| Acetta, 2010 68 | Italy, TPP | Simulated cohort of 10 million women followed from birth | To evaluate the comparative impact of screening strategies with or without the vaccination of young girls. | Specific screening protocols that were evaluated included (with varying age and screening interval):
no intervention but treatment of symptomatic cervical cancer primary cytology primary HPV testing (hybrid capture II) primary cytology followed by HPV testing for positive Pap test results (ASCUS) primary HPV with cytology triage.
| Patient-level state-transition model |
HPV DNA with Pap triage every five years dominates current screening (Pap test every 3 years) Same in both vaccinated and unvaccinated women, though a higher sequential ICER in vaccinated women
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| Balasubramanian, 201069 | US, societal | Cohort of women beginning at age 12 years and followed through age 85 years | To estimate the accuracy and cost-effectiveness of cervical cancer screening strategies based on high-risk HPV DNA testing of self-collected vaginal samples. | Screening protocols evaluated include (with tests occurring at different intervals, with vaginal tests self-done, cervical tests in clinic):
no screening was the reference primary HPV with cytology triage primary HPV primary cytology with reflex HPV for ASCUS primary cytology with repeat cytology for ASCUS primary HPV testing.
| Cohort-level state-transition model |
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| Berkhof, 201070 | Netherlands, societal | Simulated cohort of 4 million Dutch women from 10 to 100 years of age | To study the health and economic effects of HPV DNA testing in cervical screening using a simulation model. | Screening protocols evaluated include:
primary cytology at 5-year intervals from 30 to 60 years of age primary HPV with cytology triage co-testing primary cytology with HPV triage.
| Patient-level state-transition model |
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| Bistoletti, 200871 | Sweden, TPP | Simulated cohort of women from age 32 to death (of any cause, including cervical cancer) | To estimate life expectancy and health care cost per woman during the remaining lifetime for four screening strategies. | The following four strategies evaluated:
Strategy 1: Primary cytology at 3-year intervals from 32 to 50, increased to 5 between age 50 to 60 Strategy 2: Addition of HPV DNA co-testing to strategy 1 as of age 32 Strategy 3: Addition of co-testing at ages 32, 41, and 50 Strategy 4: No screening.
| Patient-level state-transition model |
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| Chuck, 201072 | Alberta, TPP | A cohort of women from 12 years of age to 80 years of age | To assess the cost-effectiveness of 21 alternative CCS strategies. | 7 alternatives at 1,2, and 3 year intervals, including the following:
primary cytology (Pap test) primary cytology (Pap test) with HPV triage primary cytology (LBC) with HPV triage primary HPV with cytology (LBC) triage applying an age restriction of HPV DNA test in scenarios above — only women above 30 years of age.
| Patient-level state-transition model |
Others on efficiency frontier:
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| Coupe, 201273 | Netherlands, societal | A cohort of Dutch women from age 12 to 100 | To assess the influence of broad spectrum vaccines and cross-protection against non-HPV 16/18 types on the cost-effectiveness of future screening programs. | Scenarios compared include: With HPV 16/18 crossprotection (8 scenarios)
With broad spectrum vaccination
| Patient-level state-transition model |
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| de Kok, 201274 | Various European countries, adjusted societal perspective (no productivity losses included) | Unvaccinated women born between 1939 and 1992 | To investigate, using a Dutch model, whether and under what variables framed for other European countries screening for HPV is preferred over cytology screening for cervical cancer, and to calculate the preferred number of examinations over a woman’s lifetime. | Nine different strategies considered:
primary cytology and cytology triage primary HPV testing and cytology or a combination of cytology and HPV triage primary cytology and HPV or combination of HPV and cytology triage.
| Agent-based model given the website of the models |
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| Diaz, 201075 | Spain, societal | A single birth cohort of girls followed from age 9 throughout their lifetime | To assess the health and economic impact of adding HPV vaccination to cervical cancer screening. | Strategies assessed included:
screening alone of women over age 25, varying frequency (every 1 to 5 years) and test and triage (cytology, HPV testing, but no primary HPV testing) HPV vaccination of 11-year-old girls combined with screening.
| Patient-level state-transition model |
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| Georgalis, 201676 | Spain, societal | A cohort of 11-year-old girls | To compare the effectiveness and cost-effectiveness of different cervical prevention scenarios, including current status and new proposed prevention strategies to inform health decision-makers in Spain. | Strategies assessed include:
vaccination alone screening alone (included cytology starting at 25 years of age or HPV testing at 30 years of age with cytology triage, each with further scenarios with varied time intervals between tests [1 to 5years]) combined vaccination and screening.
| Patient-level state-transition model |
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| Ginsberg, 200991 | Global, TPP — region-specific estimates | Unclear, groups varied based on socioeconomic status | To compare and evaluate the costs and effectiveness of different screening and prevention strategies relating to cervical cancer in all 14 WHO regions of the world. | Strategies assessed include:
primary cytology primary HPV VIA (Visual inspection after application of 3% to 5% acetic acid) Pap tri-annually, then co-testing (annually, 3, and 5 years).
| Cohort-level state-transition model |
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| Goldhaber-Feibert, 200877 | US, societal | Cohort of one million girls followed from age 9 throughout their lifetime, one vaccinated group, another unvaccinated group | To assess the QALYs, lifetime costs, and incremental cost-effectiveness ratios of screening, vaccination of pre-adolescent girls, and vaccination combined with screening. | Screening strategies varied by initiation age and interval, and included:
| Patient-level state-transition model |
For unvaccinated women, triennial cytology with HPV triage at age 21, followed by HPV with cytology triage at age 30, was most cost-effective For girls vaccinated before 12, same strategy, but beginning at 25 and switching at 35 with screening every 5 years was deemed most cost-effective
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| Goldie, 200478 | US, societal | Cohort of sexually naive women, free of disease; begins at age 13 | To conduct a comprehensive cost-effectiveness analysis of cervical cytology screening strategies that incorporate HPV DNA testing in women aged 30 years or more. | 17 strategies assessed, varying the sequence of tests, consisting of:
no screening conventional primary cytology (Pap test) primary LBC w/ HPV tests triage for ASCUS primary HPV tests with cytology triage for HPV-positive test (as of 30 years of age).
| Cohort-level state-transition model | Strategies on efficiency frontier:
no screening was reference thereafter, more costly and more effective strategies consisted of conventional Pap or liquid Pap w/ HPV triage
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| Huh, 201579 | US, TPP | A cohort of non-hysterectomized women (30years of age) who were asymptomatic for cervical cancer and had participated in cervical screening in a US health care setting over a 40-year period | To evaluate the cost-effectiveness of cervical cancer primary screening with a HPV-16/18 genotyping test, which simultaneously detects 12 other high-risk HPV types. | Four strategies assessed:
primary cytology with reflex HPV testing for ASCUS co-testing primary HPV testing with reflex cytology primary HPV testing with genotyping and reflex cytology (ASCUS threshold).
| Cohort-level state-transition model (over 40-year period) |
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| Kulasingam, 200980 | Canada, TPP | A theoretical cohort of women | To estimate lifetime costs and life expectancy of different screening strategies. | 27 strategies with different testing frequencies and starting ages:
| Cohort-level state-transition model | Strategies on efficiency frontier include:
HPV DNA at age 25, with Pap triage (5 every years, as well as every 3 years) HPV DNA at age 18 with Pap triage
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| Lew, 201623 | New Zealand, TPP | Two populations of interest:
Unvaccinated women (older cohort) Vaccinated cohort, born in 1997
| To identify optimal future screening approaches (based on cost-effectiveness) in New Zealand in both vaccinated and unvaccinated women. | 16 strategies (with varying range of screening, frequency, sequence of tests, and management of intermediate risk group), were considered, consisting of:
primary cytology with HPV triage (if 30 years of age or older) primary HPV tests with cytology triage for HPV-positive test primary HPV tests with partial genotyping co-testing co-testing with partial genotyping.
| Hybrid model: system dynamics for HPV transmission/vacci nation and cohort state-transition model | Strategies on efficiency frontier:
all 1° HPV testing were more effective and most were cost saving compared with current practice of cytology alone Intervention most likely cost-effective at lambda of 20,000 to 50,000 per life-year saved: 5 yearly 1° HPV test with partial genotyping and cytology triage was most cost-effective
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| Mittendorf, 200381 | Germany, TPP | A cohort of German women starting at 20 years of age and followed for 20 years (not lifetime) | To evaluate the efficiency of different screening procedures using the HPV test against the currently used strategy in Germany and against a “do nothing” strategy. | Four screening strategies were considered:
no screening primary cytology (every 5 years) primary HPV test (every 5 years unless positive result) HPV + cytology co-testing (every 10 years unless positive result).
| Cohort-level state-transition model (20 years) |
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| Naber, 201682 | Netherlands, Societal | A 20-year-old cohort of 100 million women with life expectancy as observed in the Netherlands, which was not affected by HPV vaccination (neither directly nor through herd immunity) | To quantify the consequences of a switch to primary HPV screening for over-screened women, taking into account its higher sensitivity but lower specificity than cytology. | 12 strategies (for both primary HPV DNA and primary cytology):
varied starting age (20, 25, 30) and screening interval (1,2,3,5) all incorporated a “cost-effective triage strategy” and the primary screening was followed by triage with the other strategy.
| Agent-based model |
Reference case was no screening Frequent screening (or over-screening) harms outweigh life-years gained when going from cytology to HPV DNA as primary test No cost-effectiveness frontier presented
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| Naber, 201683 | Netherlands, Societal | Two populations of one million women:
Pre-vaccination Vaccinated
| To determine the optimal screening strategy for a pre-vaccination population and for vaccinated women. | Four strategies considered:
primary HPV with reflex cytology triage primary cytology with reflex HPV triage co-testing primary cytology with cytology and HPV triage after 6 months and cytology triage after 18 months.
| Agent-based model |
Reference was no screening Primary HPV screening with cytology triage was the optimal strategy for both populations (8 lifetime screens in pre-vaccinated group, 3 lifetime screens in vaccinated group) Depending on Herd immunity levels, once 50% is reached, reducing screening intensity can then be considered
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| Popadiuk, 201684 | Canada, TPP | Women aged 21 to 65, 70% of whom were assumed to be vaccinated with 100% efficacy | To use the cervical cancer and HPV transmission models of the Cancer Risk Management Model to study the health and economic outcomes of primary cytology compared with HPV testing. | 14 screening scenarios with varying screening modalities and intervals:
primary cytology starting at ages 21 or 25 at 3 year intervals primary HPV testing starting at age 30 at different intervals (3, 5, 7.5, 10) combinations of primary cytology or HPV tests at different intervals starting at age 30 with triage as follow-up for primary HPV protocols.
| Dynamic event-based microsimulation (30 years, not lifetime) | Reference case was triennial cytology from age 25 Strategies on the cost-effectiveness frontier were:
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| Sherlaw-Johnson, 200485 | UK, TPP | Following women from 15 years of age | To evaluate different options for introducing LBC and HPV testing into the UK cervical cancer screening program. | Screening options included the following at 3 and 5 year intervals, both with and without LBC:
primary cytology primary cytology with HPV triage primary HPV testing as of age 30 with cytology triage (cytology until age 30) co-testing as of age 30 (cytology alone until age 30).
| Patient-level state-transition model | Strategies on efficiency frontier:
repeat cytology follow-up with LBC (5 year) cytology with HPV triage with LBC (5 year) primary HPV testing with LBC (5 year) co-testing (5 year) primary HPV testing with LBC (3 year) co-testing (3 year)
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| Sroczynski, 201086 | Germany, TPP | A cohort of 15-year-old women | To determine: What is the cost-effectiveness (in Euro per LYG) of HPV testing in primary cervical cancer screening in the German health care context? What is the optimal algorithm for HPV-based cervical cancer screening (i.e., test combination, start and stopping age of screening, screening interval), and which recommendations should be derived for the German health care context? | 18 screening strategies assessed differing by screening interval and test combinations:
no screening primary cytology (> = 20 years old) at 1, 2, 3, and 5 year intervals annual primary cytology, followed by HPV testing as of age 30 at 1, 2, 3, and 5 year intervals biennial primary cytology, then primary HPV DNA at 2, 3, or 5 years biennial primary cytology, then combined cytology and HPV as of 30 years of age at intervals of 2, 3, or 5 years biennial primary cytology, then primary HPV testing as of 30 years of age, in intervals of 2, 3, or 5 years, for HPV-negative women and Pap triage for HPV-positive women.
| Cohort-level transition-state model |
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| Sroczynski, 201187 | Germany, TPP | A cohort of 15-year-old women | To systematically evaluate the long-term effectiveness and cost-effectiveness of HPV-based primary cervical cancer screening in the German health care context using a decision-analysis approach. | 18 screening strategies assessed differing by screening interval and test combinations:
no screening primary cytology test (> = 20 years old) at 1, 2, 3, and 5 year intervals annual primary cytology test, followed by HPV testing as of age 30 at 1, 2, 3, and 5 year intervals biennial primary cytology, then primary HPV testing at 2, 3, or 5 years biennial primary cytology, then combined cytology and HPV as of 30 years of age at intervals of 2, 3, or 5 years biennial primary cytology, then primary HPV testing as of 30 years of age, in intervals of 2, 3, or 5 years, for HPV-negative women and Pap triage for HPV-positive women.
| Cohort-level transition-state model | Reference case was no screening On the cost-effectiveness frontier were:
cytology every five years cytology every three years biennial cytology, HPV every three years biennial cytology, then biennial HPV biennial cytology, then Biennial HPV and cytology triage every 2 years annual cytology from 20 to 29 then annual HPV DNA
Annual cytology dominated by HPV DNA strategies |
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| VanRosmalen, 2011 | Netherlands, societal | Dutch women without HPV vaccination at risk for cervical cancer | To compare a variety of nationally and internationally recommended HPV and cytology triage schedules. | 9 strategies were assessed (varying age range of screening and frequency):
primary cytology with cytology triage for borderline mildly abnormal smears primary HPV tests with combination of cytology and HPV tests triage for HPV-positive test primary HPV testing with cytology triage for HPV-positive test primary cytology with combination of cytology and HPV DNA tests for borderline mildly abnormal smears primary cytology with HPV tests triage for borderline mildly abnormal smears.
| Agent-based model given the website of the models | Strategies on efficiency frontier:
1° cytology with HPV triage was reference thereafter, more costly and more effective strategies consisted of 1° HPV screening with either cytology triage/combination of cytology and HPV triage
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| Vijayaraghavan, 201089 | Quebec, TPP | A cohort of women beginning at age 13 | To determine the cost-effectiveness of several cervical cancer screening strategies utilizing conventional cytology and hrHPV testing. | Six strategies were considered (cytology only prior to age 30):
no screening conventional cytology (every 1 to 3 yrs) with repeat cytology for ASCUS primary cytology with HPV triage for ASCUS (ever 1 to 3 yrs) primary HPV test (every 3 years) primary HPV test with cytology triage (every 3 years) co-screening with HPV DNA test and cytology (every 3 years).
| Patient-level state-transition model | Strategies on the efficiency frontier were those that incorporated HPV as “only” or triage
Conventional cytology was reference Thereafter, more costly and more effective strategies consisted of 1° HPV tests and HPV-only strategy
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| Vijayaraghavan, 201090 | US, TPP | A hypothetical cohort of 100,000 US women over their lifetimes, starting at age 13 year | To determine the cost-effectiveness of adding HPV-16 and 18 genotype triage to current cervical cancer screening strategies in the US. | All women underwent biennial Pap until age 30, followed by:
primary cytology (LBC) every 2 years primary cytology (LBC) every 2 years with HPV for equivocal results primary HPV test with cytology triage for HPV-positive tests co-testing every 3 years co-testing every 3 year with reflex HPV DNA genotyping and intensive follow-ups for HPV types 16/18 primary HPV test with HPV genotyping for all positive tests.
| Patient-level state-transition model |
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