Early Detection of Prostate Cancer: AUA/SUO Guideline Part I: Prostate Cancer Screening.

PURPOSE: The summary presented herein covers recommendations on the early detection of prostate cancer and provides a framework to facilitate clinical decision-making in the implementation of prostate cancer screening, biopsy, and follow-up. This is Part I of a two-part series that focuses on prostate cancer screening. Please refer to Part II for discussion of initial and repeat biopsies as well as biopsy technique. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. The systematic review was based on searches in Ovid MEDLINE and Embase and Cochrane Database of Systematic Reviews (January 1, 2000-November 21, 2022). Searches were supplemented by reviewing reference lists of relevant articles. RESULTS: The Early Detection of Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance in prostate cancer screening, initial and repeat biopsy, and biopsy technique. CONCLUSIONS: Prostate-specific antigen (PSA)-based prostate cancer screening in combination with shared decision-making (SDM) is recommended. Current data regarding risk from population-based cohorts provide a basis for longer screening intervals and tailored screening, and the use of available online risk calculators is encouraged.

[Investigation of the screening interval for population with negative colonoscopy examinations].

Objective: To investigate the colonscopy screening interval among patients with negative colonscopy. Methods: We selected 14 606 participants who completed the baseline and 3-year or 5-year colonoscopy examinations in the American Prostate, Lung, Colorectal, and Ovarian (PLCO) dataset as the target population. Sociodemographic characteristics (i.e., sex, age, marital status, race, and smoking), lifestyle, family history of cancer, and family history of colorectal cancer were collected. Cochran-Armitage trend analysis was used to examine whether the rate of positive cases (colorectal cancer, advanced adenoma, adenoma, and hyperplastic polyp) was increased with the length of screening interval. We compared the differences in number of detected cases, positive rates, and proportions of 3-year and 5-year screening interval strategies using internal standardization method. Results: The age of the population was （61.9±5.2） years and over half of them were males (54.4%) and 46.2% had family cancer history. The mean screening interval between the first and second endoscopies was （1 639.1±320.9） days. A total of 1 716 cases had positive endoscopic findings. With the screening interval extended, rate of the screened positive cases was also increased (P for trend<0.001). After standardized by the internal standardized population (14 606), 17.99 and 11.57 colorectal cancer cases and 177.37 and 240.35 advanced adenoma cases were detected by 3-year and 5-year screening interval strategies, respectively. Conclusion: Based on the initial screening negative population of colonoscopy in the United States, the 3-year screening interval strategy could detect a relatively large number of colorectal cancer cases, but its health and economic evaluation needs to be further explored.

Five-year risk of CIN3 after short-term HPV-DNA negativity in cytology-negative women: a population-based cohort study.

OBJECTIVE: To assess the 5-year risk of high-grade lesions in women with a transient high-risk HPV infection. DESIGN: Population-based cohort study. SETTING: HPV primary testing within population-based organised cervical cancer screening programmes. POPULATION: Italian women enrolled in seven pilot projects and attending the second round. METHODS: On the basis of the cytology triage performed on HPV-positive women, immediate colposcopy or HPV repeat at 12 months was recommended. Data were collected at the subsequent round 3-4 years after HPV infection clearance. MAIN OUTCOME MEASURES: Rates of HPV infection, CIN2+ and CIN3+ detection at subsequent round after HPV clearance, and relative risks (RR) in comparison with HPV-negative women (with 95% confidence interval). RESULTS: Data on 1230 women (1027 aged 25-64 years and 203 aged 35-64 years) have been analysed. Overall compliance with repeat HPV testing was 84%. In comparison with HPV-negative women, those with a transient HPV infection had higher proportions of HPV positivity (15% versus 3.7%) and of CIN2+ lesions (0.87% versus 0.23%) in round two; most of these (7/10) were CIN2; no cancers were detected, and CIN3 occurred in 3/1230 (0.24%). CONCLUSIONS: HPV-based protocols for cervical cancer screening allow long intervals for HPV-negative women; it is important to monitor the clinical outcome in the women with transient high-risk HPV infection. CIN3 detection is similar to that observed in routine European cytology-based screening programmes (CIN3+: 2.7‰); 5-year intervals may provide reasonable protection but longer intervals are not recommended. TWEETABLE ABSTRACT: A screening interval of 5 years (but no longer) appears safe in women with transient HPV detection.

Uptake of HPV testing and extended cervical cancer screening intervals following cytology alone and Pap/HPV cotesting in women aged 30-65 years.

OBJECTIVE: To evaluate the adoption of HPV testing and recommended extended cervical cancer screening intervals in clinical practice, we described yearly uptake of Pap/HPV cotesting and estimated length of time between normal screens by patient characteristics. METHODS: We examined 55,575 Pap/HPV records from 27,035 women aged 30-65 years from the Johns Hopkins Hospital Pathology Data System between 2006 and 2013. Cotest uptake and median times to next screening test for cotests and cytology only were calculated. Adjusted hazard ratios were estimated using Cox proportional hazards models, with random effects adjustment for clustering within clinic. RESULTS: Cotest usage increased from < 10% in 2006 to 78% in 2013. The median time to next screening test following normal cytology alone remained constant around 1.5 years. Screening intervals following a dual-negative cotest increased from 1.5 years in 2006/2007 to 2.5 years in 2010, coincident with increases in the proportion of women cotested. Intervals following a dual negative cotest were longer among Medicare patients (3 years) compared with privately insured women (2.5 years), and shorter among black (2 years) compared with white women (2.8 years). CONCLUSION: By mid-2013 we observed broad adoption of Pap/HPV cotesting in routine screening in a large academic medical center. Increased screening intervals were observed only among cotested women, while those screened by cytology alone continued to be screened almost annually. The influence of different combinations of race and insurance on screening intervals should be further evaluated to ensure balance of screening risks and benefits in the U.S.

Optimal interval of endoscopic screening based on stage distributions of detected gastric cancers.

BACKGROUND: Although Korea and Japan have a national gastric cancer screening program, their screening intervals are different. The optimal screening interval of endoscopic screening in Japan was investigated based on the stage distributions of screen-detected gastric cancers. METHODS: Patients with gastric cancer detected by endoscopic and radiographic screenings were selected from the Niigata City Medical Association database. The stage distributions of the detected gastric cancers were compared among patients with different screening histories in both groups. Gastric cancer specific survival rates were analyzed using the Kaplan-Meier method with the log-rank test. RESULTS: There were 1585 and 462 subjects in the endoscopic and radiographic screening groups, respectively. In the endoscopic screening group, the stage IV proportion was lower in patients with screening history 1 and 2 years before diagnosis than in patients without screening history. Stage IV development was significantly related to the absence of screening history (p < 0.001); however, there were no differences between patients who had endoscopic screening history 2 and 3 years before diagnosis. The survival rates were not significantly different between patients with endoscopic screening 1 and 2 years previously (p = 0.7763). The survival rates were significantly higher in patients with endoscopic screening history 1 and 2 years before diagnosis than in patients without screening history (p < 0.001), and in patients with endoscopic screaming 3 years before diagnosis (P < 0.0069). CONCLUSION: The endoscopic screening interval for gastric cancer can be expanded to at least 2 years based on the stage distributions of detected cancers and the patient survival rates.

Screening Intervals for Diabetic Retinopathy and Implications for Care.

PURPOSE OF REVIEW: The purpose of this study is to review the evidence that lower risk groups who could safely be screened less frequently for sight-threatening diabetic retinopathy (DR) than annually. RECENT FINDINGS: Data have demonstrated that people with no DR in either eye are at a low risk of progression to sight-threatening DR over a 2-year period (event rate 4.8 per 1000 person years), irrespective of whether the screening method is one-field non-mydriatic or two-field mydriatic digital photography. Low risk has been defined as no retinopathy on two consecutive screening episodes or no retinopathy on one screening episode combined with risk factor data. The risk of an extension to 2 years is less than 5 per 1000 person years in a population with a national screening programme, and the general standard of diabetes care is relatively good, whether low risk is defined as no retinopathy on two consecutive screening episodes or no retinopathy on one screening episode combined with other risk factor data. The definition used in different populations is likely to depend on the availability of data.

Optimal screening interval for men with low baseline prostate-specific antigen levels (≤1.0 ng/mL) in a prostate cancer screening program.

PURPOSE: To optimize the rescreening schedule for men with low baseline prostate-specific antigen (PSA) levels, we evaluated men with baseline PSA levels of ≤1.0 ng/mL in PSA-based population screening. METHODS: We enrolled 8086 men aged 55-69 years with baseline PSA levels of ≤1.0 ng/mL, who were screened annually. The relationships of baseline PSA and age with the cumulative risks and clinicopathological features of screening-detected cancer were investigated. RESULTS: Among the 8086 participants, 28 (0.35 %) and 18 (0.22 %) were diagnosed with prostate cancer and cancer with a Gleason score (GS) of ≥7 during the observation period, respectively. The cumulative probabilities of prostate cancer at 12 years were 0.42, 1.0, 3.4, and 4.3 % in men with baseline PSA levels of 0.0-0.4, 0.5-0.6, 0.7-0.8, and 0.9-1.0 ng/mL, respectively. Those with GS of ≥7 had cumulative probabilities of 0.42, 0.73, 2.8, and 1.9 %, respectively. The cumulative probabilities of prostate cancer were significantly lower when baseline PSA levels were 0.0-0.6 ng/mL compared with 0.7-1.0 ng/mL. Prostate cancer with a GS of ≥7 was not detected during the first 10 years of screening when baseline PSA levels were 0.0-0.6 ng/mL and was not detected during the first 2 years when baseline PSA levels were 0.7-1.0 ng/mL. CONCLUSIONS: Our study demonstrated that men with baseline PSA levels of 0.0-0.6 ng/mL might benefit from longer screening intervals than those recommended in the guidelines of the Japanese Urological Association. Further investigation is needed to confirm the optimal screening interval for men with low baseline PSA levels.

A 3-year interval is too short for re-screening women testing negative for human papillomavirus: a population-based cohort study.

OBJECTIVE: To compare the results from an initial negative human papillomavirus (HPV) test with re-screening after 3 years in women attending two HPV-based screening programmes. DESIGN: Population-based cohort study. SETTING: Two cervical service screening programmes in Italy. POPULATION: Women aged 25-64 years invited to screening from April 2009 to October 2015. METHODS: Eligible women were invited to undergo an HPV test. Those with a negative HPV test went on to the next screening round 3 years later. Cytology triage was performed for HPV+ (HPV by Hybrid Capture 2) samples, with immediate colposcopy (if abnormal) and HPV re-testing 1 year later (if negative). MAIN OUTCOME MEASURES: Participation rate, positivity at HPV and at triage, referral rate to colposcopy, positive predictive value for cervical intraepithelial neoplasia grade 2+ (CIN2+) at colposcopy, and detection rate for CIN2+. RESULTS: We present the results from 48 751 women at the first screening and 22 000 women at re-screening 3 years later. The response rate was slightly higher at the second screening (74.5 versus 72.1% at the first screening; referral rate, RR 1.11; 95% confidence interval, 95% CI, 1.07-1.14). Compared with the first screening, we observed a significant reduction at the second screening in terms of HPV positivity (RR 0.55, 95% CI 0.51-0.60), referral rate to colposcopy (RR 0.47, 95% CI 0.41-0.53), CIN2+ detection rate (RR 0.24, 95% CI 0.13-0.39), and positive predictive value (PPV) for CIN2+ at colposcopy (RR 0.51, 95% CI 0.29-0.87). CONCLUSIONS: The very low frequency of disease and inadequate PPV at colposcopy indicate that a 3-year interval after a negative HPV test is too short. TWEETABLE ABSTRACT: Three years after a negative HPV the frequency of cervical disease is so low that re-screening is inefficient.

Diabetes screening intervals based on risk stratification.

BACKGROUND: Guidelines for frequency of Type 2 diabetes mellitus (DM) screening remain unclear, with proposed screening intervals typically based on expert opinion. This study aims to demonstrate that HbA1c screening intervals may differ substantially when considering individual risk for diabetes. METHODS: This was a multi-institutional retrospective open cohort study. Data were collected between April 1999 to March 2014 from one urban and one rural cohort in Japan. After categorization by age, we stratified individuals based on cardiovascular disease risk (Framingham 10-year cardiovascular risk score) and body mass index (BMI). We adapted a signal-to-noise method for distinguishing true HbA1c change from measurement error by constructing a linear random effect model to calculate signal and noise of HbA1c. Screening interval for HbA1c was defined as informative when the signal-to-noise ratio exceeded 1. RESULTS: Among 96,456 healthy adults, 46,284 (48.0%) were male; age (range) and mean HbA1c (SD) were 48 (30-74) years old and 5.4 (0.4)%, respectively. As risk increased among those 30-44 years old, HbA1c screening intervals for detecting Type 2 DM consistently decreased: from 10.5 (BMI <18.5) to 2.4 (BMI > 30) years, and from 8.0 (Framingham Risk Score <10%) to 2.0 (Framingham Risk Score ≥20%) years. This trend was consistent in other age and risk groups as well; among obese 30-44 year olds, we found substantially shorter intervals compared to other groups. CONCLUSION: HbA1c screening intervals for identification of DM vary substantially by risk factors. Risk stratification should be applied when deciding an optimal HbA1c screening interval in the general population to minimize overdiagnosis and overtreatment.

Is further screening of men with baseline PSA < 1 ng ml(-1) worthwhile? The discussion continues-Results of the Swiss ERSPC (Aarau).

Recent studies indicate frequent early PSA retesting unrelated of men's baseline PSA, which increases the harms of early detection especially among men with low PSA. The current study investigates the PCa incidence among men with baseline PSA <1.0 ng ml(-1) in order to adjust retest intervals for more targeted early detection. Between 1998 and 2012, 2,416 men with baseline PSA <1.0 ng ml(-1) were prospectively observed. Primary endpoint was PCa diagnosis. Negative predictive value (NPV) and number needed to screen (NNS) to detect one PCa were calculated. During a median follow-up time of 12.1 years, 54 (2.2%) PCa were diagnosed with n = 26 (48.1%) among men with baseline PSA of 0.75 ≤ 1.0 ng ml(-1) (upper baseline PSA quartile). The 10-year probability of being diagnosed with PCa increased significantly from 0.19% (baseline PSA < 0.40 ng ml(-1) ) to 2.0% (baseline PSA 0.40 ≤ 0.56 ng ml(-1) ), 2.5% (baseline PSA 0.56 ≤ 0.75 ng ml(-1) ) over 4.4% (baseline PSA 0.75 ≤ 1.0 ng ml(-1) ) (all p values <0.0001), respectively. The frequency of Gleason ≥7 PCa increased from 1 (0.17%) to 8 (1.4%), 5 (0.8) over 11 (1.8%) in these groups. The 8-year NPV for Gleason ≥ 7 PCa were 99.8 (baseline PSA < 0.40 ng ml(-1) ), 99.8 (baseline PSA 0.40 ≤ 0.56 ng ml(-1) ), 100 (baseline PSA 0.56 ≤ 0.75 ng ml(-1) ) and 99.5 (baseline PSA 0.75 ≤ 1.0 ng ml(-1) ), respectively. During 12 years, the numbers were 99.8, 98.6, 99.2, and 98.2, respectively. Therefore, due to the very low rate of Gleason ≥ 7 PCa, further screening might be omitted in men with baseline PSA < 0.4 ng ml(-1) . Between 0.4 and 1.0 ng ml(-1) , an 8-year interval can be discussed.

Impact of the COVID-19 pandemic on cervical cancer screening participation, abnormal cytology prevalence and screening interval in Catalonia.

Background: The COVID-19 pandemic led to a national lockdown and the interruption of all cancer preventive services, including cervical cancer screening. We aimed to assess the COVID-19 pandemic impact on opportunistic screening participation, abnormal cytology (ASCUS+) prevalence and screening interval in 2020 and 2021 within the Public Health System of Catalonia, Spain. Methods: Individual data on cytology and HPV testing of women aged 25-65 from 2014 to 2021 were retrieved from the Information System for Primary Care Services (SISAP). Time-series regression models were used to estimate expected screening participation and abnormal cytology prevalence in 2020 and 2021. The impact was determined by comparing observed and expected values (ratios). Additionally, changes in screening interval trends between 2014 and 2021 were assessed by fitting a Piecewise linear regression model. Results: Cervical cancer screening participation decreased by 38.8% and 2.2% in 2020 and 2021, respectively, with the most significant impact on participation (-96.1%) occurring in April 2020. Among older women, participation was lower, and it took longer to recover. Abnormal cytology prevalence was 1.4 times higher than expected in 2020 and 2021, with variations by age (range=1.1-1.5). From June 2020 onwards, the screening interval trend significantly changed from an increase of 0.59 to 3.57 months per year, resulting in a median time of 48 months by December 2021. Conclusions: During the pandemic, fewer women have participated in cervical cancer screening, abnormal cytology prevalence has increased, and the screening interval is more prolonged than before. The potential cervical cancer lifetime risk implications highlight the need for organized HPV-based screening.

The Impact of Prostate-Specific Antigen Screening on Prostate Cancer Incidence and Mortality in China: 13-Year Prospective Population-Based Cohort Study.

BACKGROUND: The status of prostate-specific antigen (PSA) screening is unclear in China. Evidence regarding the optimal frequency and interval of serial screening for prostate cancer (PCa) is disputable. OBJECTIVE: This study aimed to depict the status of PSA screening and to explore the optimal screening frequency for PCa in China. METHODS: A 13-year prospective cohort study was conducted using the Chinese Electronic Health Records Research in Yinzhou study's data set. A total of 420,941 male participants aged ≥45 years were included between January 2009 and June 2022. Diagnosis of PCa, cancer-specific death, and all-cause death were obtained from the electronic health records and vital statistic system. Hazard ratios (HRs) with 95% CIs were estimated using Cox regression analysis. RESULTS: The cumulative rate of ever PSA testing was 17.9% with an average annual percent change (AAPC) of 8.7% (95% CI 3.6%-14.0%) in the past decade in China. People with an older age, a higher BMI, higher waist circumference, tobacco smoking and alcohol drinking behaviors, higher level of physical activity, medication use, and comorbidities were more likely to receive PSA screening, whereas those with a lower education level and a widowed status were less likely to receive the test. People receiving serial screening ≥3 times were at a 67% higher risk of PCa detection (HR 1.67; 95% CI 1.48-1.88) but a 64% lower risk of PCa-specific mortality (HR 0.36; 95% CI 0.18-0.70) and a 28% lower risk of overall mortality (HR 0.72; 95% CI 0.67-0.77). People following a serial screening strategy at least once every 4 years were at a 25% higher risk of PCa detection (HR 1.25; 95% CI 1.13-1.36) but 70% (HR 0.30; 95% CI 0.16-0.57) and 23% (HR 0.77; 95% CI 0.73-0.82) lower risks of PCa-specific and all-cause mortality, respectively. CONCLUSIONS: This study reveals a low coverage of PSA screening in China and provides the first evidence of its benefits in the general Chinese population. The findings of this study indicate that receiving serial screening at least once every 4 years is beneficial for overall and PCa-specific survival. Further studies based on a nationwide population and with long-term follow-up are warranted to identify the optimal screening interval in China.

Individualized Family Screening for Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: Clinical guidelines recommend regular screening for arrhythmogenic right ventricular cardiomyopathy (ARVC) to monitor at-risk relatives, resulting in a significant burden on clinical resources. Prioritizing relatives on their probability of developing definite ARVC may provide more efficient patient care. OBJECTIVES: The aim of this study was to determine the predictors and probability of ARVC development over time among at-risk relatives. METHODS: A total of 136 relatives (46% men, median age 25.5 years [IQR: 15.8-44.4 years]) from the Netherlands Arrhythmogenic Cardiomyopathy Registry without definite ARVC by 2010 task force criteria were included. Phenotype was ascertained using electrocardiography, Holter monitoring, and cardiac imaging. Subjects were divided into groups with "possible ARVC" (only genetic or familial predisposition) and "borderline ARVC" (1 minor task force criterion plus genetic or familial predisposition). Cox regression was performed to determine predictors and multistate modeling to assess the probability of ARVC development. Results were replicated in an unrelated Italian cohort (57% men, median age 37.0 years [IQR: 25.4-50.4 years]). RESULTS: At baseline, 93 subjects (68%) had possible ARVC, and 43 (32%) had borderline ARVC. Follow-up was available for 123 relatives (90%). After 8.1 years (IQR: 4.2-11.4 years), 41 (33%) had developed definite ARVC. Independent of baseline phenotype, symptomatic subjects (P = 0.014) and those 20 to 30 years of age (P = 0.002) had a higher hazard of developing definite ARVC. Furthermore, patients with borderline ARVC had a higher probability of developing definite ARVC compared with those with possible ARVC (1-year probability 13% vs 0.6%, 3-year probability 35% vs 5%; P < 0.01). External replication showed comparable results (P > 0.05). CONCLUSIONS: Symptomatic relatives, those 20 to 30 years of age, and those with borderline ARVC have a higher probability of developing definite ARVC. These patients may benefit from more frequent follow-up, while others may be monitored less often.

Factors associated with shorter-interval cervical cancer screening for young women in three United States healthcare systems.

Frequently changing cervical cancer screening guidelines over the past two decades have been inconsistently adopted in the United States. Current guidelines set the recommended screening interval to three years for average-risk women aged 21-29 years. Few studies have evaluated how patient and provider factors are associated with implementation of cervical cancer screening intervals among younger women. This study evaluated multilevel factors associated with screening interval length among 69,939 women aged 21-29 years with an initial negative Pap screen between 2010 and 2015 across three large health systems in the U.S. Shorter-interval screening was defined as a second screening Pap within 2.5 years of an initial negative Pap. Mixed-effects logistic regression was performed for each site to identify provider and patient characteristics associated with shorter-interval screening. The odds of shorter-interval screening decreased over the study period across all sites, though the proportion of patients screened within 2.5 years remained between 7.5% and 20.7% across sites in 2014-2015. Patient factors including insurance, race/ethnicity, and pregnancy were associated with shorter-interval screening, though the patterns differed across sites. At one site, the variation in shorter-interval screening explained by the provider was 10.6%, whereas at the other two sites, the provider accounted for < 2% of the variation in shorter-interval screening. Our results highlight the heterogeneity in factors driving cervical cancer screening interval across health systems and point to the need for tailored approaches targeted to both providers and patients to improve guideline-concordant screening.

Overcoming barriers: Modelling the effect of potential future changes of organized breast cancer screening in Italy.

OBJECTIVES: Organized breast cancer screening may not achieve its full potential due to organizational and cultural barriers. In Italy, two identified barriers were low attendance in Southern Italy and, in Italy as a whole, underscreening and overscreening in parts of the eligible population. The objective of this study was to identify potential changes to overcome these barriers and to quantify their costs and effects. METHODS: To assess the impact of potential measures to improve breast cancer screening in Italy, we performed an evaluation of costs and effects for increasing adherence for Southern Italy and harmonizing screening intervals (biennial screening) for the whole of Italy, using an online tool (EU-TOPIA evaluation tool) based on the MIcrosimulation SCreening ANalysis (MISCAN) model. RESULTS: Increasing adherence in Southern Italy through investing in mobile screening units has an acceptable cost-effectiveness ratio of €9531 per quality-adjusted life year gained. Harmonizing the screening interval by investing in measures to reduce opportunistic screening and simultaneously investing in mobile screening units to reduce underscreening is predicted to gain 1% fewer life-years, while saving 19% of total screening costs compared to the current situation. CONCLUSIONS: Increasing adherence in Southern Italy and harmonizing the screening interval could result in substantial improvements at acceptable costs, or in the same benefits at lower costs. This example illustrates a systematic approach that can be easily applied to other European countries, as the online tools can be used by stakeholders to quantify effects and costs of a broad range of specific barriers, and ways to overcome them.

Long-term esophageal cancer risk and distinct surveillance intervals after a single endoscopy screening: a multicentre population-based cohort study.

Background: Endoscopy surveillance is recommended for mild-moderate dysplasia and negative endoscopy findings every 3 years and 5 years, respectively, but evidence is limited. This study aimed to assess long-term esophageal cancer (EC) incidence and mortality after a single endoscopy screening. Methods: We included individuals at high risk of EC aged 40-69 years who underwent endoscopy screening in 2007-2012 at six centres in rural China and had a baseline diagnosis of negative endoscopy findings, mild dysplasia, or moderate dysplasia. Participants were followed up for EC incidence and mortality. Cumulative incidence and mortality rates of EC were estimated by Kaplan-Meier analyses. Cox regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between baseline endoscopy diagnosis and the risk of EC incidence and mortality. EC incidence and mortality after a single endoscopy screening were compared with those of the population in rural China by the standardized incidence ratio (SIR) and standardized mortality ratio (SMR). Findings: A total of 42,827 participants (40,977 with negative endoscopy findings, 1562 with mild dysplasia, and 288 with moderate dysplasia) were included; 268 EC cases and 128 EC deaths were identified during a median follow-up of 10.62 years. The cumulative EC incidence at 10 years was 0.45% (0.38-0.52) in the group with negative endoscopy findings, 2.39% (1.62-3.16) in the mild dysplasia group, and 8.90% (5.57-12.24) in the moderate dysplasia group, and the cumulative EC mortality at 10 years was 0.23% (0.18-0.27), 0.96% (0.46-1.46), and 2.50% (0.67-4.33), respectively. Compared with individuals with negative endoscopy findings, the HRs for EC incidence and mortality in the mild dysplasia group were 3.52 (2.49-4.97) and 2.43 (1.41-4.19), and those in the moderate dysplasia group were 13.18 (8.78-19.76) and 6.46 (3.13-13.29), respectively. The SIR was 0.53 (0.40-0.70) for the group with negative endoscopy findings, 1.95 (1.69-2.24) for the mild dysplasia group, and 6.75 (6.25-7.28) for the moderate dysplasia group, with the SMRs of 0.43 (0.31-0.58), 1.07 (0.88-1.29) and 2.67 (2.36-3.01), respectively. Interpretation: Individuals with negative endoscopy findings after a single endoscopy screening had a lower EC risk than the general population for up to 10.62 years, while those with mild-moderate dysplasia had an elevated risk. Our results support endoscopy surveillance for mild-moderate dysplasia every 3 years and suggest extending the interval to 10 years after a negative endoscopy finding. Funding: National Key R&D Programme of China, Special Project of Beijing-Tianjin-Hebei Basic Research Cooperation, and Sanming Project of Medicine in Shenzhen.

Bone Mineral Density Screening Interval and Transition to Osteoporosis in Asian Women.

BACKGRUOUND: Bone mineral density (BMD) testing is indicated for women aged 65 years, but screening strategies for osteoporosis are controversial. Currently, there is no study focusing on the BMD testing interval in Asian populations. The current study aimed to evaluate the estimated time interval for screening osteoporosis. METHODS: We conducted a study of 6,385 subjects aged 50 years and older who underwent dual-energy X-ray absorptiometry screening more than twice at Samsung Medical Center as participants in a routine health checkup. Subjects were divided based on baseline T-score into mild osteopenia (T-score, <-1.0 to >-1.5), moderate osteopenia (T-score, ≤-1.5 to >-2.0), and severe osteopenia (T-score, ≤-2.0 to >-2.5). Information about personal medical and social history was collected by a structured questionnaire. RESULTS: The adjusted estimated BMD testing interval for 10% of the subjects to develop osteoporosis was 13.2 years in mild osteopenia, 5.0 years in moderate osteopenia, and 1.5 years in severe osteopenia. CONCLUSION: Our study provides extended information about BMD screening intervals in Asian female population. Baseline T-score was important for predicting BMD screening interval, and repeat BMD testing within 5 years might not be necessary in mild osteopenia subjects.

Women with a positive high-risk human papillomavirus (HPV) test remain at increased risk of HPV infection and cervical precancer ≥15 years later.

Little is known about the long-term association between high-risk human papillomavirus (hrHPV) test results in women participating in a hrHPV-based cervical cancer screening program. To address this question, we collected data of 2217 women who participated in the POBASCAM hrHPV-based screening trial (enrolment 1999/2002) and also attended the Dutch hrHPV-based screening program between January 2017 and March 2018. Among 143 women who tested hrHPV-positive in 1999/2002, 45 (31.5%) had ≥ CIN2 or hysterectomy before 2017 and 17 (11.9%) tested hrHPV-positive at the 2017/2018 screen. In comparison, among 2074 women who tested hrHPV-negative in 1999/2002, 10 (0.5%) had ≥ CIN2 or hysterectomy before 2017 and 119 (5.7%) tested hrHPV-positive at the 2017/2018 screen. It follows that in the group of women who were not treated for ≥ CIN2 or had a hysterectomy in between the two screens 15 years apart (N = 2162), women who were hrHPV-positive in 1999/2002 had a higher risk of being hrHPV-positive in 2017/2018 than those who were hrHPV-negative in 1999/2002 (OR 3.4, 95% CI 1.8-6.1). A similar association was found at the genotype level for genotype-concordant results (5.1, 1.0-11.3) and for genotype non-concordant results (3.7, 1.6-6.7). Women who were hrHPV-positive in 2017/2018 had a higher risk of CIN3 after a hrHPV-positive result in 1999/2002 than after a hrHPV-negative result (5.8, 1.0-27.8). In conclusion, a positive hrHPV result in screening gives a long-term increased risk of a hrHPV-positive result, also for different genotypes, and a long-term increased risk of CIN3. This supports the concept of risk-stratification in hrHPV-based cervical cancer screening where previous hrHPV results are included in screening recommendations.

Breast cancer screening with mammography in women aged 40-49 years: Impact of length of screening interval on effectiveness of the program.

OBJECTIVES: To estimate the impact on the effectiveness of Swedish breast cancer screening program in women aged 40-49 years of shortening the screening interval from 21 months to 18 or 12 months. METHODS: The reduction in breast cancer mortality among participants in screening with mammography was previously estimated in the Swedish SCReening of Young women (SCRY) study to be 29%. The expected increased effectiveness with a hypothetical shorter screening interval than the average of 21 months in SCRY was calculated using data about the women who died from breast cancer even though they participated in the SCRY program. RESULTS: During the study period, 547 women who participated in the index screening round died from breast cancer. Shortening the screening interval to 18 months led to an improved effectiveness of 0.7-3.9% considering interval cancers only and of 1.3-7.6% considering screening-detected cancers only, and for both interval and screening-detected cancers the improvement was 1.9-11.5% when the assumed mortality reduction for the deceased cases varied from 5% to 30%. Shortening the screening interval to 12 months increased the effectiveness by 1.6-9.8% for interval cancers and by 2.9-17.4% for both interval and screening-detected cancers. CONCLUSION: Shortening the screening interval for women aged 40-49 years to 18 or 12 months might further reduce the breast cancer mortality rate.

An Evolutionary Algorithm to Personalize Stool-Based Colorectal Cancer Screening.

BACKGROUND: Fecal immunochemical testing (FIT) is an established method for colorectal cancer (CRC) screening. Measured FIT-concentrations are associated with both present and future risk of CRC, and may be used for personalized screening. However, evaluation of personalized screening is computationally challenging. In this study, a broadly applicable algorithm is presented to efficiently optimize personalized screening policies that prescribe screening intervals and FIT-cutoffs, based on age and FIT-history. METHODS: We present a mathematical framework for personalized screening policies and a bi-objective evolutionary algorithm that identifies policies with minimal costs and maximal health benefits. The algorithm is combined with an established microsimulation model (MISCAN-Colon), to accurately estimate the costs and benefits of generated policies, without restrictive Markov assumptions. The performance of the algorithm is demonstrated in three experiments. RESULTS: In Experiment 1, a relatively small benchmark problem, the optimal policies were known. The algorithm approached the maximum feasible benefits with a relative difference of 0.007%. Experiment 2 optimized both intervals and cutoffs, Experiment 3 optimized cutoffs only. Optimal policies in both experiments are unknown. Compared to policies recently evaluated for the USPSTF, personalized screening increased health benefits up to 14 and 4.3%, for Experiments 2 and 3, respectively, without adding costs. Generated policies have several features concordant with current screening recommendations. DISCUSSION: The method presented in this paper is flexible and capable of optimizing personalized screening policies evaluated with computationally-intensive but established simulation models. It can be used to inform screening policies for CRC or other diseases. For CRC, more debate is needed on what features a policy needs to exhibit to make it suitable for implementation in practice.