Emily Burger

• Aas, Eline; Burger, Emily & Pedersen, Kine (2019). Economic Evaluation of Medical Screening, In Jonathan H. Hamilton (ed.),  Oxford Research Encyclopedias: Economics and Finance.  Oxford University Press.  ISBN 9780190625979.  Jun2019.
• Burger, Emily; de Kok, Inge; Groene, Emily; Killen, Jame; Canfell, Karen; Kulasingam, Shalini; Kuntz, Karen; Matthijsse, Suzette; Regan, Catherine; Simms, Kate; Smith, Megan; Sy, Stephen; Alarid-Escudero, Fernando; Vaidyanathan, V; van Ballegooijen, Marjolein & Kim, Jane J (2019). Estimating the Natural History of Cervical Carcinogenesis Using Simulation Models: A CISNET Comparative Analysis.. Journal of the National Cancer Institute.  ISSN 0027-8874. . doi: 10.1093/jnci/djz227
• Hylin, Hannah Douglass; Thrane, Helene; Pedersen, Kine; Kristiansen, Ivar Sønbø & Burger, Emily (2019). The healthcare costs of treating human papillomavirus-related cancers in Norway. BMC Cancer.  ISSN 1471-2407.  19(1) . doi: 10.1186/s12885-019-5596-2
• Portnoy, Allison; Campos, Nicole; Sy, Stephen; Burger, Emily; Cohen, Jamie; Regan, Catherine & Kim, Jane J (2019). Impact and Cost-Effectiveness of Human Papillomavirus Vaccination Campaigns. Cancer Epidemiology, Biomarkers and Prevention.  ISSN 1055-9965.  29(1), s 22- 30 . doi: 10.1158/1055-9965.EPI-19-0767
• Rodin, Danielle; Burger, Emily; Atun, Rifat; Barton, Michael; Gospodarowicz, Mary; Grover, Surbhi; Hanna, Timothy P; Jaffray, David A; Knaul, Felicia M; Lievens, Yolande; Zubizarreta, Eduardo & Milosevic, Michael (2019). Scale-up of radiotherapy for cervical cancer in the era of human papillomavirus vaccination in low-income and middle-income countries: a model-based analysis of need and economic impact. The Lancet Oncology.  ISSN 1470-2045.  20(7), s 915- 923 . doi: 10.1016/S1470-2045(19)30308-0
• Burger, Emily; Campos, Nicole G.; Sy, Stephen; Catherine, Regan & Kim, Jane J (2018). Health and economic benefits of single-dose HPV vaccination in a Gavi-eligible country. Vaccine.  ISSN 0264-410X.  36(32), s 4823- 4829 . doi: 10.1016/j.vaccine.2018.04.061 Full text in Research Archive.
• Burger, Emily; Dyer, Michael; Sy, Stephen; Palefsky, Joel M.; de Pokomandy, Alexandra; Coutlee, François; Silverberg, Michael & Kim, Jane J (2018). Development and Calibration of a Mathematical Model of Anal Carcinogenesis for High-Risk HIV-Infected Men. Journal of Acquired Immune Deficiency Syndromes.  ISSN 1525-4135.  79(1), s 10- 19 . doi: 10.1097/QAI.0000000000001727 Show summary

  OBJECTIVES: Men who have sex with men who are living with HIV are at highest risk for anal cancer. Our objective was to use empirical data to develop a comprehensive disease simulation model that reflects the most current understanding of anal carcinogenesis, which is uniquely positioned to evaluate future anal cancer screening strategies and provide insight on the unobservable course of the disease. SETTING: North America. METHODS: The individual-based simulation model was calibrated leveraging primary data from empirical studies, such as a longitudinal HIV-positive men who have sex with men cohort study [Human Immunodeficiency and Papilloma Virus Research Group (HIPVIRG); n = 247] and the North American AIDS Cohort Collaboration on Research and Design [(NA-ACCORD); n = 13,146]. We used the model to infer unobservable progression probabilities from high-grade precancer to invasive anal cancer by CD4 nadir and human papillomavirus (HPV) genotype. RESULTS: The calibrated model had good correspondence to data on genotype- and age-specific HPV prevalence; genotype frequency in precancer and cancer; and age- and nadir CD4-specific cancer incidence. The model-projected progression probabilities differed substantially by HPV genotype and nadir CD4 status. For example, among individuals with CD4 nadir <200, the median monthly progression probability from a high-grade lesion to invasive cancer was 0.054% (ie, 6.28% 10-year probability) and 0.004% (ie, 0.48% 10-year probability) for men with an HPV-16 infection versus without a detectable HPV infection, respectively. CONCLUSIONS: We synthesized existing evidence into a state-of-the-art anal cancer disease simulation model that will be used to quantify the tradeoffs of harms and benefits of alternative strategies, understand critical uncertainties, and inform national anal cancer prevention policy.

• Castle, Philip E.; Xie, X; Xue, X; Poitras, N; Lorey, T; Kinney, Walter; Wentzensen, Nicolas; Burger, Emily & Strickler, H (2018). Impact of human papillomavirus vaccination on the clinical meaning of cervical screening results. Preventive Medicine.  ISSN 0091-7435.  118, s 44- 50 . doi: 10.1016/j.ypmed.2018.10.001 Show summary

  Women previously vaccinated against human papillomavirus (HPV) type 16 and 18 are now reaching the age (21 years) at which cervical-cancer screening is recommended in the U.S. The impact of HPV vaccination on risks of cervical precancer following a positive and negative screen among women aged 21-24 years who just started routine cervical screening are not well described. Therefore, three-year absolute and relative (RR) cumulative risks of cervical intraepithelial neoplasia grade 2 or more severe diagnoses (≥CIN2) and grade 3 or more severe diagnoses (≥CIN3) were estimated for women undergoing cervical screening at Kaiser Permanente Northern California. Risks were estimated in women aged 21-24 years (n = 75,008) undergoing cervical screening since late 2006, 6 months after HPV vaccination became available; women were categorized vaccinated at ages <18, 18-20, and 21-24 years and compared to those who were unvaccinated. Three-year risks were estimated for normal, low-grade, and high-grade cytology results. Three-year risks of ≥CIN2 and ≥CIN3 for unvaccinated women following low-grade cytology were 10.89% for and 3.70%, respectively. By comparison, Three-year risks of ≥CIN2 and ≥CIN3 were 5.26% (RR = 0.48, 95%CI = 0.24-0.99) and 0.99% (RR = 0.27, 95%CI = 0.06-1.13), respectively, for women vaccinated under the age of 18 years. Three-year ≥CIN2 and ≥CIN3 risks were lower for those HPV vaccinated at younger age for any screening result (ptrend ≤ 0.01 for all comparisons). These data support initiating cervical screening at an older age or changing the management of a low-grade cytology result in women aged 21-24 years who were vaccinated against HPV younger than age of 18 years.

• Kim, Jane J; Burger, Emily; Regan, Catherine & Sy, Stephen (2018). Screening for cervical cancer in primary care a decision analysis for the us preventive services task force. Journal of the American Medical Association (JAMA).  ISSN 0098-7484.  320(7), s 706- 714 . doi: 10.1001/jama.2017.19872 Full text in Research Archive.
• Pedersen, Kine; Burger, Emily; Nygård, Mari; Kristiansen, Ivar Sønbø & Kim, Jane J. (2018). Adapting cervical cancer screening for women vaccinated against human papillomavirus infections: The value of stratifying guidelines. European Journal of Cancer.  ISSN 0959-8049.  91, s 68- 75 . doi: 10.1016/j.ejca.2017.12.018 Full text in Research Archive.
• Pedersen, Kine; Fogelberg, Sara; Thamsborg, Lise H.; Clements, Mark; Nygård, Mari; Kristiansen, Ivar Sønbø; Lynge, Elsebeth; Sparén, Pär; Kim, Jane J & Burger, Emily (2018). An overview of cervical cancer epidemiology and prevention in Scandinavia. Acta Obstetricia et Gynecologica Scandinavica.  ISSN 0001-6349.  97(7), s 795- 807 . doi: 10.1111/aogs.13313 Full text in Research Archive.
• Vervaart, Mathyn; Burger, Emily & Aas, Eline (2018). Acknowledging patient heterogeneity in colorectal cancer screening: An example from Norway. Nordic Journal of Health Economics.  ISSN 1892-9729.  6(1), s 83- 98 . doi: 10.5617/njhe.4881 Full text in Research Archive.
• Burger, Emily; Kim, Jane J.; Sy, Stephen & Castle, Philip E. (2017). Age of acquiring causal human papillomavirus (HPV) infections: Leveraging simulation models to explore the natural history of HPV-induced cervical cancer. Clinical Infectious Diseases.  ISSN 1058-4838.  65(6), s 893- 899 . doi: 10.1093/cid/cix475 Show summary

  Background. Although new human papillomavirus (HPV) infections can occur at all ages, the age at which women acquire their “causal” HPV infection that develops into cervical cancer is poorly understood and practically unobservable. We aimed to estimate the age distribution at which individuals acquired their causal HPV infection in the absence of HPV vaccination or screening to help guide the optimal use of both. Methods. Using an empirically calibrated mathematical model that simulates the natural history of cervical cancer, we estimated the cumulative number of causal HPV infections by age, stratified by HPV genotype (HPV16 vs. other HPV genotypes), and the direct age-specific reduction in cancer incidence for alternative vaccination initiation scenarios (i.e., age 9-45 years). Results. Our model projected that among all cervical cancers, 50% and 75% of women acquired their causal HPV infection by ages 20.6 (range: 20.1-21.1) and 30.6 (range: 29.6-31.6) years, respectively. HPV16 infections were acquired at an earlier age. Assuming 95% efficacy against HPV16 and HPV18 infections, the direct reduction in lifetime risk of cervical cancer varied from 58% (range: 56-59%) among women vaccinated at age 9 years to 6% (range: 5-8%) among women vaccinated at age 45 years. Similar patterns were observed for the second-generation vaccine. Conclusions. Although new HPV infections and precancers can occur throughout a woman’s lifetime, only a small proportion are acquired in mid-adult women and are vaccine-preventable. Our simulations highlight the potential limitations of using surrogate endpoints for vaccine efficacy studies of mid-adult women to guide policy decisions for implementation.

• Burger, Emily; Pedersen, Kine; Sy, Stephen; Kristiansen, Ivar Sønbø & Kim, Jane J (2017). Choosing wisely: a model-based analysis evaluating the trade-offs in cancer benefit and diagnostic referrals among alternative HPV testing strategies in Norway. British Journal of Cancer.  ISSN 0007-0920.  117(6), s 783- 790 . doi: 10.1038/bjc.2017.248 Full text in Research Archive.
• Burger, Emily; Sy, Stephen; Nygård, Mari & Kim, Jane J (2017). The cost-effectiveness of cervical self-sampling to improve routine cervical cancer screening: The importance of respondent screening history and compliance. Cancer Epidemiology, Biomarkers and Prevention.  ISSN 1055-9965.  26(1), s 95- 103 . doi: 10.1158/1055-9965.EPI-16-0350 Show summary

  Background: Human papillomavirus (HPV) testing allows women to self-collect cervico-vaginal cells at home (i.e., self-sampling). Using primary data from a randomized pilot study, we evaluated the long-term consequences and cost-effectiveness of using self-sampling to improve participation to routine cervical cancer screening in Norway. Methods: We compared a strategy reflecting screening participation (using reminder letters) to strategies that involved mailing self-sampling device kits to women non-compliant to screening within a 5-year or 10-year period under two scenarios: A) self-sampling respondents had moderate under-screening histories, or B) respondents to self-sampling had moderate and severe under-screening histories. Model outcomes included quality-adjusted life-years (QALY) and lifetime costs. The 'most cost-effective' strategy was identified as the strategy just below $100,000 per QALY gained. Results: Mailing self-sampling device kits to all women non-compliant to screening within a 5-year or 10-year period can be more effective and less costly than the current reminder letter policy; however, the optimal self-sampling strategy was dependent on the profile of self-sampling respondents. For example, '10-yearly self-sampling' is preferred ($95,500 per QALY gained) if '5-yearly self-sampling' could only attract moderate under-screeners; however, '5-yearly self-sampling' is preferred if this strategy could additionally attract severe under-screeners. Conclusions: Targeted self-sampling of non-compliers likely represents good value-for-money; however, the preferred strategy is contingent on the screening histories and compliance of respondents. Impact: The magnitude of the health benefit and optimal self-sampling strategy is dependent on the profile and behavior of respondents. Health authorities should understand these factors prior to selecting and implementing a self-sampling policy.

• Kim, Jane J; Burger, Emily; Sy, Stephen & Campos, Nicole G. (2017). Optimal cervical cancer screening in women vaccinated against human papillomavirus. Journal of the National Cancer Institute.  ISSN 0027-8874.  109(2) . doi: 10.1093/jnci/djw216
• Pedersen, Kine; Burger, Emily; Campbell, Suzanne; Nygård, Mari; Aas, Eline & Lönnberg, Stefan (2017). Advancing the evaluation of cervical cancer screening: development and application of a longitudinal adherence metric. European Journal of Public Health.  ISSN 1101-1262. . doi: /10.1093/eurpub/ckx073 Full text in Research Archive.
• Pedersen, Kine; Sørbye, Sveinung Wergeland; Kristiansen, Ivar Sønbø & Burger, Emily (2017). Using novel biomarkers to triage young adult women with minor cervical lesions: a cost-effectiveness analysis. BJOG: an International Journal of Obstetrics and Gynaecology.  ISSN 1470-0328.  124(3), s 474- 484 . doi: 10.1111/1471-0528.14135 Show summary

  Objective To evaluate the short-term consequences and cost-effectiveness associated with the use of novel biomarkers to triage young adult women with minor cervical cytological lesions. Design Model-based economic evaluation using primary epidemiological data from Norway, supplemented with data from European and American clinical trials. Setting Organised cervical cancer screening in Norway. Population Women aged 25–33 years with minor cervical cytological lesions detected at their primary screening test. Methods We expanded an existing simulation model to compare 12 triage strategies involving alternative biomarkers (i.e. reflex human papillomavirus (HPV) DNA/mRNA testing, genotyping, and dual staining) with the current Norwegian triage guidelines. Main outcome measures The number of high-grade precancers detected and resource use (e.g. monetary costs and colposcopy referrals) for a single screening round (3 years) for each triage strategy. Cost-efficiency, defined as the additional cost per additional precancer detected of each strategy compared with the next most costly strategy. Results Five strategies were identified as cost-efficient, and are projected to increase the precancer detection rate between 18 and 57%, compared with current guidelines; however, the strategies did not uniformly require additional resources. Strategies involving HPV mRNA testing required fewer resources, whereas HPV DNA-based strategies detected >50% more precancers, but were more costly and required twice as many colposcopy referrals compared with the current guidelines. Conclusion Strategies involving biomarkers to triage younger women with minor cervical cytological lesions have the potential to detect additional precancers, yet the optimal strategy depends on the resources available as well as decision-makers' and women's acceptance of additional screening procedures.

• Rutter, Carolyn; Kim, Jane J; Meester, RGS; Sprague, BL; Burger, Emily; Zauber, Ann G.; Ergun, MA; Campos, Nicole G.; Doubeni, CA; Trentham-Dietz, Amy; Sy, Stephen; Alagoz, Oguz; Stout, Natasha K.; Lansdorp-Vogelaar, Iris; Corley, Douglas & Tosteson, A (2017). Effect of Time to Diagnostic Testing for Breast, Cervical, and Colorectal Cancer Screening Abnormalities on Screening Efficacy: A Modeling Study. Cancer Epidemiology, Biomarkers and Prevention.  ISSN 1055-9965. . doi: 10.1158/1055-9965.EPI-17-0378
• Burger, Emily; Lee, Kyueun; Saraiya, Mona; Thompson, Trevor D.; Chesson, Harrell W.; Markowitz, Lauri E. & Kim, Jane J. (2016). Racial and ethnic disparities in human papillomavirus-associated cancer burden with first-generation and second-generation human papillomavirus vaccines. Cancer.  ISSN 0008-543X.  122(13), s 2057- 2066 . doi: 10.1002/cncr.30007 Show summary

  BACKGROUND: In the United States, the burden of human papillomavirus (HPV)-associated cancers varies by racial/ethnic group. HPV vaccination may provide opportunities for primary prevention of these cancers. Herein, the authors projected changes in HPV-associated cancer burden among racial/ethnic groups under various coverage assumptions with the available first-generation and second-generation HPV vaccines to evaluate changes in racial/ethnic disparities. METHODS: Cancer-specific mathematical models simulated the burden of 6 HPV-associated cancers. Model parameters, informed using national registries and epidemiological studies, reflected sex-specific, age-specific, and racial/ethnic-specific heterogeneities in HPV type distribution, cancer incidence, stage of disease at detection, and mortality. Model outcomes included the cumulative lifetime risks of developing and dying of 6 HPV-associated cancers. The level of racial/ethnic disparities was evaluated under each alternative HPV vaccine scenario using several metrics of social group disparity. RESULTS: HPV vaccination is expected to reduce the risks of developing and dying of HPV-associated cancers in all racial/ethnic groups as well as reduce the absolute degree of disparities. However, alternative metrics suggested that relative disparities would persist and in some scenarios worsen. For example, when assuming high uptake with the second-generation HPV vaccine, the lifetime risk of dying of an HPV-associated cancer for males decreased by approximately 60%, yet the relative disparity increased from 3.0 to 3.9. CONCLUSIONS: HPV vaccines are expected to reduce the overall burden of HPV-associated cancers for all racial/ethnic groups and to reduce the absolute disparity gap. However, even with the second-generation vaccine, relative disparities will likely still exist and may widen if the underlying causes of these disparities remain unaddressed. Cancer 2016;122:2057-66.

• Pedersen, Kine; Burger, Emily; Sy, Stephen; Kristiansen, Ivar Sønbø & Kim, Jane J. (2016). Cost-effective management of women with minor cervical lesions: Revisiting the application of HPV DNA testing.. Gynecologic Oncology.  ISSN 0090-8258.  143(2), s 326- 333 . doi: 10.1016/j.ygyno.2016.08.231 Full text in Research Archive. Show summary

  Background Lack of consensus in management guidelines for women with minor cervical lesions, coupled with novel screening approaches, such as human papillomavirus (HPV) genotyping, necessitate revisiting prevention policies. We evaluated the cost-effectiveness and resource trade-offs of alternative triage strategies to inform cervical cancer prevention in Norway. Methods We used a decision-analytic model to compare the lifetime health and economic consequences associated with ten novel candidate approaches to triage women with minor cervical lesions. Candidate strategies varied by: 1) the triage test(s): HPV testing in combination with cytology, HPV testing alone with or without genotyping for HPV-16 and -18, and immediate colposcopy, and 2) the length of time between index and triage testing (i.e., 6, 12 or 18 months). Model outcomes included quality-adjusted life-years (QALYs), lifetime societal costs, and resource use (e.g., colposcopy referrals). Results The current Norwegian guidelines were less effective and more costly than candidate strategies. Given a commonly-cited willingness-to-pay threshold in Norway of $100,000 per QALY gained, the preferred strategy involved HPV genotyping with immediate colposcopy referral for HPV-16 or -18 positive and repeat HPV testing at 12 months for non-HPV-16 or -18 positive ($78,010 per QALY gained). Differences in health benefits among candidate strategies were small, while resource use varied substantially. More effective strategies required a moderate increase in colposcopy referrals (e.g., a 9% increase for the preferred strategy) compared with current levels. Conclusion New applications of HPV testing may improve management of women with minor cervical lesions, yet are accompanied by a trade-off of increased follow-up procedures.

• Burger, Emily; Sy, Stephen; Nygård, Mari; Kristiansen, Ivar Sønbø & Kim, Jane J (2015). Too late to vaccinate? The incremental benefits and cost-effectiveness of a delayed catch-up program using the 4-valent human papillomavirus vaccine in Norway. Journal of Infectious Diseases.  ISSN 0022-1899.  211(2), s 206- 215 . doi: 10.1093/infdis/jiu413 Show summary

  Background: Human papillomavirus (HPV) vaccines are ideally administered prior to HPV exposure; therefore catch-up programs for girls past adolescence have not been readily funded. We evaluated the benefits and cost-effectiveness of a delayed, 1-year female catch-up vaccination program in Norway. Methods: We calibrated a dynamic HPV transmission model to Norwegian data and projected the costs and benefits associated with eight HPV-related conditions while varying the upper vaccination age limit to 20, 22, 24 or 26 years. We explored the impact of vaccine protection in women with prior vaccine-targeted HPV infections, vaccine cost, coverage, and natural- and vaccine-induced immunity. Results: The incremental benefits and cost-effectiveness decreased as the upper age limit for catch-up increased. Assuming a vaccine cost of $150/dose, vaccination up to age 20 remained below Norway’s willingness-to-pay threshold (≈$83,000/ quality-adjusted life year gained); extension to age 22 was cost-effective at a lower cost-per-dose ($50-$75). At high levels of vaccine protection in women with prior HPV exposure, vaccinating up to age 26 was cost-effective. Results were stable with lower coverage. Conclusions: HPV vaccination catch-up programs may be warranted five years after routine implementation; however, even at low vaccine cost per dose, the cost-effectiveness of vaccinating beyond age 22 remains uncertain.

• Hansen, Bo Terning; Campbell, Suzanne; Burger, Emily & Nygård, Mari (2015). Correlates of HPV vaccine uptake in school-based routine vaccination of preadolescent girls in Norway: A register-based study of 90,000 girls and their parents. Preventive Medicine.  ISSN 0091-7435.  77, s 4- 10 . doi: 10.1016/j.ypmed.2015.04.024 Show summary

  Objective To assess demographic, socioeconomic and behavioural correlates of HPV vaccination of preadolescent girls in a publicly funded, school-based vaccination programme. Methods Data for all Norwegian girls born 1997–1999, eligible for routine school-based HPV vaccination in 2009–2011 (n = 90,842), and their registered mother and father, were merged from national registries. Correlates of girl vaccination status were analysed by unadjusted and multivariable logistic regression. Results In total, 78.2% of the girls received the first dose of the HPV vaccine, 74.6% received three doses, and 94.8% received the MMR vaccine. Correlates associated with initiation of HPV vaccination included parental age, income and education, maternal occupational status and cervical screening attendance, and girl receipt of the MMR vaccine. Rates of completion of HPV vaccination among initiators were high, and disparities in completion were negligible. Maternal and paternal correlates of daughter HPV vaccination status were similar. Conclusions Routine school-based vaccination generally provides equitable delivery, yet some disparities exist. Information campaigns designed to reach the sub-groups with relatively low vaccine uptake could reduce disparities. In none of the sub-groups investigated did uptake of the HPV vaccine approach that of the MMR vaccine, further demonstrating a general potential for improvement in HPV vaccine uptake.

• Kim, J.J.; Campos, Nicole G.; Sy, Stephen; Burger, Emily; Cuzick, Jack; Castle, P; Hunt, W; Wheeler, Cosette M. & Waxman, Alan (2015). Inefficiencies and High-Value Improvements in U.S. Cervical Cancer Screening Practice: A Cost-Effectiveness Analysis. Annals of Internal Medicine.  ISSN 0003-4819.  163(8), s 589- 597 . doi: 10.7326/M15-0420 Show summary

  BACKGROUND: Studies suggest that cervical cancer screening practice in the United States is inefficient. The cost and health implications of nonadherence in the screening process compared with recommended guidelines are uncertain. OBJECTIVE: To estimate the benefits, costs, and cost-effectiveness of current cervical cancer screening practice and assess the value of screening improvements. DESIGN: Model-based cost-effectiveness analysis. DATA SOURCES: New Mexico HPV Pap Registry; medical literature. TARGET POPULATION:Cohort of women eligible for routine screening. TIME HORIZON:Lifetime. PERSPECTIVE:Societal. INTERVENTION: Current cervical cancer screening practice; improved adherence to guidelines-based screening interval, triage testing, diagnostic referrals, and precancer treatment referrals. OUTCOME MEASURES: Reductions in lifetime cervical cancer risk, quality-adjusted life-years (QALYs), lifetime costs, incremental cost-effectiveness ratios, and incremental net monetary benefits (INMBs). RESULTS OF BASE-CASE ANALYSIS:Current screening practice was associated with lower health benefit and was not cost-effective relative to guidelines-based strategies. Improvements in the screening process were associated with higher QALYs and small changes in costs. Perfect adherence to screening every 3 years with cytologic testing and adherence to colposcopy/biopsy referrals were associated with the highest INMBs ($759 and $741, respectively, at a willingness-to-pay threshold of $100 000 per QALY gained); together, the INMB increased to $1645. RESULTS OF SENSITIVITY ANALYSIS: Current screening practice was inefficient in 100% of simulations. The rank ordering of screening improvements according to INMBs was stable over a range of screening inputs and willingness-to-pay thresholds. LIMITATION: The effect of human papillomavirus vaccination was not considered. CONCLUSIONS: The added health benefit of improving adherence to guidelines, especially the 3-year interval for cytologic screening and diagnostic follow-up, may justify additional investments in interventions to improve U.S. cervical cancer screening practice.

• Pedersen, Kine; Lönnberg, Stefan; Skare, Gry Baadstrand; Sørbye, Sveinung Wergeland; Burger, Emily & Kristiansen, Ivar Sønbø (2015). Kostnader ved Masseundersøkelsen mot livmorhalskreft. Sykepleien Forskning.  ISSN 1890-2936.  s 62- 71 . doi: 10.4220/Sykepleienf.2015.53414 Full text in Research Archive.
• Pedersen, Kine; Sørbye, Sveinung Wergeland; Burger, Emily; Lönnberg, Stefan & Kristiansen, Ivar Sønbø (2015). Using decision-analytic modeling to isolate interventions that are feasible, efficient and optimal: an application from the Norwegian Cervical Cancer Screening Program. Value in Health.  ISSN 1098-3015.  18(8), s 1088- 1097 . doi: 10.1016/j.jval.2015.08.003 Full text in Research Archive.
• Rochau, Ursula; Jahn, Beate; Qerimi, Vjollca; Burger, Emily; Kurzthaler, Christina; Kluibenschaedl, Martina; Willenbacher, Ella; Gastl, Günther; Willenbacher, Wolfgang & Siebert, Uwe (2015). Decision-analytic modeling studies: An overview for clinicians using multiple myeloma as an example. Critical Reviews in Oncology/Hematology.  ISSN 1040-8428.  94(2), s 164- 178 . doi: 10.1016/j.critrevonc.2014.12.017
• Burger, Emily & Kim, Jane J (2014). The value of improving failures within a cervical cancer screening program: An example from Norway. International Journal of Cancer.  ISSN 0020-7136.  135(8), s 1931- 1939 . doi: 10.1002/ijc.28838 Show summary

  Failures in cervical cancer (CC) screening include nonparticipation, underscreening and loss to follow-up of abnormal results. We estimated the long-term health benefits from and maximum investments in interventions targeted to improving compliance to guidelines while remaining cost-effective. We used a mathematical model empirically calibrated to simulate the natural history of CC in Norway. A baseline scenario reflecting current practice using cytology-based screening was compared to scenarios that target different sources of noncompliance: (i) failure to follow-up women with abnormal results, (ii) screening less frequently than recommended (i.e., underscreening) and (iii) absence of screening. A secondary analysis included human papillomavirus (HPV)-based screening as the primary test. Model outcomes included reductions in lifetime cancer risk and incremental net monetary benefit (INMB) resulting from improvements with compliance. Compared to the status quo, improving all sources of noncompliance leads to important health gains and produced positive INMBs across a range of developed-country willingness-to-pay (WTP) thresholds. For example, a 2% increase in compliance could reduce lifetime cancer risk by 1–3%, depending on the targeted source of noncompliance and primary screening method. Assuming a WTP threshold of $83,000 per year of life saved and cytology-based screening, interventions that increase follow-up of abnormal results yielded the highest INMB per 2% increase in coverage [$19 ($10–21)]. With HPV-based screening, recruiting nonscreeners resulted in the largest INMB [$23 ($18–32)]. Considerable funds could be allocated toward policies that improve compliance with screening under the current cytology-based program or toward adoption of primary HPV-based screening while remaining cost-effective.

• Burger, Emily; Nygård, Mari; Gyrd-Hansen, Dorte; Moger, Tron Anders & Kristiansen, Ivar Sønbø (2014). Does the primary screening test influence women's anxiety and intention to screen for cervical cancer? A randomized survey of Norwegian women. BMC Public Health.  ISSN 1471-2458.  14:360 . doi: 10.1186/1471-2458-14-360 Full text in Research Archive.
• Burger, Emily; Sy, Stephen; Nygård, Mari; Kristiansen, Ivar Sønbø & Kim, Jane J (2014). Prevention of HPV-Related Cancers in Norway: Cost-Effectiveness of Expanding the HPV Vaccination Program to Include Pre-Adolescent Boys. PLOS ONE.  ISSN 1932-6203.  9(3), s e89974 . doi: 10.1371/journal.pone.0089974 Full text in Research Archive. Show summary

  Background: Increasingly, countries have introduced female vaccination against human papillomavirus (HPV), causally linked to several cancers and genital warts, but few have recommended vaccination of boys. Declining vaccine prices and strong evidence of vaccine impact on reducing HPV-related conditions in both women and men prompt countries to reevaluate whether HPV vaccination of boys is warranted. Methods: A previously-published dynamic model of HPV transmission was empirically calibrated to Norway. Reductions in the incidence of HPV, including both direct and indirect benefits, were applied to a natural history model of cervical cancer, and to incidence-based models for other non-cervical HPV-related diseases. We calculated the health outcomes and costs of the different HPV-related conditions under a gender-neutral vaccination program compared to a female-only program. Results: Vaccine price had a decisive impact on results. For example, assuming 71% coverage, high vaccine efficacy and a reasonable vaccine tender price of $75 per dose, we found vaccinating both girls and boys fell below a commonly cited cost-effectiveness threshold in Norway ($83,000/quality-adjusted life year (QALY) gained) when including vaccine benefit for all HPV-related diseases. However, at the current market price, including boys would not be considered ‘good value for money.’ For settings with a lower cost-effectiveness threshold ($30,000/QALY), it would not be considered cost-effective to expand the current program to include boys, unless the vaccine price was less than $36/dose. Increasing vaccination coverage to 90% among girls was more effective and less costly than the benefits achieved by vaccinating both genders with 71% coverage. Conclusions: At the anticipated tender price, expanding the HPV vaccination program to boys may be cost-effective and may warrant a change in the current female-only vaccination policy in Norway. However, increasing coverage in girls is uniformly more effective and cost-effective than expanding vaccination coverage to boys and should be considered a priority.

• Campos, Nicole G.; Burger, Emily; Sy, Stephen; Sharma, Monisha; Schiffman, Mark; Rodriguez, Ana Cecilia; Hildesheim, Allan; Herrero, Rolando & Kim, Jane J. (2014). An updated natural history model of cervical cancer: Derivation of model parameters. American Journal of Epidemiology.  ISSN 0002-9262.  180(5), s 545- 555 . doi: 10.1093/aje/kwu159 Show summary

  Mathematical models of cervical cancer have been widely used to evaluate the comparative effectiveness and cost-effectiveness of preventive strategies. Major advances in the understanding of cervical carcinogenesis motivate the creation of a new disease paradigm in such models. To keep pace with the most recent evidence, we updated a previously developed microsimulation model of human papillomavirus (HPV) infection and cervical cancer to reflect 1) a shift towards health states based on HPV rather than poorly reproducible histological diagnoses and 2) HPV clearance and progression to precancer as a function of infection duration and genotype, as derived from the control arm of the Costa Rica Vaccine Trial (2004–2010). The model was calibrated leveraging empirical data from the New Mexico Surveillance, Epidemiology, and End Results Registry (1980–1999) and a state-of-the-art cervical cancer screening registry in New Mexico (2007–2009). The calibrated model had good correspondence with data on genotype- and age-specific HPV prevalence, genotype frequency in precancer and cancer, and age-specific cancer incidence. We present this model in response to a call for new natural history models of cervical cancer intended for decision analysis and economic evaluation at a time when global cervical cancer prevention policy continues to evolve and evidence of the long-term health effects of cervical interventions remains critical.

• Burger, Emily; Ortendahl, J D; Sy, S; Kristiansen, Ivar Sønbø & Kim, J.J. (2012). Cost-effectiveness of cervical cancer screening with primary human papillomavirus testing in Norway. British Journal of Cancer.  ISSN 0007-0920.  106(9), s 1571- 1578 . doi: 10.1038/bjc.2012.94
• Burger, Emily; Kornør, Hege; Klemp, Marianne; Lauvrak, Vigdis & Kristiansen, Ivar Sønbø (2011). HPV mRNA tests for the detection of cervical intraepithelial neoplasia: A systematic review. Gynecologic Oncology.  ISSN 0090-8258.  120(3), s 430- 438 . doi: 10.1016/j.ygyno.2010.11.013 Show summary

  Objective. Perform a systematic review to determine the test performance of HPV mRNA testing compared to DNA testing using CIN2+ as the target condition. Methods. We searched bibliographic databases (MEDLINE, EMBASE and Cochrane Library) from January 1996 through August 2010 using a predefined search strategy. The reference standard used to diagnose precancerous lesions was histologically confirmed cervical intraepithelial neoplasia 2+ (CIN2+). Two reviewers independently assessed study eligibility, extracted data, and assessed risk of bias. Sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratios were calculated for each study. In addition, we fitted a series of summary receiver operating characteristics (SROC) curves. A subgroup analysis was performed according to specific inclusion covariates. Results. Out of 3179 potentially relevant citations, 12 publications (11 studies) met our inclusion criteria. The included studies were of varying methodological quality, and were predominately performed in a secondary screening setting. Eight studies investigated the performance of the PreTect Proofer/NucliSENS EasyQ, two studies investigated the performance of the APTIMA assay and one study investigated both mRNA tests on the same patient samples. Due to few studies and considerable clinical heterogeneity, pooling of data was not possible. Instead, we compiled a ‘best evidence synthesis’ for E6/E7 mRNA HPV testing. Sensitivities ranged from 0.41 to 0.86 and from 0.90 to 0.95 for the PreTect Proofer/Easy Q and APTIMA assay, respectively. Specificities ranged from 0.63 to 0.97 and from 0.42 to 0.61 for the PreTect Proofer/Easy Q and APTIMA assay, respectively. The SROC curves for both mRNA tests were to the left of the diagonal and the APTIMA assay performed closest to the DNA tests. Conclusion. The review suggests that mRNA tests have diagnostic relevance, but additional studies and economic evaluations must be conducted in order to make a solid conclusion regarding the clinical applicability of HPV mRNA testing.

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• Castle, Philip E.; Wheeler, Cosette M.; Campos, Nicole G.; Sy, Stephen; Burger, Emily & Kim, Jane J. (2018). Inefficiencies of over-screening and under-screening for cervical cancer prevention in the U.S.. Preventive Medicine.  ISSN 0091-7435.  111, s 177- 179 . doi: 10.1016/j.ypmed.2018.03.011
• Burger, Emily; Dyer, Michael; Palefsky, Joel M.; Sy, Stephen; de Pokomandy, Alexandra; Coutlee, François; Silverberg, Michael & Kim, Jane J. (2017). A Natural History Model of Anal Carcinogenesis for High-risk HIV-positive Men: Model Development and Calibration.
• Burger, Emily; Kim, Jane J.; Sy, Stephen & Castle, Philip E. (2017). Exposing the Insulting Infection: Leveraging Models to Explore the Natural History of HPV Infections.
• Burger, Emily; Pedersen, Kine; Sy, Stephen; Kristiansen, Ivar Sønbø & Kim, Jane J. (2017). Primary HPV-based Cervical Cancer Screening: Balancing Health Benefits Colposcopy Referrals.
• Castle, Philip E. & Burger, Emily (2016). Age of HPV vaccination?. Lancet. Infectious Diseases (Print).  ISSN 1473-3099.  16(10), s 1091- 1093 . doi: 10.1016/S1473-3099(16)30144-X
• Pedersen, Kine; Burger, Emily; Sy, Stephen; Kristiansen, Ivar Sønbø & Kim, Jane J. (2016). Cost-effective management of women with minor cervical lesions: Revisiting the application of HPV DNA testing.
• Burger, Emily; Castle, P & Kim, Jane J (2015). The Optimal Age for Vaccinated Women to Initiate Cervical Cancer Screening in the United States.
• Burger, Emily; Lee, Kyueun & Kim, Jane J. (2015). Racial and Ethnic Disparities in HPV-related Cancer Incidence and Mortality with First- and Second-generation HPV Vaccines in the United States.
• Pedersen, Kine; Burger, Emily; Campbell, Suzanne; Nygård, Mari & Lönnberg, Stefan (2015). Risk of cervical cancer by screening intensity: A registry-based analysis.
• Pedersen, Kine; Sørbye, Sveinung Wergeland; Burger, Emily; Lönnberg, Stefan & Kristiansen, Ivar Sønbø (2015). Quantifying benefits and harms in cervical cancer screening: A decision analytic approach.
• Pedersen, Kine; Sørbye, Sveinung Wergeland; Kristiansen, Ivar Sønbø & Burger, Emily (2015). Novel Biomarkers to Triage Women with Minor Cervical Lesions: Quantifying the Cost-Effectiveness Tradeoffs to Ensure Feasible Implementation..
• Sørbye, Sveinung Wergeland; Sæterdal, Ingvil Von Mehren; Hansen, Bo Terning; Nygård, Mari & Burger, Emily (2015, 14. desember). Vurderer på nytt å hpv-vaksinere gutter. [Internett].  Sykepleien. Show summary

  Spørsmålet om å gi hpv-vaksinen til gutter er ikke avgjort. Samtidig øker tilfellene av hpv-kreft blant både menn og kvinner. Sannsynligvis ikke kostnadseffektivt, var konklusjonen da Kunnskapssenteret for helsetjenesten gjorde en økonomisk evaluering av hpv-vaksine til gutter. – Men rapporten så først og fremst på gevinsten ved mindre hpv-kreft hos jenter, i mindre grad på forekomst av hpv-kreft blant gutter, påpeker Sveinung Wergeland Sørbye, overlege i klinisk patologi ved Universitetssykehuset i Nord-Norge.

• Pedersen, Kine; Sørbye, Sveinung Wergeland; Lönnberg, Stefan; Burger, Emily & Kristiansen, Ivar Sønbø (2014). Trade-offs in cervial cancer screening - Balancing detected cancer precursors and resource use. Show summary

  Reflex HPV-testing allows for improvements in both effectiveness and cost-effectiveness of the current screening algorithm. Candidate strategies can detect a larger number of precancers while using fewer resources compared to current practice; however, the optimal strategy depends on society’s willingness to pay costs and accept harms. Ultimately, the down-stream effectiveness of the alternative algorithms will depend on the extent to which precancers regress or progress into cancer.

• Sørbye, Sveinung Wergeland; Burger, Emily; Eide, Maj Liv; Iversen, Ole-Erik & Jørstad, Rolf Gunnar (2014, 25. september). Feiltolkninger koster tjue liv i året.  Avisa Nordland. Show summary

  Hvert år får 300 kvinner livmorhalskreft. Én av tre dør av sykdommen. Overlege i patologi, Sveinung W. Sørbye, tror liv kunne vært spart dersom den norske screeningmetoden hadde blitt byttet ut. – I Norge dør det årlig 10-20 kvinner som følge av feiltolkede celleprøver. Han mener tiden er moden for å innføre HPV-testing i screeningprogrammet, for å få ned antall dødsfall.

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