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Cervical screening and human papillomavirus (HPV) vaccination have been implemented in most high-income countries; however, coverage is low in low-income and middle-income countries (LMICs). In 2018, the Director-General of WHO announced a call to action for the elimination of cervical cancer as a public health problem. WHO has called for global action to scale-up vaccination, screening, and treatment of precancer, early detection and prompt treatment of early invasive cancers, and palliative care. An elimination threshold in terms of cervical cancer incidence has not yet been defined, but an absolute rate of cervical cancer incidence could be chosen for such a threshold. In this study, we aimed to quantify the potential cumulative effect of scaled up global vaccination and screening coverage on the number of cervical cancer cases averted over the 50 years from 2020 to 2069, and to predict outcomes beyond 2070 to identify the earliest years by which cervical cancer rates could drop below two absolute levels that could be considered as possible elimination thresholds—the rare cancer threshold (six new cases per 100 000 women per year, which has been observed in only a few countries), and a lower threshold of four new cases per 100 000 women per year. In this statistical trends analysis and modelling study, we did a statistical analysis of existing trends in cervical cancer worldwide using high-quality cancer registry data included in the Cancer Incidence in Five Continents series published by the International Agency for Research on Cancer. We then used a comprehensive and extensively validated simulation platform, Policy1-Cervix, to do a dynamic multicohort modelled analysis of the impact of potential scale-up scenarios for cervical cancer prevention, in order to predict the future incidence rates and burden of cervical cancer. Data are presented globally, by Human Development Index (HDI) category, and at the individual country level. In the absence of further intervention, there would be 44·4 million cervical cancer cases diagnosed globally over the period 2020–69, with almost two-thirds of cases occurring in low-HDI or medium-HDI countries. Rapid vaccination scale-up to 80–100% coverage globally by 2020 with a broad-spectrum HPV vaccine could avert 6·7–7·7 million cases in this period, but more than half of these cases will be averted after 2060. Implementation of HPV-based screening twice per lifetime at age 35 years and 45 years in all LMICs with 70% coverage globally will bring forward the effects of prevention and avert a total of 12·5–13·4 million cases in the next 50 years. Rapid scale-up of combined high-coverage screening and vaccination from 2020 onwards would result in average annual cervical cancer incidence declining to less than six new cases per 100 000 individuals by 2045–49 for very-high-HDI countries, 2055–59 for high-HDI countries, 2065–69 for medium-HDI countries, and 2085–89 for low-HDI countries, and to less than four cases per 100 000 by 2055–59 for very-high-HDI countries, 2065–69 for high-HDI countries, 2070–79 for medium-HDI countries, and 2090–2100 or beyond for low-HDI countries. However, rates of less than four new cases per 100 000 would not be achieved in all individual low-HDI countries by the end of the century. If delivery of vaccination and screening is more gradually scaled up over the period 2020–50 (eg, 20–45% vaccination coverage and 25–70% once-per-lifetime screening coverage by 2030, increasing to 40–90% vaccination coverage and 90% once-per-lifetime screening coverage by 2050, when considered as average coverage rates across HDI categories), end of the century incidence rates will be reduced by a lesser amount. In this scenario, average cervical cancer incidence rates will decline to 0·8 cases per 100 000 for very-high-HDI countries, 1·3 per 100 000 for high-HDI countries, 4·4 per 100 000 for medium-HDI countries, and 14 per 100 000 for low-HDI countries, by the end of the century. More than 44 million women will be diagnosed with cervical cancer in the next 50 years if primary and secondary prevention programmes are not implemented in LMICs. If high coverage vaccination can be implemented quickly, a substantial effect on the burden of disease will be seen after three to four decades, but nearer-term impact will require delivery of cervical screening to older cohorts who will not benefit from HPV vaccination. Widespread coverage of both HPV vaccination and cervical screening from 2020 onwards has the potential to avert up to 12·5–13·4 million cervical cancer cases by 2069, and could achieve average cervical cancer incidence of around four per 100 000 women per year or less, for all country HDI categories, by the end of the century. A draft global strategy to accelerate cervical cancer elimination, with goals and targets for the period 2020–30, will be considered at the World Health Assembly in 2020. The findings presented here have helped inform initial discussions of elimination targets, and ongoing comparative modelling with other groups is supporting the development of the final goals and targets for cervical cancer elimination. National Health and Medical Research Council (NHMRC) Australia, part-funded via the NHMRC Centre of Excellence for Cervical Cancer Control (C4; APP1135172).

Many countries are transitioning from cytology-based to longer-interval HPV screening. Trials comparing HPV-based screening to cytology report an increase in CIN2/3 detection at the first screen, and longer-term reductions in CIN3+; however, population level year-to-year transitional impacts are poorly understood. We undertook a comprehensive evaluation of switching to longer-interval primary HPV screening in the context of HPV vaccination. We used Australia as an example setting, since Australia will make this transition in December 2017. Using a model of HPV vaccination, transmission, natural history and cervical screening, Policy1-Cervix, we simulated the planned transition from recommending cytology every two years for sexually-active women aged 18-20 to 69, to recommending HPV screening every five years for women aged 25-74 years. We estimated rates of CIN2/3, cervical cancer incidence, and mortality for each year from 2005 to 2035, considering ranges for HPV test accuracy and screening compliance in the context of HPV vaccination (current coverage ~82% in females; ~76% in males). Transient increases are predicted to occur in rates of CIN2/3 detection and invasive cervical cancer in the first two to three years following the screening transition (of 16-24% and 11-14% in respectively, compared to 2017 rates). However, by 2035, CIN2/3 and invasive cervical cancer rates are predicted to fall by 40-44% and 42-51%, respectively, compared to 2017 rates. Cervical cancer mortality rates are predicted to remain unchanged until ~2020, then decline by 34-45% by 2035. Over the period 2018-2035, switching to primary HPV screening in Australia is expected to avert 2,006 cases of invasive cervical cancer and save 587 lives. Transient increases in detected CIN2/3 and invasive cancer, which may be detectable at the population level, are predicted following a change to primary HPV screening. This is due to improved test sensitivity bringing forward diagnoses, resulting in longer term reductions in both cervical cancer incidence and mortality. Fluctuations in health outcomes due to the transition to a longer screening interval are predicted to occur for 10-15 years, but cervical cancer rates will be significantly reduced thereafter due to the impact of HPV vaccination and HPV screening. In order to maintain confidence in primary HPV screening through the transitional phase, it is important to widely communicate that an initial increase in CIN2/3 and perhaps even invasive cervical cancer is expected after a national transition to primary HPV screening, that this phenomenon is due to increased prevalent disease detection, and that this effect represents a marker of screening success.

A nonavalent human papillomavirus (HPV) vaccine has been licensed for use in women and men up to age 45 years in the United States. The cost-effectiveness of HPV vaccination for women and men aged 30 to 45 years in the context of cervical cancer screening practice was evaluated to inform national guidelines. We utilized 2 independent HPV microsimulation models to evaluate the cost-effectiveness of extending the upper age limit of HPV vaccination in women (from age 26 years) and men (from age 21 years) up to age 30, 35, 40, or 45 years. The models were empirically calibrated to reflect the burden of HPV and related cancers in the US population and used standardized inputs regarding historical and future vaccination uptake, vaccine efficacy, cervical cancer screening, and costs. Disease outcomes included cervical, anal, oropharyngeal, vulvar, vaginal, and penile cancers, as well as genital warts. Both models projected higher costs and greater health benefits as the upper age limit of HPV vaccination increased. Strategies of vaccinating females and males up to ages 30, 35, and 40 years were found to be less cost-effective than vaccinating up to age 45 years, which had an incremental cost-effectiveness ratio (ICER) greater than a commonly accepted upper threshold of $200,000 per quality-adjusted life year (QALY) gained. When including all HPV-related outcomes, the ICER for vaccinating up to age 45 years ranged from $315,700 to $440,600 per QALY gained. Assumptions regarding cervical screening compliance, vaccine costs, and the natural history of noncervical HPV-related cancers had major impacts on the cost-effectiveness of the vaccination strategies. Key limitations of the study were related to uncertainties in the data used to inform the models, including the timing of vaccine impact on noncervical cancers and vaccine efficacy at older ages. Our results from 2 independent models suggest that HPV vaccination for adult women and men aged 30 to 45 years is unlikely to represent good value for money in the US.

WHO is developing a global strategy towards eliminating cervical cancer as a public health problem, which proposes an elimination threshold of four cases per 100 000 women and includes 2030 triple-intervention coverage targets for scale-up of human papillomavirus (HPV) vaccination to 90%, twice-lifetime cervical screening to 70%, and treatment of pre-invasive lesions and invasive cancer to 90%. We assessed the impact of achieving the 90–70–90 triple-intervention targets on cervical cancer mortality and deaths averted over the next century. We also assessed the potential for the elimination initiative to support target 3.4 of the UN Sustainable Development Goals (SDGs)—a one-third reduction in premature mortality from non-communicable diseases by 2030. The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC) involves three independent, dynamic models of HPV infection, cervical carcinogenesis, screening, and precancer and invasive cancer treatment. Reductions in age-standardised rates of cervical cancer mortality in 78 low-income and lower-middle-income countries (LMICs) were estimated for three core scenarios: girls-only vaccination at age 9 years with catch-up for girls aged 10–14 years; girls-only vaccination plus once-lifetime screening and cancer treatment scale-up; and girls-only vaccination plus twice-lifetime screening and cancer treatment scale-up. Vaccination was assumed to provide 100% lifetime protection against infections with HPV types 16, 18, 31, 33, 45, 52, and 58, and to scale up to 90% coverage in 2020. Cervical screening involved HPV testing at age 35 years, or at ages 35 years and 45 years, with scale-up to 45% coverage by 2023, 70% by 2030, and 90% by 2045, and we assumed that 50% of women with invasive cervical cancer would receive appropriate surgery, radiotherapy, and chemotherapy by 2023, which would increase to 90% by 2030. We summarised results using the median (range) of model predictions. In 2020, the estimated cervical cancer mortality rate across all 78 LMICs was 13·2 (range 12·9–14·1) per 100 000 women. Compared to the status quo, by 2030, vaccination alone would have minimal impact on cervical cancer mortality, leading to a 0·1% (0·1–0·5) reduction, but additionally scaling up twice-lifetime screening and cancer treatment would reduce mortality by 34·2% (23·3–37·8), averting 300 000 (300 000–400 000) deaths by 2030 (with similar results for once-lifetime screening). By 2070, scaling up vaccination alone would reduce mortality by 61·7% (61·4–66·1), averting 4·8 million (4·1–4·8) deaths. By 2070, additionally scaling up screening and cancer treatment would reduce mortality by 88·9% (84·0–89·3), averting 13·3 million (13·1–13·6) deaths (with once-lifetime screening), or by 92·3% (88·4–93·0), averting 14·6 million (14·1–14·6) deaths (with twice-lifetime screening). By 2120, vaccination alone would reduce mortality by 89·5% (86·6–89·9), averting 45·8 million (44·7–46·4) deaths. By 2120, additionally scaling up screening and cancer treatment would reduce mortality by 97·9% (95·0–98·0), averting 60·8 million (60·2–61·2) deaths (with once-lifetime screening), or by 98·6% (96·5–98·6), averting 62·6 million (62·1–62·8) deaths (with twice-lifetime screening). With the WHO triple-intervention strategy, over the next 10 years, about half (48% [45–55]) of deaths averted would be in sub-Saharan Africa and almost a third (32% [29–34]) would be in South Asia; over the next 100 years, almost 90% of deaths averted would be in these regions. For premature deaths (age 30–69 years), the WHO triple-intervention strategy would result in rate reductions of 33·9% (24·4–37·9) by 2030, 96·2% (94·3–96·8) by 2070, and 98·6% (96·9–98·8) by 2120. These findings emphasise the importance of acting immediately on three fronts to scale up vaccination, screening, and treatment for pre-invasive and invasive cervical cancer. In the next 10 years, a one-third reduction in the rate of premature mortality from cervical cancer in LMICs is possible, contributing to the realisation of the 2030 UN SDGs. Over the next century, successful implementation of the WHO elimination strategy would reduce cervical cancer mortality by almost 99% and save more than 62 million women's lives. WHO, UNDP, UN Population Fund, UNICEF–WHO–World Bank Special Program of Research, Development and Research Training in Human Reproduction, Germany Federal Ministry of Health, National Health and Medical Research Council Australia, Centre for Research Excellence in Cervical Cancer Control, Canadian Institute of Health Research, Compute Canada, and Fonds de recherche du Québec–Santé.

The WHO Director-General has issued a call for action to eliminate cervical cancer as a public health problem. To help inform global efforts, we modelled potential human papillomavirus (HPV) vaccination and cervical screening scenarios in low-income and lower-middle-income countries (LMICs) to examine the feasibility and timing of elimination at different thresholds, and to estimate the number of cervical cancer cases averted on the path to elimination. The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC), which consists of three independent transmission-dynamic models identified by WHO according to predefined criteria, projected reductions in cervical cancer incidence over time in 78 LMICs for three standardised base-case scenarios: girls-only vaccination; girls-only vaccination and once-lifetime screening; and girls-only vaccination and twice-lifetime screening. Girls were vaccinated at age 9 years (with a catch-up to age 14 years), assuming 90% coverage and 100% lifetime protection against HPV types 16, 18, 31, 33, 45, 52, and 58. Cervical screening involved HPV testing once or twice per lifetime at ages 35 years and 45 years, with uptake increasing from 45% (2023) to 90% (2045 onwards). The elimination thresholds examined were an average age-standardised cervical cancer incidence of four or fewer cases per 100 000 women-years and ten or fewer cases per 100 000 women-years, and an 85% or greater reduction in incidence. Sensitivity analyses were done, varying vaccination and screening strategies and assumptions. We summarised results using the median (range) of model predictions. Girls-only HPV vaccination was predicted to reduce the median age-standardised cervical cancer incidence in LMICs from 19·8 (range 19·4–19·8) to 2·1 (2·0–2·6) cases per 100 000 women-years over the next century (89·4% [86·2–90·1] reduction), and to avert 61·0 million (60·5–63·0) cases during this period. Adding twice-lifetime screening reduced the incidence to 0·7 (0·6–1·6) cases per 100 000 women-years (96·7% [91·3–96·7] reduction) and averted an extra 12·1 million (9·5–13·7) cases. Girls-only vaccination was predicted to result in elimination in 60% (58–65) of LMICs based on the threshold of four or fewer cases per 100 000 women-years, in 99% (89–100) of LMICs based on the threshold of ten or fewer cases per 100 000 women-years, and in 87% (37–99) of LMICs based on the 85% or greater reduction threshold. When adding twice-lifetime screening, 100% (71–100) of LMICs reached elimination for all three thresholds. In regions in which all countries can achieve cervical cancer elimination with girls-only vaccination, elimination could occur between 2059 and 2102, depending on the threshold and region. Introducing twice-lifetime screening accelerated elimination by 11–31 years. Long-term vaccine protection was required for elimination. Predictions were consistent across our three models and suggest that high HPV vaccination coverage of girls can lead to cervical cancer elimination in most LMICs by the end of the century. Screening with high uptake will expedite reductions and will be necessary to eliminate cervical cancer in countries with the highest burden. WHO, UNDP, UN Population Fund, UNICEF–WHO–World Bank Special Program of Research, Development and Research Training in Human Reproduction, Canadian Institute of Health Research, Fonds de recherche du Québec–Santé, Compute Canada, National Health and Medical Research Council Australia Centre for Research Excellence in Cervical Cancer Control.

In 2020, the World Health Organization (WHO) launched a strategy to eliminate cervical cancer as a public health problem. To support the strategy, the WHO published updated cervical screening guidelines in 2021. To inform this update, we used an established modeling platform, Policy1-Cervix , to evaluate the impact of seven primary screening scenarios across 78 low- and lower-middle-income countries (LMICs) for the general population of women. Assuming 70% coverage, we found that primary human papillomavirus (HPV) screening approaches were the most effective and cost-effective, reducing cervical cancer age-standardized mortality rates by 63–67% when offered every 5 years. Strategies involving triaging women before treatment (with 16/18 genotyping, cytology, visual inspection with acetic acid (VIA) or colposcopy) had close-to-similar effectiveness to HPV screening without triage and fewer pre-cancer treatments. Screening with VIA or cytology every 3 years was less effective and less cost-effective than HPV screening every 5 years. Furthermore, VIA generated more than double the number of pre-cancer treatments compared to HPV. In conclusion, primary HPV screening is the most effective, cost-effective and efficient cervical screening option in LMICs. These findings have directly informed WHO’s updated cervical screening guidelines for the general population of women, which recommend primary HPV screening in a screen-and-treat or screen-triage-and-treat approach, starting from age 30 years with screening every 5 years or 10 years. A modelled evaluation of screening and treatment strategies for prevention of cervical cancer in 78 low- and lower-middle-income countries provides evidence to support the World Health Organization’s recommendation of primary HPV testing for women in the general population.

Women with HIV have an elevated risk of HPV infection, and eventually, cervical cancer. Tanzania has a high burden of both HIV and cervical cancer, with an HIV prevalence of 5.5% in women in 2018, and a cervical cancer incidence rate among the highest globally, at 59.1 per 100,000 per year, and an estimated 9,772 cervical cancers diagnosed in 2018. We aimed to quantify the impact that interventions intended to control HIV have had and will have on cervical cancer in Tanzania over a period from 1995 to 2070. A deterministic transmission-dynamic compartment model of HIV and HPV infection and natural history was used to simulate the impact of voluntary medical male circumcision (VMMC), anti-retroviral therapy (ART), and targeted pre-exposure prophylaxis (PrEP) on cervical cancer incidence and mortality from 1995-2070. We estimate that VMMC has prevented 2,843 cervical cancer cases and 1,039 cervical cancer deaths from 1995-2020; by 2070 we predict that VMMC will have lowered cervical cancer incidence and mortality rates by 28% (55.11 cases per 100,000 women in 2070 without VMMC, compared to 39.93 with VMMC only) and 26% (37.31 deaths per 100,000 women in 2070 without VMMC compared to 27.72 with VMMC), respectively. We predict that ART will temporarily increase cervical cancer diagnoses and deaths, due to the removal of HIV death as a competing risk, but will ultimately further lower cervical cancer incidence and mortality rates by 7% (to 37.31 cases per 100,000 women in 2070) and 5% (to 26.44 deaths per 100,000 women in 2070), respectively, relative to a scenario with VMMC but no ART. A combination of ART and targeted PrEP use is anticipated to lower cervical cancer incidence and mortality rates to 35.82 and 25.35 cases and deaths, respectively, per 100,000 women in 2070. HIV treatment and control measures in Tanzania will result in long-term reductions in cervical cancer incidence and mortality. Although, in the near term, the life-extending capability of ART will result in a temporary increase in cervical cancer rates, continued efforts towards HIV prevention will reduce cervical cancer incidence and mortality over the longer term. These findings are critical background to understanding the longer-term impact of achieving cervical cancer elimination targets in Tanzania.

Several countries are implementing a transition to HPV testing for cervical screening in response to the introduction of HPV vaccination and evidence indicating that HPV screening is more effective than cytology. In Australia, a 2017 transition from 2-yearly conventional cytology in 18-20 to 69 years to 5-yearly primary HPV screening in 25 to 74 years will involve partial genotyping for HPV 16/18 with direct referral to colposcopy for this higher risk group. The objective of this study was to determine the optimal management of women positive for other high-risk HPV types (not 16/18) ('OHR HPV'). We used a dynamic model of HPV transmission, vaccination, natural history and cervical screening to determine the optimal management of women positive for OHR HPV. We assumed cytology triage testing was used to inform management in this group and that those with high-grade cytology would be referred to colposcopy and those with negative cytology would receive 12-month surveillance. For those with OHR HPV and low-grade cytology (considered to be a single low-grade category in Australia incorporating ASC-US and LSIL), we evaluated (1) the 20-year risk of invasive cervical cancer assuming this group are referred for 12-month follow-up vs. colposcopy, and compared this to the risk in women with low-grade cytology under the current program (i.e. an accepted benchmark risk for 12-month follow-up in Australia); (2) the population-level impact of the whole program, assuming this group are referred to 12-month surveillance vs. colposcopy; and (3) the cost-effectiveness of immediate colposcopy compared to 12-month follow-up. Evaluation was performed both for HPV-unvaccinated cohorts and cohorts offered vaccination (coverage ~72%). The estimated 20-year risk of cervical cancer is ≤1.0% at all ages if this group are referred to colposcopy vs. ≤1.2% if followed-up in 12 months, both of which are lower than the ≤2.6% benchmark risk in women with low-grade cytology in the current program (who are returned for 12-month follow-up). At the population level, immediate colposcopy referral provides an incremental 1-3% reduction in cervical cancer incidence and mortality compared with 12-month follow-up, but this is in the context of a predicted 24-36% reduction associated with the new HPV screening program compared to the current cytology-based program. Furthermore, immediate colposcopy substantially increases the predicted number of colposcopies, with >650 additional colposcopies required to avert each additional case of cervical cancer compared to 12-month follow-up. Compared to 12-month follow-up, immediate colposcopy has an incremental cost-effectiveness ratio (ICER) of A$104,600/LYS (95%CrI:A$100,100-109,100) in unvaccinated women and A$117,100/LYS (95%CrI:A$112,300-122,000) in cohorts offered vaccination [Indicative willingness-to-pay threshold: A$50,000/LYS]. In primary HPV screening programs, partial genotyping for HPV16/18 or high-grade triage cytology in OHR HPV positive women can be used to refer the highest risk group to colposcopy, but 12-month follow-up for women with OHR HPV and low-grade cytology is associated with a low risk of developing cervical cancer. Direct referral to colposcopy for this group would be associated with a substantial increase in colposcopy referrals and the associated harms, and is also cost-ineffective; thus, 12-month surveillance for women with OHR HPV and low-grade cytology provides the best balance between benefits, harms and cost-effectiveness.

Background The burden of cancer can be altered by screening. The field of cancer screening is constantly evolving; from the initiation of program for new cancer types as well as exploring innovative screening strategies (e.g. new screening tests). The aim of this study was to perform a landscape analysis of existing cancer screening programs in South-East Asia and the Western Pacific. Methods We conducted an overview of cancer screening in the region with the goal of summarizing current designs of cancer screening programs. First, a selective narrative literature review was used as an exploration to identify countries with organized screening programs. Second, representatives of each country with an organized program were approached and asked to provide relevant information on the organizations of their national or regional cancer screening program. Results There was wide variation in the screening strategies offered in the considered region with only eight programs identified as having an organized design. The majority of these programs did not meet all the essential criteria for being organized screening. The greatest variation was observed in the starting and stopping ages. Conclusions Essential criteria of organized screening are missed. Improving organization is crucial to ensure that the beneficial effects of screening are achieved in the long-term. It is strongly recommended to consider a regional cancer screening network.

Information on healthcare costs in low-and-middle-income countries is limited. This study presents a framework to perform healthcare cost estimates for each province in China. This study has two aims. Using cervical cancer as an example, the first aim is to use data (including micro-costing data) from one province to derive estimates for other provinces in China. This used provincial and national Chinese-language statistical reports and considered levels of service delivery, hospital-seeking behaviour, and the urban/rural population distribution. The second aim is to characterise the relationship between the reference costs estimated using the method mentioned above and two sets of cost estimates derived using simplified cost-scaling method with per capita Gross Domestic Product (GDP), and the Human Development Index (HDI). For simplified methods, regression modelling characterised the relationship between province-specific healthcare costs and macro-economic indicators, then we used the exponential fit to extrapolate costs. Using the reference method, the estimated costs were found to vary substantially by urban/rural regions and between provinces; the ratios of highest to lowest provincial costs were 3.5 for visual inspection with acetic acid (VIA), 4.4 for cold knife conisation (CKC) and 4.6 for stage II cancer treatment. The HDI-based scaling method generally resulted in a better fit to reference costs than the GDP method. These reference costs for cervical cancer can inform cost-effectiveness evaluation of cervical screening and HPV vaccination in China. HDI-based methods for cost-scaling-based on social, as well as purely economic, factors-have potential to provide more accurate estimates.