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Objectives To quantify the secondary impacts of the COVID-19 pandemic disruptions to cervical cancer screening in the United States, stratified by step in the screening process and primary test modality, on cervical cancer burden. Methods We conducted a comparative model-based analysis using three independent NCI Cancer Intervention and Surveillance Modeling Network cervical models to quantify the impact of eight alternative COVID-19-related screening disruption scenarios compared to a scenario of no disruptions. Scenarios varied by the duration of the disruption (6 or 24 months), steps in the screening process being disrupted (primary screening, surveillance, colposcopy, excisional treatment), and primary screening modality (cytology alone or cytology plus human papillomavirus “cotesting”). Results The models consistently showed that COVID-19-related disruptions yield small net increases in cervical cancer cases by 2027, which are greater for women previously screened with cytology compared with cotesting. When disruptions affected all four steps in the screening process under cytology-based screening, there were an additional 5–7 and 38–45 cases per one million screened for 6- and 24-month disruptions, respectively. In contrast, under cotesting, there were additional 4–5 and 35–45 cases per one million screened for 6- and 24-month disruptions, respectively. The majority (58–79%) of the projected increases in cases under cotesting were due to disruptions to surveillance, colposcopies, or excisional treatment, rather than to primary screening. Conclusions Women in need of surveillance, colposcopies, or excisional treatment, or whose last primary screen did not involve human papillomavirus testing, may comprise priority groups for reintroductions.

Primary care provider's (PCP) perceptions of colorectal cancer screening test effectiveness and their recommendations for testing intervals influence patient screening uptake. Few large studies have examined providers’ perceptions and recommendations, including their alignment with evidence suggesting comparable test effectiveness and guideline recommendations for screening frequency. Providers (n = 1,281) within four healthcare systems completed a survey in 2017–2018 regarding their perceptions of test effectiveness and recommended intervals for colonoscopy and fecal immunochemical testing (FIT) for patients ages 40–49, 50–74, and ≥75 years. For patients 50–74 (screening eligible), 82.9% of providers rated colonoscopy as very effective versus 59.6% for FIT, and 26.3% rated colonoscopy as more effective than FIT. Also, for this age group, 77.9% recommended colonoscopy every 10 years and 92.4% recommended FIT annually. For patients ages 40–49 and ≥75, more than one-third of providers believed the tests were somewhat or very effective, although >80% did not routinely recommend screening by either test for these age groups. Provider screening test interval recommendations generally aligned with colorectal cancer guidelines; however, 25% of providers believed colonoscopy was more effective than FIT for mortality reduction, which differs from some modeling studies that suggest comparable effectiveness. The latter finding may have implications for health systems where FIT is the dominant screening strategy. Only one-third of providers reported believing these screening tests were effective in younger and older patients (i.e.

Objectives Many patients with cancer believe that something has gone wrong in their care but are reluctant to speak up. This pilot study sought to evaluate the impact of an intervention of active outreach to patients undergoing cancer treatment, wherein patients were encouraged to speak up if they had concerns about their care and to describe the types of concerns patients reported. Methods Patients receiving cancer care at two sites were randomly assigned to an intervention or control group. Intervention patients received a brochure encouraging them to speak up about any concerns and an outreach telephone call during which the interviewer explicitly asked about concerns. Participants in both groups received baseline and follow-up questionnaires assessing their perceptions of their care and whether anything had "gone wrong" and provided ratings of health care providers' communication and responsiveness. Qualitative content coding was used to categorize patient-reported concerns collected through the baseline and follow-up questionnaires (both groups) and during telephone outreach (intervention patients only). The primary outcome was the number of patients reporting a concern about their care. Communication and responsiveness ratings for intervention and control group patients were compared using t tests. Results Of the 60 patients in the intervention group, 34 (56.7%) reported at least one problem or concern, compared with 16 (29.1%) of the 55 patients in the control group (P = 0.003). The telephone outreach in particular resulted in more than half of those reached reporting a new concern (55.3%). We detected no impact of the intervention on patients' ratings of communication or support for speaking up. Conclusions Patients in this study reported a variety of concerns in response to active outreach, demonstrating that active outreach to patients can provide healthcare teams and systems the opportunity to offer a real-time response to the patient, identify where system improvements are needed, and implement policies, procedures, or programs to prevent recurrences.

Since 2012, cervical cancer screening guidelines allow for choice of screening test for women age 30–65 years (i.e., Pap every 3 years or Pap with human papillomavirus co-testing every 5 years). Intended to give patients and providers options, this flexibility reflects a trend in the growing complexity of screening guidelines. Our objective was to characterize variation in cervical screening at the individual, provider, clinic/facility, and healthcare system levels. The analysis included 296,924 individuals receiving screening from 3626 providers at 136 clinics/facilities in three healthcare systems, 2010 to 2017. Main outcome was receipt of co-testing vs. Pap alone. Co-testing was more common in one healthcare system before the 2012 guidelines (adjusted odds ratio (AOR) of co-testing at the other systems relative to this system 0.00 and 0.50) but was increasingly implemented over time in a second with declining uptake in the third (2017: AORs shifted to 7.32 and 0.01). Despite system-level differences, there was greater heterogeneity in receipt of co-testing associated with providers than clinics/facilities. In the three healthcare systems, providers in the highest quartile of co-testing use had an 8.35, 8.81, and 25.05-times greater odds of providing a co-test to women with the same characteristics relative to the lowest quartile. Similarly, clinics/ facilities in the highest quartile of co-testing use had a 4.20, 3.14, and 6.56-times greater odds of providing a co-test relative to the lowest quartile. Variation in screening test use is associated with health system, provider, and clinic/facility levels even after accounting for patient characteristics.

In 2012, United States consensus guidelines were modified to recommend that cervical cancer screening not begin before age 21 and, since 2014, the Health Effectiveness Data and Information Set (HEDIS), a health plan quality measurement too, has included a measure for non-recommended cervical cancer screening among females ages 16-20. Our goal was to describe prevalence over time of cervical cancer screening before age 21 following the 2012 guideline change, and provide information to help understand how rapidly new guidelines may be disseminated and implemented into clinical practice. We used longitudinal clinical and administrative data from three diverse healthcare systems in the Population-based Research to Optimize the Screening Process (PROSPR II) consortium to examine annual trends in screening before age 21. We identified 55,316 average-risk, screening-eligible females ages 18-20 between 2011 and 2017. For each calendar year, we estimated the proportion of females who received a Papanicolaou (Pap) test. We observed a steady decline in the proportion of females under age 21 who received a Pap test, from an average of 8.3% in 2011 to1% in 2017 across the sites. The observed steady decline suggests growing adherence to the 2012 consensus guidelines. This trend was consistent across diverse geographic regions, healthcare systems, and patient populations, strengthening the generalizability of the results; however, since we only had 1-2 years of study data prior to the consensus guidelines, we cannot discern whether screening under age 21 was already in decline. Nonetheless, these results provide data to compare with other guideline changes to de-implement non-recommended screening practices.

The first step in evaluating the effectiveness of cervical screening is defining exposure to screening. Our aim was to describe the spectrum of screening exposure definitions used in studies of the effectiveness of cervical screening. This systematic review included case-control studies in a population-based screening setting. Outcome was incidence of cervical cancer. Three electronic databases were searched from January 1, 2012 to December 6, 2018. Articles prior to 2012 were identified from a previous review. The qualitative synthesis focused on describing screening exposure definitions reported in the literature and the methodologic differences that could have an impact on the association between screening and cervical cancer. Forty-one case–control studies were included. Six screening exposure definitions were identified. Cervical cancer risk on average decreased by 66% when screening exposure was defined as ever tested, by 77% by time since last negative test, and by 79% after two or more previous tests. Methodologic differences included composition of the reference group and whether diagnostic and/or symptomatic tests were excluded from the analysis. Consensus guidelines to standardize exposure definitions are needed to ensure evaluations of cervical cancer screening can accurately measure the impact of transitioning from cytology to human papillomavirus–based screening and to allow comparisons between programs.

Background Cancer screening is a complex process encompassing risk assessment, the initial screening examination, diagnostic evaluation, and treatment of cancer precursors or early cancers. Metrics that enable comparisons across different screening targets are needed. We present population-based screening metrics for breast, cervical, and colorectal cancers for nine sites participating in the Population-based Research Optimizing Screening through Personalized Regimens consortium. Methods We describe how selected metrics map to a trans-organ conceptual model of the screening process. For each cancer type, we calculated calendar year 2013 metrics for the screen-eligible target population (breast: ages 40–74 years; cervical: ages 21–64 years; colorectal: ages 50–75 years). Metrics for screening participation, timely diagnostic evaluation, and diagnosed cancers in the screened and total populations are presented for the total eligible population and stratified by age group and cancer type. Results The overall screening-eligible populations in 2013 were 305 568 participants for breast, 3 160 128 for cervical, and 2 363 922 for colorectal cancer screening. Being up-to-date for testing was common for all three cancer types: breast (63.5%), cervical (84.6%), and colorectal (77.5%). The percentage of abnormal screens ranged from 10.7% for breast, 4.4% for cervical, and 4.5% for colorectal cancer screening. Abnormal breast screens were followed up diagnostically in almost all (96.8%) cases, and cervical and colorectal were similar (76.2% and 76.3%, respectively). Cancer rates per 1000 screens were 5.66, 0.17, and 1.46 for breast, cervical, and colorectal cancer, respectively. Conclusions Comprehensive assessment of metrics by the Population-based Research Optimizing Screening through Personalized Regimens consortium enabled systematic identification of screening process steps in need of improvement. We encourage widespread use of common metrics to allow interventions to be tested across cancer types and health-care settings.

Little is known about the effect of evolving risk-based cervical cancer screening and management guidelines on United States (US) clinical practice and patient outcomes. We describe the National Cancer Institute's Population-based Research Optimizing Screening through Personalized Regimens (PROSPR I) consortium, methods and baseline findings from its cervical sites: Kaiser Permanente Washington, Kaiser Permanente Northern California, Kaiser Permanente Southern California, Parkland Health & Hospital System/University of Texas Southwestern (Parkland-UTSW) and New Mexico HPV Pap Registry housed by University of New Mexico (UNM-NMHPVPR). Across these diverse healthcare settings, we collected data on human papillomavirus (HPV) vaccinations, screening tests/results, diagnostic and treatment procedures/results and cancer diagnoses on nearly 4.7 million women aged 18-89 years from 2010 to 2014. We calculated baseline (2012 for UNM-NMHPVPR; 2010 for other sites) frequencies for sociodemographics, cervical cancer risk factors and key screening process measures for each site's cohort. Healthcare delivery settings, cervical cancer screening strategy, race/ethnicity and insurance status varied among sites. The proportion of women receiving a Pap test during the baseline year was similar across sites (26.1-36.1%). Most high-risk HPV tests were performed either reflexively or as cotests, and utilization pattern varied by site. Prevalence of colposcopy or biopsy was higher at Parkland-UTSW (3.6%) than other sites (1.3-1.4%). Incident cervical cancer was rare. HPV vaccination among age-eligible women not already immunized was modest across sites (0.1-7.2%). Cervical PROSPR I makes available high-quality, multilevel, longitudinal screening process data from a large and diverse cohort of women to evaluate and improve the effectiveness of US cervical cancer screening delivery.

Introduction: Infection with certain types of human papillomavirus (HPV) can lead to cervical cancer as well as other cancers in both men and women. However, the requirement for multiple doses may limit the vaccine’s effectiveness for cancer prevention. We conducted a pilot study to investigate barriers to HPV vaccine series completion among members of an integrated healthcare system with clinical documentation of only 1 dose. Methods: We surveyed parents or legal guardians of 11-17-year-old girls (n = 10) and boys (n = 18), as well as 18-31-year-old women (n = 20) and men (n = 9), about their reasons for not completing the HPV vaccine series. Results: Most participants (70.2%) were non-Hispanic white. Among parents of children, commonly reported barriers to HPV vaccine series completion included not being aware or informed of the need for additional doses (28.6%), as well as the inconvenience of returning for additional doses (17.9%). Concerns about the HPV vaccine or vaccines in general were more common among parents of girls (30.0%) compared with parents of boys (16.7%). Among adults, barriers to HPV vaccine series completion included the inconvenience of returning for additional doses (31.0%), not being aware or informed of the need for additional doses (10.3%), and forgetting (10.3%). Conclusion: Our findings suggest that clinicians and healthcare systems can play a greater role in promoting awareness of the multiple-dose requirement, addressing vaccine concerns, and increasing opportunistic vaccination in a variety of settings. Increasing these efforts may facilitate HPV vaccine completion and increase its effectiveness in cancer prevention.

Screening can decrease the burden of breast, cervical, and colorectal cancers. The COVID-19 pandemic led many countries to suspend cancer screening services as part of their response to the pandemic. The International Cancer Screening Network (ICSN) carried out an online survey to assess the effects of the first wave of the COVID-19 pandemic on cancer screening. A 33-item survey was distributed to 834 email addresses to gather information about settings and assess decision-making processes that led to cancer screening suspension. Information about communication, impact on resources, and patient follow-up was collected. Quantitative data was analyzed as frequencies overall and by setting, while a comment section under each survey item captured nuanced details. Responses were recategorized into 66 settings, representing 35 countries. Most settings suspended cancer screening services (n = 60, 90.9%) in March 2020 (n = 45, 68.2%), guided by a government decision (n = 51, 77.3%). Few settings made the decision whether to suspend services based on a preparedness plan (n = 17, 25.8%). In most settings, professionals were reassigned (n = 41, 62.1%) and infrastructure repurposed (n = 35, 53.0%). The first wave of the COVID-19 pandemic has had profound effects on cancer screening worldwide, including the suspension of services in almost all settings. Most settings were unprepared to deal with the scale of the pandemic but demonstrated flexibility in the response. These results contribute to inform, through experiences and lessons learned, the next steps for the global cancer screening community to further evaluate the impact of COVID-19 and prepare for future disruptions.

PURPOSE: BRAF mutation and DNA hypermethylation have linked sessile serrated adenomas/polyps (SSA/Ps) to serrated colorectal cancer (CRC) in cross-sectional studies, but they have not been evaluated in a longitudinal study. We aimed to evaluate the associations between molecular markers of serrated polyps and subsequent advanced colorectal neoplasia. METHODS: Study subjects included Kaiser Permanente Washington members aged 20–75 years who received an index colonoscopy between 1/1/1998 and 12/31/2007 and had hyperplastic polyps (HPs) or SSA/Ps according to study pathology review. Polyps from index colonoscopies were removed and assayed for BRAF mutation, CpG island methylator phenotype (CIMP), and MLH1 methylation. Pathology reports and biopsies from the subsequent lower gastrointestinal endoscopy through 1/1/2013 were reviewed for advanced colorectal neoplasia. We identified additional incident CRC cases through linkage to the Seattle-Puget Sound Surveillance Epidemiology and End Results registry. We used generalized estimating equations to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for subsequent advanced colorectal neoplasia, comparing index serrated polyps with different molecular markers. RESULTS: We included 553 individuals with index serrated polyps (420 HPs and 133 SSA/Ps) and 795 subsequent endoscopies. The prevalence of BRAF-mutant, CIMP-high, and MLH1-methylated serrated polyps were 51%, 4%, and 2%, respectively. BRAF and CIMP were not associated with subsequent advanced colorectal neoplasia. MLH1-methylated SSP/As were significantly more likely to have subsequent advanced neoplasia (OR = 4.66, 95% CI 1.06–20.51). CONCLUSION: Our results suggest that BRAF-mutant and CIMP-high serrated polyps are not associated with subsequent advanced colorectal neoplasia. Among SSA/Ps, MLH1 methylation may be an important marker to identify high-risk CRC precursors.

Objective To incorporate blood pressure (BP), diagnoses codes, and medication fills from electronic medical records (EMR) to identify pregnant women with hypertension. Study design A retrospective cohort study of singleton pregnancies at three US integrated health delivery systems during 2005–2014. Main outcome measures Women were considered hypertensive if they had any of the following: (1) ≥2 high BPs (≥140/90 mmHg) within 30 days during pregnancy (High BP); (2) an antihypertensive medication fill in the 120 days before pregnancy and a hypertension diagnosis from 1 year prior to pregnancy through 20 weeks gestation (Treated Chronic Hypertension); or (3) a high BP, a hypertension diagnosis, and a prescription fill within 7 days during pregnancy (Rapid Treatment). We described characteristics of these pregnancies and conducted medical record review to understand hypertension presence and severity. Results Of 566,624 pregnancies, 27,049 (4.8%) met our hypertension case definition: 24,140 (89.2%) with High BP, 5,409 (20.0%) with Treated Chronic Hypertension, and 5,363 (19.8%) with Rapid Treatment (not mutually exclusive). Of hypertensive pregnancies, 19,298 (71.3%) received a diagnosis, 9,762 (36.1%) received treatment and 11,226 (41.5%) had a BP ≥ 160/110. In a random sample (n = 55) of the 7,559 pregnancies meeting the High BP criterion with no hypertension diagnosis, clinical statements about hypertension were found in medical records for 58% of them. Conclusion Incorporating EMR BP identified many pregnant women with hypertension who would have been missed by using diagnosis codes alone. Future studies should seek to incorporate BP to study treatment and outcomes of hypertension in pregnancy.

COVID-19 has proved enormously disruptive to the provision of cancer screening, which does not just represent an initial test but an entire process, including risk detection, diagnostic follow-up, and treatment. Successful delivery of services at all points in the process has been negatively affected by the pandemic. There is a void in empirical high-quality evidence to support a specific strategy for administering cancer screening during a pandemic and its resolution phase, but several pragmatic considerations can help guide prioritization efforts. Targeting guideline-eligible people who have never been screened, or those who are significantly out of date with screening, has the potential to maximize benefits now and into the future. Disruptions to care due to the pandemic could represent an unparalleled opportunity to reassess early detection programs towards an explicit, thoughtful, and just prioritization of populations historically experiencing cancer disparities. By focusing screening services on populations that have the most to gain, and by careful and deliberate planning for the period following the pandemic, we can positively affect cancer outcomes for all.

We studied harms related to cervical cancer screening and management of screen-positive women in the United States (US) and the Netherlands. We utilized data from four US integrated health care systems (SEARCH), the US National Health Interview Survey, New Mexico state, the Netherlands national histopathology registry, and included studies on adverse health effects of cervical screening. We compared the number of Papanicolaou (Pap) smear tests, abnormal test results, punch biopsies, treatments, health problems (anxiety, pain, bleeding and discharge) and preterm births associated with excisional treatments. Results were age-standardized to the 2007 US population. Based on SEARCH, an estimated 36 million Pap tests were performed in 2007 for 91 million US women aged 21–65 years, leading to 2.3 million abnormal Pap tests, 1.5 million punch biopsies, 0.3 million treatments for precancerous lesions, 5 thousand preterm births and over 8 million health problems. Under the Netherlands screening practice, fewer Pap tests (58%), abnormal test results (64%), punch biopsies (75%), treatment procedures (40%), preterm births (60%) and health problems (63%) would have occurred. The SEARCH data did not differ much from other US data for 2007 or from more recent data up to 2013. Thus compared to the less intensive screening practice in the Netherlands, US practice of cervical cancer screening may have resulted in two- to threefold higher harms, while the effects on cervical cancer incidence and mortality are similar. The results are also of high relevance in making recommendations for HPV screening. Systematic collection of harms data is needed for monitoring and for better incorporation of harms in making screening recommendations.

Background: Despite the importance of characterizing colonoscopy indication for quality monitoring and cancer screening program evaluation, there is no standard approach to documenting colonoscopy indication in medical records.Methods: We applied two algorithms in three health care systems to assign colonoscopy indication to persons 50–89 years old who received a colonoscopy during 2010–2013. Both algorithms used standard procedure, diagnostic, and laboratory codes. One algorithm, the KPNC algorithm, used a hierarchical approach to classify exam indication into: diagnostic, surveillance, or screening; whereas the other, the SEARCH algorithm, used a logistic regression-based algorithm to provide the probability that colonoscopy was performed for screening. Gold standard assessment of indication was from medical records abstraction.Results: There were 1,796 colonoscopy exams included in analyses; age and racial/ethnic distributions of participants differed across health care systems. The KPNC algorithm’s sensitivities and specificities for screening indication ranged from 0.78–0.82 and 0.78–0.91, respectively; sensitivities and specificities for diagnostic indication ranged from 0.78–0.89 and 0.74–0.82, respectively. The KPNC algorithm had poor sensitivities (ranging from 0.11–0.67) and high specificities for surveillance exams. The Area Under the Curve (AUC) of the SEARCH algorithm for screening indication ranged from 0.76–0.84 across health care systems. For screening indication, the KPNC algorithm obtained higher specificities than the SEARCH algorithm at the same sensitivity.Conclusion: Despite standardized implementation of these indication algorithms across three health care systems, the capture of colonoscopy indication data was imperfect. Thus, we recommend that standard, systematic documentation of colonoscopy indication should be added to medical records to ensure efficient and accurate data capture.

PURPOSE: Colonoscopy and flexible sigmoidoscopy are both recommended colorectal cancer (CRC) screening strategies, but their relative effectiveness is unclear. We sought to evaluate the ability of each of these two modalities to reduce CRC mortality. METHODS: We conducted a case-control study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Cases were persons aged 70–85 years who died of CRC and were matched to up to three non-CRC controls. Receipt of endoscopy was ascertained from Medicare claims and endoscopy indication assigned using a validated algorithm. Conditional logistic regression models were developed to estimate the association between screening colonoscopy or sigmoidoscopy and CRC mortality. We conducted secondary analyses by race, sex, and endoscopist characteristics, and with varying duration of the look-back period. RESULTS: In the initial analysis using all available look-back years, screening flexible sigmoidoscopy was associated with a 35% reduction in CRC mortality (OR 0.65, 95% CI 0.48, 0.89), while screening colonoscopy was associated with a 74% reduction (OR 0.26, 95% CI 0.23, 0.30). Sigmoidoscopy was not associated with any reduction in proximal CRC mortality. The association between colonoscopy and reduced CRC mortality was stronger in the distal than the proximal colon. Results were similar in analyses using a 5-year look-back period. CONCLUSIONS: Screening colonoscopy was associated with greater reductions in CRC mortality than screening sigmoidoscopy, and with a greater reduction in the distal than the proximal colon. These results provide additional information on the relative benefits of screening for CRC with sigmoidoscopy and colonoscopy.

PURPOSE: Colorectal cancer (CRC) screening guidelines recommend increased surveillance of individuals with sessile serrated adenomas/polyps (SSA/Ps), but there is uncertainty about the risk associated with SSA/Ps. We aimed to determine the association between SSA/Ps and subsequent advanced colorectal neoplasia. METHODS: This case-control study included Kaiser Permanente Washington (KPWA) members who received an index colonoscopy between 1/1/1998 and 12/31/2007, and had hyperplastic polyps (HPs) or SSA/Ps but no conventional adenomas according to study pathologist histologic review. Subsequent pathology reports and biopsies through 1/1/2013 were reviewed for advanced colorectal neoplasia. We linked to the Seattle-Puget Sound Surveillance Epidemiology and End Results (SEER) registry to identify additional CRC cases. We used generalized estimating equations with a logit link to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for advanced colorectal neoplasia, comparing those with SSA/Ps to those with HPs. RESULTS: There were 161 individuals with index SSA/Ps, 548 with HPs, and 918 subsequent endoscopies included in analyses. Of those with index SSA/Ps, 19 had subsequent advanced colorectal neoplasia; 39 with HPs had subsequent advanced colorectal neoplasia. Compared to those with HPs, those with SSA/Ps were not statistically significantly more likely to have subsequent advanced colorectal neoplasia (adjusted OR 1.79; CI 0.98–3.28). Polyp size ≥ 10 mm, right colon location, and the presence of multiple serrated polyps were also not associated with advanced colorectal neoplasia. CONCLUSIONS: Our results suggest that there is not a strong association between SSA/Ps and subsequent advanced colorectal neoplasia during the 5 years following SSA/P removal.

Case-control studies evaluating a screening test's efficacy in reducing cancer mortality require accurate classification of test indication to obtain a valid result. However, for analogous studies of cancer incidence, determination of test indication is not as critical because, to define exposure, we need consider only tests that can identify precursor lesions whose treatment might prevent cancer, not tests leading to cancer diagnosis. This study utilizes US Surveillance, Epidemiology, and End Results (SEER)-Medicare data, which do not include information about colonoscopy indication, to evaluate the efficacy of colonoscopy in preventing colorectal cancer (CRC) incidence. Cases were Medicare enrollees diagnosed with CRC between 1996 and 2013; up to 3 controls were matched to each case. Colonoscopy receipt prior to presumed onset of occult cancer was associated with an approximately 60% reduction in CRC incidence (odds ratio = 0.41, 95% confidence interval: 0.40, 0.42). The association was robust to differing exposure windows and estimates of occult cancer duration and is similar to those from CRC incidence studies in which exam indication was available. Our results suggest that, when it is impractical/impossible to determine whether tests were conducted for screening, the efficacy of a test in preventing cancer incidence can still be estimated using a case-control study design.

BackgroundFlexible sigmoidoscopy and colonoscopy are both recommended colorectal cancer screening options, but their relative effectiveness needs clarification. The aim of this study was to compare the effectiveness of colonoscopy and flexible sigmoidoscopy for reduction of colorectal cancer incidence.MethodsWe conducted a case-control study within the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Cases were subjects age 70-85 years in the SEER-Medicare database diagnosed with CRC during 2004-2013. Up to 3 controls were matched to each case by birth year, sex, race, and SEER region. Receipt of screening colonoscopy or flexible sigmoidoscopy was ascertained from Medicare claims. Conditional logistic regression models were developed to estimate the odds ratios (ORs) and 95% confidence intervals (CI) for a history of screening in cases vs. controls. We conducted secondary analyses by sex, race, endoscopist characteristics, and with varying timing and duration of the look-back period.ResultsReceipt of screening colonoscopy and sigmoidoscopy was associated with a 59% (OR 0.41, 95%CI 0.39, 0.43) and 22% reduction (OR 0.78, 95%CI 0.67, 0.92) in colorectal cancer incidence, respectively. Colonoscopy was associated with greater reduction in the distal colorectal cancer incidence (OR 0.22, 95%CI 0.20, 0.24) than proximal colorectal cancer incidence (OR 0.62, 95%CI 0.59, 0.66). Sigmoidoscopy was associated with a 52% reduction in distal colorectal cancer incidence (OR 0.48, 95%CI 0.37, 0.63), but with no reduction in proximal colorectal cancer incidence. These associations were stronger in men than in women. No differences by race or endoscopist characteristics were observed.ConclusionBoth screening colonoscopy and sigmoidoscopy were associated with reductions in overall colorectal cancer incidence, with a greater magnitude of reduction observed with colonoscopy.

Expert recommendations differ for colorectal cancer screening in the elderly. Recent studies suggest that healthy adults aged75 years may benefit from screening. This study examined screening use and follow-up, and how they varied by health status within age strata, among a large cohort of elderly individuals in community settings.A population-based, longitudinal cohort study was conducted among health plan members aged 65-89 years enrolled during 2011-2012 in three integrated healthcare systems participating in the Population-Based Research Optimizing Screening through Personalized Regimens consortium. Comorbidity measurements used the Charlson index. Analyses, conducted in 2015, comprised descriptive statistics and multivariable modeling that estimated age by comorbidity-specific percentages of patients for two outcomes: colorectal cancer screening uptake and follow-up of abnormal fecal blood tests.Among 846,267 patients, 72% were up-to-date with colorectal cancer screening. Of patients with a positive fecal blood test, 65% received follow-up colonoscopy within 3 months. Likelihood of being up-to-date and receiving timely follow-up was significantly lower for patients aged ≥76 years than their younger counterparts (p0.001). Comorbidity was less influential than age and more strongly related to timely follow-up than being up-to-date. In all age groups, considerable numbers of patients with no/low comorbidity were not up-to-date or did not receive timely follow-up.In three integrated healthcare systems, many older, relatively healthy patients were not screening up-to-date, and some relatively young, healthy patients did not receive timely follow-up. Findings suggest a need for re-evaluating age-based screening guidelines and improving screening completion among the elderly.

Exposures derived from electronic health records (EHR) may be misclassified, leading to biased estimates of their association with outcomes of interest. An example of this problem arises in the context of cancer screening where test indication, the purpose for which a test was performed, is often unavailable. This poses a challenge to understanding the effectiveness of screening tests because estimates of screening test effectiveness are biased if some diagnostic tests are misclassified as screening. Prediction models have been developed for a variety of exposure variables that can be derived from EHR, but no previous research has investigated appropriate methods for obtaining unbiased association estimates using these predicted probabilities. The full likelihood incorporating information on both the predicted probability of exposure-class membership and the association between the exposure and outcome of interest can be expressed using a finite mixture model. When the regression model of interest is a generalized linear model (GLM), the expectation-maximization algorithm can be used to estimate the parameters using standard software for GLMs. Using simulation studies, we compared the bias and efficiency of this mixture model approach to alternative approaches including multiple imputation and dichotomization of the predicted probabilities to create a proxy for the missing predictor. The mixture model was the only approach that was unbiased across all scenarios investigated. Finally, we explored the performance of these alternatives in a study of colorectal cancer screening with colonoscopy. These findings have broad applicability in studies using EHR data where gold-standard exposures are unavailable and prediction models have been developed for estimating proxies.

Electronic health records and administrative databases provide rich, longitudinal data for health-related research. These data cover large, diverse populations creating excellent research opportunities, but have limitations. In particular, information is available only for individuals who are enrolled in a particular health system; thus, studies often exclude individual's with short enrollment history. Such cohort restriction may cause selection bias in absolute risk estimates for the full enrollee population. We use hazard ratios (HRs) to estimate the association between length of prior enrollment and cancer and all-cause mortality risk. HRs different from one indicate restricted cohorts would produce biased risk estimates for the full enrollee population. Our study sample included 170,708 enrollees of a Western Washington healthcare delivery system. Unadjusted models found individuals with 10 or more years of prior enrollment had higher risk of cancer and death compared to those with less than 5 years prior enrollment (HRs ranged from 1.29 - 3.01). Age- and sex-adjusted models accounted for much of this difference (HRs: 0.93 - 1.24). Models adjusting for additional covariates had similar results (HRs: 0.91 - 1.14). After evaluating potential selection bias, we conclude that, in this setting, age- and sex-standardizing risk estimates can remove most of the bias due to lengthy, prior-enrollment cohort restrictions. Before generalizing estimates based on a selected sample of patients meeting prior enrollment criteria, researchers should assess the potential for selection bias.

Primary care providers and health systems have prominent roles in guiding effective cancer screening. To characterize variation in screening abnormality rates and timely initial follow-up for common cancer screening tests. Population-based cohort undergoing screening in 2011, 2012, or 2013 at seven research centers comprising the National Cancer Institute-sponsored Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. Adults undergoing mammography with or without digital breast tomosynthesis (n = 97,683 ages 40–75 years), fecal occult blood or fecal immunochemical tests (n = 759,553 ages 50–75 years), or Papanicolaou with or without human papillomavirus tests (n = 167,330 ages 21–65 years). Breast, colorectal, or cervical cancer screening. Abnormality rates per 1000 screens; percentage with timely initial follow-up (within 90 days, except 9-month window for BI-RADS 3). Primary care clinic-level variation in percentage with screening abnormality and percentage with timely initial follow-up. There were 10,248/97,683 (104.9 per 1000) abnormal breast cancer screens, 35,847/759,553 (47.2 per 1000) FOBT/FIT-positive colorectal cancer screens, and 13,266/167,330 (79.3 per 1000) abnormal cervical cancer screens. The percentage with timely follow-up was 93.2 to 96.7 % for breast centers, 46.8 to 68.7 % for colorectal centers, and 46.6 % for the cervical cancer screening center (low-grade squamous intraepithelial lesions or higher). The primary care clinic variation (25th to 75th percentile) was smaller for the percentage with an abnormal screen (breast, 8.5–10.3 %; colorectal, 3.0–4.8 %; cervical, 6.3–9.9 %) than for the percentage with follow-up within 90 days (breast, 90.2–95.8 %; colorectal, 43.4–52.0 %; cervical, 29.6–61.4 %). Variation in both the rate of screening abnormalities and their initial follow-up was evident across organ sites and primary care clinics. This highlights an opportunity for improving the delivery of cancer screening through focused study of patient, provider, clinic, and health system characteristics associated with timely follow-up of screening abnormalities.

Kaiser Permanente (KP) is an ideal environment to study the spectrum of cancer prevention and control because it provides comprehensive cancer care to a large and diverse community. The Kaiser Permanente Research Bank (KPRB) is collecting biospecimens and a survey of health-related behaviors and other risk factors from about 400,000 adults aged 18 years and older across all eight KP regions. The KPRB includes a cancer cohort and cases are identified from KP region-specific algorithms designed to identify cancer cases within days of diagnosis, and from linkage with regional tumor registries. KPRB participation involves completing an online informed consent and survey, and providing a blood or saliva sample. KPRB participants consent to linkage to their electronic health record (EHR), which includes comprehensive information about cancer screening, diagnosis and treatment. A key strength of this cohort is its diversity with respect to age, race/ethnicity, and geographic location (Hawai’i, Oregon, Washington state, California, Colorado, Georgia, and the Washington, DC area). To date, the KPRB includes 68,000 cancer cases, 56% are women, and 30% are non-white. Over 8,500 cases were diagnosed before the age of 50 and the cohort includes substantial numbers of cancer cases among Asian and Pacific Islanders (n=8,941), Hispanics (n=7,678), and non-Hispanic blacks (n=5,367). Although all cohort members have insurance, and thus, presumably access to care, we observed disparities in stage at diagnosis. Compared to non- Hispanic whites, non-Hispanic Blacks are more likely to be diagnosed at stage 4 (5% versus 16%, respectively, of all cases); participants describing themselves as multi- racial or “other” race similarly have a very high proportion (25%) of cases diagnosed at stage 4. Research is planned to examine the factors associated with this disparity. The extensive EHR, access to stored tissue specimens, detailed treatment data, and ability to follow patients over time for recurrence and mortality make the KPRB Cancer Cohort an exceptional resource for exploring the factors that contribute to cancer etiology, progression, and survival. We invite investigators to apply to use the KPRB (https://researchbank.kaiserpermanente.org/) to accelerate progress toward improving cancer care. Citation Format: Heather S. Feigelson, Christina Clarke, Andrea Burnett- Hartman, Stephen Van Den Eeden, Sheila Weinmann, Monica Ter-Minassian, Stacey Honda, Deborah Young, Aruna Kamineni, Sarah Rowell, Alan Bauck, Elizabeth McGlynn. The Kaiser Permanente Research Bank cancer cohort: A diverse resource to improve cancer care [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-178.

Background & Aims The long-term risks of colorectal cancer (CRC) and CRC-related death following adenoma removal are uncertain. Data are needed to inform evidence-based surveillance guidelines, which vary in follow-up recommendations for some polyp types. Using data from a large, community-based integrated health care setting, we examined the risks of CRC and related death by baseline colonoscopy adenoma findings. Methods Participants at 21 medical centers underwent baseline colonoscopies from 2004 through 2010; findings were categorized as no adenoma, low-risk adenoma, or high-risk adenoma. Participants were followed until the earliest of CRC diagnosis, death, health plan disenrollment, or December 31, 2017. Risks of CRC and related deaths among the high- and low-risk adenoma groups were compared with the no adenoma group using Cox regression adjusting for confounders. Results Among 186,046 patients, 64,422 met eligibility criteria (54.3% female; mean age, 61.6±7.1 y; median follow-up time, 8.1 y from the baseline colonoscopy). Compared with the no-adenoma group (45,881 patients), the high-risk adenoma group (7563 patients) had a higher risk of CRC (hazard ratio [HR], 2.61; 95% CI, 1.87–3.63) and related death (HR, 3.94; 95% CI, 1.90–6.56), whereas the low-risk adenoma group (10,978 patients) did not have a significant increase in risk of CRC (HR, 1.29; 95% confidence interval, 0.89–1.88) or related death (HR, 0.65; 95% CI, 0.19–2.18). Conclusions With up to 14-years of follow-up, high-risk adenomas were associated with an increased risk of CRC and related death, supporting early colonoscopy surveillance. Low-risk adenomas were not associated with a significantly increased risk of CRC or related deaths. These results can inform current surveillance guidelines for high- and low-risk adenomas.

Background The fecal immunochemical test (FIT) is commonly used for colorectal cancer (CRC) screening. Despite demographic variations in stool hemoglobin concentrations, few data exist regarding optimal positivity thresholds by age and sex. Objective To identify programmatic (multitest) FIT performance characteristics and optimal FIT quantitative hemoglobin positivity thresholds in a large, population-based, screening program. Design Retrospective cohort study. Setting Kaiser Permanente Northern and Southern California. Participants Adults aged 50 to 75 years who were eligible for screening and had baseline quantitative FIT results (2013 to 2014) and 2 years of follow-up. Nearly two thirds (411 241) had FIT screening in the previous 2 years. Measurements FIT programmatic sensitivity for CRC and number of positive test results per cancer case detected, overall and by age and sex. Results Of 640 859 persons who completed a baseline FIT and were followed for 2 years, 481 817 (75%) had at least 1 additional FIT and 1245 (0.19%) received a CRC diagnosis. Cancer detection (programmatic sensitivity) increased at lower positivity thresholds, from 822 in 1245 (66.0%) at 30 µg/g to 925 (74.3%) at 20 µg/g and 987 (79.3%) at 10 µg/g; the number of positive test results per cancer case detected increased from 43 at 30 µg/g to 52 at 20 µg/g and 85 at 10 µg/g. Reducing the positivity threshold from 20 to 15 µg/g would detect 3% more cancer cases and require 23% more colonoscopies. At the conventional FIT threshold of 20 µg/g, programmatic sensitivity decreased with increasing age (79.0%, 73.4%, and 68.9% for ages 50 to 59, 60 to 69, and 70 to 75 years, respectively; P = 0.009) and was higher in men than women (77.0% vs. 70.6%; P = 0.011). Limitation Information on advanced adenoma was lacking. Conclusion Increased cancer detection at lower positivity thresholds is counterbalanced by substantial increases in positive tests. Tailored thresholds may provide screening benefits that are more equal among different demographic groups, depending on local resources. Primary Funding Source National Cancer Institute.

Objective: Hypertension is a major risk factor for poor pregnancy outcomes. Many observational studies have relied on diagnosis codes, particularly from the delivery hospitalization, to identify hypertension in pregnancy. We augmented diagnosis codes with electronic blood pressure (BP) data to improve the identification of pregnant women with hypertension. Methods: We studied pregnant women aged 15-49 years enrolled in three Kaiser Permanente health plans who delivered during 2005-2014. Using diagnosis codes, BP values, and antihypertensive medication dispensings, we defined hypertension as: (1) ≥ 2 high BPs (≥ 140/90 mmHg) within 30 days of each other (2highBPs); or (2) ≥ 1 antihypertensive medication fill with ≥1 hypertension diagnosis code from 120 days prior to pregnancy through 20 weeks gestation (chronicHTN); or (3) ≥ 1 high BP, a hypertension diagnosis code, and an antihypertensive fill within 7 days (RapidTx). Among women meeting our study definition, we examined receipt of hypertension diagnosis codes and prevalence of severe hypertension (1+ BP ≥160/110 mmHg). Results: Among 553,477 eligible women, 29,933 (5%) met our definition of hypertension, including 26,855 identified via 2highBPs, 5,774 via chronicHTN and 6,198 via RapidTx (not mutually exclusive). Among women meeting our hypertension definition overall, only 64% had 1+ hypertension diagnosis code assigned during pregnancy, and 49% had one at delivery. Among hypertensive women identified via 2highBPs, only 60% (16,057/26,855) had a hypertension diagnosis code in pregnancy and 45% (12,131/ 26,855) at delivery. However, 53% of our hypertensive women (14,972/ 29,933) overall and 56% (14,972/ 26,855) of the 2highBPs women had severe hypertension at some time during pregnancy. Conclusion: Incorporating BP values identifies additional pregnant women with hypertension who would have been missed by approaches using diagnosis codes alone. Women identified by our method frequently had severely elevated BP, showing the importance of including these women in future studies of hypertension during pregnancy.

Objective: In the U.S., 1.3 million women of reproductive age take antihypertensive medications for chronic hypertension. However, some of these medications are considered unsafe during pregnancy. We evaluated the burden of switching and stopping medications during pregnancy among women receiving treatment for chronic hypertension. Study Design: We identified a population-based cohort of women with chronic hypertension who received antihypertensive medications within 120 days before pregnancy and gave birth to a singleton between 2005 and 2014 within three Kaiser Permanente regions. We characterized women’s antihypertensive medication use from 120 days before pregnancy through delivery. We ascertained the highest systolic and diastolic blood pressures in the 120 days before the start of pregnancy and supplemented these values with measures up through 8 weeks’ gestation when pre-pregnancy values were missing. Results: 5,782 pregnant women were included. Prior to pregnancy, the most commonly used medication classes were thiazide diuretics (2,370/5,782, 41%), beta-blockers (1,569/5,782, 27%) and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) (1,391/5,782, 24%). In contrast, the predominant medications during pregnancy were labetalol (2,165/5,782, 37%) and methyldopa (1,593/5,782, 28%). During pregnancy, 18% of the cohort (1,037/5,782) had no antihypertensive medication fills. Women taking ACEI/ARBs or thiazides before pregnancy were the most likely to have no medication fills in pregnancy (23% and 20%, respectively). Many women (n=881) had at least one severe high BP (SBP ≥160 or DBP ≥110) before pregnancy, and in this group, 15% (132/881) filled no medications throughout pregnancy. Conclusion: Women with chronic hypertension frequently stop antihypertensive medications during pregnancy, even women with a severely high BP documented before pregnancy. Research is needed to understand impact of these treatment interruptions on pregnancy outcomes and women’s long-term health.

BACKGROUND Cervical cancer screening and follow-up guidelines have changed considerably in recent years, but to the authors' knowledge few published reports exist to estimate the impact of these changes in community-based settings. The authors examined the patterns and results of cervical cancer testing and follow-up over a decade in 4 geographically diverse US health care systems to inform the future evaluation of changes resulting from increased uptake of the human papillomavirus (HPV) vaccination. METHODS The authors studied women aged 21 to 65 years who were members of one of these health systems at any time between 1998 and 2007. Data were collected and standardized across sites, based on receipt of Papanicolaou (Pap) and HPV tests, HPV vaccination, cervical biopsies, and treatment of cervical dysplasia. Annual rates (per 1000 person-years) of Pap testing, HPV testing, and cervical biopsy and treatment procedures were calculated. Screening intervals and trends in the results of screening Pap tests and cervical biopsies also were examined. RESULTS Pap testing rates decreased (from 483 per 1000 person-years in 2000 to 412 per 1000 person-years in 2007) and HPV testing rates increased over the study period. Screening frequency varied across health care systems, and many women continued to receive annual testing. All 4 sites moved to less frequent screening over the study period without marked changes in the overall use of cervical biopsy or treatment. CONCLUSIONS Despite differences over time and across health plans in rates of cervical cancer testing and follow-up cervical procedures, the authors found no notable differences in Pap test results, diagnostic or treatment procedure rates, or pathological outcomes. This finding suggests that the longer screening intervals did not lead to more procedures or more cancer diagnoses. Cancer 2015;121:2976–2983. © 2015 American Cancer Society.

Describe the prevalence of colonoscopy before age 50, when guidelines recommend initiation of colorectal cancer screening for average risk individuals.We assembled administrative health records that captured receipt of colonoscopy between 40 and 49-years of age for a cohort of 204,758 50-year-old members of four US health plans and used backward recurrence time models to estimate trends in receipt of colonoscopy before age 50 and variation in early colonoscopy by age and sex. We also used self-reported receipt of colonoscopy from 27,157 40- to 49-year-old respondents to the 2010 National Health Interview Survey (NHIS) to estimate the association between early colonoscopy and sex, race/ethnicity, and geographic location based on logistic regression models that accounted for the complex NHIS sampling design.About 5% of the health plan cohort had a record of colonoscopy before age 50. Receipt of early colonoscopy increased significantly from 1999 to 2010 (test for linear trend, p0.0001), was more likely among women than men (RR=1.9, 95% CI 1.14-1.24) and in the east coast health plan compared to west coast and Hawaii plans. The NHIS analysis found that early colonoscopy was more likely in Northeastern residents compared to residents in the West (odds ratio=1.75, 95% CI 1.28-2.39).Colonoscopy before age 50 is increasingly common.

Objectives Analysis of cancer screening effectiveness is challenging in part because of competing tests, which are additional screening tests that identify the condition of interest. For example, studies investigating screening with faecal occult blood tests to prevent colorectal cancer mortality need to consider the occurrence of screening colonoscopy. This paper compares analytic approaches to accounting for competing tests in analyses of cancer screening data. Methods We used simulations to compare bias and efficiency across approaches in different scenarios, quantify bias, and make recommendations for analyzing the effectiveness of a screening test in the presence of competing tests. Results Under all scenarios, the best performing approach for accommodating competing screening tests was censoring at the time of the competing screening test (range in bias across scenarios: −7.6% to 1.6%). Bias from other approaches ranged from 23.9% to 652.1%. Conclusions Censoring at the competing screening exam is the recommended approach for studying cancer screening effectiveness in the presence of competing tests. Censoring avoids confounding by prior competing test results and selection bias resulting from analyzing data on participants after they received a competing screening exam. Results from this study are broadly applicable to screening studies for other conditions, including other types of cancer.

Previous research shows that patients in integrated health systems experience fewer racial disparities compared with more traditional healthcare systems. Little is known about patterns of racial/ethnic disparities between safety-net and non safety-net integrated health systems. We evaluated racial/ethnic differences in body mass index (BMI) and the Charlson comorbidity index from 3 non safety-net- and 1 safety-net integrated health systems in a cross-sectional study. Multinomial logistic regression modeled comorbidity and BMI on race/ethnicity and health care system type adjusting for age, sex, insurance, and zip-code-level income The study included 1.38 million patients. Higher proportions of safety-net versus non safety-net patients had comorbidity score of 3+ (11.1% vs. 5.0%) and BMI ≥35 (27.7% vs. 15.8%). In both types of systems, blacks and Hispanics were more likely than whites to have higher BMIs. Whites were more likely than blacks or Hispanics to have higher comorbidity scores in a safety net system, but less likely to have higher scores in the non safety-nets. The odds of comorbidity score 3+ and BMI 35+ in blacks relative to whites were significantly lower in safety-net than in non safety-net settings. Racial/ethnic differences were present within both safety-net and non safety-net integrated health systems, but patterns differed. Understanding patterns of racial/ethnic differences in health outcomes in safety-net and non safety-net integrated health systems is important to tailor interventions to eliminate racial/ethnic disparities in health and health care.

BACKGROUND To the authors' knowledge, few studies to date have examined adherence to recommended guidelines for follow-up and outcomes after an unsatisfactory Papanicolaou (Pap) test (UPT) with liquid-based technologies. METHODS Within 4 US health plans, the median time to follow-up and the percentage of patients with follow-up testing by 120 days was calculated after a UPT. Multivariable analyses evaluated the association between clinical factors and follow-up testing. The authors compared the risk of a diagnosis of cervical intraepithelial neoplasia of type 2 or worse (CIN2+) after a UPT with the risk after a satisfactory Pap test while controlling for study site, test year, and other covariates. RESULTS A total of 634,644 Pap tests performed between 2004 and 2010 were included in the current study. Of 1442 UPTs, 53.4% had follow-up testing within 120 days; follow-up differed across the health plans (P

Background: We describe patterns of colorectal cancer screening uptake in a U.S. insured population as individuals become newly eligible for screening at age 50 and assess temporal trends and patient characteristics with screening uptake. Methods: We identified a cohort of 81,223 men and women who were members of Group Health and turned 50 years old from 1996 to 2010. We ascertained receipt of colorectal cancer screening within five years. Time to screening was estimated by year of cohort entry using cumulative incidence curves and Cox proportional hazards models–estimated patient characteristics associated with screening uptake. Results: Stool-based screening tests were the most common, 72% of first screening tests. The proportion of individuals initiating colorectal cancer screening via colonoscopy increased from 8% in 1996 to 1998 to 33% in 2008 to 2010. Patient factors associated with increased colorectal cancer screening were: turning 50 more recently (2008–2010; Ptrend < 0.0001) or Asian race [HR, 1.14; 95% confidence interval (CI), 1.10–1.19]. Patient factors associated with decreased screening were: being a woman (HR, 0.70; 95% CI, 0.68–0.72), Native American (HR, 0.68; 95% CI, 0.60–0.78), or Pacific Islander race (HR, 0.82; 95% CI, 0.72–0.95), and having prevalent diabetes (HR, 0.78; 95% CI, 0.75–0.82) and higher body mass index (Ptrend < 0.0001). Conclusions: Patient characteristics associated with initiation of colorectal cancer screening in a newly eligible population are similar to characteristics associated with overall screening participation in all age-eligible adults. Our results identify patient populations to target in outreach programs. Impact: Disparities in receipt of colorectal cancer screening are evident from onset of an age-eligible cohort, identifying key groups for future interventions for screening. Cancer Epidemiol Biomarkers Prev; 23(7); 1230–7. ©2014 AACR.

Recent research suggests that cervical screening of older women is associated with a considerable decrease in cervical cancer incidence. We sought to quantify the efficacy of cervical cytology screening to reduce death from this disease. Among enrollees of 2 US health plans, we compared Papanicolaou smear screening histories of women aged 55–79 years who died of cervical cancer during 1980–2010 (cases) to those of women at risk of cervical cancer (controls). Controls were matched 2:1 to cases on health plan, age, and enrollment duration. Cytology screening during the detectable preclinical phase, estimated as the 5–7 years before diagnosis during which cervical neoplasia is asymptomatic but cytologically detectable, was ascertained from medical records. A total of 39 cases and 80 controls were eligible. The odds ratio of cervical cancer death associated with screening during the presumed detectable preclinical phase was 0.26 (95% confidence interval: 0.10, 0.63) after adjustment for matching characteristics, smoking, marital status, and race/ethnicity using logistic regression. We estimate that cervical cytology screening of all women aged 55–79 years in the United States could avert 630 deaths annually. These results provide a minimum estimate of the efficacy of human papillomavirus DNA screening—a more sensitive test—to reduce cervical cancer death among older women.

Genetic association studies have identified more than a dozen genes associated with risk of pancreatic cancer. Given this genetic heterogeneity, family history can be useful for identifying individuals at high risk for this disease. The goal of this analysis was to evaluate associations of family history of diabetes and family history of pancreatic cancer with risk of pancreatic cancer. PACIFIC is a case–control study based on two large health plans. Cases were diagnosed with pancreatic ductal adenocarcinoma (PDA) and controls were selected from the health plan enrollment databases and frequency matched to cases. Family history data were collected using an interviewer-administered questionnaire and were available on 654 cases and 697 controls. Logistic regression was used for the association analyses. First-degree relative history of diabetes was statistically significantly associated with increased risk of PDA [OR, 1.37; 95% confidence interval (CI), 1.10–1.71]. The highest risk of PDA was observed for an offspring with diabetes (OR, 1.95; 95% CI, 1.23–3.09). In addition, history of pancreatic cancer increased risk for PDA with an OR of 2.79 (95% CI, 1.44–4.08) for any first-degree relative history of pancreatic cancer. This population-based analysis showed that family history of diabetes was associated with increased risk of PDA and confirmed previous studies showing that first-degree family history of pancreatic cancer is associated with PDA. These results support the need for ongoing studies of genetic influences on pancreatic cancer in large samples and investigations of possible pleiotropic genetic effects on diabetes and pancreatic cancer. Cancer Epidemiol Biomarkers Prev; 22(10); 1913–7. ©2013 AACR.

Although the effectiveness of cervical cancer screening has been firmly established in reproductive-age women, its usefulness in older women is unclear. We sought to evaluate the efficacy of cervical cancer screening in older women.We conducted a case-control study within two integrated health care systems in the northwestern United States. Cases (n = 69) were women aged 55-79 years who were diagnosed with invasive cervical cancer during 1980-1999. Controls (n = 208) were women with an intact uterus and no diagnosis of cervical cancer, but otherwise similar to cases in terms of age and length of enrollment in the health plan. We reviewed medical records to ascertain screening history during the 7 years prior to reference date.Compared to cases, controls were more likely to have received a Pap test. After adjustment for age and current smoking status, screening prior to an estimated 1-year duration of the occult invasive phase of cervical cancer was associated with a substantial reduction in risk [odds ratio (OR) 0.23; 95% CI 0.11-0.44]. Similar results were obtained using different estimates of the duration of the occult invasive phase. Analysis of the relative incidence of invasive cervical cancer in relation to the time following a negative screening test suggested a large reduction during the first year (OR 0.09; 95% CI 0.03-0.24). The incidence remained low for several years thereafter, returning to the incidence among unscreened women after 5-7 years.Cervical cancer screening by means of cytology is highly efficacious in older women. Our findings also suggest that five-yearly screening is approximately as efficacious as more frequent screening.

Objectives: To examine the effect of breast cancer and its treatment on fracture risk in older breast cancer survivors. Design: A 10-year prospective cohort study beginning 5 years after a diagnosis of breast cancer for survivors and match date for comparison women. Setting: Six integrated healthcare systems. Participants: Women aged 65 and older (1,286 survivors, 1,286 comparison women, mean age 77.7 in both groups, white, non-Hispanic: survivors, 81.6%; comparison women, 85.2%) who were alive and recurrence free 5 years after a diagnosis of early-stage breast cancer and matched on age, study site, and enrollment year to a comparison cohort without breast cancer. Measurements: Cox proportional hazards models were used to estimate the association between fracture risk and survivor-comparison status, adjusting for drugs and risk factors associated with bone health. A subanalysis was used to evaluate the association between tamoxifen exposure and fracture risk. Results: No difference was observed in fracture rates between groups (hazard ratio (HR) = 1.1, 95% confidence interval (CI) = 0.9�1.3). The protective effect of tamoxifen was not statistically significant (HR = 0.9, 95% CI = 0.6�1.2). Conclusion: Long-term survivors of early-stage breast cancer diagnosed at age 65 and older are not at greater risk of osteoporotic fractures than age-matched women without breast cancer. There appears to be no long-term protection from fractures with tamoxifen use.

Comparative effectiveness research (CER) on preventive services can shape policy and help patients, their providers, and public health practitioners select regimens and programs for disease prevention. Patients and providers need information about the relative effectiveness of various regimens they may choose. Decision makers need information about the relative effectiveness of various programs to offer or recommend. The goal of this paper is to define and differentiate measures of relative effectiveness of regimens and programs for disease prevention. Cancer screening is used to demonstrate how these measures differ in an example of two hypothetical screening regimens and programs. Conceptually and algebraically defined measures of relative regimen and program effectiveness also are presented. The measures evaluate preventive services that range from individual tests through organized, population-wide prevention programs. Examples illustrate how effective screening regimens may not result in effective screening programs and how measures can vary across subgroups and settings. Both regimen and program relative effectiveness measures assess benefits of prevention services in real-world settings, but each addresses different scientific and policy questions. As the body of CER grows, a common lexicon for various measures of relative effectiveness becomes increasingly important to facilitate communication and shared understanding among researchers, healthcare providers, patients, and policymakers.

Background: To reduce colorectal cancer mortality, positive fecal blood tests must be followed by colonoscopy. Methods: We identified 62,384 individuals ages 50 to 89 years with a positive fecal blood test between January 1, 2011 and December 31, 2012 in four health care systems within the Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. We estimated the probability of follow-up colonoscopy and 95% confidence intervals (CI) using the Kaplan–Meier method. Overall differences in cumulative incidence of follow-up across health care systems were assessed with the log-rank test. HRs and 95% CIs were estimated from multivariate Cox proportional hazards models. Results: Most patients who received a colonoscopy did so within 6 months of their positive fecal blood test, although follow-up rates varied across health care systems (P Conclusion: Individual characteristics and health care system were associated with colonoscopy after positive fecal blood tests. Patterns were consistent across health care systems, but proportions of patients receiving follow-up varied. These findings suggest that there is room to improve follow-up of positive colorectal cancer screening tests. Impact: Understanding the timing of colonoscopy after positive fecal blood tests and characteristics associated with lack of follow-up may inform future efforts to improve follow-up. Cancer Epidemiol Biomarkers Prev; 25(2); 344–50. ©2016 AACR.

Altres ajuts: The authors acknowledge the contribution of the staff of the Cancer Genomics Research Laboratory (CGR) at the National Cancer Institute, NIH, for their help throughout the project. This work was supported by the Intramural Research Program of the US National Institutes of Health (NIH), National Cancer Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Additional acknowledgements for individual participating studies are listed in the Supplemental Materials. Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88×10 −15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22×10 −9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70×10 −8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L - TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7×10 −8). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5×10 −4 -2.0×10 −3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.

Type 2 diabetes is associated with higher fracture risk. Diabetes-related conditions may account for this risk. Cardiovascular Health Study participants (N=5641; 42.0% men; 15.5% black; 72.8±5.6 years) were followed 10.9±4.6 years. Diabetes was defined as hypoglycemic medication use or fasting glucose (FG)≥126 mg/dL. Peripheral artery disease (PAD) was defined as ankle-arm index ≥25 to ≥30. Adjusting for BMI, sex, race, and age, diabetes was related to fractures (HR = 1.34; 95% CI: 1.01–1.78). PAD (HR = 1.25 (95% CI: 0.92–1.57)) and longer walk time (HR = 1.07 (95% CI: 1.04–1.10)) modified the fracture risk in diabetes (HR = 1.17 (95% CI: 0.87–1.57)). Diabetes was associated with higher hip fracture risk after adjusting for BMI though this association was modified by diabetes-related conditions.

Type 2 diabetes is an established risk factor for cardiovascular disease (CVD). This increased risk may be due in part to the increased levels of inflammatory factors associated with diabetes. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a risk marker for CVD and has pro-inflammatory effects in atherosclerotic plaques. We therefore sought to determine whether Lp-PLA(2) levels partially explain the greater prevalence of subclinical CVD and greater incidence of CVD outcomes associated with type 2 diabetes in the Cardiovascular Health Study.We conducted a cross-sectional and prospective study of 4,062 men and women without previous CVD from the Cardiovascular Health Study (1989 to 2007). Lp-PLA(2) mass and activity were measured in baseline plasma. Subclinical disease was determined at baseline and incident CVD was ascertained annually. We used logistic regression for cross-sectional analyses and Cox proportional hazards models for incident analyses.At baseline, Lp-PLA(2) mass did not differ significantly by type 2 diabetes status; however, Lp-PLA(2) activity was significantly higher among type 2 diabetic individuals. Baseline subclinical disease was significantly associated with baseline diabetes and this association was similar in models unadjusted or adjusted for Lp-PLA(2) (OR 1.68 [95% CI 1.31-2.15] vs OR 1.67 [95% CI 1.30-2.13]). Baseline type 2 diabetes was also significantly associated with incident CVD events, including fatal CHD, fatal myocardial infarction (MI) and non-fatal MI in multivariable analyses. There were no differences in these estimates after further adjustment for Lp-PLA(2) activity.In this older cohort, differences in Lp-PLA(2) activity did not explain any of the excess risk for subclinical disease or CVD outcomes related to diabetes.

Background: Type 2 diabetes (T2D) remains an important public health issue in the United States. There are limited and inconsistent data on the association between egg consumption and fasting glucose or incident diabetes. Objectives: We assessed the association between egg intake and incident diabetes in older adults. Design: In this prospective study of 3898 men and women from the Cardiovascular Health Study (1989–2007), we assessed egg consumption by using a picture-sorted food questionnaire and ascertained incident T2D annually by using information on hypoglycemic agents and plasma glucose. We used Cox proportional hazards models to estimate adjusted relative risks. Results: During a mean follow-up of 11.3 y, 313 new cases of T2D occurred. Crude incidence rates of T2D were 7.39, 6.83, 7.00, 6.72, and 12.20 per 1000 person-years in people who reported egg consumption of never

Recent studies indicate that subclavian stenosis (SS), diagnosed by a large systolic blood pressure difference (SBPD) between the right and left brachial arteries, is associated with cardiovascular disease (CVD) risk factors and outcomes. We sought to describe the epidemiology of SS and determine its association with markers of subclinical CVD in the baseline cohort of the Multi-Ethnic Study of Atherosclerosis.We defined SS by an absolute SBPDor=15 mmHg. Peripheral artery disease (PAD) was defined by an ankle-brachial indexor=0.90. The coronary artery calcium score (CAC) and the common carotid artery intima-media thickness (CCA-IMT) were measured by computed tomography and B-mode ultrasound, respectively. Odds ratios for the associations of SS with risk factors and subclinical disease were estimated using logistic regression.Of 6743 subjects studied, 307 participants (4.6%) had SS, with a higher prevalence in women (5.1%) than men (3.9%), and in African Americans (7.4%) and non-Hispanic whites (5.1%) than Hispanic (1.9%) or Chinese (1.0%) participants (p0.01). In a model including age, gender, ethnicity, traditional and novel CVD risk factors, significant associations with SS were observed for C-reactive protein (highest vs. three lower quartiles: OR=1.41; 95%CI: 1.06-1.87) and brachial artery pulse pressure (OR=1.12/10 mmHg; 95%CI: 1.03-1.21). Adjusted for age, gender, ethnicity, traditional and novel CVD risk factors, SS was significantly associated with PAD (OR=2.35; 1.55-3.56), with CCA-IMT (highest vs. the lower three quartiles: OR=1.32; 1.00-1.75), and high CAC (score100 vs. score=0; OR=1.43; 1.03-2.01).The subclavian stenosis is positively associated with other markers of subclinical atherosclerosis.

International audience; The authors aimed to determine differences in the prevalence of peripheral arterial disease (PAD) and its associations with cardiovascular disease (CVD) risk factors, using different methods of calculating the ankle-brachial index (ABI). Using measurements taken in the bilateral brachial, dorsalis pedis, and posterior tibial arteries, the authors calculated ABI in 3 ways: 1) with the lowest ankle pressure (dorsalis pedis artery or posterior tibial artery) ("ABI-LO"), 2) with the highest ankle pressure ("ABI-HI"), and 3) with the mean of the ankle pressures ("ABI-MN"). For all 3 methods, the index ABI was the lower of the ABIs calculated from the left and right legs. PAD was defined as an ABI less than 0.90. Among 6,590 subjects from a multiethnic cohort (baseline examination: 2000-2002), in comparison with ABI-HI, the relative prevalence of PAD was 3.95 times higher in women and 2.74 times higher in men when ABI-LO was used. The relative magnitudes of the associations were largest between PAD and both subclinical atherosclerosis and CVD risk factors when ABI-HI was used, except when risk estimates for PAD were less than 1.0, where the largest relative magnitudes of association were found using ABI-LO. PAD prevalence and its associations with CVD risk factors and subclinical atherosclerosis measures depend on the ankle pressure used to compute the ABI.

Recent guidelines from the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology recommend cessation of cervical cancer screening at age 65 years for women with an “adequate” history of negative Papanicolaou smears. In our view, those who formulated these guidelines did not consider a growing body of evidence from nonrandomized studies that provides insight into the efficacy of cervical cancer screening among older women. First, older women are not at indefinitely low risk following negative screening results. Second, recent data from the United States, the United Kingdom, and Sweden suggest that screening of older women is associated with substantial reductions in cervical cancer incidence and mortality, even among previously screened women. It may be that after consideration of the reduced incidence of (and reduced mortality from) cervical cancer that may result from screening older women, the harms and economic costs of screening will be judged to outweigh its benefits. However, it is essential to consider the now-documented benefits of cervical screening when formulating screening guidelines for older women, and recommendations that do not do so will lack an evidence base.

Reducing colorectal cancer mortality by promoting screening has been a national goal for two decades. The NCI's Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium is the first federal initiative to foster coordinated, transdisciplinary research evaluating the entire cancer screening process in community settings. PROSPR is creating a central data repository to facilitate research evaluating the breast, cervical, and colorectal cancer screening process across different patient populations, provider types, and delivery systems. Data are being collected and organized at the multiple levels in which individuals are nested (e.g., healthcare systems, facilities, providers, and patients). Here, we describe a conceptual model of the colorectal cancer screening process guiding data collection and highlight critical research questions that will be addressed through pooled data. We also describe the three research centers focused on colorectal cancer screening with respect to study populations, practice settings, and screening policies. PROSPR comprehensively elucidates the complex screening process through observational study, and has potential to improve care delivery beyond the healthcare systems studied. Findings will inform intervention designs and policies to optimize colorectal cancer screening delivery and advance the Institute of Medicine's goals of effective, efficient, coordinated, timely, and safe health care with respect to evidence-based cancer screening. Cancer Epidemiol Biomarkers Prev; 23(7); 1147–58. ©2014 AACR.