State-level disparities in cervical cancer prevention and impact on outcomes in the U.S.: A modeling study.

Background: Despite the availability of HPV vaccines for over a decade, coverage across the United States (US) is varied. While some states have made concerted efforts to increase HPV vaccination coverage, most model-based analyses have estimated vaccine impact on the US. We estimated the impact of hypothetical changes in HPV vaccination coverage at the state level for three states with varying levels of HPV vaccination coverage and cervical cancer incidence (California, New York, Texas) using a mathematical model. Methods: We developed a new mathematical model of HPV transmission and cervical cancer tailored to state-level cancer incidence and mortality. We quantified the public health impact of increasing HPV vaccination coverage to 80% by 2025 or 2030 and the effect on time to elimination in the three states. Results: Increasing vaccination coverage to 80% in Texas in 10 years could reduce cervical cancer incidence by 50.9% (95%-CrI: 46.6-56.1%) by 2100. In New York and California, achieving the same coverage could reduce incidence by 27.3% (95%-CrI: 23.9-31.5%) and 24.4% (95%-CrI: 20.0-30.0%), respectively. Achieving 80% coverage in 5 years will slightly increase the reduction. If 2019 vaccination coverage continues, cervical cancer elimination would be reached in the US by 2051 (95%-Crl: 2034-2064). However, the timeline by which individual states reach elimination could vary by decades. Conclusion: Achieving an HPV vaccination coverage target of 80% by 2030 will benefit states with low vaccination coverage and high cervical cancer incidence the most. Our results highlight the value of more geographically focused analyses to inform priorities.

The Natural Disease Course of Pancreatic Cyst-Associated Neoplasia, Dysplasia, and Ductal Adenocarcinoma: Results of a Microsimulation Model.

BACKGROUND & AIMS: Estimates on the progression of precursor lesions to pancreatic cancer (PC) are scarce. We used microsimulation modeling to gain insight into the natural disease course of PC and its precursors. This information is pivotal to explore the efficacy of PC screening. METHODS: A Microsimulation Screening Analysis model was developed in which pancreatic intraepithelial neoplasms and cysts can evolve from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) to PC. The model was calibrated to Dutch PC incidence data and Japanese precursor prevalence data (autopsy cases without PC) and provides estimates of PC progression (precursor lesion onset and stage duration). RESULTS: Mean LGD state durations of cysts and pancreatic intraepithelial neoplasms were 15.8 years and 17.1 years, respectively. Mean HGD state duration was 5.8 years. For lesions that progress to PC, the mean duration was 4.8-4.9 years for LGD lesions and 4.0-4.1 years for HGD lesions. In 13.7% of individuals who developed PC, the HGD state lasted less than 1 year. The probability that an individual at age 50 years developed PC in the next 20 years was estimated to be 1.8% in the presence of any cyst and 6.1% in case of an LGD mucinous cyst. This 20-year PC risk was estimated to be 5.1% for individuals with an LGD pancreatic intraepithelial neoplasm. CONCLUSIONS: Mean duration of HGD lesions before development of PC was estimated to be 4.0 years. This implies a window of opportunity for screening, presuming the availability of a reliable diagnostic test. The probability that an LGD cyst will progress to cancer was predicted to be low.

Acceptability of risk-based triage in cervical cancer screening: A focus group study.

BACKGROUND: Compared to the previous cytology-based program, the introduction of primary high-risk human papillomavirus (hrHPV) based screening in 2017 has led to an increased number of referrals. To counter this, triage of hrHPV-positive women in cervical cancer screening can potentially be optimized by taking sociodemographic and lifestyle risk factors for cervical abnormalities into account. Therefore, it is essential to gain knowledge of the views of women (30-60 years) eligible for cervical cancer screening. OBJECTIVE: The main goal of this qualitative study was to gain insight in the aspects that influence acceptability of risk-based triage in cervical cancer screening. DESIGN: A focus group study in which participants were recruited via four general medical practices, and purposive sampling was used to maximize heterogeneity with regards to age, education level, and cervical cancer screening experiences. APPROACH: The focus group discussions were transcribed verbatim and analyzed using reflexive thematic analysis. PARTICIPANTS: A total of 28 women (average age: 45.2 years) eligible for cervical cancer screening in The Netherlands participated in seven online focus group discussions. Half of the participants was higher educated, and the participants differed in previous cervical cancer screening participation and screening result. KEY RESULTS: In total, 5 main themes and 17 subthemes were identified that determine the acceptability of risk-stratified triage. The main themes are: 1) adequacy of the screening program: an evidence-based program that is able to minimize cancer incidence and reduce unnecessary referrals; 2) personal information (e.g., sensitive topics and stigma); 3) emotional impact: fear and reassurance; 4) communication (e.g., transparency); and 5) autonomy (e.g., prevention). CONCLUSION: The current study highlights several challenges regarding the development and implementation of risk-based triage that need attention in order to be accepted by the target group. These challenges include dealing with sensitive topics and a transparent communication strategy.

The effect of extended participation windows on attendance at cervical cancer screening.

Research has long since confirmed the benefits of regular cervical cancer screening (CCS) worldwide. However, some developed countries have low participation rates despite well-organized screening programs. Given that studies in Europe typically define participation in 12-month windows from an invitation, we evaluated both whether extending this defined time window could reveal the true participation rate and how sociodemographic determinants affect participation delays. This involved linking data from the Lifelines population-based cohort with CCS-related data from the Dutch Nationwide Pathology Databank and including data for 69 185 women eligible for screening in the Dutch CCS program between 2014 and 2018. We then estimated and compared the participation rates for 15- and 36-month time windows and categorized women by the primary screening window into timely participation (within 15 months) and delayed participation (within 15-36 months) groups, before performing multivariable logistic regression to evaluate the association between delayed participation and the sociodemographic determinants. Participation rates for the 15- and 36-month windows were 71.1% and 77.0%, respectively, with participation considered timely in 49 224 cases and delayed in 4047 cases. Delayed participation was associated with age 30-35 years (odds ratio [OR]: 2.88, 95 %CI: 2.67-3.11), higher education (OR: 1.50, 95 %CI: 1.35-1.67), the high-risk human papillomavirus test-based program (OR: 1.67, 95 %CI: 1.56-1.79), and pregnancy (OR: 4.61, 95 %CI: 3.88-5.48). These findings show that a 36-month window for monitoring attendance at CCS better reflects the actual participation rate by accommodating possible delayed uptake among younger, pregnant, and highly educated women.

Projections of costs and quality adjusted life years lost due to dementia from 2020 to 2050: A population-based microsimulation study.

INTRODUCTION: Efficient healthcare planning requires reliable projections of the future increase in costs and quality-adjusted life years (QALYs) lost due to dementia. METHODS: We used the microsimulation model MISCAN-Dementia to simulate life histories and dementia occurrence using population-based Rotterdam Study data and nationwide birth cohort demographics. We estimated costs and QALYs lost in the Netherlands from 2020 to 2050, incorporating literature estimates of cost and utility for patients and caregivers by dementia severity and care setting. RESULTS: Societal costs and QALYs lost due to dementia are estimated to double between 2020 and 2050. Costs are incurred predominantly through institutional (34%), formal home (31%), and informal home care (20%). Lost QALYs are mostly due to shortened life expectancy (67%) and, to a lesser extent, quality of life with severe dementia (14%). DISCUSSION: To limit healthcare costs and quality of life losses due to dementia, interventions are needed that slow symptom progression and reduce care dependency.

The impact of pancreatic cancer screening on life expectancy: A systematic review of modeling studies.

Evidence supporting the effectiveness of pancreatic cancer (PC) screening is scant. Most clinical studies concern small populations with short follow-up durations. Mathematical models are useful to estimate long-term effects of PC screening using short-term indicators. This systematic review aims to evaluate the impact of PC screening on life expectancy (LE) in model-based studies. Therefore, we searched four databases (Embase, Medline, Web-of-science, Cochrane) until 30 May 2022 to identify model-based studies evaluating the impact of PC screening on LE in different risk populations. Two authors independently screened identified papers, extracted data and assessed the methodological quality of studies. A descriptive analysis was performed and the impact of screening strategies on LE of different risk groups was reported. Our search resulted in 419 studies, of which eight met the eligibility criteria (mathematical model, PC screening, LE). Reported relative risks (RR) for PC varied from 1 to 70. In higher risk individuals (RR > 5), annual screening (by imaging with 56% sensitivity for HGD/early stage PC) predicted to increase LE of screened individuals by 20 to 260 days. In the general population, one-time PC screening was estimated to decrease LE (2-110 days), depending on the test characteristics and treatment mortality risk. In conclusion, although the models use different and sometimes outdated or unrealistic assumptions, it seems that PC screening in high-risk populations improves LE, and that this gain increases with a higher PC risk. Updated model studies, with data from large clinical trials are necessary to predict the long-term effect of PC screening more accurately.

Sociodemographic Characteristics and Screening Outcomes of Women Preferring Self-Sampling in the Dutch Cervical Cancer Screening Programme: A Population-Based Study.

BACKGROUND: In the Netherlands, lower high-risk human papillomavirus (hrHPV) positivity but higher cervical intraepithelial neoplasia (CIN) 2+ detection were found in self-collected compared with clinician-collected samples. To investigate the possible reason for these differences, we compared sociodemographic and screening characteristics of women and related these to screening outcomes. METHODS: We extracted data from PALGA on all primary hrHPV screens and associated follow-up tests for 857,866 screened women, invited in 2017 and 2018. We linked these data with sociodemographic data from Statistics Netherlands. Logistic regression was performed for hrHPV positivity and CIN 2+/3+ detection. RESULTS: Out of the 857,866 women, 6.8% chose to use a self-sampling device. A higher proportion of self-sampling users was ages 30 to 35 years, was not previously screened, was living in a one-person household, or was the breadwinner in the household. After adjustment for these factors self-sampling had lower hrHPV positivity (aOR, 0.65; 95% CI, 0.63-0.68)) as compared with clinician-collected sampling, as well as lower odds of CIN 2+ (aOR, 0.76; 95% CI, 0.70-0.82) and CIN 3+ (aOR, 0.86; 95% CI, 0.78-0.95) detection. CONCLUSIONS: It is likely that the observed differences between the two sampling methods are not only related to sociodemographic differences, but related to differences in screening test accuracy and/or background risk. IMPACT: Self-sampling can be used for targeting underscreened women, as a more convenient screening tool. Further investigation is required to evaluate how to implement self-sampling, when it is used as a primary instrument in routine screening. See related commentary by Arbyn et al., p. 159.

Rapid elimination of cervical cancer while maintaining the harms and benefits ratio of cervical cancer screening: a modelling study.

BACKGROUND: Human papillomavirus (HPV) vaccination and intensifying screening expedite cervical cancer (CC) elimination, yet also deteriorate the balance between harms and benefits of screening. We aimed to find screening strategies that eliminate CC rapidly but maintain an acceptable harms-benefits ratio of screening. METHODS: Two microsimulation models (STDSIM and MISCAN) were applied to simulate HPV transmission and CC screening for the Dutch female population between 2022 and 2100. We estimated the CC elimination year and harms-benefits ratios of screening for 228 unique scenarios varying in vaccination (coverage and vaccine type) and screening (coverage and number of lifetime invitations in vaccinated cohorts). The acceptable harms-benefits ratio was defined as the number of women needed to refer (NNR) to prevent one CC death under the current programme for unvaccinated cohorts (82.17). RESULTS: Under current vaccination conditions (bivalent vaccine, 55% coverage in girls, 27.5% coverage in boys), maintaining current screening conditions is projected to eliminate CC by 2042, but increases the present NNR with 41%. Reducing the number of lifetime screens from presently five to three and increasing screening coverage (61% to 70%) would prevent an increase in harms and only delay elimination by 1 year. Scaling vaccination coverage to 90% in boys and girls with the nonavalent vaccine is estimated to eliminate CC by 2040 under current screening conditions, but exceeds the acceptable NNR with 23%. Here, changing from five to two lifetime screens would keep the NNR acceptable without delaying CC elimination. CONCLUSIONS: De-intensifying CC screening in vaccinated cohorts leads to little or no delay in CC elimination while it substantially reduces the harms of screening. Therefore, de-intensifying CC screening in vaccinated cohorts should be considered to ensure acceptable harms-benefits ratios on the road to CC elimination.

A model-based analysis of the health impacts of COVID-19 disruptions to primary cervical screening by time since last screen for current and future disruptions.

We evaluated how temporary disruptions to primary cervical cancer (CC) screening services may differentially impact women due to heterogeneity in their screening history and test modality. We used three CC models to project the short- and long-term health impacts assuming an underlying primary screening frequency (i.e., 1, 3, 5, or 10 yearly) under three alternative COVID-19-related screening disruption scenarios (i.e., 1-, 2-, or 5-year delay) versus no delay in the context of both cytology-based and human papillomavirus (HPV)-based screening. Models projected a relative increase in symptomatically detected cancer cases during a 1-year delay period that was 38% higher (Policy1-Cervix), 80% higher (Harvard), and 170% higher (MISCAN-Cervix) for underscreened women whose last cytology screen was 5 years prior to the disruption period compared with guidelines-compliant women (i.e., last screen 3 years prior to disruption). Over a woman's lifetime, temporary COVID-19-related delays had less impact on lifetime risk of developing CC than screening frequency and test modality; however, CC risks increased disproportionately the longer time had elapsed since a woman's last screen at the time of the disruption. Excess risks for a given delay period were generally lower for HPV-based screeners than for cytology-based screeners. Our independent models predicted that the main drivers of CC risk were screening frequency and screening modality, and the overall impact of disruptions from the pandemic on CC outcomes may be small. However, screening disruptions disproportionately affect underscreened women, underpinning the importance of reaching such women as a critical area of focus, regardless of temporary disruptions.

Health impacts of COVID-19 disruptions to primary cervical screening by time since last screen: A model-based analysis for current and future disruptions.

Background: We evaluated how temporary disruptions to primary cervical cancer (CC) screening services may differentially impact women due to heterogeneity in their screening history and test modality. Methods: We used three CC models to project the short- and long-term health impacts assuming an underlying primary screening frequency (i.e., 1, 3, 5, or 10 yearly) under three alternative COVID-19-related screening disruption scenarios (i.e., 1-, 2- or 5-year delay) versus no delay, in the context of both cytology-based and HPV-based screening. Results: Models projected a relative increase in symptomatically-detected cancer cases during a 1-year delay period that was 38% higher (Policy1-Cervix), 80% higher (Harvard) and 170% higher (MISCAN-Cervix) for under-screened women whose last cytology screen was 5 years prior to the disruption period compared with guidelines-compliant women (i.e., last screen three years prior to disruption). Over a woman's lifetime, temporary COVID-19-related delays had less impact on lifetime risk of developing CC than screening frequency and test modality; however, CC risks increased disproportionately the longer time had elapsed since a woman's last screen at the time of the disruption. Excess risks for a given delay period were generally lower for HPV-based screeners than for cytology-based screeners. Conclusions: Our independent models predicted that the main drivers of CC risk were screening frequency and screening modality, and the overall impact of disruptions from the pandemic on CC outcomes may be small. However, screening disruptions disproportionately affect under-screened women, underpinning the importance of reaching such women as a critical area of focus, regardless of temporary disruptions. Funding: This study was supported by funding from the National Cancer Institute (U01CA199334). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Megan A Smith receives salary support from the National Health and Medical Research Council, Australia (APP1159491) and Cancer Institute NSW (ECF181561). Matejka Rebolj is funded by Cancer Research UK (reference: C8162/A27047). James O'Mahony is funded by Ireland's Health Research Board (EIA2017054). Karen Canfell receives salary support from the National Health and Medical Research Council, Australia (APP1194679). Emily A. Burger receives salary support from the Norwegian Cancer Society.

Projected prevalence and incidence of dementia accounting for secular trends and birth cohort effects: a population-based microsimulation study.

There is need for accurate projections of the future dementia burden to prepare healthcare systems and policymakers. Existing projections only account for population ageing, not for observed declines in age-specific dementia incidence of 13% per decade. We developed a dementia microsimulation model that synthesizes population-based data from the Rotterdam Study with changes in demographics between birth cohorts from the early 1900s onwards. We determined dementia prevalence and incidence until 2050 for three different dementia incidence trend scenarios: (1) stable age-specific incidence, (2) linear decline by 13% per decade, (3) nonlinear declines averaging 13% per decade. Assuming a stable age-specific incidence resulted in a 130% increase in incidence and 118% in prevalence between 2020 and 2050. By contrast, the linearly declining trend resulted in substantially smaller increases of 58% in incidence (95%CI: 29-87%), and 43% in prevalence (95%CI: 13-66%), corresponding to 39% lower incidence and 36% lower prevalence by 2050 than in the stable-incidence scenario. Results for various non-linear declines fell between the stable and linear trend. The future burden of dementia is highly susceptible to achievable changes in age-specific incidence. Extension of previously established secular trends globally would reduce widely upheld projections of new dementia cases until 2050 by 39%.

Shift in harms and benefits of cervical cancer screening in the era of HPV screening and vaccination: a modelling study.

OBJECTIVE: To calculate the changes in harms and benefits of cervical cancer screening over the first three screening rounds of the Dutch high-risk human papillomavirus (hrHPV) screening programme. DESIGN: Microsimulation study. SETTING: Dutch hrHPV screening programme; women are invited for screening every 5 or 10 years (depending on age and screening history) from age 30 to 65. POPULATION: Partly vaccinated population of 100 million Dutch women. METHODS: Microsimulation model MISCAN was used to estimate screening effects. Sensitivity analyses were performed on test characteristics and attendance. MAIN OUTCOME MEASURES: Harms (screening tests, unnecessary referrals, treatment-related health problems), benefits (CIN2+ diagnoses) and programme efficiency (number needed to screen [NNS]) over the first (period 2017-2021), second (period 2022-2026) and third (period 2027-2031) rounds of hrHPV-based screening. RESULTS: The number of screening tests and CIN2+ diagnoses decreased from the first to the second round (-25.8% and -23.6%, respectively). In the third screening round, these numbers decreased further, albeit only slightly (-2.7% and -5.3%, respectively). NNS to detect a CIN2+ remained constant over the rounds; however, it increased in younger age groups while decreasing in older age groups. CONCLUSION: Both harms and benefits of hrHPV screening decreased over the first screening rounds. For younger women, the efficiency would decrease, whereas longer screening intervals would lead to increased efficiency in older women. Programme efficiency overall remained stable, showing the importance of longer intervals for low-risk women. TWEETABLE ABSTRACT: Cervical cancer screening: both harms and benefits of hrHPV screening will decrease in the future.

Clinical performance of high-risk HPV testing on self-samples versus clinician samples in routine primary HPV screening in the Netherlands: An observational study.

BACKGROUND: High-risk human papillomavirus (hrHPV) testing on self-collected samples has potential as a primary screening tool in cervical screening, but real-world evidence on its accuracy in hrHPV-based screening programmes is lacking. METHODS: In the Netherlands, women aged 30-60 years invited for cervical screening can choose between sampling at the clinician's office (Cervex Brush) or self-sampling at home (Evalyn Brush). HrHPV testing is performed using Roche Cobas 4800. We collected screening test results between January 2017 and March 2018 and histological follow-up until August 2019. The main outcome measures were mean cycle threshold (Ct) value, cervical intraepithelial neoplasia (CIN) grade 3 or cancer (CIN3+) and CIN grade 2 or worse (CIN2+). FINDINGS: 30,808 women had a self-collected and 456,207 had a clinician-collected sample. In hrHPV-positive women with adequate cytology, Ct values were higher for self-collection than clinician-collection with a mean Ct difference of 1·25 (95% CI 0·98-1·52) in women without CIN2+, 2·73 (1·75-3·72) in CIN2 and 3·59 (3·03-4·15) in CIN3+. The relative sensitivity for detecting CIN3+ was 0·94 (0·90-0·97) for self-collection versus clinician-collection and the relative specificity was 1·02 (1·02-1·02). INTERPRETATION: The clinical accuracy of hrHPV testing on a self-collected sample for detection of CIN3+ is high and supports its use as a primary screening test for all invited women. Because of the slightly lower sensitivity of hrHPV testing on a self-collected compared to a clinician-collected sample, an evaluation of the workflow procedure to optimise clinical performance seems warranted. FUNDING: National Institute for Public Health and the Environment (the Netherlands) and the European Commission.

Heterogeneity in Reports of Dementia Disease Duration and Severity: A Review of the Literature.

BACKGROUND: The burden of dementia is changing due to population aging and changes in incidence and risk factor profiles. Reliable projections of future disease burden require accurate estimates of disease duration across different stages of dementia severity. OBJECTIVE: To provide an overview of current evidence on severity stage and disease duration in patients with dementia. METHODS: We reviewed the literature on duration of mild cognitive impairment (MCI), dementia, and various dementia severity stages. Data on study setting, country, sample size, severity stages, dementia type, and definition of disease duration was collected. Weighted averages and Q-statistics were calculated within severity stages and duration definitions. RESULTS: Of 732 screened articles, 15 reported the duration of one or more severity stages and only half of those reported severity stage onset to conversion to the following stage. In those studies, MCI, very mild dementia, and mild dementia stages lasted 3-4 years and moderate and severe dementia stages lasted 1-2 years. Information on the disease duration was reported in 93 (13%) of screened articles and varied from 1 to 17 years. Reporting of dementia severity stage and disease duration in the literature was highly heterogeneous, which was accounted for only in part by dementia type, study setting, or continent of data collection. CONCLUSION: The duration of dementia disease stages shortens with advancing stage. However, reliable modelling of future dementia burden and informing of intervention strategies will require more consistently reported duration estimates from studies that follow individuals longitudinally throughout their entire disease course.

Molecular markers for cervical cancer screening.

INTRODUCTION: Cervical cancer remains a significant healthcare problem, notably in low- to middle-income countries. While a negative test for hrHPV has a predictive value of more than 99.5%, its positive predictive value is less than 10% for CIN2+ stages. This makes the use of a so-called triage test indispensable for population-based screening to avoid referring women, that are ultimately at low risk of developing cervical cancer, to a gynecologist. This review will give an overview of tests that are based on epigenetic marker panels and protein markers. AREAS COVERED: There is a medical need for molecular markers with a better predictive value to discriminate hrHPV-positive women that are at risk of developing cervical cancer from those that are not. Areas covered are epigenetic and protein markers as well as health economic considerations in view of the fact that most cases of cervical cancer arise in low-to-middle-income countries. EXPERT OPINION: While there are biomarker assays based on changes at the nucleic acid (DNA methylation patterns, miRNAs) and at the protein level, they are not widely used in population screening. Combining nucleic acid-based and protein-based tests could improve the overall specificity for discriminating CIN2+ lesions that carry a low risk of progressing to cervical cancer within the screening interval from those that carry an elevated risk. The challenge is to reduce unnecessary referrals without an undesired increase in false-negative diagnoses resulting in cases of cervical cancer that could have been prevented. A further challenge is to develop tests for low-and middle-income countries, which is critical to reduce the worldwide burden of cervical cancer.

Impact of disruptions and recovery for established cervical screening programs across a range of high-income country program designs, using COVID-19 as an example: A modelled analysis.

COVID-19 has disrupted cervical screening in several countries, due to a range of policy-, health-service and participant-related factors. Using three well-established models of cervical cancer natural history adapted to simulate screening across four countries, we compared the impact of a range of standardised screening disruption scenarios in four countries that vary in their cervical cancer prevention programs. All scenarios assumed a 6- or 12-month disruption followed by a rapid catch-up of missed screens. Cervical screening disruptions could increase cervical cancer cases by up to 5-6%. In all settings, more than 60% of the excess cancer burden due to disruptions are likely to have occurred in women aged less than 50 years in 2020, including settings where women in their 30s have previously been offered HPV vaccination. Approximately 15-30% of cancers predicted to result from disruptions could be prevented by maintaining colposcopy and precancer treatment services during any disruption period. Disruptions to primary screening had greater adverse effects in situations where women due to attend for screening in 2020 had cytology (vs. HPV) as their previous primary test. Rapid catch-up would dramatically increase demand for HPV tests in 2021, which it may not be feasible to meet because of competing demands on the testing machines and reagents due to COVID tests. These findings can inform future prioritisation strategies for catch-up that balance potential constraints on resourcing with clinical need.

Cervical screening during the COVID-19 pandemic: optimising recovery strategies.

Disruptions to cancer screening services have been experienced in most settings as a consequence of the COVID-19 pandemic. Ideally, programmes would resolve backlogs by temporarily expanding capacity; however, in practice, this is often not possible. We aim to inform the deliberations of decision makers in high-income settings regarding their cervical cancer screening policy response. We caution against performance measures that rely solely on restoring testing volumes to pre-pandemic levels because they will be less effective at mitigating excess cancer diagnoses than will targeted measures. These measures might exacerbate pre-existing inequalities in accessing cervical screening by disregarding the risk profile of the individuals attending. Modelling of cervical screening outcomes before and during the pandemic supports risk-based strategies as the most effective way for screening services to recover. The degree to which screening is organised will determine the feasibility of deploying some risk-based strategies, but implementation of age-based risk stratification should be universally feasible.

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

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.

Modeling Strategies to Optimize Cancer Screening in USPSTF Guideline-Noncompliant Women.

Importance: In 2018, only half of US women obtained all evidence-based cancer screenings. This proportion may have declined during the COVID-19 pandemic because of social distancing, high-risk factors, and fear. Objective: To evaluate optimal screening strategies in women who obtain some, but not all, US Preventive Services Task Force (USPSTF)-recommended cancer screenings. Design, Setting, and Participants: This modeling study was conducted from January 31, 2017, to July 20, 2020, and used 4 validated mathematical models from the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network using data from 20 million simulated women born in 1965 in the US. Interventions: Forty-five screening strategies were modeled that combined breast, cervical, colorectal, and/or lung cancer (LC) screenings; restricted to 1, 2, 3 or 4 screenings per year; or all eligible screenings once every 5 years. Main Outcomes and Measures: Modeled life-years gained from restricted cancer screenings as a fraction of those attainable from full compliance with USPSTF recommendations (maximum benefits). Results were stratified by LC screening eligibility (LC-eligible/ineligible). We repeated the analysis with 2018 adherence rates, evaluating the increase in adherence required for restricted screenings to have the same population benefit as USPSTF recommendations. Results: This modeling study of 20 million simulated US women found that it was possible to reduce screening intensity to 1 carefully chosen test per year in women who were ineligible for LC screening and 2 tests per year in eligible women while maintaining 94% or more of the maximum benefits. Highly ranked strategies screened for various cancers, but less often than recommended by the USPSTF. For example, among LC-ineligible women who obtained just 1 screening per year, the optimal strategy frequently delayed breast and cervical cancer screenings by 1 year and skipped 3 mammograms entirely. Among LC-eligible women, LC screening was essential; strategies omitting it provided 25% or less of the maximum benefits. The top-ranked strategy restricted to 2 screenings per year was annual LC screening and alternating fecal immunochemical test with mammography (skipping mammograms when due for cervical cancer screening, 97% of maximum benefits). If adherence in a population of LC-eligible women obtaining 2 screenings per year were to increase by 1% to 2% (depending on the screening test), this model suggests that it would achieve the same benefit as USPSTF recommendations at 2018 adherence rates. Conclusions and Relevance: This modeling study of 45 cancer screening strategies suggests that women who are noncompliant with cancer screening guidelines may be able to reduce USPSTF-recommended screening intensity with minimal reduction in overall benefits.