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Summary Background 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. Methods 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. Findings 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. Interpretation 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. Funding 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 Quebec–Sante.

Summary Background 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. Methods 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. Findings 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. Interpretation 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. Funding 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 Quebec–Sante, Compute Canada, National Health and Medical Research Council Australia Centre for Research Excellence in Cervical Cancer Control.