % (90 % confidence interval [CI] 10.4-10.9 %) of the eligible population. We estimate that 30.6 % (90 % CI 26.4-34.8 %) of eligible women aged 40-64 were screened outside the NBCCEDP, and 58.8 % (90 % CI 54.6-63.0 %) were not screened. The proportion of eligible women screened by the NBCCEDP varied across states, with an estimated range of 3.2 % (90 % CI 2.9-3.5 %) to 52.8 % (90 % CI 36.1-69.6 %) and a median of 13.7 % (90 % CI 11.0-16.4 %). The estimated proportion of eligible women aged 40-64 who received mammograms through the NBCCEDP was relatively constant over time, 11.1 % (90 % CI 10.2-11.9 %) in 1998-1999 and 10.6 % (90 % CI 10.4-11.9 %) in 2011-2012 (p = 0.23), even as the number of women screened increased from 343,692 to 549,043. CONCLUSIONS: Although the NBCCEDP provided screening services to over a half million low-income uninsured women for mammography, it served a small percentage of those eligible. The majority of low-income, uninsured women were not screened.

Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism.

INTRODUCTION: Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. There is limited understanding of the biological mechanisms that predispose patients to recurrent VTE. OBJECTIVES: To identify whole blood gene expression profiles that distinguished patients with clinically distinct patterns of VTE. PATIENTS/METHODS: We studied 107 patients with VTE separated into 3 groups: (1) 'low-risk' patients had one or more provoked VTE; (2) 'moderate-risk' patients had a single unprovoked VTE; (3) 'high-risk' patients had ≥2 unprovoked VTE. Each patient group was also compared to twenty-five individuals with no personal history of VTE. Total RNA from whole blood was isolated and hybridized to Illumina HT-12V4 Beadchips to assay whole genome expression. RESULTS: Using class prediction analysis, we distinguished high-risk patients from low-risk patients and healthy controls with good receiver operating curve characteristics (AUC=0.81 and 0.84, respectively). We also distinguished moderate-risk individuals and low-risk individuals from healthy controls with AUC's of 0.69 and 0.80, respectively. Using differential expression analysis, we identified several genes previously implicated in thrombotic disorders by genetic analyses, including SELP, KLKB1, ANXA5, and CD46. Protein levels for several of the identified genes were not significantly different between the different groups. CONCLUSION: Gene expression profiles are capable of distinguishing patients with different clinical presentations of VTE, and genes relevant to VTE risk are frequently differentially expressed in these comparisons.

State-based surveillance for selected hemoglobinopathies.

PURPOSE: The lack of an ongoing surveillance system for hemoglobinopathies in the United States impedes the ability of public health organizations to identify individuals with these conditions, monitor their health-care utilization and clinical outcomes, and understand the effect these conditions have on the health-care system. This article describes the results of a pilot program that supported the development of the infrastructure and data collection methods for a state-based surveillance system for selected hemoglobinopathies. METHODS: The system was designed to identify and gather information on all people living with a hemoglobinopathy diagnosis (sickle cell diseases or thalassemias) in the participating states during 2004-2008. Novel, three-level case definitions were developed, and multiple data sets were used to collect information. RESULTS: In total, 31,144 individuals who had a hemoglobinopathy diagnosis during the study period were identified in California; 39,633 in Florida; 20,815 in Georgia; 12,680 in Michigan; 34,853 in New York, and 8,696 in North Carolina. CONCLUSION: This approach provides a possible model for the development of state-based hemoglobinopathy surveillance systems.

Transfusion complications in thalassemia patients: a report from the Centers for Disease Control and Prevention (CME).

BACKGROUND: Transfusions are the primary therapy for thalassemia but have significant cumulative risks. In 2004, the Centers for Disease Control and Prevention (CDC) established a national blood safety monitoring program for thalassemia. This report summarizes the population and their previous nonimmune and immune transfusion complications. STUDY DESIGN AND METHODS: The CDC Thalassemia Blood Safety Network is a consortium of centers longitudinally following patients. Enrollment occurred from 2004 through 2012. Demographics, transfusion history, infectious exposures, and transfusion and nontransfusion complications were summarized. Logistic regression analyses of factors associated with allo- and autoimmunization were employed. RESULTS: The race/ethnicity of these 407 thalassemia patients was predominantly Asian or Caucasian. The mean ± SD age was 22.3 ± 13.2 years and patients had received a mean ± SD total number of 149 ± 103.4 units of red blood cells (RBCs). Multiorgan dysfunction was common despite chelation. Twenty-four percent of transfused patients had previous exposure to possible transfusion-associated pathogens including one case of babesia. As 27% were immigrants, the infection source cannot be unequivocally linked to transfusion. Transfusion reactions occurred in 48%, including allergic, febrile, and hemolytic; 19% were alloimmunized. Common antigens were E, Kell, and C. Years of transfusion was the strongest predictor of alloimmunization. Autoantibodies occurred in 6.5% and were associated with alloimmunization (p < 0.0001). Local institutional policies, not patient characteristics, were major determinants of blood preparation and transfusion practices. CONCLUSION: Hemosiderosis, transfusion reactions, and infections continue to be major problems in thalassemia. New pathogens were noted. National guidelines for RBC phenotyping and preparation are needed to decrease transfusion-related morbidity.

Developing public health surveillance for deep vein thrombosis and pulmonary embolism.

Deep vein thrombosis (DVT) and pulmonary embolism (PE), collectively known as venous thromboembolism (VTE), are an important and growing public health issue, associated with considerable morbidity and mortality. Presently, there is no national surveillance for DVT and PE. This article provides a summary of an expert workgroup meeting convened January 12, 2010, by the CDC. The purpose of the meeting was to inform CDC on the development of U.S. population-based public health surveillance activities for DVT/PE. Topics discussed included: (1) stakeholders, needs, gaps, and target populations; (2) requirements of surveillance systems; (3) challenges, limitations, and potential barriers to implementation of surveillance activities; and (4) integration of research and education with surveillance activities.