Trends in HPV-associated cancer incidence in Texas medically underserved regions.

BACKGROUND: While cervical cancer incidence rates (IR) in the United States have dropped in the last 20 years, non-cervical human papillomavirus (HPV) associated cancers increased. Many people in Texas (TX) live in medically underserved areas and have higher risk of developing HPV-associated cancers. Since previous studies of these regions focused on cervical cancer, we included other HPV-associated cancers in our analysis of IR in East TX and the TX-Mexico Border compared to other TX regions. METHODS: Cancer data from 2006 to 2019 were obtained from the TX Cancer Registry. Cases of HPV-associated cervical, vaginal, vulvar, penile, anal, and oropharyngeal cancers and corresponding patient-level demographic data were included. We calculated IR per 100,000 and drew heat maps to visualize cancer IR by county. To control potential confounders, we added county-level risk factors: rates for smoking, excessive drinking, obesity, STIs, primary care provider availability and dentist availability, from the County Health Rankings and Roadmaps program. We reported IRs by region and time and estimated unadjusted and adjusted risk ratio (RR) for association of each type of cancer and region. Lastly, we created adjusted models for each cancer by period to see time trends of regional differences. RESULTS: Risk of anal, cervical, and oropharyngeal cancer was lower at parts of the Border than in the rest of TX in the adjusted model. We also observed increasing anal and oropharyngeal cancer risk and decreasing cervical and vaginal cancer risk over time. CONCLUSION: Patient sociodemographics, behavioral risk factors, and access to care may contribute to some observed differences in cancer IR across regions. This indicates that targeted prevention efforts towards these regions, especially in low socioeconomic status communities, may benefit future generations.

Using Geospatial Analysis to Identify Priority Communities for Cervical Cancer Prevention in Texas.

Introduction: Despite being almost entirely preventable, cervical cancer is the fourth most frequently diagnosed cancer among women worldwide. Cervical cancer incidence suggests missed opportunities for prevention. Geospatial analysis could strategically guide public health interventions. This study aimed to identify geographic clusters of cervical cancer incidence in Texas, a state with higher than national rates of cervical cancer incidence and mortality. Methods: In this population-based cross-sectional study, the authors analyzed incident cervical cancer data among Texas women aged 30-64 years, from 2014 to 2018. The authors conducted a purely spatial Poisson-based analysis function in SaTScan to examine geographic clusters of higher-than-expected proportions of cervical cancer incidence (i.e., hot spots) and adjusted for age. Results: A total of 5,060 women aged 30-64 years with incident cervical cancer diagnosis (mean age: 45.7 years, SD=9.6), including 1,840 (36.4%) Hispanic, 591 (11.7%) non-Hispanic Black, 2,397 (47.4%) non-Hispanic White, and 232 (4.6%) other races, were analyzed. Spatial scan analysis detected 7 significant hot spots of cervical cancer incidence. Hot spots were identified in the South Texas Plains (near Mexico border), Gulf Coast (Houston), Prairies and Lakes (North Texas), Panhandle Plains (Northwest Texas), and Piney Woods (Southeast Texas) regions of Texas. Hot spots, compared with the rest of Texas, had higher proportions of Hispanic population and individuals with socioeconomic disadvantages. Conclusions: This study found spatial variation in cervical cancer incidence in Texas. The hot spot areas can benefit from targeted, novel, scalable, and cost-effective interventions to increase human papillomavirus vaccination and screening and early detection and treatment of precancerous cervical lesions.

Cervical cancer screening utilization among kidney transplant recipients, 2001-2018.

BACKGROUND: Kidney transplant recipients (KTRs) have elevated risks of cervical pre-cancers and cancers, and guidelines recommend more frequent cervical cancer screening exams. However, little is known about current trends in cervical cancer screening in this unique population. We described patterns in the uptake of cervical cancer screening exams among female KTRs and identified factors associated with screening utilization. METHODS: This retrospective cohort study included female KTRs between 20-65 years old, with Texas Medicare fee-for-service coverage, who received a transplant between January 1, 2001, and December 31, 2017. We determined the cumulative incidence of receiving cervical cancer screening post-transplant using ICD-9, ICD-10, and CPT codes and assessed factors associated with screening utilization, using the Fine and Gray model to account for competing events. Subdistribution hazards models were used to assess factors associated with screening uptake. RESULTS: Among 2,653 KTRs meeting the inclusion and exclusion criteria, the 1-, 2-, and 3-year cumulative incidences of initiating a cervical cancer screening exam post-transplant were 31.7% (95% confidence interval (CI), 30.0-33.6%), 48.0% (95% CI, 46.2-49.9%), and 58.5% (95% CI, 56.7-60.3%), respectively. KTRs who were 55-64 years old (vs. <45 years old) and those with a higher Charlson Comorbidity Score post-transplant were less likely to receive cervical cancer screening post-transplant. CONCLUSIONS: Cervical cancer screening uptake is low in the years immediately following a kidney transplant. IMPACT: Our findings highlight a need for interventions to improve cervical cancer screening utilization among KTRs.

Temporal Trends in Treatment and Outcomes of Endometrial Carcinoma in the United States, 2005-2020.

Endometrial cancer has continued to see a rising incidence in the US over the years. The main aim of this study was to assess current trends in patients' characteristics and outcomes of treatment for endometrial carcinoma over 16 years. A dataset from the National Cancer Database (NCDB) for patients diagnosed with endometrial carcinoma from 2005 to 2020 was used in this retrospective, case series study. The main outcomes and measures of interest included tumor characteristics, hospitalization, treatments, mortality, and overall survival. Then, 569,817 patients who were diagnosed with endometrial carcinoma were included in this study. The mean (SD) age at diagnosis was 62.7 (11.6) years, but 66,184 patients (11.6%) were younger than 50 years, indicating that more patients are getting diagnosed at younger ages. Of the patients studied, 37,079 (6.3%) were Hispanic, 52,801 (9.3%) were non-Hispanic Black, 432,058 (75.8%) were non-Hispanic White, and 48,879 (8.6%) were other non-Hispanic. Patients in the 4th period from 2017 to 2020 were diagnosed more with stage IV (7.1% vs. 5.2% vs. 5.4% vs. 5.9%; p < 0.001) disease compared with those in the other three periods. More patients with severe comorbidities (Charlson Comorbidity Index score of three) were seen in period 4 compared to the first three periods (3.9% vs. ≤1.9%). Systemic chemotherapy use (14.1% vs. 17.7% vs. 20.4% vs. 21.1%; p < 0.001) and immunotherapy (0.01% vs. 0.01% vs. 0.2% vs. 1.1%; p < 0.001) significantly increased from period 1 to 4. The use of laparotomy decreased significantly from 42.1% in period 2 to 16.7% in period 4, while robotic surgery usage significantly increased from 41.5% in period 2 to 64.3% in period 4. The 30-day and 90-day mortality decreased from 0.6% in period 1 to 0.2% in period 4 and 1.4% in period 1 to 0.6% in period 4, respectively. Over the period studied, we found increased use of immunotherapy, chemotherapy, and minimally invasive surgery for the management of endometrial cancer. Overall, the time interval from cancer diagnosis to final surgery increased by about 6 days. The improvements observed in the outcomes examined can probably be associated with the treatment trends observed.

Cost-Effectiveness of Population-Based Multigene Testing for Breast and Ovarian Cancer Prevention.

Importance: The current method of BRCA testing for breast and ovarian cancer prevention, which is based on family history, often fails to identify many carriers of pathogenic variants. Population-based genetic testing offers a transformative approach in cancer prevention by allowing for proactive identification of any high-risk individuals and enabling early interventions. Objective: To assess the lifetime incremental effectiveness, costs, and cost-effectiveness of population-based multigene testing vs family history-based testing. Design, Setting, and Participants: This economic evaluation used a microsimulation model to assess the cost-effectiveness of multigene testing (BRCA1, BRCA2, and PALB2) for all women aged 30 to 35 years compared with the current standard of care that is family history based. Carriers of pathogenic variants were offered interventions, such as magnetic resonance imaging with or without mammography, chemoprevention, or risk-reducing mastectomy and salpingo-oophorectomy, to reduce cancer risk. A total of 2000 simulations were run on 1 000 000 women, using a lifetime time horizon and payer perspective, and costs were adjusted to 2022 US dollars. This study was conducted from September 1, 2020, to December 15, 2023. Main Outcomes and Measures: The main outcome measure was the incremental cost-effectiveness ratio (ICER), quantified as cost per quality-adjusted life-year (QALY) gained. Secondary outcomes included incremental cost, additional breast and ovarian cancer cases prevented, and excess deaths due to coronary heart disease (CHD). Results: The study assessed 1 000 000 simulated women aged 30 to 35 years in the US. In the base case, population-based multigene testing was more cost-effective compared with family history-based testing, with an ICER of $55 548 per QALY (95% CI, $47 288-$65 850 per QALY). Population-based multigene testing would be able to prevent an additional 1338 cases of breast cancer and 663 cases of ovarian cancer, but it would also result in 69 cases of excess CHD and 10 excess CHD deaths per million women. The probabilistic sensitivity analyses show that the probability that population-based multigene testing is cost-effective was 100%. When the cost of the multigene test exceeded $825, population-based testing was no longer cost-effective (ICER, $100 005 per QALY; 95% CI, $87 601-$11 6323). Conclusions and Relevance: In this economic analysis of population-based multigene testing, population-based testing was a more cost-effective strategy for the prevention of breast cancer and ovarian cancer when compared with the current family history-based testing strategy at the $100 000 per QALY willingness-to-pay threshold. These findings support the need for more comprehensive genetic testing strategies to identify pathogenic variant carriers and enable informed decision-making for personalized risk management.

Geographic Variation in Late-Stage Cervical Cancer Diagnosis.

Importance: There are stark disparities in cervical cancer burden in the United States, notably by race and ethnicity and geography. Late-stage diagnosis is an indicator of inadequate access to and utilization of screening. Objective: To identify geospatial clusters of late-stage cervical cancer at time of diagnosis in Texas. Design, Setting, and Participants: This population-based cross-sectional study used incident cervical cancer data from the Texas Cancer Registry from 2014 to 2018 of female patients aged 18 years or older. Late-stage cervical cancer cases were geocoded at the census tract level (n = 5265) using their residential coordinates (latitude and longitude) at the time of diagnosis. Statistical analysis was performed from April to September 2023. Exposures: Census tract of residence at diagnosis. Main Outcome and Measures: Late-stage cervical cancer diagnosis (ie, cases classified by the National Cancer Institute Surveillance, Epidemiology and End Results summary stages 2 to 4 [regional spread] or 7 [distant metastasis]). A Poisson probability-based model of the SaTScan purely spatial scan statistics was applied at the census tract-level to identify geographic clusters of higher (hot spots) or lower (cold spots) proportions than expected of late-stage cervical cancer diagnosis and adjusted for age. Results: Among a total of 6484 female patients with incident cervical cancer cases (mean [SD] age, 48.7 [14.7] years), 2300 (35.5%) were Hispanic, 798 (12.3%) were non-Hispanic Black, 3090 (47.6%) were non-Hispanic White, and 296 (4.6%) were other race or ethnicity. Of the 6484 patients, 2892 with late-stage diagnosis (mean [SD] age, 51.8 [14.4] years were analyzed. Among patients with late-stage diagnosis, 1069 (37.0%) were Hispanic, 417 (14.4%) were non-Hispanic Black, 1307 (45.2%) were non-Hispanic White, and 99 (3.4%) were other race or ethnicity. SaTScan spatial analysis identified 7 statistically significant clusters of late-stage cervical cancer diagnosis in Texas, of which 4 were hot spots and 3 were cold spots. Hot spots included 1128 census tracts, predominantly in the South Texas Plains, Gulf Coast, and Prairies and Lakes (North Texas) regions. Of the 2892 patients with late-stage cervical cancer, 880 (30.4%) were observed within hot spots. Census tract-level comparison of characteristics of clusters suggested that hot spots differed significantly from cold spots and the rest of Texas by proportions of racial and ethnic groups, non-US born persons, and socioeconomic status. Conclusions and Relevance: In this cross-sectional study examining geospatial clusters of late-stage cervical cancer diagnosis, place-based disparities were found in late-stage cervical cancer diagnosis in Texas. These findings suggest that these communities may benefit from aggressive cervical cancer interventions.

The Impact of Neisseria gonorrhoeae Mono- and Coinfection on Adverse Pregnancy Outcomes.

Background: Sexually transmitted infections (STIs) have recently been linked to hypertensive disorders of pregnancy (HDP). However, the impact of Neisseria gonorrhoeae on risk of HDP is not well understood. This study determined the impact of gonorrhea and gonorrhea coinfection on HDP and other adverse pregnancy outcomes in a population with a high screening rate and presumed treatment. Methods: This retrospective study included 29 821 singleton births between 2016 and 2021. The STI testing results, demographic variables, and pregnancy outcomes were identified from electronic health records. The HDP were primary outcomes of interest including gestational hypertension, preeclampsia, and superimposed preeclampsia. We further examined preeclampsia subtypes defined by severe features and gestational age of delivery (term and preterm preeclampsia). Secondary outcomes included preterm premature rupture of membranes, chorioamnionitis, and preterm delivery. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Models were adjusted for maternal age, maternal race/ethnicity, and smoking. Results: Gonorrhea screening occurred in 95% of the population. Gonorrhea increased the odds of preterm preeclampsia (adjusted OR [ORadj.], 1.95; 95% CI, 1.02-3.73) and preterm birth (ORadj., 1.78; 95% CI, 1.22-2.60). Furthermore, gonorrhea-chlamydia coinfection was associated with preterm birth (ORadj., 1.77; 95% CI, 1.03-3.04). However, results were similar when we examined gonorrhea monoinfection (ORadj., 1.76; 95% CI, 1.04-2.97). Conclusions: Among a diverse population of pregnant individuals, gonorrhea increased odds of preterm preeclampsia and preterm delivery Further research is needed to determine the burden of STIs on HDP, including investigations into biological effects during pregnancy.

Incomplete HPV Vaccination among Individuals Aged 27-45 Years in the United States: A Mixed-Effect Analysis of Individual and Contextual Factors.

Background: In the United States, the human papillomavirus (HPV) vaccine is approved for use in individuals up to age 45. Individuals 15 years and older require three doses of the vaccine to complete the recommended dosing series. Incomplete HPV vaccination rates (i.e., one or two doses) among those over age 26, however, remain high. This study examined the independent effects of individual- and neighborhood-level factors on incomplete HPV vaccination rates in the United States (U.S.) among those aged 27-45 years. Methods: This retrospective cohort study used administrative data from Optum's de-identified Clinformatics® Data Mart Database to identify individuals aged 27-45 years who received one or more doses of HPV vaccine between July 2019 and June 2022. Multilevel multivariable logistic regression models were applied to the data on 7662 individuals identified as being fully or partially vaccinated against HPV, nested within 3839 neighborhoods across the U.S. Results: Approximately half of the patients in this study (52.93%) were not completely vaccinated against HPV. After adjusting for all other covariates in the final model, being older than 30 years old decreased the odds of not completing the HPV vaccine series. Participants living in South-region neighborhoods of the U.S. had enhanced odds of not completing the vaccine series compared with those residing in Northeast-region neighborhoods (aOR 1.21; 95% CrI 1.03-1.42). There was significant clustering of incomplete HPV vaccination rates at the neighborhood level. Conclusions: This study revealed that individual- and neighborhood-level factors were associated with the risk of not completing the HPV vaccine series among individuals aged 27-45 years in the U.S. Interventions to improve HPV vaccination series completion rates for this age group should take into consideration both individual and contextual factors.

Incidence of human papillomavirus-related cancers among males and females aged 15-34 years in the United States.

Postmarket surveillance of the incidence of human papillomavirus (HPV)-related cancers is essential to monitor the effectiveness of HPV vaccines. We directly compared HPV-related cancer incidences during the pre- and postvaccine era to assess the effects of HPV vaccination among vaccine-eligible age groups in the United States using data from the US Cancer Statistics database. The 5-year average annual incidence rates for HPV-related cancers decreased in 2015-2019 compared with 2002-2006 among females aged 15-24 years and 25-34 years. Overall, a decrease in young males was not observed, whereas males aged 25-34 years experienced a slight decline in oropharyngeal squamous cell carcinoma between 2005-2009 and 2015-2019. Incidence rates for HPV-related cancers statistically significantly decreased in the vaccine era compared with the prevaccine era among females aged 15-34 years, suggesting the potential early effects of the introduction of HPV vaccination in the United States.

Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000-2018.

BACKGROUND: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15-59 years across SSA. METHODS: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. RESULTS: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. CONCLUSIONS: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA.

Antibiotic use and deprivation: an analysis of Welsh primary care antibiotic prescribing data by socioeconomic status.

OBJECTIVES: To examine the association between socioeconomic status (SES) and antibiotic prescribing, controlling for the presence of common chronic conditions and other potential confounders and variation amongst GP practices and clusters. METHODS: This was an electronic cohort study using linked GP and Welsh Index of Multiple Deprivation (WIMD) data. The setting was GP practices contributing to the Secure Anonymised Information Linkage (SAIL) Databank 2013-17. The study involved 2.9 million patients nested within 339 GP practices, nested within 67 GP clusters. RESULTS: Approximately 9 million oral antibiotics were prescribed between 2013 and 2017. Antibiotic prescribing rates were associated with WIMD quintile, with more deprived populations receiving more antibiotics. This association persisted after controlling for patient demographics, smoking, chronic conditions and clustering by GP practice and cluster, with those in the most deprived quintile receiving 18% more antibiotic prescriptions than those in the least deprived quintile (incidence rate ratio = 1.18; 95% CI = 1.181-1.187). We found substantial unexplained variation in antibiotic prescribing rates between GP practices [intra-cluster correlation (ICC) = 47.31%] and GP clusters (ICC = 12.88%) in the null model, which reduced to ICCs of 3.50% and 0.85% for GP practices and GP clusters, respectively, in the final adjusted model. CONCLUSIONS: Antibiotic prescribing in primary care is increased in areas of greater SES deprivation and this is not explained by differences in the presence of common chronic conditions or smoking status. Substantial unexplained variation in prescribing supports the need for ongoing antimicrobial stewardship initiatives.

Addressing the under-reporting of adverse drug reactions in public health programs controlling HIV/AIDS, Tuberculosis and Malaria: A prospective cohort study.

BACKGROUND: Adverse Drug Reactions (ADRs) are a major clinical and public health problem world-wide. The prompt reporting of suspected ADRs to regulatory authorities to activate drug safety surveillance and regulation appears to be the most pragmatic measure for addressing the problem. This paper evaluated a pharmacovigilance (PV) training model that was designed to improve the reporting of ADRs in public health programs treating the Human Immunodeficiency Virus (HIV), Tuberculosis (TB) and Malaria. METHODS: A Structured Pharmacovigilance and Training Initiative (SPHAR-TI) model based on the World Health Organization accredited Structured Operational Research and Training Initiative (SOR-IT) model was designed and implemented over a period of 12 months. A prospective cohort design was deployed to evaluate the outcomes of the model. The primary outcomes were knowledge gained and Individual Case Safety Reports (ICSR) (completed adverse drug reactions monitoring forms) submitted, while the secondary outcomes were facility based Pharmacovigilance Committees activated and health facility healthcare workers trained by the participants. RESULTS: Fifty-five (98%) participants were trained and followed up for 12 months. More than three quarter of the participants have never received training on pharmacovigilance prior to the course. Yet, a significant gain in knowledge was observed after the participants completed a comprehensive training for six days. In only seven months, 3000 ICSRs (with 100% completeness) were submitted, 2,937 facility based healthcare workers trained and 46 Pharmacovigilance Committees activated by the participants. Overall, a 273% increase in ICSRs submission to the National Agency for Food and Drug Administration and Control (NAFDAC) was observed. CONCLUSION: Participants gained knowledge, which tended to increase the reporting of ADRs. The SPHAR-TI model could be an option for strengthening the continuous reporting of ADRs in public health programs in resource limited settings.

Recurrence of cervical intraepithelial lesions after thermo-coagulation in HIV-positive and HIV-negative Nigerian women.

BACKGROUND: The burden of cervical cancer remains huge globally, more so in sub-Saharan Africa. Effectiveness of screening, rates of recurrence following treatment and factors driving these in Africans have not been sufficiently studied. The purpose of this study therefore was to investigate factors associated with recurrence of cervical intraepithelial lesions following thermo-coagulation in HIV-positive and HIV-negative Nigerian women using Visual Inspection with Acetic Acid (VIA) or Lugol's Iodine (VILI) for diagnosis. METHODS: A retrospective cohort study was conducted, recruiting participants from the cervical cancer "see and treat" program of IHVN. Data from 6 sites collected over a 4-year period was used. Inclusion criteria were: age ≥18 years, baseline HIV status known, VIA or VILI positive and thermo-coagulation done. Logistic regression was performed to examine the proportion of women with recurrence and to examine factors associated with recurrence. RESULTS: Out of 177 women included in study, 67.8 % (120/177) were HIV-positive and 32.2 % (57/177) were HIV-negative. Recurrence occurred in 16.4 % (29/177) of participants; this was 18.3 % (22/120) in HIV-positive women compared to 12.3 % (7/57) in HIV-negative women but this difference was not statistically significant (p-value 0.31). Women aged ≥30 years were much less likely to develop recurrence, adjusted OR = 0.34 (95 % CI = 0.13, 0.92). Among HIV-positive women, CD4 count <200cells/mm(3) was associated with recurrence, adjusted OR = 5.47 (95 % CI = 1.24, 24.18). CONCLUSION: Recurrence of VIA or VILI positive lesions after thermo-coagulation occurs in a significant proportion of women. HIV-positive women with low CD4 counts are at increased risk of recurrent lesions and may be related to immunosuppression.

Effect of Using the Same vs Different Order for Second Readings of Screening Mammograms on Rates of Breast Cancer Detection: A Randomized Clinical Trial.

IMPORTANCE: Interpreting screening mammograms is a difficult repetitive task that can result in missed cancers and false-positive recalls. In the United Kingdom, 2 film readers independently evaluate each mammogram to search for signs of cancer and examine digital mammograms in batches. However, a vigilance decrement (reduced detection rate with time on task) has been observed in similar settings. OBJECTIVE: To determine the effect of changing the order for the second film reader of batches of screening mammograms on rates of breast cancer detection. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, double-blind, cluster randomized clinical trial conducted at 46 specialized breast screening centers from the National Health Service Breast Screening Program in England for 1 year (all between December 20, 2012, and November 3, 2014). Three hundred sixty readers participated (mean, 7.8 readers per center)-186 radiologists, 143 radiography advanced practitioners, and 31 breast clinicians, all fully qualified to report mammograms in the NHS breast screening program. INTERVENTIONS: The 2 readers examined each batch of digital mammograms in the same order in the control group and in the opposite order to one another in the intervention group. MAIN OUTCOMES AND MEASURES: The primary outcome was cancer detection rate; secondary outcomes were rates of recall and disagreements between readers. RESULTS: Among 1,194,147 women (mean age, 59.3; SD, 7.49) who had screening mammograms (596,642 in the intervention group; 597,505 in the control group), the images were interpreted in 37,688 batches (median batch size, 35; interquartile range [IQR]; 16-46), with each reader interpreting a median of 176 batches (IQR, 96-278). After completion of all subsequent diagnostic tests, a total of 10,484 cases (0.88%) of breast cancer were detected. There was no significant difference in cancer detection rate with 5272 cancers (0.88%) detected in the intervention group vs 5212 cancers (0.87%) detected in the control group (difference, 0.01% points; 95% CI, -0.02% to 0.04% points; recall rate, 24,681 [4.14%] vs 24,894 [4.17%]; difference, -0.03% points; 95% CI, -0.10% to 0.04% points; or rate of reader disagreements, 20,471 [3.43%] vs 20,793 [3.48%]; difference, -0.05% points; 95% CI, -0.11% to 0.02% points). CONCLUSIONS AND RELEVANCE: Interpretation of batches of mammograms by qualified screening mammography readers using a different order vs the same order for the second reading resulted in no significant difference in rates of detection of breast cancer. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN46603370.