Publications by authors named "Steffie K Naber"

32 Publications

The optimal age to stop endoscopic surveillance of Barrett's esophagus patients based on sex and comorbidity: a comparative cost-effectiveness analysis.

Gastroenterology 2021 May 8. Epub 2021 May 8.

Department of Public Health, Erasmus MC University Medical Center Rotterdam, The Netherlands.

Background & Aims: Current guidelines recommend surveillance for non-dysplastic Barrett's esophagus (NDBE) patients but do not include a recommended age for discontinuing surveillance. This study aimed to determine the optimal age for last surveillance of NDBE patients stratified by sex and level of comorbidity.

Methods: We used three independently developed models to simulate patients diagnosed with NDBE, varying in age, sex, and comorbidity level (no, mild, moderate, severe). All patients had received regular surveillance until their current age. We calculated incremental costs and quality-adjusted life-years (QALYs) gained from one additional endoscopic surveillance at the current age versus not performing surveillance at that age. We determined the optimal age to end surveillance as the age at which incremental cost-effectiveness ratio (ICER) of one more surveillance was just below the willingness-to-pay threshold of $100,000/QALY.

Results: The benefit of having one more surveillance endoscopy strongly depended on age, sex and comorbidity. For men with NDBE and severe comorbidity, one additional surveillance at age 80 years provided 4 more QALYs per 1,000 BE patients at an additional cost of $1,2 million, while for women with severe comorbidity the benefit at that age was 7 QALYs at a cost of $1.3 million. For men with no, mild, moderate and severe comorbidity, the optimal ages of last surveillance were 81, 80, 77 and 73 years, respectively. For women, these ages were lower: 75, 73, 73 and 69 years, respectively.

Conclusions: Our comparative modeling analysis illustrates the importance of considering comorbidity status and sex when deciding upon the age to discontinue surveillance in patients with NDBE.
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http://dx.doi.org/10.1053/j.gastro.2021.05.003DOI Listing
May 2021

The Differential Risk of Cervical Cancer in HPV-Vaccinated and -Unvaccinated Women: A Mathematical Modeling Study.

Cancer Epidemiol Biomarkers Prev 2021 May 9;30(5):912-919. Epub 2021 Apr 9.

Erasmus Medical Center-University Medical Center, Department of Public Health, Rotterdam, the Netherlands.

Background: With increased uptake of vaccination against human papillomavirus (HPV), protection against cervical cancer will also increase for unvaccinated women, due to herd immunity. Still, the differential risk between vaccinated and unvaccinated women might warrant a vaccination-status-screening approach. To understand the potential value of stratified screening protocols, we estimated the risk differentials in HPV and cervical cancer between vaccinated and unvaccinated women.

Methods: We used STDSIM, an individual-based model of HPV transmission and control, to estimate the HPV prevalence reduction over time, after introduction of HPV vaccination. We simulated scenarios of bivalent or nonavalent vaccination in females-only or females and males, at 20% coverage increments. We estimated relative HPV-type-specific prevalence reduction compared with a no-vaccination counterfactual and then estimated the age-specific cervical cancer risk by vaccination status.

Results: The relative cervical cancer risk for unvaccinated compared with vaccinated women ranged from 1.7 (bivalent vaccine for females and males; 80% coverage) to 10.8 (nonavalent vaccine for females-only; 20% coverage). Under 60% vaccination coverage, which is a representative coverage for several western countries, including the United States, the relative risk (RR) varies between 2.2 (bivalent vaccine for females and males) and 9.2 (nonavalent vaccine for females).

Conclusions: We found large cervical cancer risk differences between vaccinated and unvaccinated women. In general, our model shows that the RR is higher in lower vaccine coverages, using the nonavalent vaccine, and when vaccinating females only.

Impact: To avoid a disbalance in harms and benefits between vaccinated and unvaccinated women, vaccination-based screening needs serious consideration.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102319PMC
May 2021

Cost-effectiveness analysis of colorectal cancer screening in a low incidence country: The case of Saudi Arabia.

Saudi J Gastroenterol 2021 Apr 7. Epub 2021 Apr 7.

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background: Colorectal cancer (CRC) screening is cost-effective in many Western countries, and many have successfully implemented CRC screening programs. For countries with a lower CRC incidence, like Saudi Arabia, the value of CRC screening is less evident and requires careful weighing of harms, benefits, and costs.

Methods: We used the MISCAN-Colon microsimulation model to simulate a male and female cohort with life expectancy and CRC risk as observed in Saudi Arabia. For both cohorts, we evaluated strategies without screening, with annual or biennial faecal immunochemical testing (FIT), and with 10-yearly or once-only colonoscopy. We also considered different start and end ages of screening. For both cohorts, we estimated lifetime costs and effects of each strategy. We then identified a set of potentially cost-effective strategies using incremental cost-effectiveness ratios (ICERs) defined as the additional cost per additional quality-adjusted life year (QALY).

Results: Without CRC screening, an estimated 14 per 1,000 males would develop CRC during their lifetime and 9 would die from CRC. Several strategies proved potentially cost-effective including biennial FIT at ages 55-65 (ICER of $7,400), once-only colonoscopy at age 55 (ICER of $7,700), and 10-yearly colonoscopy at ages 50-65, 45-65, and 45-75 (ICERs of $34,000, 71,000, and 375,000, respectively). For females, risk of CRC was lower and CRC screening was therefore less cost-effective, but efficient strategies were largely similar.

Conclusions: Despite low CRC incidence in Saudi Arabia, some FIT or colonoscopy screening strategies may meet reasonable thresholds of cost-effectiveness. The optimal strategy will depend on multiple factors including the willingness to pay per QALY, the colonoscopy capacity, and the accepted budget impact.
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http://dx.doi.org/10.4103/sjg.sjg_526_20DOI Listing
April 2021

Identifying key factors for the effectiveness of pancreatic cancer screening: A model-based analysis.

Int J Cancer 2021 Jul 25;149(2):337-346. Epub 2021 Mar 25.

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Pancreatic cancer (PC) survival is poor, as detection usually occurs late, when treatment options are limited. Screening of high-risk individuals may enable early detection and a more favorable prognosis. Knowledge gaps prohibit establishing the effectiveness of screening. We developed a Microsimulation Screening Analysis model to analyze the impact of relevant uncertainties on the effect of PC screening in high-risk individuals. The model simulates two base cases: one in which lesions always progress to PC and one in which indolent and faster progressive lesions coexist. For each base case, the effect of annual and 5-yearly screening with endoscopic ultrasonography/magnetic resonance imaging was evaluated. The impact of variance in PC risk, screening test characteristics and surgery-related mortality was evaluated using sensitivity analyses. Screening resulted in a reduction of PC mortality by at least 16% in all simulated scenarios. This reduction depended strongly on the natural disease course (annual screening: -57% for "Progressive-only" vs -41% for "Indolent Included"). The number of screen and surveillance tests needed to prevent one cancer death was impacted most by PC risk. A 10% increase in test sensitivity reduced mortality by 1.9% at most. Test specificity is important for the number of surveillance tests. In conclusion, screening reduces PC mortality in all modeled scenarios. The natural disease course and PC risk strongly determines the effectiveness of screening. Test sensitivity seems of lesser influence than specificity. Future research should gain more insight in PC pathobiology to establish the true value of PC screening in high-risk individuals.
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http://dx.doi.org/10.1002/ijc.33540DOI Listing
July 2021

Reducing unnecessary referrals for colposcopy in hrHPV-positive women within the Dutch cervical cancer screening programme: A modelling study.

Gynecol Oncol 2021 Mar 12;160(3):713-720. Epub 2021 Jan 12.

Department of Public Health, Erasmus MC University Medical Center, 3015GD, Rotterdam, the Netherlands.

Background: With the implementation of primary high-risk human papillomavirus (hrHPV) screening in the Netherlands, an increase was observed in the number of unnecessary referrals (≤Cervical Intraepithelial Neoplasia (CIN) 1) to colposcopy. We aimed to investigate which alternative triage strategies safely reduce unnecessary referrals in HPV-based cervical cancer screening programmes.

Methods: Microsimulation model MISCAN was used to simulate an unvaccinated cohort of ten million 30-year old Dutch women. We calculated unnecessary referrals, cervical cancer incidence, mortality, costs and QALYs for 24 triage strategies. Condition for direct referral (atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), conditional on HPV-genotype 16/18/other high risk (OHR)), type of triage test (cytology alone or combined with hrHPV) and time to triage test (6 or 12 months) was varied.

Results: The 24 triage strategies had varying effects on the number of unnecessary referrals ranging from -72% to +35%. Adjusting conditions for referral to 'HPV16/18+ and ASC-US+' and 'HPVOHR+ and HSIL+' and extending the interval between tests to 12 months resulted in a reduction in unnecessary referrals of 40% (incidence +0%, mortality -1%). Reduction in unnecessary referrals without genotyping was achieved by adjusting conditions for direct referral to LSIL (12 months to repeat test) (unnecessary referrals -37%, incidence +2%, mortality +0%).

Conclusions: To reduce the number of unnecessary referrals without increasing incidence and mortality by more than 2% in the Dutch cervical cancer screening programme, genotyping for HPV16 or HPV16/18 should be implemented with 12 months to repeat testing.
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http://dx.doi.org/10.1016/j.ygyno.2020.12.038DOI Listing
March 2021

The Impact of the Policy-Practice Gap on Costs and Benefits of Barrett's Esophagus Management.

Am J Gastroenterol 2020 07;115(7):1026-1035

Department of Public Health, Erasmus MC University Medical Center, Rotterdam, the Netherlands.

Introduction: Clinical guidelines recommend surveillance of patients with Barrett's esophagus (BE). However, the surveillance intervals in practice are shorter than policy recommendations. We aimed to determine how this policy-practice gap affects the costs and benefits of BE surveillance.

Methods: We used the Netherlands as an exemplary Western country and simulated a cohort of 60-year-old patients with BE using the Microsimulation Screening Analysis model-esophageal adenocarcinoma (EAC) microsimulation model. We evaluated surveillance according to the Dutch guideline and more intensive surveillance of patients without dysplastic BE and low-grade dysplasia. For each strategy, we computed the quality-adjusted life years (QALYs) gained and costs compared with no surveillance. We also performed a budget impact analysis to estimate the increased costs of BE management in the Netherlands for 2017.

Results: Compared with no surveillance, the Dutch guideline incurred an additional &OV0556;5.0 ($5.7) million per 1,000 patients with BE for surveillance and treatment, whereas 57 esophageal adenocarcinoma (EAC) cases (>T1a) were prevented. With intensive and very intensive surveillance strategies for both nondysplastic BE and low-grade dysplasia, the net costs increased by another &OV0556;2.5-5.6 ($2.8-6.5) million while preventing 10-19 more EAC cases and gaining 33-60 more QALYs. On a population level, this amounted to &OV0556;21-47 ($24-54) million (+32%-70%) higher healthcare costs in 2017.

Discussion: The policy-practice gap in BE surveillance intervals results in 50%-114% higher net costs for BE management for only 10%-18% increase in QALYs gained, depending on actual intensity of surveillance. Incentives to eliminate this policy-practice gap should be developed to reduce the burden of BE management on patients and healthcare resources.
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http://dx.doi.org/10.14309/ajg.0000000000000578DOI Listing
July 2020

The Impact of Different Screening Model Structures on Cervical Cancer Incidence and Mortality Predictions: The Maximum Clinical Incidence Reduction (MCLIR) Methodology.

Med Decis Making 2020 05 3;40(4):474-482. Epub 2020 Jun 3.

Department of Public Health, Erasmus MC-University Medical Center, Rotterdam, Zuid-Holland, The Netherlands.

. To interpret cervical cancer screening model results, we need to understand the influence of model structure and assumptions on cancer incidence and mortality predictions. Cervical cancer cases and deaths following screening can be attributed to 1) (precancerous or cancerous) disease that occurred after screening, 2) disease that was present but not screen detected, or 3) disease that was screen detected but not successfully treated. We examined the relative contributions of each of these using 4 Cancer Intervention and Surveillance Modeling Network (CISNET) models. . The maximum clinical incidence reduction (MCLIR) method compares changes in the number of clinically detected cervical cancers and mortality among 4 scenarios: 1) no screening, 2) one-time perfect screening at age 45 that detects all existing disease and delivers perfect (i.e., 100% effective) treatment of all screen-detected disease, 3) one-time realistic-sensitivity cytological screening and perfect treatment of all screen-detected disease, and 4) one-time realistic-sensitivity cytological screening and realistic-effectiveness treatment of all screen-detected disease. . Predicted incidence reductions ranged from 55% to 74%, and mortality reduction ranged from 56% to 62% within 15 years of follow-up for scenario 4 across models. The proportion of deaths due to disease not detected by screening differed across the models (21%-35%), as did the failure of treatment (8%-16%) and disease occurring after screening (from 1%-6%). . The MCLIR approach aids in the interpretation of variability across model results. We showed that the reasons why screening failed to prevent cancers and deaths differed between the models. This likely reflects uncertainty about unobservable model inputs and structures; the impact of this uncertainty on policy conclusions should be examined via comparing findings from different well-calibrated and validated model platforms.
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http://dx.doi.org/10.1177/0272989X20924007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322998PMC
May 2020

Calculation of Stop Ages for Colorectal Cancer Screening Based on Comorbidities and Screening History.

Clin Gastroenterol Hepatol 2021 Mar 23;19(3):547-555. Epub 2020 May 23.

Department of Public Health, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background & Aims: Routine screening for colorectal cancer typically is recommended until age 74 years. Although it has been proposed that a screening stop age could be determined based on sex and comorbidity, less is known about the impact of screening history. We investigated the effects of screening history on the selection of an optimal age to stop screening.

Methods: We used the Microsimulation Screening Analysis-Colon model to estimate the harms and benefits of screening with biennial fecal immunochemical tests by sex, comorbidity status, and screening history. The optimal screening stop age was determined based on the incremental number needed for 1 additional life-year per 1000 screened individuals compared with the threshold provided by stopping screening at 76 years in the average-health population with a perfect screening history (attended all required screening, diagnostic, and follow-up tests) to biennial fecal immunochemical testing from age 50 years.

Results: For persons age 76 years, 157 women and 108 men with a perfect screening history would need to be screened to gain 1 life-year per 1000 screened individuals. Previously unscreened women with no comorbid conditions and no history of screening could undergo an initial screening through 90 years, whereas unscreened men could undergo initial screening through 88 years, before this balance is reached. As screening adherence improved or as comorbidities increased, the optimal age to stop screening decreased to a point that, regardless of sex, individuals with severe comorbidities and a perfect screening history should stop screening at age 66 years or younger.

Conclusions: Based on the harm-benefit balance, the optimal stop age for colorectal cancer screening ranges from 66 years for unhealthy individuals with a perfect screening history to 90 years for healthy individuals without prior screening. These findings can be used to assist patients and clinicians in making decisions about screening participation.
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http://dx.doi.org/10.1016/j.cgh.2020.05.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982961PMC
March 2021

Cost-effectiveness of inactivated influenza vaccination in children with medical risk conditions in the Netherlands.

Vaccine 2020 04 28;38(17):3387-3396. Epub 2020 Feb 28.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

Background: In many countries, annual immunization with inactivated influenza vaccine (IIV) is recommended for children with medical risk conditions. Prior cost-effectiveness analyses found such immunization to be cost saving, but assumed effectiveness against non-severe influenza outcomes and a higher effectiveness against severe influenza outcomes than recent studies would suggest. However, recent vaccine studies do not indicate any reduction in community or outpatient disease episodes in IIV immunized individuals. We therefore evaluated cost-effectiveness of IIV immunization in children with medical risk conditions in the Netherlands, assuming that IIV reduces influenza-related hospitalization and death, but has no meaningful impact on non-severe health outcomes.

Methods: A health economic decision tree model was developed to evaluate health effects and costs of annual IIV immunization versus no immunization. Model inputs were based on our study on influenza-related primary care visits and other literature. Immunization was considered cost effective if associated costs were less than €20,000 per quality-adjusted life year (QALY) gained. Probabilistic sensitivity analyses were performed to assess robustness of results, and one-way sensitivity analyses and scenario analyses were done to assess the influence of individual parameters.

Results: Annual IIV prevents an average of 1.59 influenza-related hospitalizations and 0.02 deaths per 1,000 children with medical risk conditions. This results in an expected QALY gain of 0.43 at incremental costs of €21,564 per 1,000 children, corresponding to an incremental cost-effectiveness ratio (ICER) of €50,297/QALY compared to no immunization. Under base case assumptions, immunization had a 5% probability of being cost effective. Results were most influenced by vaccine efficacy against fatal influenza, QALY loss due to death, and mortality rate.

Conclusions: If IIV only reduces severe disease outcomes, as current evidence suggests, annual immunization of medical risk children is unlikely to be cost effective. Results should however be interpreted with caution as cost-effectiveness is largely dependent on incidence and QALY losses for fatal influenza, for which evidence is scarce.
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http://dx.doi.org/10.1016/j.vaccine.2020.01.057DOI Listing
April 2020

Cost-Effectiveness of Risk-Stratified Colorectal Cancer Screening Based on Polygenic Risk: Current Status and Future Potential.

JNCI Cancer Spectr 2020 Feb 14;4(1):pkz086. Epub 2019 Oct 14.

See the Notes section for the full list of authors' affiliations.

Background: Although uniform colonoscopy screening reduces colorectal cancer (CRC) mortality, risk-based screening may be more efficient. We investigated whether CRC screening based on polygenic risk is a cost-effective alternative to current uniform screening, and if not, under what conditions it would be.

Methods: The MISCAN-Colon model was used to simulate a hypothetical cohort of US 40-year-olds. Uniform screening was modeled as colonoscopy screening at ages 50, 60, and 70 years. For risk-stratified screening, individuals underwent polygenic testing with current and potential future discriminatory performance (area under the receiver-operating curve [AUC] of 0.60 and 0.65-0.80, respectively). Polygenic testing results were used to create risk groups, for which colonoscopy screening was optimized by varying the start age (40-60 years), end age (70-85 years), and interval (1-20 years).

Results: With current discriminatory performance, optimal screening ranged from once-only colonoscopy at age 60 years for the lowest-risk group to six colonoscopies at ages 40-80 years for the highest-risk group. While maintaining the same health benefits, risk-stratified screening increased costs by $59 per person. Risk-stratified screening could become cost-effective if the AUC value would increase beyond 0.65, the price per polygenic test would drop to less than $141, or risk-stratified screening would lead to a 5% increase in screening participation.

Conclusions: Currently, CRC screening based on polygenic risk is unlikely to be cost-effective compared with uniform screening. This is expected to change with a greater than 0.05 increase in AUC value, a greater than 30% reduction in polygenic testing costs, or a greater than 5% increase in adherence with screening.
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http://dx.doi.org/10.1093/jncics/pkz086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988584PMC
February 2020

Optimizing Management of Patients With Barrett's Esophagus and Low-Grade or No Dysplasia Based on Comparative Modeling.

Clin Gastroenterol Hepatol 2020 08 6;18(9):1961-1969. Epub 2019 Dec 6.

Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington.

Background & Aims: Endoscopic treatment is recommended for patients with Barrett's esophagus (BE) with high-grade dysplasia, yet clinical management recommendations are inconsistent for patients with BE without dysplasia (NDBE) or with low-grade dysplasia (LGD). We used a comparative modeling analysis to identify optimal management strategies for these patients.

Methods: We used 3 independent population-based models to simulate cohorts of 60-year-old individuals with BE in the United States. We followed up each cohort until death without surveillance and treatment (natural disease progression), compared with 78 different strategies of management for patients with NDBE or LGD. We determined the optimal strategy using cost-effectiveness analyses, at a willingness-to-pay threshold of $100,000 per quality-adjusted life-year (QALY).

Results: In the 3 models, the average cumulative incidence of esophageal adenocarcinoma was 111 cases, with costs totaling $5.7 million per 1000 men with BE. Surveillance and treatment of men with BE prevented 23% to 75% of cases of esophageal adenocarcinoma, but increased costs to $6.2 to $17.3 million per 1000 men with BE. The optimal strategy was surveillance every 3 years for men with NDBE and treatment of LGD after confirmation by repeat endoscopy (incremental cost-effectiveness ratio, $53,044/QALY). The average results for women were consistent with the results for men for LGD management, but the optimal surveillance interval for women with NDBE was 5 years (incremental cost-effectiveness ratio, $36,045/QALY).

Conclusions: Based on analyses from 3 population-based models, the optimal management strategy for patient with BE and LGD is endoscopic eradication, but only after LGD is confirmed by a repeat endoscopy. The optimal strategy for patients with NDBE is endoscopic surveillance, using a 3-year interval for men and a 5-year interval for women.
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http://dx.doi.org/10.1016/j.cgh.2019.11.058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447845PMC
August 2020

Cost-Effectiveness of Personalized Screening for Colorectal Cancer Based on Polygenic Risk and Family History.

Cancer Epidemiol Biomarkers Prev 2020 01 20;29(1):10-21. Epub 2019 Nov 20.

Erasmus MC, University Medical Center Rotterdam, Department of Public Health, Rotterdam, the Netherlands.

Background: There is growing evidence for personalizing colorectal cancer screening based on risk factors. We compared the cost-effectiveness of personalized colorectal cancer screening based on polygenic risk and family history to uniform screening.

Methods: Using the MISCAN-Colon model, we simulated a cohort of 100 million 40-year-olds, offering them uniform or personalized screening. Individuals were categorized based on polygenic risk and family history of colorectal cancer. We varied screening strategies by start age, interval and test and estimated costs, and quality-adjusted life years (QALY). In our analysis, we (i) assessed the cost-effectiveness of uniform screening; (ii) developed personalized screening scenarios based on optimal screening strategies by risk group; and (iii) compared the cost-effectiveness of both.

Results: At a willingness-to-pay threshold of $50,000/QALY, the optimal uniform screening scenario was annual fecal immunochemical testing (FIT) from ages 50 to 74 years, whereas for personalized screening the optimal screening scenario consisted of annual and biennial FIT screening except for those at highest risk who were offered 5-yearly colonoscopy from age 50 years. Although these scenarios gained the same number of QALYs (17,887), personalized screening was not cost-effective, costing an additional $428,953 due to costs associated with determining risk (assumed to be $240 per person). Personalized screening was cost-effective when these costs were less than ∼$48.

Conclusions: Uniform colorectal cancer screening currently appears more cost-effective than personalized screening based on polygenic risk and family history. However, cost-effectiveness is highly dependent on the cost of determining risk.

Impact: Personalized screening could become increasingly viable as costs for determining risk decrease.
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http://dx.doi.org/10.1158/1055-9965.EPI-18-1123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159991PMC
January 2020

Cost-effectiveness of Active Identification and Subsequent Colonoscopy Surveillance of Lynch Syndrome Cases.

Clin Gastroenterol Hepatol 2020 11 17;18(12):2760-2767.e12. Epub 2019 Oct 17.

Department of Surgery, LiKaShing Knowledge Institute, St Michael's Hospital, Toronto, Canada.

Background & Aims: The province of Ontario, Canada is considering immunohistochemical followed by cascade analyses of all patients who received a diagnosis of colorectal cancer (CRC) at an age younger than 70 years to identify individuals with Lynch syndrome. We evaluated the costs and benefits of testing for Lynch syndrome and determined the optimal surveillance interval for first-degree relatives (FDRs) found to have Lynch syndrome.

Methods: We developed a patient flow diagram to determine costs and yield of immunohistochemical testing for Lynch syndrome in CRC cases and, for those found to have Lynch syndrome, their FDRs, accounting for realistic uptake. Subsequently, we used the MISCAN-colon model to compare costs and benefits of annual, biennial, and triennial surveillance in FDRs identified with Lynch syndrome vs colonoscopy screening every 10 years (usual care for individuals without a diagnosis of Lynch syndrome).

Results: Testing 1000 CRC cases was estimated to identify 20 CRC index cases and 29 FDRs with Lynch syndrome at a cost of $310,274. Despite the high cost of Lynch syndrome tests, offering the FDRs with Lynch syndrome biennial colonoscopy surveillance was cost-effective at $8785 per life-year gained compared with usual care because of a substantial increase in life-years gained (+122%) and cost savings in CRC care. Triennial surveillance was more costly and less effective, and annual surveillance showed limited additional benefit compared with biennial surveillance.

Conclusions: Immunohistochemical testing for Lynch syndrome in persons younger than 70 years who received a diagnosis of CRC and then testing FDRs of those found to have Lynch syndrome provide a good balance between costs and long-term benefits. Colonoscopy surveillance every 2 years is the optimal surveillance interval for patients with Lynch syndrome.
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http://dx.doi.org/10.1016/j.cgh.2019.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162709PMC
November 2020

Cost-effectiveness of a multitarget stool DNA test for colorectal cancer screening of Medicare beneficiaries.

PLoS One 2019 4;14(9):e0220234. Epub 2019 Sep 4.

Erasmus MC, University Medical Center Rotterdam, Department of Public Health, Rotterdam, The Netherlands.

Background: In 2014, the Centers for Medicare and Medicaid Services (CMS) began covering a multitarget stool DNA (mtSDNA) test for colorectal cancer (CRC) screening of Medicare beneficiaries. In this study, we evaluated whether mtSDNA testing is a cost-effective alternative to other CRC screening strategies reimbursed by CMS, and if not, under what conditions it could be.

Methods: We use three independently-developed microsimulation models to simulate a cohort of previously unscreened US 65-year-olds who are screened with triennial mtSDNA testing, or one of six other reimbursed screening strategies. Main outcome measures are discounted life-years gained (LYG) and lifetime costs (CMS perspective), threshold reimbursement rates, and threshold adherence rates. Outcomes are expressed as the median and range across models.

Results: Compared to no screening, triennial mtSDNA screening resulted in 82 (range: 79-88) LYG per 1,000 simulated individuals. This was more than for five-yearly sigmoidoscopy (80 (range: 71-89) LYG), but fewer than for every other simulated strategy. At its 2017 reimbursement rate of $512, mtSDNA was the most costly strategy, and even if adherence were 30% higher than with other strategies, it would not be a cost-effective alternative. At a substantially reduced reimbursement rate ($6-18), two models found that triennial mtSDNA testing was an efficient and potentially cost-effective screening option.

Conclusions: Compared to no screening, triennial mtSDNA screening reduces CRC incidence and mortality at acceptable costs. However, compared to nearly all other CRC screening strategies reimbursed by CMS it is less effective and considerably more costly, making it an inefficient screening option.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220234PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726189PMC
March 2020

Modeling in Colorectal Cancer Screening: Assessing External and Predictive Validity of MISCAN-Colon Microsimulation Model Using NORCCAP Trial Results.

Med Decis Making 2018 11 20;38(8):917-929. Epub 2018 Oct 20.

Department of Public Health, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (MB, AG, AKN, ETZ, HJdK, ILV).

Background: Microsimulation models are increasingly being used to inform colorectal cancer (CRC) screening recommendations. MISCAN-Colon is an example of such a model, used to inform the Dutch CRC screening program and US Preventive Services Task Force guidelines. Assessing the validity of these models is essential to provide transparency regarding their performance. In this study, we tested the external and predictive validity of MISCAN-Colon.

Methods: We validated MISCAN-Colon using the Norwegian Colorectal Cancer Prevention (NORCCAP) trial, a randomized controlled trial that examined the effectiveness of once-only flexible sigmoidoscopy (FS) screening. We simulated the study population and design of the NORCCAP trial in MISCAN-Colon and compared 10- to 12-year model-predicted hazard ratios (HRs) for overall and distal CRC incidence and mortality to those observed. In addition, we compared the numbers of screen-detected neoplasia. Finally, we predicted the trial's future results to allow for the assessment of predictive validity.

Results: MISCAN-Colon predicted an HR for overall CRC incidence (0.85), distal CRC incidence (0.82), overall CRC mortality (0.68), and distal CRC mortality (0.62). These were within the limits of the 95% confidence intervals of the NORCCAP trial results. Similar results were observed for the number of screen-detected cancers. The model significantly underestimated the number of screen-detected adenomas. Model-predicted HRs for CRC incidence and mortality up to 15- to 17-year follow-up were 0.84 and 0.72, respectively.

Conclusion: Although the underestimation of screen-detected adenomas requires further investigation, MISCAN-Colon is able to make a valid replication of the CRC incidence and mortality reduction of an FS screening trial, which suggests that it can be considered a useful tool to support decision making on CRC screening.
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http://dx.doi.org/10.1177/0272989X18806497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6705122PMC
November 2018

The health impact of human papillomavirus vaccination in the situation of primary human papillomavirus screening: A mathematical modeling study.

PLoS One 2018 4;13(9):e0202924. Epub 2018 Sep 4.

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Background: Human papillomavirus (HPV) vaccination and the implementation of primary HPV screening in the Netherlands will lead to a lower cervical disease burden. For evaluation and further improvement of prevention, it is important to estimate the magnitude and timing of health benefits of current and alternative vaccination strategies such as vaccination of boys or adults.

Methods And Findings: We evaluated the impact of the current girls-only vaccination program and alternative strategies on cervical disease burden among the first four vaccinated five-year birth cohorts, given the context of primary HPV screening. We integrated the existing microsimulation models STDSIM (HPV transmission model) and MISCAN-Cervix (cervical cancer screening model). Alternative vaccination strategies include: improved vaccination uptake, including routine boys vaccination, and offering adult vaccination at sexual health clinics. Our models show that the current vaccination program is estimated to reduce cervical cancers and cancer deaths by about 35% compared to primary HPV screening in the absence of vaccination. The number needed to vaccinate (NNV) to gain 1 life year is 45. The most efficient alternative vaccination strategies are: 1) improving coverage of girls to 80% (NNV = 42); and 2) routine vaccination for girls and boys at 80% coverage (incremental NNV = 155), with cervical cancer mortality reductions estimated at 50% and 60% respectively.

Conclusions: While the current program already substantially reduces cervical cancer incidence and mortality, prevention can be further improved by increasing vaccination uptake and extending vaccination to boys. As not all cervical cancer deaths will be prevented, screening participation should still be encouraged.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0202924PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122803PMC
February 2019

Costs and outcomes of Lynch syndrome screening in the Australian colorectal cancer population.

J Gastroenterol Hepatol 2018 Oct 17;33(10):1737-1744. Epub 2018 May 17.

Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia.

Background And Aim: Individuals with Lynch syndrome (LS) are at increased risk of LS-related cancers including colorectal cancer (CRC). CRC tumor screening for mismatch repair (MMR) deficiency is recommended in Australia to identify LS, although its cost-effectiveness has not been assessed. We aim to determine the cost-effectiveness of screening individuals with CRC for LS at different age-at-diagnosis thresholds.

Methods: We developed a decision analysis model to estimate yield and costs of LS screening. Age-specific probabilities of LS diagnosis were based on Australian data. Two CRC tumor screening pathways were assessed (MMR immunohistochemistry followed by MLH1 methylation (MLH1-Pathway) or BRAF V600E testing (BRAF-Pathway) if MLH1 expression was lost) for four age-at-diagnosis thresholds-screening < 50, screening < 60, screening < 70, and universal screening.

Results: Per 1000 CRC cases, screening < 50 identified 5.2 LS cases and cost $A7041 per case detected in the MLH1-Pathway. Screening < 60 increased detection by 1.5 cases for an incremental cost of $A25 177 per additional case detected. Screening < 70 detected 1.6 additional cases at an incremental cost of $A40 278 per additional case detected. Compared with screening < 70, universal screening detected no additional LS cases but cost $A158 724 extra. The BRAF-Pathway identified the same number of LS cases for higher costs.

Conclusions: The MLH1-Pathway is more cost-effective than BRAF-Pathway for all age-at-diagnosis thresholds. MMR immunohistochemistry tumor screening in individuals diagnosed with CRC aged < 70 years resulted in higher LS case detection at a reasonable cost. Further research into the yield of LS screening in CRC patients ≥ 70 years is needed to determine if universal screening is justified.
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http://dx.doi.org/10.1111/jgh.14154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403824PMC
October 2018

Effect of Cervical Cancer Screening Programs on Preterm Birth: A Decision and Cost-Effectiveness Analysis.

Obstet Gynecol 2017 12;130(6):1207-1217

Center for Reproductive Medicine, Department of Obstetrics and Gynaecology, Academic Medical Center, University of Amsterdam, and the Department of Obstetrics and Gynaecology, VU University Medical Center, Amsterdam, the Netherlands; the Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; and The Robinson Institute, School of Pediatrics and Reproductive Health, University of Adelaide, North Adelaide, Australia.

Objective: To assess the effect of age at initiation and interval of cervical cancer screening in women of reproductive age on the risk of future preterm birth and subsequent adverse neonatal outcome relative to maternal life-years gained and cost of both screening and preterm birth.

Methods: In this decision and cost-effectiveness analysis, we compared eight cytology-based screening programs varying in age of onset (21, 24, 25, 27, or 30 years) and screening interval (3 or 5 years) in a fictive cohort of 100,000 women. We used the microsimulation screening analysis model to estimate number of cervical intraepithelial neoplasia diagnoses, large loop excisions of the transformation zone (LLETZs), life-years gained, cervical cancer cases, deaths, and costs of screening and treatment. We used the number of LLETZs to calculate additional preterm births, subsequent neonatal morbidity, mortality, and associated costs.

Results: The number of LLETZs per 100,000 women varied from 9,612 for the most intensive screening (every 3 years from age 21 years) to 4,646 for the least intensive screening (every 5 years from age 30 years). Compared with the least intensive program, the most intensive program increased maternal life-years gained by 9% (10,728 compared with 9,839), decreased cervical cancer cases by 67% (52 compared with 158), and cervical cancer deaths by 75% (four compared with 16) at the expense of 250% (158 compared with 45) more preterm births and 320% (four compared with one) more neonatal deaths while increasing total costs by $55 million ($77 compared with $23 million). The number of maternal life-years gained per additional preterm birth varied from 68 to 258 with subsequent total costs per maternal life-years gained of $7,212 and $2,329.

Conclusion: Cervical cancer screening every 3 years and subsequent treatment in women aged younger than 30 years yield limited life-years but may have substantial perinatal adverse effects. Consequently, women who plan to have children may benefit from a more cautious screening approach, taking into account their risk for both cancer and preterm birth.
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http://dx.doi.org/10.1097/AOG.0000000000002366DOI Listing
December 2017

Cost Effectiveness of Age-Specific Screening Intervals for People With Family Histories of Colorectal Cancer.

Gastroenterology 2018 01 28;154(1):105-116.e20. Epub 2017 Sep 28.

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background & Aims: Relative risk of colorectal cancer (CRC) decreases with age among individuals with a family history of CRC. However, no screening recommendations specify less frequent screening with increasing age. We aimed to determine whether such a refinement would be cost effective.

Methods: We determined the relative risk for CRC for individuals based on age and number of affected first-degree relatives (FDRs) using data from publications. For each number of affected FDRs, we used the Microsimulation Screening Analysis model to estimate costs and effects of colonoscopy screening strategies with different age ranges and intervals. Screening was then optimized sequentially, starting with the youngest age group, and allowing the interval of screening to change at certain ages. Strategies with an incremental cost effectiveness ratio below $100,000 per quality-adjusted life year were considered cost effective.

Results: For people with 1 affected FDR (92% of those with a family history), screening every 3 years beginning at an age of 40 years is most cost effective. If no adenomas are found, the screening interval can gradually be extended to 5 and 7 years, at ages 45 and 55 years, respectively. From a cost-effectiveness perspective, individuals with more affected FDRs should start screening earlier and at shorter intervals. However, frequency can be reduced if no abnormalities are found.

Conclusions: Using a microsimulation model, we found that for individuals with a family history of CRC, it is cost effective to gradually increase the screening interval if several subsequent screening colonoscopies have negative results and no new cases of CRC are found in family members.
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http://dx.doi.org/10.1053/j.gastro.2017.09.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104831PMC
January 2018

Cervical cancer incidence after normal cytological sample in routine screening using SurePath, ThinPrep, and conventional cytology: population based study.

BMJ 2017 Feb 14;356:j504. Epub 2017 Feb 14.

Department of Public Health, Erasmus MC, University Medical Center, 3000 CA Rotterdam, Netherlands.

 To compare the cumulative incidence of cervical cancer diagnosed within 72 months after a normal screening sample between conventional cytology and liquid based cytology tests SurePath and ThinPrep. Retrospective population based cohort study. Nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA), January 2000 to March 2013. Women with 5 924 474 normal screening samples (23 833 123 person years). Use of SurePath or ThinPrep versus conventional cytology as screening test. 72 month cumulative incidence of invasive cervical cancer after a normal screening sample for each screening test. Cox regression analyses assessed the hazard ratios, adjusted for calendar time, age, screening history, and socioeconomic status and including laboratories as random effects. The 72 month cumulative cancer incidence was 58.5 (95% confidence interval 54.6 to 62.7) per 100 000 normal conventional cytology samples, compared with 66.8 (56.7 to 78.7) for ThinPrep and 44.6 (37.8 to 52.6) for SurePath. Compared with conventional cytology, the hazard of invasive cancer was 19% lower (hazard ratio 0.81, 95% confidence interval 0.66 to 0.99) for SurePath, mainly caused by a 27% lower hazard (0.73, 0.57 to 0.93) of a clinically detected cancer. For ThinPrep, the hazard was on average 15% higher (hazard ratio 1.15, 0.95 to 1.38), mainly caused by a 56% higher hazard of a screen detected cancer (1.56, 1.17 to 2.08). These findings should provoke reconsideration of the assumed similarity in sensitivity to detect progressive cervical intraepithelial neoplasia between different types of liquid based cytology and conventional cytology.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421440PMC
http://dx.doi.org/10.1136/bmj.j504DOI Listing
February 2017

Public Health Benefits of Routine Human Papillomavirus Vaccination for Adults in the Netherlands: A Mathematical Modeling Study.

J Infect Dis 2016 09 20;214(6):854-61. Epub 2016 Jun 20.

Department of Public Health.

Background: Expanding routine human papillomavirus (HPV) vaccination to adults could be an effective strategy to improve prevention of HPV infection and cervical cancer.

Methods: We evaluated the following adult vaccination strategies for women only and for both women and men in addition to the current girls-only vaccination program in the Netherlands, using the established STDSIM microsimulation model: one-time mass campaign, vaccination at the first cervical cancer screening visit, vaccination at sexual health clinics, and combinations of these strategies.

Results: The estimated impact of expanding routine vaccination to adult women is modest, with the largest incremental reductions in the incidence of HPV infection occurring when offering vaccination both at the cervical cancer screening visit and during sexually transmitted infection (STI) consultations (about 20% lower after 50 years for both HPV-16 and HPV-18). Adding male vaccination during STI consultations leads to more-substantial incidence reductions: 63% for HPV-16 and 84% for HPV-18. The incremental number needed to vaccinate among women is 5.48, compared with 0.90 for the current vaccination program.

Conclusions: Offering vaccination to adults, especially at cervical cancer screening visits (for women) and during STI consultations (for both sexes), would substantially reduce HPV incidence and would be an efficient policy option to improve HPV prevention and subsequently avert cervical and possibly male HPV-related cancers.
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http://dx.doi.org/10.1093/infdis/jiw256DOI Listing
September 2016

Estimation of Benefits, Burden, and Harms of Colorectal Cancer Screening Strategies: Modeling Study for the US Preventive Services Task Force.

JAMA 2016 Jun;315(23):2595-609

Department of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis.

Importance: The US Preventive Services Task Force (USPSTF) is updating its 2008 colorectal cancer (CRC) screening recommendations.

Objective: To inform the USPSTF by modeling the benefits, burden, and harms of CRC screening strategies; estimating the optimal ages to begin and end screening; and identifying a set of model-recommendable strategies that provide similar life-years gained (LYG) and a comparable balance between LYG and screening burden.

Design, Setting, And Participants: Comparative modeling with 3 microsimulation models of a hypothetical cohort of previously unscreened US 40-year-olds with no prior CRC diagnosis.

Exposures: Screening with sensitive guaiac-based fecal occult blood testing, fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy with or without stool testing, computed tomographic colonography (CTC), or colonoscopy starting at age 45, 50, or 55 years and ending at age 75, 80, or 85 years. Screening intervals varied by modality. Full adherence for all strategies was assumed.

Main Outcomes And Measures: Life-years gained compared with no screening (benefit), lifetime number of colonoscopies required (burden), lifetime number of colonoscopy complications (harms), and ratios of incremental burden and benefit (efficiency ratios) per 1000 40-year-olds.

Results: The screening strategies provided LYG in the range of 152 to 313 per 1000 40-year-olds. Lifetime colonoscopy burden per 1000 persons ranged from fewer than 900 (FIT every 3 years from ages 55-75 years) to more than 7500 (colonoscopy screening every 5 years from ages 45-85 years). Harm from screening was at most 23 complications per 1000 persons screened. Strategies with screening beginning at age 50 years generally provided more LYG as well as more additional LYG per additional colonoscopy than strategies with screening beginning at age 55 years. There were limited empirical data to support a start age of 45 years. For persons adequately screened up to age 75 years, additional screening yielded small increases in LYG relative to the increase in colonoscopy burden. With screening from ages 50 to 75 years, 4 strategies yielded a comparable balance of screening burden and similar LYG (median LYG per 1000 across the models): colonoscopy every 10 years (270 LYG); sigmoidoscopy every 10 years with annual FIT (256 LYG); CTC every 5 years (248 LYG); and annual FIT (244 LYG).

Conclusions And Relevance: In this microsimulation modeling study of a previously unscreened population undergoing CRC screening that assumed 100% adherence, the strategies of colonoscopy every 10 years, annual FIT, sigmoidoscopy every 10 years with annual FIT, and CTC every 5 years performed from ages 50 through 75 years provided similar LYG and a comparable balance of benefit and screening burden.
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http://dx.doi.org/10.1001/jama.2016.6828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493310PMC
June 2016

The role of pre-invasive disease in overdiagnosis: A microsimulation study comparing mass screening for breast cancer and cervical cancer.

J Med Screen 2016 12 11;23(4):210-216. Epub 2016 Apr 11.

Department of Public Health, Erasmus MC, Rotterdam, The Netherlands.

Objective: Although early detection of cancer through screening can prevent cancer deaths, a drawback of screening is overdiagnosis. Overdiagnosis has been much debated in breast cancer screening, but less so in cervical cancer screening. We examined the impact of overdiagnosis by comparing two screening programmes in the Netherlands.

Methods: We estimated overdiagnosis rates by microsimulation for breast cancer screening and cervical cancer screening, using a cohort of women born in 1982 with lifelong follow-up. Overdiagnosis estimates were made analogous to two definitions formed by the UK 2012 breast screening review. Pre-invasive disease was included in both definitions.

Results: Screening prevented 921 cervical cancers (-55%) and 378 cervical cancer deaths (-59%), and 169 (-1.3%) breast cancer cases and 970 breast cancer deaths (-21%). The cervical cancer overdiagnosis rate was 74.8% (including pre-invasive disease). Breast cancer overdiagnosis was estimated at 2.5% (including pre-invasive disease). For women of all ages in breast cancer screening, an excess of 207 diagnoses/100,000 women was found, compared with an excess of 3999 diagnoses/100,000 women in cervical cancer screening.

Conclusions: For breast cancer, the frequency of overdiagnosis in screening is relatively low, but consequences are evident. For cervical cancer, the frequency of overdiagnosis in screening is high, because of detection of pre-invasive disease, but the consequences per case are relatively small due to less invasive treatment. This illustrates that it is necessary to present overdiagnosis in relation to disease stage and consequences.
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http://dx.doi.org/10.1177/0969141316629505DOI Listing
December 2016

The potential harms of primary human papillomavirus screening in over-screened women: a microsimulation study.

Cancer Causes Control 2016 Apr 12;27(4):569-81. Epub 2016 Mar 12.

Department of Public Health, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.

Background: It is well acknowledged that HPV testing should not be performed at young age and at short intervals. Cytological screening practices have shown that over-screening, i.e., from a younger age and at shorter intervals than recommended, is hard to avoid. We quantified the consequences of a switch to primary HPV screening for over-screened women, taking into account its higher sensitivity but lower specificity than cytology.

Methods: The health effects of using the HPV test instead of cytology as the primary screening method were determined with the MISCAN-Cervix model. We varied the age women start screening and the interval between screens. In the sensitivity analyses, we varied the background risk of cervical cancer, the HPV prevalence, the discount rate, the triage strategy after cytology, and the test characteristics of both cytology and the HPV test.

Results: For women screened 5 yearly from age 30, 32 extra deaths per 100,000 simulated women were prevented when switching from primary cytology to primary HPV testing. For annual screening from age 20, such a switch resulted in 6 extra deaths prevented. It was associated with 9,044 more positive primary screens in the former scenario versus 76,480 in the latter. Under all conditions, for women screened annually, switching to HPV screening resulted in a net loss of quality-adjusted life years.

Conclusion: For over-screened women, the harms associated with a lower test specificity outweigh the life years gained when switching from primary cytology to primary HPV testing. The extent of over-screening should be considered when deciding on inclusion of primary HPV screening in cervical cancer screening guidelines.
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http://dx.doi.org/10.1007/s10552-016-0732-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4796367PMC
April 2016

Cervical Cancer Screening in Partly HPV Vaccinated Cohorts - A Cost-Effectiveness Analysis.

PLoS One 2016 29;11(1):e0145548. Epub 2016 Jan 29.

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Background: Vaccination against the oncogenic human papillomavirus (HPV) types 16 and 18 will reduce the prevalence of these types, thereby also reducing cervical cancer risk in unvaccinated women. This (measurable) herd effect will be limited at first, but is expected to increase over time. At a certain herd immunity level, tailoring screening to vaccination status may no longer be worth the additional effort. Moreover, uniform screening may be the only viable option. We therefore investigated at what level of herd immunity it is cost-effective to also reduce screening intensity in unvaccinated women.

Methods: We used the MISCAN-Cervix model to determine the optimal screening strategy for a pre-vaccination population and for vaccinated women (~80% decreased risk), assuming a willingness-to-pay of €50,000 per quality-adjusted life year gained. We considered HPV testing, cytology testing and co-testing and varied the start age of screening, the screening interval and the number of lifetime screens. We then calculated the incremental cost-effectiveness ratio (ICER) of screening unvaccinated women with the strategy optimized to the pre-vaccination population as compared to with the strategy optimized to vaccinated women, assuming different herd immunity levels.

Results: Primary HPV screening with cytology triage was the optimal strategy, with 8 lifetime screens for the pre-vaccination population and 3 for vaccinated women. The ICER of screening unvaccinated women 8 times instead of 3 was €28,085 in the absence of herd immunity. At around 50% herd immunity, the ICER reached €50,000.

Conclusion: From a herd immunity level of 50% onwards, screening intensity based on the pre-vaccination risk level becomes cost-ineffective for unvaccinated women. Reducing the screening intensity of uniform screening may then be considered.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145548PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732771PMC
July 2016

Beware of Kinked Frontiers: A Systematic Review of the Choice of Comparator Strategies in Cost-Effectiveness Analyses of Human Papillomavirus Testing in Cervical Screening.

Value Health 2015 12 17;18(8):1138-51. Epub 2015 Nov 17.

Department of Public Health, Erasmus Medical Centre, Erasmus University, Rotterdam, The Netherlands.

Objectives: To systematically review the choice of comparator strategies in cost-effectiveness analyses (CEAs) of human papillomavirus testing in cervical screening.

Methods: The PubMed, Web of Knowledge, and Scopus databases were searched to identify eligible model-based CEAs of cervical screening programs using human papillomavirus testing. The eligible CEAs were reviewed to investigate what screening strategies were chosen for analysis and how this choice might have influenced estimates of the incremental cost-effectiveness ratio (ICER). Selected examples from the reviewed studies are presented to illustrate how the omission of relevant comparators might influence estimates of screening cost-effectiveness.

Results: The search identified 30 eligible CEAs. The omission of relevant comparator strategies appears likely in 18 studies. The ICER estimates in these cases are probably lower than would be estimated had more comparators been included. Five of the 30 studies restricted relevant comparator strategies to sensitivity analyses or other subanalyses not part of the principal base-case analysis. Such exclusion of relevant strategies from the base-case analysis can result in cost-ineffective strategies being identified as cost-effective.

Conclusions: Many of the CEAs reviewed appear to include insufficient comparator strategies. In particular, they omit strategies with relatively long screening intervals. Omitting relevant comparators matters particularly if it leads to the underestimation of ICERs for strategies around the cost-effectiveness threshold because these strategies are the most policy relevant from the CEA perspective. Consequently, such CEAs may not be providing the best possible policy guidance and lead to the mistaken adoption of cost-ineffective screening strategies.
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http://dx.doi.org/10.1016/j.jval.2015.09.2939DOI Listing
December 2015

Comparing SurePath, ThinPrep, and conventional cytology as primary test method: SurePath is associated with increased CIN II+ detection rates.

Cancer Causes Control 2016 Jan 12;27(1):15-25. Epub 2015 Oct 12.

Department of Public Health, Erasmus MC, University Medical Center, Room Na-2223, PO Box 2040, 3000, CA, Rotterdam, The Netherlands.

Purpose: Within the last decade, SurePath and ThinPrep [both liquid-based cytology (LBC) tests] have replaced conventional cytology (CC) as primary test method in cervical cancer screening programs of multiple countries. The aim of our study was to examine the effect in the Dutch screening program.

Methods: All primary smears taken within this program from 2000 to 2011 were analyzed using the nationwide registry of histo- and cytopathology (PALGA) with a follow-up until March 2013. The percentage of smears classified as borderline/mildly dyskaryotic (BMD) and >BMD as well as CIN and cervical cancer detection rates were compared between SurePath and ThinPrep versus CC by logistic regression analyses (adjusted for age, screen region, socioeconomic status, and calendar time).

Results: We included 3,118,685 CC, 1,313,731 SurePath, and 1,584,587 ThinPrep smears. Using SurePath resulted in an increased rate of primary smears classified as >BMD [odds ratio (OR) = 1.12 (95% confidence interval (CI) 1.09-1.16)]. CIN I and II(+) detection rates increased by 14 % [OR = 1.14 (95% CI 1.08-1.20)] and 8 % [OR = 1.08 (95% CI 1.05-1.12)]. Cervical cancer detection rates were unaffected. Implementing ThinPrep did not result in major alterations of the cytological classification of smears, and it did not affect CIN detection rates. While not significant, cervical cancer detection rates were lower [OR = 0.87 (95% CI 0.75-1.01)].

Conclusions: The impact of replacing CC by LBC as primary test method depends on the type of LBC test used. Only the use of SurePath was associated with increased CIN II(+) detection, although it simultaneously increased the detection of CIN I.
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http://dx.doi.org/10.1007/s10552-015-0678-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703623PMC
January 2016

The estimated impact of natural immunity on the effectiveness of human papillomavirus vaccination.

Vaccine 2015 Oct 5;33(41):5357-5364. Epub 2015 Sep 5.

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.

Background: Mathematical modelling is used to estimate the effectiveness of HPV vaccination. These estimates depend strongly on herd immunity and thus on naturally acquired immunity, a mechanism of which little is known. We estimated the impact of different vaccination strategies on HPV-16 and HPV-18 transmission and cervical cancer incidence in the Netherlands, considering different acquired immunity mechanisms.

Methods: We used the STDSIM microsimulation model, and considered two mechanisms for acquired immunity after infection: (I) full immunity with variable duration; (II) cumulatively decreasing susceptibility to reinfection. Girls aged 13-16 years received vaccination (94.7% efficacy for HPV-16 and 92.3% for HPV-18) during a once-off catch-up campaign with 50% coverage, followed by annual vaccination of 12-year-old girls (60% coverage). Alternative vaccination scenarios included increased coverage, including boys, and lower vaccine efficacy.

Results: HPV-16 incidence reduced by 64% under mechanism I and 75% under mechanism II; HPV-18 incidence reduced by 58% and 73%, respectively, and these reductions lead to 48-56% fewer cervical cancer cases. Increasing coverage can lead to over 96% reduction in HPV incidence. Vaccinating boys reduced incidence by 79-89% for HPV-16 and 83-98% for HPV-18 in women.

Conclusions: Effectiveness estimates of HPV vaccination differ slightly between different acquired immunity mechanisms, yet these differences are unlikely to affect policy decisions. Offering vaccination to boys as well may be considered to further reduce cancer incidence.
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http://dx.doi.org/10.1016/j.vaccine.2015.08.079DOI Listing
October 2015

When is it effective to offer self-sampling to non-attendees--response.

Cancer Epidemiol Biomarkers Prev 2015 Aug;24(8):1296

Department of Public Health, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

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http://dx.doi.org/10.1158/1055-9965.EPI-15-0523DOI Listing
August 2015