Cost effectiveness of different cervical screening strategies in Islamic Republic of Iran: a middle-income country with a low incidence rate of cervical cancer

Objective: Invasive cervical cancer (ICC) is the fourth most common cancer among women worldwide. Cervical screening programs have reduced the incidence and mortality rates of ICC. We studied the cost-effectiveness of different cervical screening strategies in the Islamic Republic of Iran, a Muslim country with a low incidence rate of ICC. Methods: We constructed an 11-state Markov model, in which the parameters included regression and progression probabilities, test characteristics, costs, and utilities; these were extracted from primary data and the literature. Our strategies included Pap smear screening and human papillomavirus (HPV) DNA testing plus Pap smear triaging with different starting ages and screening intervals. Model outcomes included lifetime costs, life years gained, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis was performed to examine the stability of the results. Results: We found that the prevented mortalities for the 11 strategies compared with no screening varied from 26% to 64%. The most cost-effective strategy was HPV screening, starting at age 35 years and repeated every 10 years. The ICER of this strategy was $8,875 per QALY compared with no screening. We found that screening at 5-year intervals was also cost-effective based on GDP per capita in Iran. Conclusion: We recommend organized cervical screening with HPV DNA testing for women in Iran, beginning at age 35 and repeated every 10 or 5 years. The results of this study could be generalized to other countries with low incidence rates of cervical cancer

Does lowering the screening age for cervical cancer in The Netherlands make sense?\ud

Recommendations for the age to initiate cervical cancer screening should be directed towards maximum detection of early cervical cancer. However, the screening programme should do more good than harm. The aim of this analysis was to determine whether the target age for cervical cancer screening should be lowered in view of apparent increases in new cases of invasive cancer below age 30 and in age group 30–44 years in The Netherlands. Therefore, all cervical cancer cases diagnosed between January 1, 1989 and December 31, 2003 were selected from the nationwide population-based Netherlands Cancer Registry. For age group 25–39 years, incidence data were also available for 2004 and 2005. To describe trends, the estimated annual percentage of change and joinpoint analysis were used. Between ages 25 and 28 years, the absolute number of new cases of cervical cancer annually has varied between 0 and 9 per age. Significantly decreasing trends in incidence were observed for age groups 35–39 and 45–49 (p < 0.0001 and p = 0.01, respectively). The annual number of deaths fluctuated with a decreasing trend for age groups 30–34 and 35–39 years (p = 0.01 and p = 0.03, respectively). Because the incidence and mortality rates for cervical cancer among women younger than 30 are low and not increasing, lowering the age for cervical cancer screening is not useful at this time. Although the number of years of life gained is high for every case of cervical cancer prevented, the disadvantages of lowering the screening age would be very large and even become disproportionate compared to the potential advantage

Optimal Mammography Schedule Estimates Under Varying Disease Burden, Infrastructure Availability, and Other Cause Mortality: A Comparative Analyses of Six Low- and Middle- Income Countries

Low-and-middle-income countries (LMICs) have a higher mortality-to-incidence ratio for breast cancer compared to high-income countries (HICs) because of late-stage diagnosis. Mammography screening is recommended for early diagnosis, however, current screening guidelines are only generalized by economic disparities, and are based on extrapolation of data from randomized controlled trials in HICs, which have different disease burdens and all-cause mortality compared to LMICs. Moreover, the infrastructure capacity in LMICs is far below that needed for adopting current screening guidelines. This study analyzes the impact of disease burden, infrastructure availability, and other cause mortality on optimal mammography screening schedules for LMICs. Further, these key features are analyzed under the context of overdiagnosis, epidemiologic/clinical uncertainty in pathways of the initial stage of cancer, and variability in technological availability for diagnosis and treatment. It uses a Markov decision process (MDP) model to estimate optimal schedules under varying assumptions of resource availability, applying it to six LMICs. Results suggest that screening schedules should change with disease burden and life-expectancy. For countries with similar life-expectancy but different disease burden, the model suggests to screen age groups with higher incidence rates. For countries with similar incidence rate and different life expectancy, the model suggests to screen younger age groups for countries with lower life-expectancy. Overdiagnosis and differences in screening technology had minimal impact on optimal schedules. Optimality of screening schedules were sensitive to epidemiologic/clinical uncertainty. Results from this study suggest that, instead of generalized screening schedules, those tailored to disease burden and infrastructure capacity could help optimize resources. Results from this study can help inform current screening guidelines and future health investment plans

A proposed new generation of evidence-based microsimulation models to inform global control of cervical cancer

Health decision models are the only available tools designed to consider the lifetime natural history of human papillomavirus (HPV) infection and pathogenesis of cervical cancer, and the estimated long-term impact of preventive interventions. Yet health decision modeling results are often considered a lesser form of scientific evidence due to the inherent needs to rely on imperfect data and make numerous assumptions and extrapolations regarding complex processes. We propose a new health decision modeling framework that de-emphasizes cytologic-colposcopic-histologic diagnoses due to their subjectivity and lack of reproducibility, relying instead on HPV type and duration of infection as the major determinants of subsequent transition probabilities. We posit that the new model health states (normal, carcinogenic HPV infection, precancer, cancer) and corollary transitions are universal, but that the probabilities of transitioning between states may vary by population. Evidence for this variability in host response to HPV infections can be inferred from HPV prevalence patterns in different regions across the lifespan, and might be linked to different average population levels of immunologic control of HPV infections. By prioritizing direct estimation of model transition probabilities from longitudinal data (and limiting reliance on model-fitting techniques that may propagate error when applied to multiple transitions), we aim to reduce the number of assumptions for greater transparency and reliability. We propose this new microsimulation model for critique and discussion, hoping to contribute to models that maximally inform efficient strategies towards global cervical cancer elimination

Distribution Patterns of Infection with Multiple Types of Human Papillomaviruses and Their Association with Risk Factors

Background: Infection with multiple types of human papillomavirus (HPV) is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1, 810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively. Principal Findings: The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%), while this risk decreased in women who had given birth more than 4 times (-31.1%), or were of mestizo (-24.6%) or black (-40.9%) ethnicity. Conclusions: According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2-4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies.This project was funded by Asociacion Investigacion Solidaria SADAR, Caja Navarra (Navarra, Spain) and the Spanish Agency for International Development Cooperation (AECID) (Project 08-CAP2-0609)

Cervical cancer screening in low- and middle-income countries: A systematic review of economic evaluation studies

Economic assessments are relevant to support the decision to incorporate more cost-effective strategies to reduce Cervical Cancer (CC) mortality. This systematic review analyzes the economic evaluation studies of CC prevention strategies (HPV DNA-based tests and conventional cytology) in low- and middle-income countries. Medline, EMBASE, CRD, and LILACS were searched for economic evaluation studies that reported cost and effectiveness measures of HPV DNA-based tests for CC screening and conventional cytology in women, without age, language, or publication date restrictions. Selection and data extraction were carried out independently. For comparability of results, cost-effectiveness measures were converted to international dollars (2019). Report quality was assessed using the CHEERS checklist. The Dominance Matrix Ranking (DRM) was used to analyze and interpret the results. The review included 15 studies from 12 countries, with cost-effectiveness analyzes from the health system's perspective and a 3% discount rate. The strategies varied in age and frequency of screening. Most studies used the Markov analytical model, and the cost-benefit threshold was based on the per capita GDP of each country. The sensitivity analysis performed in most studies was deterministic. The completeness of the report was considered sufficient in most of the items evaluated by CHEERS. The Dominance Interpretation (DRM) varied; in 6 studies, the HPV test was dominant, 5 studies showed a weak dominance evaluating greater effectiveness of the HPV test at a higher cost, yet in 2 studies conventional cytology was dominant. Although the context-dependent nature of economic evaluations, this review points out the challenge of methodological standardization in the analytical models

Focal Spot, Summer/Fall 2005

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