Providing more balanced information on the harms and benefits of cervical cancer screening: A randomized survey among US and Norwegian women.

We aimed to identify how additional information about benefits and harms of cervical cancer (CC) screening impacted intention to participate in screening, what type of information on harms women preferred receiving, from whom, and whether it differed between two national healthcare settings. We conducted a survey that randomized screen-eligible women in the United States (n = 1084) and Norway (n = 1060) into four groups according to the timing of introducing additional information. We found that additional information did not significantly impact stated intentions-to-participate in screening or follow-up testing in either country; however, the proportion of Norwegian women stating uncertainty about seeking precancer treatment increased from 7.9% to 14.3% (p = 0.012). Women reported strong system-specific preferences for sources of information: Norwegians (59%) preferred it come from a national public health agency while Americans (59%) preferred it come from a specialist care provider. Regression models revealed having a prior Pap-test was the most important predictor of intentions-to-participate in both countries, while having lower income reduced the probabilities of intentions-to-follow-up and seek precancer treatment among U.S. women. These results suggest that additional information on harms is unlikely to reduce participation in CC screening but could increase decision uncertainty to seek treatment. Providing unbiased information would improve on the ethical principle of respect for autonomy and self-determination. However, the clinical impact of additional information on women's understanding of the trade-offs involved with CC screening should be investigated. Future studies should also consider country-specific socioeconomic barriers to screening if communication re-design initiatives aim to improve CC screening participation.

Using novel biomarkers to triage young adult women with minor cervical lesions: a cost-effectiveness analysis.

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. TWEETABLE ABSTRACT: Women with minor cervical lesions may be triaged more accurately and effectively using novel biomarkers.

Decision-analytic modeling studies: An overview for clinicians using multiple myeloma as an example.

PURPOSE: The purpose of this study was to provide a clinician-friendly overview of decision-analytic models evaluating different treatment strategies for multiple myeloma (MM). METHODS: We performed a systematic literature search to identify studies evaluating MM treatment strategies using mathematical decision-analytic models. We included studies that were published as full-text articles in English, and assessed relevant clinical endpoints, and summarized methodological characteristics (e.g., modeling approaches, simulation techniques, health outcomes, perspectives). RESULTS: Eleven decision-analytic modeling studies met our inclusion criteria. Five different modeling approaches were adopted: decision-tree modeling, Markov state-transition modeling, discrete event simulation, partitioned-survival analysis and area-under-the-curve modeling. Health outcomes included survival, number-needed-to-treat, life expectancy, and quality-adjusted life years. Evaluated treatment strategies included novel agent-based combination therapies, stem cell transplantation and supportive measures. CONCLUSION: Overall, our review provides a comprehensive summary of modeling studies assessing treatment of MM and highlights decision-analytic modeling as an important tool for health policy decision making.

Cost-effectiveness of cervical cancer screening with primary human papillomavirus testing in Norway.

BACKGROUND: New screening technologies and vaccination against human papillomavirus (HPV), the necessary cause of cervical cancer, may impact optimal approaches to prevent cervical cancer. We evaluated the cost-effectiveness of alternative screening strategies to inform cervical cancer prevention guidelines in Norway. METHODS: We leveraged the primary epidemiologic and economic data from Norway to contextualise a simulation model of HPV-induced cervical cancer. The current cytology-only screening was compared with strategies involving cytology at younger ages and primary HPV-based screening at older ages (31/34+ years), an option being actively deliberated by the Norwegian government. We varied the switch-age, screening interval, and triage strategies for women with HPV-positive results. Uncertainty was evaluated in sensitivity analysis. RESULTS: Current cytology-only screening was less effective and more costly than strategies that involve switching to primary HPV testing in older ages. For unvaccinated women, switching at age 34 years to primary HPV testing every 4 years was optimal given the Norwegian cost-effectiveness threshold ($83,000 per year of life saved). For vaccinated women, a 6-year screening interval was cost-effective. When we considered a wider range of strategies, we found that an earlier switch to HPV testing (at age 31 years) may be preferred. CONCLUSIONS: Strategies involving a switch to HPV testing for primary screening in older women is expected to be cost-effective compared with current recommendations in Norway.

HPV mRNA tests for the detection of cervical intraepithelial neoplasia: a systematic review.

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.