All cases of invasive cervical cancer (ICC) and subsets of high-grade cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) and adenocarcinoma in situ (AIS) in Norway are tested for 37 human papillomavirus (HPV) genotypes, within a mandatory national surveillance system. We assessed the proportional attribution of HPV types in cervical lesions from predominantly unvaccinated women reported during 2017-2021 (baseline population) and the HPV type distribution by vaccination status in vaccine-eligible cases reported during 2017-2024. Among baseline CIN2/3 cases (n = 3087), 48% were attributable to HPV16/18, 28% to HPV31/33/45, 12% to HPV52/58 and 8% to other high-risk types (HPV35/39/51/56/59). For AIS (n = 550), almost all cases were attributed to HPV16/18 (91%) and HPV45 (6%). For ICC (n = 1265), 75% were attributable to HPV16/18, 15% to HPV31/33/45, 3% to HPV52/58 and 4% to other high-risk types. Among CIN2/3 cases born 1997 or later (eligible for vaccination at age 11-12 years, n = 154), HPV16-attribution was higher in unvaccinated cases (49.9%, 95% CI: 33.7-66.1) than in cases vaccinated before age 15 (1.1%, 95% CI: 0-3.4). In CIN2/3 cases born 1991-1996 (eligible for catch-up vaccination, n = 1541), HPV16-attribution was 45.7% (95% CI: 41.9-49.7) in unvaccinated versus 35.5% (95% CI: 32.5-38.6) in vaccinated cases. Minor differences by vaccination status were observed for catch-up-eligible AIS (n = 445) and ICC (n = 135) cases. In conclusion, the baseline genotype distribution in high-grade cervical lesions and ICC in Norway aligns with global data. Strong protection against HPV16-induced CIN2/3 was seen in women vaccinated before age 15 years.

Screening recommendations in the United States have not been modified for women who have been vaccinated against human papillomavirus (HPV). Using 3 independent Cancer Intervention and Surveillance Modeling Network (CISNET) models (Policy1-Cervix, Harvard and STDSIM-MISCAN), we evaluated the impact of switching from 3-yearly cytology-based screening for ages 21-65 ("cytology alone") to primary-HPV-16/18 screening for ages 25-65 every 5-years ("standardized 5-yearly HPV screening"), or every 8-10 years for younger vaccinated cohorts ("tailored HPV screening"). Compared to cytology alone, switching to standardized 5-yearly HPV screening for all women would reduce total cervical cancer deaths over the period 2020-2099 by 9%-14% and total colposcopies by 15%-49%, and achieve cervical cancer elimination by 2030-2037, 4 years earlier than cytology screening alone. Compared to cytology alone, tailored HPV screening would reduce cervical cancer deaths over the period 2020-2099 by 2%-14%, colposcopies by 30%-59%, and achieve elimination by 2030-2040, 1-4-years earlier. In conclusion, primary HPV screening in all women would be associated with improved health outcomes and would reduce colposcopy referrals in the longer term compared to older, cytology approaches. Tailoring the HPV screening interval to vaccination status has potential to increase efficiencies and maintain effectiveness and elimination timing.

BackgroundThe Norwegian public-private partnership, CONNECT, identified the reimbursement submission case of selpercatinib-a first-line targeted therapy for RET fusion-positive non-small cell lung cancer (NSCLC)-as a unique opportunity to assess the role of structured expert elicitation (SEE) in conjunction with phase II evidence.ObjectiveThis study aims to compare the potential of using SEE and other sources of external evidence with phase III clinical trial results to explore the possibility of facilitating earlier (conditional) reimbursement decisions.MethodsWe conducted a series of cost-effectiveness analyses, grouping different sources of evidence (i.e., published clinical evidence and SEE) to estimate the long-term health and economic consequences of selpercatinib versus pembrolizumab plus pemetrexed and platinum-based chemotherapy for patients with advanced RET fusion-positive NSCLC in Norway. We developed a probabilistic partitioned survival model to estimate and compare costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) associated with evidence potentially available early in the product lifecycle, including SEE, with those using phase III evidence.ResultsICERs consistently ranged between $8257 and $19,819 per QALY gained when we used SEE, either alone or in combination with additional external evidence, or when we used the phase III randomized controlled trial (RCT) evidence.ConclusionsThe consistent cost-effectiveness results between pre-submission and post-submission phases support the potential of SEE to complement health technology assessment (HTA) and potentially inform earlier (conditional) reimbursement decisions for this single case study. However, future research should focus on refining SEE protocols for continued methodological development and validation to improve generalizability and applicability.

Background:Adult women in the United States (US) currently comprise a mix of birth cohorts with different human papillomavirus (HPV) vaccination uptake and thus markedly different risks of cervical cancer, while cervical screening recommendations do not currently reflect these differences. We used comparative modeling to determine the optimal screening protocols for these cohorts. Methods:We used three independent models calibrated to US data to simulate three birth cohorts: unvaccinated females born in 1980, females born in 1993 (predominantly offered bivalent/quadrivalent HPV vaccines), and females born in 2003 (predominantly offered nonavalent HPV vaccine). We considered primary cytology, primary HPV testing, and co-testing, and varied the starting age (21-30 years) and screening frequency (three- to ten-yearly), resulting in 92 strategies. Strategies that were on the cost-effectiveness frontier for at least one model and were associated with incremental cost-effectiveness ratios between US$50,000 and US$200,000 per life-year gained were considered optimal; we compared health outcomes, colposcopies, and precancer treatments for these strategies to those estimated under current guidelines. Findings:For all three birth cohorts, optimal screening strategies involved primary HPV testing and decreasing the screening intervals, i.e., five-yearly from age 25 years for the unvaccinated birth cohort, eight-yearly from age 25 for the 1993 cohort, and 10-yearly from age 27 for the 2003 cohort. Interpretation:Primary HPV screening is the optimal approach regardless of vaccine protection exposure but US cervical cancer screening intervals should be extended for vaccinated cohorts to maintain cost-effectiveness. This would reduce harms while remaining more effective than current guidelines in pre-vaccine cohorts. Funding:US National Cancer Institute.

BACKGROUND:Widespread vaccination for human papillomavirus (HPV) alters the landscape of cervical cancer (CC) risk, requiring adaptations to the CC screening program. OBJECTIVE:To assess the cost-effectiveness and harm-benefit tradeoffs of adapting CC screening strategies on the basis of age at HPV vaccination. DESIGN:Individual-based mathematical modeling study. DATA SOURCES:Published data. TARGET POPULATION:Hypothetical cohorts of women vaccinated in 7 different age groups (12, 13 to 15, 16 to 18, 19 to 21, 22 to 24, 25 to 27, and 28 to 30 years) with either bivalent or nonavalent vaccines in Norway. TIME HORIZON:Lifetime. PERSPECTIVE:Extended health care sector (that is, including patient time and travel costs). INTERVENTION:HPV-based screening strategies that varied screening start age, interval, and number of lifetime screening tests. OUTCOME MEASURES:Incremental cost-effectiveness ratios, defined as the additional cost per quality-adjusted life-year (QALY) gained. "Preferred" (that is, cost-effective) screening for each age group was identified using a cost-effectiveness threshold of $55 000 per QALY. Harm-benefit tradeoffs were quantified as the ratio of colposcopy referrals to CC cases averted. RESULTS OF BASE-CASE ANALYSIS:For all vaccination age groups and both vaccines, less frequent screening with longer intervals between screening than the 5-year interval currently recommended was consistently preferred at the threshold of $55 000 per QALY, but the preferred strategy varied by age at vaccination. For women vaccinated between ages 12 and 24 years, preferred strategies involved screening every 15 to 25 years, resulting in screening 2 to 3 times per lifetime. RESULTS OF SENSITIVITY ANALYSIS:Less frequent screening remained a preferred strategy under imperfect screening adherence and in scenarios that excluded bivalent vaccine cross-protection. LIMITATION:The analysis did not address screening for unvaccinated women, who may benefit from herd immunity. CONCLUSION:A high-value screening program likely involves less frequent screening for women who were vaccinated against HPV by age 30 years. Strategies could be tailored on the basis of age at vaccination and type of HPV vaccine. PRIMARY FUNDING SOURCE:Norwegian Cancer Society and National Cancer Institute.

Background:Evidence supporting the non-inferior efficacy of single-dose human papillomavirus (HPV) vaccination has prompted reconsideration of existing multi-dose HPV vaccination schedules. We evaluated the long-term health impact of adopting single-dose HPV vaccination in the United States to inform policy deliberations. Methods:We applied two validated individual-based simulation models of HPV transmission and cervical cancer to project the impact of switching from a two-dose to a single-dose HPV vaccination schedule in 2025 in the context of historical HPV vaccination uptake in the United States. Four scenarios were simulated: continuation of two-dose vaccination (or equivalent single-dose efficacy of 98%) and three alternative pessimistic single-dose strategies with lower vaccine efficacy (90%) and/or duration of protection (average of 25 years). Outcomes included age-standardized incidence rates of HPV-16 infection and cervical cancer from years 2005-2099. Additional analyses examined effects under lower vaccination coverage observed in select U.S. regions. Findings:Maintaining two doses or switching to a non-inferior single-dose HPV vaccination schedule was projected to nearly eliminate HPV-16 infections and reduce cervical cancer incidence by over 90% by the end of the century. Scenarios assuming a lower efficacy or waning protection showed increases in cervical cancer incidence of less than 2 percentage points decades after a switch to single-dose vaccination with no impact on the timeframe to cervical cancer elimination. Interpretation:Switching to a single-dose HPV vaccination schedule is projected to maintain reductions in cervical cancer, even under pessimistic efficacy and durability assumptions. Continued monitoring of single-dose HPV vaccine efficacy over time remains critical. Funding:PATH on behalf of the Single-Dose HPV Vaccine Evaluation Consortium; Bill and Melinda Gates Foundation (grant No. OPP48979), and the US National Institutes of Health/National Cancer Institute (Grant Number U01 CA253912).

Objectives Disparities in access to potential innovative health technologies (pIHTs) persist across Europe due to differing healthcare budgets, pricing policies, and health technology assessment (HTA) practices. The ASCERTAIN project aims to reduce these inequalities by developing integrated pricing, cost-effectiveness, and reimbursement approaches that enhance affordability, long-term sustainability, and timely patient access. Methods The project applies a mixed-methods approach, including literature review, stakeholder surveys, interviews, and focus groups, to ensure relevance across diverse health systems. It integrates access-based pricing, value-driven HTA, and adaptable reimbursement models into a practical, open-access ACCESS2MEDS Toolbox. This includes access-based pricing frameworks, cost-effectiveness models, and budget impact and reimbursement analyses, all adaptable to country-specific conditions to reduce uncertainty and improve transparency. Tools are co-created with patients, developers, clinicians, and policymakers and will be tested and validated using three use cases representing high-impact areas of innovation: precision oncology medicines, cell and gene therapies, and next-generation sequencing tests. Results Outputs will include validated tools enabling improved evaluation of clinical benefit, cost-effectiveness, and financial sustainability, strengthening value-based decision-making across Europe. Innovative access- and outcome-based pricing strategies will support responsible innovation while encouraging fair reimbursement and improved budget control. Policy roadmaps will guide the adoption of equitable access models and support system-level implementation. Conclusions ASCERTAIN will provide a harmonized framework that balances cost control, innovation incentives, and patient-centered care. By facilitating consistent, evidence-based pricing and reimbursement decisions, the project supports fair and sustainable access to pIHTs across Europe, with continued multi-stakeholder collaboration driving its wider adoption and real-world impact. Public interest abstract Many lifesaving medical breakthroughs, like advanced cancer therapies and gene treatments, are becoming available, but not everyone in Europe can access them equally. Differences in healthcare funding and pricing decisions mean that patients in some countries wait much longer for the care they need. The ASCERTAIN project is working to change this. By bringing together patients, health technology developers, clinicians, and policymakers, the project is creating new tools to help health systems decide how to pay for cutting-edge technologies in a fair and affordable way. These tools also make sure that these technologies are paid for based on how well they work for patients in real life. By improving transparency and reducing financial pressure on health services, ASCERTAIN aims to ensure that people across Europe benefit from innovative technologies sooner, supporting healthier lives and a more sustainable future for healthcare.

PurposeSexual transmission of human papillomavirus (HPV) infection is important for capturing the indirect effects of interventions in mathematical models, but limited data create challenges for reflecting sexual behavior patterns over the lifespan of individuals and across heterogenous populations. We used nationally representative data from the United States to parameterize, calibrate, and validate a heterosexual transmission model of HPV.MethodsBased on sexual behavior data from the National Survey of Family Growth (2011-2019), we categorized respondents into 4 sexual activity categories, using their percentile of cumulative lifetime partners compared with others within their same sex and age group. We modeled probabilistic partnership acquisition and dissolution by age, sex, and sexual activity category. Partnership data were incorporated into an existing agent-based model of HPV transmission in the United States. We calibrated 1) per-partnership HPV transmission and 2) reduced risk of type-specific reinfection from natural immunity to fit age- and type-specific HPV prevalence using the National Health and Nutrition Examination Survey (NHANES 2002-2008). We validated the final model by comparing model-based projections of HPV prevalence against empirical data in the US population before and after widespread HPV vaccination.ResultsAfter calibrating to fit overall HPV prevalence, model validation exercises indicated that the distribution of prevaccine HPV prevalence across sexual activity categories closely matched NHANES estimates. Simulating vaccination rates over 10 y, the model replicated postvaccine NHANES data for prevalence of HPV16.ConclusionCapturing HPV transmission dynamics requires an understanding of sexual behavior across populations and over time. Defining sexual activity categories based on cumulative lifetime partners can capture patterns of HPV risk over a lifespan to reflect the dynamics of HPV transmission and vaccination.HighlightsUsing data from a large national survey, we developed sexual behavior inputs for an agent-based model of HPV transmission.We define 4 heterogenous risk groups using cumulative lifetime sexual behavior for males and females and find we can recreate validation data on both lifetime sexual patterns and age-specific HPV prevalence.Our calibrated model also reproduces early patterns of HPV reduction following HPV vaccine introduction.Modelers seeking to understand the long-term effects of the HPV vaccine should carefully consider the heterogeneity of sexual behavior across groups as well as changes in behavior over the lifespan.

The 3rd Annual Lung Cancer Symposium (Oslo Cancer Cluster, 25 September 2025) gathered experts from all the Nordic countries, Norway, Finland, Iceland, Denmark, Sweden, as well as Germany, the UK and the USA to present new evidence and implementation experiences in low-dose chest tomography lung cancer screening, with cross-cutting attention to risk stratification, health economics, AI-enabled workflows, and equity. The symposium was organized by Oslo Cancer Cluster, Levanger Hospital and the Norwegian University of Science and Technology, as a continuation of previous years´ annual efforts to gather and showcase the experiences and the progress of the Nordic countries with lung cancer screening. Across settings, LDCT screening is associated with stage shift and potential mortality reduction, consistent with large trials (NLST, NELSON) and maturing real-world experience (HANSE pilot study, programs in Croatia, Taiwan, the UK, and the US). Emerging Nordic pilots demonstrate feasibility, early-stage detection, and high adherence, while European coordination (SOLACE) is accelerating guideline harmonization and implementation pilots. Key themes included: (1) superiority of multivariable risk models over categorical criteria; (2) the necessity of integrating smoking cessation; (3) program economics that are likely acceptable under Nordic decision thresholds; (4) capacity and downstream pathway planning; and (5) equity-by-design to avoid widening disparities. This report synthesizes country updates and implications for Nordic and European scale-up.

Objective: Perform a cost-utility analysis for return-to-work interventions with missing health-related quality-of-life (HRQoL) data while transparently demonstrating the impact of different methods of handling missing data on outcomes. Methods: The costs and quality-adjusted life-years over a 2-year period were estimated for 2 return-to-work interventions, inpatient multimodal occupational rehabilitation (I-MORE) and outpatient acceptance and commitment therapy (O-ACT), using a healthcare perspective and a limited societal perspective. Four methods were used to handle the missing HRQoL data: complete case analysis, single imputation, multiple imputation, and linear mixed models. The cost-effectiveness outcomes were expressed as incremental net monetary benefit. Results: The average incremental quality-adjusted life-years comparing I-MORE with O-ACT ranged between –0.001 and 0.330 depending on missingness method. From a healthcare perspective, I-MORE was consistently not cost-effective (incremental net monetary benefits ranged from –€7,094 to –€9,363) while from a limited societal perspective, I-MORE was consistently cost-effective (incremental net monetary benefits ranged from €1,293 to €16,277). Conclusion: While cost-effectiveness findings remained consistent within each analytical perspective, the choice of different missingness methods led to variations in incremental quality-adjusted life-years. Multiple imputation is recommended to handle missing HRQoL data as it is transparent and flexible. How-ever, a thorough investigation of the missing data mechanism should still be conducted.

Clinical trials have shown that low‐dose computed tomography (LDCT) screening reduces lung cancer mortality among selected groups of ever‐smokers. Nordic countries have yet to implement lung cancer screening programs in part due to limited evidence on the associated health and economic consequences. This study evaluated the cost‐effectiveness of LDCT screening compared with no screening for Norwegian individuals aged 50–74 years who ever smoked, using the Dutch–Belgian NELSON screening‐eligibility criteria and trial outcomes. In addition, we evaluated the potential need and value of additional research to improve decision‐making about LDCT screening implementation. We developed a probabilistic simulation model reflecting the Dutch–Belgian NELSON trial outcomes and Norwegian epidemiological, cost, and health‐related quality‐of‐life data to evaluate long‐term (discounted) health and economic consequences from an extended healthcare perspective. Model outputs included sex‐stratified clinical and economic outcomes. Cost‐effectiveness was summarized using incremental cost‐effectiveness ratios (ICERs). Compared with no screening, NELSON‐like LDCT screening provided an additional 0.043 quality‐adjusted life‐years (QALYs) per screened man for an additional $1286, yielding an ICER of $30,672 per QALY gained. For women, screening yielded greater health benefits and therefore a lower ICER (i.e., $22,249 per QALY gained), though there was greater uncertainty around health benefits. Additional analyses indicated potential value in collecting further evidence on screening‐related outcomes to reduce decision uncertainty, particularly for women. Given Norwegian benchmarks for good value and achieving similar mortality benefits to the NELSON trial, LDCT lung cancer screening for individuals who ever smoked under “NELSON‐like” criteria may be considered cost‐effective for both men and women in Norway.

OBJECTIVES:The rate of sickness absence in Norway is at its highest point since 2009, and policymakers need tools to make informed decisions on high-value interventions to address sick leave. Using trial-linked registry data, multi-state modeling, and decision-analytic modeling, we assessed the cost-effectiveness of 2 return-to-work (RTW) interventions for individuals with musculoskeletal and psychological disorders in Norway. METHODS:Using data from 166 individuals in a randomized trial, we developed a decision-analytic model to compare 2 multidomain RTW interventions: outpatient acceptance and commitment therapy (O-ACT) and inpatient multimodal occupational rehabilitation (I-MORE). The probabilistic model was informed using trial-based input parameters, including transition probabilities, healthcare costs, production loss, and health-related quality of life to project long-term costs and quality-adjusted life-years (QALYs) over a 25-year time horizon for each intervention. RESULTS:Modeled outcomes were consistent with the trial outcomes, showing that I-MORE led participants to RTW more quickly. However, assuming a healthcare perspective and a cost-effectiveness threshold of $50 000 per QALY, I-MORE was not considered cost-effective in 98% of our simulations (probabilistic incremental cost-effectiveness ratio, $356 447 per QALY gained) compared with O-ACT. In contrast, when accounting for production loss, I-MORE not only became cost-effective but also was projected to be more beneficial and less costly than O-ACT. CONCLUSIONS:Under current Norwegian benchmarks for cost-effectiveness, I-MORE would not be considered cost-effective unless production loss was included. Our findings emphasize the key role of a broader societal perspective in economic evaluations, which, although it is being considered, is currently not recommended in Norwegian guidelines.

Background We estimated the impact of screening on morbidity and mortality of human papillomavirus (HPV)16-positive oropharyngeal cancer among US men aged 45-79 years.Methods We developed an individual-level, state-transition natural history microsimulation model to estimate the impact of screening using oral HPV16 detection, HPV16-E6 antibody detection, and transcervical ultrasound of neck/oropharynx. We compared clinical detection to counterfactual screen detection for cancer stage, single- vs multiple-modality treatment, and survival. Screening scenarios encompassed 4 progression speeds across cancer stages (very slow, slow, fast, and very fast) and 4 screening frequencies.Results Among US men aged 45-79 years in 2021 (n = 54 881 311), 163 958 clinically diagnosed human papillomavirus (HPV)-positive oropharyngeal cancers and 32 009 deaths would occur through age 84 in the absence of screening. Assuming very-fast progression, 4%, 20%, 31%, and 60% of these cancers would be detected by one-off, 5-yearly, 3-yearly, and annual screening. Annual screening (very-fast progression) could reduce the number of cancers diagnosed at advanced stages (American Joint Committee on Cancer, 7th edition, stages III/IV: 90.0% with no screening vs 59.1%) and treated by multiple modalities (80.6% with no screening vs 50.6%). Cancer mortality would also be reduced by 36.2%, with a gain of 106 000 life-years. Annual screening would have a number needed to screen (NNS) of 561 per screen-detected cancer, 1118 per additional cancer treated by single modality, 4740 per death prevented, and 520 per life-year gained; such high NNS reflect potential inefficiency of population-level screening.Conclusions If proven efficacious in randomized trials and cost-effective, screening for HPV-positive oropharyngeal cancers could provide considerable population-level reductions in advanced stage cancers, treatment-related morbidities, and mortality.

BackgroundSentinel lymph node biopsy (SLN) is increasingly used for surgical staging of endometrial carcinoma.ObjectiveTo estimate the effect and cost-effectiveness of the implementation of an SLN algorithm for surgical staging in patients with intermediate- and high-risk endometrial carcinoma compared with lymphadenectomy.MethodsWe performed a model-based, cost-effectiveness analysis using primary data from a tertiary referral hospital that included 829 patients with endometrial carcinoma undergoing surgical staging. We quantified the health and economic outcomes from two time periods, before and after implementation of the SLN algorithm by robotic surgery. Costs were measured directly from the hospital’s financial department, while long-term health outcomes were estimated using self-reported lymphedema and health-related quality-of-life among survivors. Sensitivity analyses were conducted to evaluate uncertainty.ResultsWe projected that the SLN implementation period, predominately reflecting use of robotic SLN, simultaneously improved health outcomes (0.08 incremental quality-adjusted life-years) and lowered costs (US$1051) compared with the prior period involving robotic or open lymphadenectomy. SLN remained more beneficial and less costly across key sensitivity analyses—namely, varying the cost of the robotic platform, surgical equipment, number of yearly robotic procedures, percentage of robotic procedures versus percentage of laparotomies, length of stay, and lymphedema development. After 1000 simulations of the model, SLN implementation provided greater health benefits for lower costs (ie, cost saving) in 89% of simulations.ConclusionImplementation of an SLN algorithm in the staging of intermediate- and high-risk endometrial carcinoma improved health outcomes for lower costs compared with lymphadenectomy. Cost-effectiveness could further improve by continuing to increase the proportion of robotic procedures.

Population-level estimates in time frames for reaching cervical cancer elimination (ie, <4 cases per 100 000 women) in the United States may mask potential disparities in achieving elimination among subpopulations. We used 3 independent Cancer Intervention and Surveillance Modeling Network models to estimate differences in the time to cervical cancer elimination across 7 strata of correlated screening and human papillomavirus vaccination uptake, based on national survey data. Compared with the average population, elimination was achieved at least 22 years earlier for the high-uptake strata and at least 27 years later for the most extreme low-uptake strata. Accounting for correlated uptake impacted the population average time frame by no more than 1 year. Consequently, national average elimination time frames mask substantial disparities in reaching elimination among subpopulations. Addressing inequalities in cervical cancer control could shorten elimination time frames and would ensure more equitable elimination across populations. Furthermore, country-level elimination monitoring could be supplemented by monitoring progress in subpopulations.

We estimated the impact of screening on morbidity and mortality of HPV16-positive oropharyngeal cancer among US men aged 45-79 years. We developed an individual-level, state-transition natural history microsimulation model to estimate the impact of screening using oral HPV16 detection, HPV16-E6 antibody detection, and transcervical-ultrasound of neck/oropharynx. We compared clinical detection to counterfactual screen detection for cancer stage, single- vs multiple-modality treatment, and survival. Screening scenarios encompassed four progression speeds across cancer stages (very-slow, slow, fast, and very-fast) and four screening frequencies. Among US men aged 45-79 years in 2021 (N = 54,881,311), 163,958 clinically diagnosed HPV-positive oropharyngeal cancers and 32,009 deaths would occur through age 84 in the absence of screening. Assuming very-fast progression, 4%, 20%, 31%, and 60% of these cancers would be detected by one-off, 5-yearly, 3-yearly, and annual screening. Annual screening (very-fast progression) could reduce the number of cancers diagnosed at advanced stages (AJCC 7, Stages III/IV: 90.0% with no screening vs 59.1%) and treated by multiple-modalities (80.6% with no screening vs 50.6%). Cancer mortality would also be reduced by 36.2%, with a gain of 106,000 life-years. Annual screening would have a number needed to screen (NNS) of 561 per screen-detected cancer, 1,118 per additional cancer treated by single-modality, 4,740 per death prevented, and 520 per life-year gained; such high NNS reflect potential inefficiency of population-level screening. If proven efficacious in randomized trials and cost-effective, screening for HPV-positive oropharyngeal cancers could provide considerable population-level reductions in advanced stage cancers, treatment-related morbidities, and mortality.

Background: In Sweden, the cervical cancer screening programme is based on primary human papillomavirus (HPV) testing with either clinician-collected cervical sampling or home-based vaginal self-sampling. We assessed the effectiveness and cost-effectiveness of primary HPV clinician-collected sampling and primary HPV self-collected sampling for unvaccinated cohorts of Swedish women. Methods: A model-based analysis was performed to project long-term costs and quality-adjusted life-years (QALYs). Screening strategies included no screening, 18 clinician-collected strategies and 36 self-sampling strategies, with variations in the screening frequency, start age and follow-up management. We estimated incremental cost-effectiveness ratios benchmarked against willingness-to-pay (WTP) thresholds of 50,000EUR and 100,000EUR per QALY gained. Results: Compared with the 2022 recommendations (with primary clinician-collected HPV testing from ages 23 with 5-yearly screening to age 50 and 7-yearly screening through to age 64), self-sampling at the same intensity would lead to similar effectiveness and a 36% reduction in costs. Among the clinician-collected sampling strategies, the optimal strategies involved primary HPV testing from age 25 with 10-yearly screening with extended genotyping (at 50,000EUR per QALY gained), or 7- and 10-yearly screening for 100,000EUR. Across all strategies, the optimal strategies included primary self-sampling from age 25 with direct referral to colposcopy for HPV-16/18/45 with 7- and 10-yearly screening at 50,000EUR per QALY gained, and 5- and 7-yearly screening for 100,000EUR per QALY gained. These results were sensitive to the assumed accuracy of self-sampling compared with clinician-collected sampling. Conclusions: Transitioning from clinician-collected cervical sampling to vaginal HPV self-sampling is likely to be cost-effective for unvaccinated women in Sweden. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by: the Swedish Cancer Society (Cancerfonden; grant No. CAN21/1512); Swedish Research Council (Vetenskapradet; grant No. VR 2022-00684 and the Swedish eScience Research Centre); and the European Commission (HEAP grant No. 874662). The funding sources had no involvement in the conduct of the research or preparation of the article. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All relevant data are within the manuscript and its Supporting Information files.

BACKGROUND:Screening pregnant women for gestational diabetes mellitus (GDM) has recently been expanded in Norway, although screening eligibility criteria continue to be debated. We aimed to compare the cost-effectiveness of alternative GDM screening strategies and explored structural uncertainty and the value of future research in determining the most cost-effective eligibility criteria for GDM screening in Norway. DESIGN:We developed a probabilistic decision tree to estimate the total costs and health benefits (i.e., quality-adjusted life-years; QALYs) associated with 4 GDM screening strategies (universal, current guidelines, high-risk, and no screening). We identified the most cost-effective strategy as the strategy with the highest incremental cost-effectiveness ratio below a Norwegian benchmark for cost-effectiveness ($28,400/QALY). We excluded inconclusive evidence on the effects of screening on later maternal type 2 diabetes mellitus (T2DM) in the primary analysis but included this outcome in a secondary analysis using 2 different sources of evidence (i.e., Cochrane or US Preventive Services Task Force). To quantify decision uncertainty, we conducted scenario analysis and value-of-information analyses. RESULTS:Current screening recommendations were considered inefficient in all analyses, while universal screening was most cost-effective in our primary analysis ($26,014/QALY gained) and remained most cost-effective when we assumed a preventive effect of GDM treatment on T2DM. When we assumed no preventive effect, high-risk screening was preferred ($19,115/QALY gained). When we assumed GDM screening does not prevent perinatal death in scenario analysis, all strategies except no screening exceeded the cost-effectiveness benchmark. In most analyses, decision uncertainty was high. CONCLUSIONS:The most cost-effective screening strategy, ranging from no screening to universal screening, depended on the source and inclusion of GDM treatment effects on perinatal death and T2DM. Further research on these long-term outcomes could reduce decision uncertainty. HIGHLIGHTS:This article analyses the cost-effectiveness of 4 alternative gestational diabetes mellitus (GDM) screening strategies in Norway: universal screening, current (broad) screening, high-risk screening, and no screening.The current Norwegian screening recommendations were considered inefficient under all analyses.The most cost-effective screening strategy ranged from no screening to universal screening depending on the source and inclusion of GDM treatment effects on later maternal diabetes and perinatal death.The parameters related to later maternal diabetes and perinatal death accounted for most of the decision uncertainty.