The potential harms of primary human papillomavirus screening in over-screened women: a microsimulation study.
ABSTRACT: It is well acknowledged that HPV testing should not be performed at young age and at short intervals. Cytological screening practices have shown that over-screening, i.e., from a younger age and at shorter intervals than recommended, is hard to avoid. We quantified the consequences of a switch to primary HPV screening for over-screened women, taking into account its higher sensitivity but lower specificity than cytology.The health effects of using the HPV test instead of cytology as the primary screening method were determined with the MISCAN-Cervix model. We varied the age women start screening and the interval between screens. In the sensitivity analyses, we varied the background risk of cervical cancer, the HPV prevalence, the discount rate, the triage strategy after cytology, and the test characteristics of both cytology and the HPV test.For women screened 5 yearly from age 30, 32 extra deaths per 100,000 simulated women were prevented when switching from primary cytology to primary HPV testing. For annual screening from age 20, such a switch resulted in 6 extra deaths prevented. It was associated with 9,044 more positive primary screens in the former scenario versus 76,480 in the latter. Under all conditions, for women screened annually, switching to HPV screening resulted in a net loss of quality-adjusted life years.For over-screened women, the harms associated with a lower test specificity outweigh the life years gained when switching from primary cytology to primary HPV testing. The extent of over-screening should be considered when deciding on inclusion of primary HPV screening in cervical cancer screening guidelines.
Project description:Current US cervical cancer screening guidelines do not differentiate recommendations based on a woman's human papillomavirus (HPV) vaccination status. Changes to cervical cancer screening policies in HPV-vaccinated women should be evaluated.We utilized an individual-based mathematical model of HPV and cervical cancer in US women to project the health benefits, costs, and harms associated with screening strategies in women vaccinated with the bivalent, quadrivalent, or nonavalent vaccine. Strategies varied by the primary screening test, including cytology, HPV, and combined cytology and HPV "cotesting"; age of screening initiation and/or switching to a new test; and interval between routine screens. Cost-effectiveness analysis was conducted from the societal perspective to identify screening strategies that would be considered good value for money according to thresholds of $50 000 to $200 000 per quality-adjusted life-year (QALY) gained.Among women fully vaccinated with the bivalent or quadrivalent vaccine, optimal screening strategies involved either cytology or HPV testing alone every five years starting at age 25 or 30 years, with cost-effectiveness ratios ranging from $34 680 to $138 560 per QALY gained. Screening earlier or more frequently was either not cost-effective or associated with exceedingly high cost-effectiveness ratios. In women vaccinated with the nonavalent vaccine, only primary HPV testing was efficient, involving decreased frequency (ie, every 10 years) starting at either age 35 years ($40 210 per QALY) or age 30 years ($127 010 per QALY); with lower nonavalent vaccine efficacy, 10-year HPV testing starting at earlier ages of 25 or 30 years was optimal. Importantly, current US guidelines for screening were inefficient in HPV-vaccinated women.This model-based analysis suggests screening can be modified to start at later ages, occur at decreased frequency, and involve primary HPV testing in HPV-vaccinated women, providing more health benefit at lower harms and costs than current screening guidelines.
Project description:The availability of human papillomavirus (HPV) DNA testing and vaccination against HPV types 16 and 18 (HPV-16,18) motivates questions about the cost-effectiveness of cervical cancer prevention in the United States for unvaccinated older women and for girls eligible for vaccination.An empirically calibrated model was used to assess the quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (2004 US dollars per QALY) of screening, vaccination of preadolescent girls, and vaccination combined with screening. Screening varied by initiation age (18, 21, or 25 years), interval (every 1, 2, 3, or 5 years), and test (HPV DNA testing of cervical specimens or cytologic evaluation of cervical cells with a Pap test). Testing strategies included: 1) cytology followed by HPV DNA testing for equivocal cytologic results (cytology with HPV test triage); 2) HPV DNA testing followed by cytology for positive HPV DNA results (HPV test with cytology triage); and 3) combined HPV DNA testing and cytology. Strategies were permitted to switch once at age 25, 30, or 35 years.For unvaccinated women, triennial cytology with HPV test triage, beginning by age 21 years and switching to HPV testing with cytology triage at age 30 years, cost $78,000 per QALY compared with the next best strategy. For girls vaccinated before age 12 years, this same strategy, beginning at age 25 years and switching at age 35 years, cost $41,000 per QALY with screening every 5 years and $188,000 per QALY screening triennially, each compared with the next best strategy. These strategies were more effective and cost-effective than screening women of all ages with cytology alone or cytology with HPV triage annually or biennially.For both vaccinated and unvaccinated women, age-based screening by use of HPV DNA testing as a triage test for equivocal results in younger women and as a primary screening test in older women is expected to be more cost-effective than current screening recommendations.
Project description: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.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.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.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.
Project description:Forthcoming cervical cancer screening strategies involving human papillomavirus (HPV) testing for women not vaccinated against HPV infections may increase colposcopy referral rates. We quantified health and resource trade-offs associated with alternative HPV-based algorithms to inform decision-makers when choosing between candidate algorithms.We used a mathematical simulation model of HPV-induced cervical carcinogenesis in Norway. We compared the current cytology-based strategy to alternative strategies that varied by the switching age to primary HPV testing (ages 25-34 years), the routine screening frequency (every 3-10 years), and management of HPV-positive, cytology-negative women. Model outcomes included reductions in lifetime cervical cancer risk, relative colposcopy rates, and colposcopy rates per cervical cancer prevented.The age of switching to primary HPV testing and the screening frequency had the largest impacts on cancer risk reductions, which ranged from 90.9% to 96.3% compared to no screening. In contrast, increasing the follow-up intensity of HPV-positive, cytology-negative women provided only minor improvements in cancer benefits, but generally required considerably higher rates of colposcopy referrals compared to current levels, resulting in less efficient cervical cancer prevention.We found that in order to maximise cancer benefits HPV-based screening among unvaccinated women should not be delayed: rather, policy makers should utilise the triage mechanism to control colposcopy referrals.
Project description:The switch from primary cytology to primary high risk papillomavirus (HR-HPV) testing for cervical screening is now being implemented in a number of countries. The advantages of this are to increase screening sensitivity which will save lives, and at the same time to extend screening intervals. The challenge with HR-HPV testing is its relatively poor specificity which means identifying a large number of women who are HR-HPV positive with negative cytology. One way of tackling this is to use early recall, in order to select referral to colposcopy to those women who do not clear the virus over a period of 1-2 years, as done in the recently published English Pilot Study. Another challenge in optimising screening is to recognise that wide coverage with prophylactic vaccination will require fewer screens over the lifetime of vaccinated women to maintain cost-effectiveness. HR-HPV testing allows self sampling which could both encourage more women to be screened and be more convenient for those who do wish to be screened. Cervical cancer prevention which combines vaccination and screening now offers a future in which cervical cancer could become a rarity, but efficient strategies need to be implemented.
Project description:BACKGROUND:Sweden revised their cervical cancer screening program in 2017 to include cytology-based screening for women aged 23-29 years and primary human papillomavirus (HPV) testing for women aged 30-64 years; however, alternative strategies may be preferred. To inform cervical cancer prevention policies for unvaccinated women, we evaluated the cost-effectiveness of alternative screening strategies, including the current Swedish guidelines. METHODS:We adapted a mathematical simulation model of HPV and cervical cancer to the Swedish context using primary epidemiologic data. We compared the cost-effectiveness of alternative screening strategies that varied by the age to start screening, the age to switch from cytology to HPV testing, HPV strategies not preceded by cytology, screening frequency, and management of HPV-positive/cytology-negative women. RESULTS:We found that the current Swedish guidelines were more costly and less effective than alternative primary HPV-based strategies. All cost-efficient strategies involved primary HPV testing not preceded by cytology for younger women. Given a cost-effectiveness threshold of €85,619 per quality-adjusted life year gained, the optimal strategy involved 5-yearly primary HPV-based screening for women aged 23-50 years and 10-yearly HPV-based screening for women older than age 50 years. CONCLUSIONS:Primary screening based on HPV alone may be considered for unvaccinated women for those countries with similar HPV burdens.
Project description:The aim of this study is to compare the cost and benefit of four different cervical cancer screening strategies involving primary HPV 16/18 genotyping, hrHPV testing alone and cytology for detecting CIN2 +.Economical analysis using Markov modeling approach to combine the epidemiological data from current population-based study of The National Cancer Institute of Thailand. A cohort of 100,000 hypothetical female population age 30-65 years was simulated in each strategy. The compared strategies are HPV 16/18 genotyping with reflexed cytology, hrHPV testing alone followed by colposcopy, Papanicolaou standard cytology and liquid based cytology followed by colposcopy. The interval of screening was 5 years' interval. The main outcomes were defined as a number of CIN2 + cases and cost per 100,000 women screening over 35 years.Model predictions indicated that, the most cost-effectiveness strategy is hrHPV testing alone by reducing cost and also increase CIN2 + detection rate. It identify an additional 130 cases and decrease cost by 46,950,840 THB (1,394,441 USD) per 100,000 women screened when compared to HPV 16/18 genotyping. Compared with cytology, hrHPV testing decrease cost by 51,279,781 THB (1,523,011 USD) and detected more 506 cases of CIN2 +. From sensitivity analysis, the cost of HPV testing, cost of colposcopy, incidence of HPV infection and sensitivity of cytology may affect the results. (1 USD = 33.67 Baht).The results of this cost-effectiveness analysis support the full scale implementation of HPV testing as a primary cervical cancer screening in Thailand.
Project description:Women vaccinated against HPV16/18 are approaching the age for cervical screening; however, an updated screening algorithm has not been agreed. We use a microsimulation model calibrated to real published data to determine the appropriate screening intensity for vaccinated women. Natural histories in the absence of vaccination were simulated for 300,000 women using 10,000 sets of transition probabilities. Vaccination with (i) 100% efficacy against HPV16/18, (ii) 15% cross-protection, (iii) 22% cross-protection, (iv) waning vaccine efficacy and (v) 100% efficacy against HPV16/18/31/33/45/52/58 was added, as were a range of screening scenarios appropriate to the UK. To benchmark cost-benefits of screening for vaccinated women, we evaluated the proportion of cancers prevented per additional screen (incremental benefit) of current cytology and likely HPV screening scenarios in unvaccinated women. Slightly more cancers are prevented through vaccination with no screening (70.3%, 95% CR: 65.1-75.5) than realistic compliance to the current UK screening programme in the absence of vaccination (64.3%, 95% CR: 61.3-66.8). In unvaccinated women, when switching to HPV primary testing, there is no loss in effectiveness when doubling the screening interval. Benchmarking supports screening scenarios with incremental benefits of ?2.0%, and rejects scenarios with incremental benefits ?0.9%. In HPV16/18-vaccinated women, the incremental benefit of offering a third lifetime screen was at most 3.3% (95% CR: 2.2-4.5), with an incremental benefit of 1.3% (-0.3-2.8) for a fourth screen. For HPV16/18/31/33/45/52/58-vaccinated women, two lifetime screens are supported. It is important to know women's vaccination status; in these simulations, HPV16/18-vaccinated women require three lifetime screens, HPV16/18/31/33/45/52/58-vaccinated women require two lifetime screens, yet unvaccinated women require seven lifetime screens.
Project description:BACKGROUND:Self-sampling for human papillomavirus (HPV) offered to women who do not participate in cervical cancer screening is an increasingly popular method to increase screening coverage. The rationale behind self-sampling is that unscreened women harbour a high proportion of undetected precancer lesions. Here, we compare the cervical intraepithelial neoplasia grade 2 or worse (?CIN2) detection rate between non-attenders who participated in self-sampling and women attending routine screening. METHODS:A total of 23?632 women who were qualified as non-attenders in the Copenhagen Region were invited for HPV-based self-sampling. Of these, 4824 women returned a self-sample, and HPV-positive women were referred for cytology and HPV co-testing as follow-up. The entire cohort and a reference cohort (3347 routinely screened women) were followed for histopathology confirmed ?CIN2. Odds ratio (OR) and the relative positive predictive value of ?CIN2 detection between the two populations were estimated. RESULTS:Women participating in self-sampling had a higher ?CIN2 detection than women undergoing routine cytology-based screening (OR=1.83, 95% CI: 1.21-2.77) and a similar detection as routinely screened women tested with cytology and HPV testing (OR=1.03, 95% CI: 0.75-1.40). The positive predictive value for ?CIN2 was higher in screening non-attenders than in routinely HPV- and cytology-screened screened women (36.5% vs 25.6%, respectively). CONCLUSIONS:Self-sampling offered to non-attenders showed higher detection rates for ?CIN2 than routine cytology-based screening, and similar detection rates as HPV and cytology co-testing. This reinforces the importance of self-sampling for screening non-attenders in organised cervical cancer screening.
Project description:OBJECTIVE:To determine the most cost-effective screening programme for cervical cancer. DESIGN:Cost-effectiveness analysis from a societal perspective. SETTING:The Netherlands. POPULATION:Dutch women who have not been invited for human papillomavirus (HPV) vaccination. METHODS:We calibrated the microsimulation screening analysis (MISCAN) model to Dutch epidemiological data. We used this model to consider nine screening strategies that use: (i) cytological testing with cytology triage for borderline/mildly abnormal smears; (ii) HPV testing with cytology triage for HPV-positive smears; or (iii) cytological testing with HPV triage for borderline/mildly abnormal smears. For each strategy, we varied the number of screening rounds, the time interval, the age of the first screening, and the type of cytological testing (conventional or liquid-based cytology). MAIN OUTCOME MEASURES:Quality-adjusted life years (QALYs) gained and costs from a societal perspective. RESULTS:Under the base-case assumptions, primary HPV testing with cytology triage is the most cost-effective strategy. Using cost-effectiveness thresholds of € 20,000 and € 50,000 per QALY gained yields optimal screening programmes with three and seven screening rounds, respectively. The results are sensitive to several uncertain model inputs, most importantly the costs of the HPV test. For women aged 32 years or younger, primary cytology screening is more cost-effective than primary HPV testing. CONCLUSIONS:Increasing the interval between screening rounds and changing the primary test from cytology to HPV testing can improve the effectiveness and decrease the costs of cervical cancer screening in the Netherlands.