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      Impact of HPV vaccination and cervical screening on cervical cancer elimination: a comparative modelling analysis in 78 low-income and lower-middle-income countries

      research-article
      , Prof, PhD a , b , c , , * , , Prof, PhD d , , , DPhil e , f , g , , , PhD a , , PhD a , , PhD d , h , , PhD a , , PhD e , f , , MSc a , , Prof, PhD a , b , c , , MS d , , BA d , , PhD e , f , , DPhil e , f , , PhD e , f , , PhD e , f , , PhD a , , Prof, PhD i , j , k , , Prof, MD a , b , l , , PhD m , , MD n , , MPH o , , MBA o , , MD p , , PhD o
      Lancet (London, England)
      Elsevier

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          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 Québec–Santé, Compute Canada, National Health and Medical Research Council Australia Centre for Research Excellence in Cervical Cancer Control.

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          Most cited references28

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          Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women

          The Lancet, 374(9686), 301-314
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            HPV screening for cervical cancer in rural India.

            In October 1999, we began to measure the effect of a single round of screening by testing for human papillomavirus (HPV), cytologic testing, or visual inspection of the cervix with acetic acid (VIA) on the incidence of cervical cancer and the associated rates of death in the Osmanabad district in India. In this cluster-randomized trial, 52 clusters of villages, with a total of 131,746 healthy women between the ages of 30 and 59 years, were randomly assigned to four groups of 13 clusters each. The groups were randomly assigned to undergo screening by HPV testing (34,126 women), cytologic testing (32,058), or VIA (34,074) or to receive standard care (31,488, control group). Women who had positive results on screening underwent colposcopy and directed biopsies, and those with cervical precancerous lesions or cancer received appropriate treatment. In the HPV-testing group, cervical cancer was diagnosed in 127 subjects (of whom 39 had stage II or higher), as compared with 118 subjects (of whom 82 had advanced disease) in the control group (hazard ratio for the detection of advanced cancer in the HPV-testing group, 0.47; 95% confidence interval [CI], 0.32 to 0.69). There were 34 deaths from cancer in the HPV-testing group, as compared with 64 in the control group (hazard ratio, 0.52; 95% CI, 0.33 to 0.83). No significant reductions in the numbers of advanced cancers or deaths were observed in the cytologic-testing group or in the VIA group, as compared with the control group. Mild adverse events were reported in 0.1% of screened women. In a low-resource setting, a single round of HPV testing was associated with a significant reduction in the numbers of advanced cervical cancers and deaths from cervical cancer. 2009 Massachusetts Medical Society
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              Coverage of Cervical Cancer Screening in 57 Countries: Low Average Levels and Large Inequalities

              Emmanuela Gakidou and colleagues find that coverage of cervical cancer screening in developing countries is on average 19% compared to 63% in developed countries.
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                Author and article information

                Contributors
                Journal
                Lancet
                Lancet
                Lancet (London, England)
                Elsevier
                0140-6736
                1474-547X
                22 February 2020
                22 February 2020
                : 395
                : 10224
                : 575-590
                Affiliations
                [a ]Centre de recherche du CHU de Québec - Universite Laval, Québec, QC, Canada
                [b ]Department of Social and Preventive Medicine, Universite Laval, Québec, QC, Canada
                [c ]MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK
                [d ]Center for Health Decision Science, Harvard T.H. Chan School of Public Health, Boston, MA, USA
                [e ]Cancer Research Division, Cancer Council NSW, Sydney, NSW, Australia
                [f ]School of Public Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia
                [g ]Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia
                [h ]Department of Health Management and Health Economics, University of Oslo, Oslo, Norway
                [i ]Centre for Mathematical Modelling of Infectious Disease, London School of Hygiene and Tropical Medicine, London, UK
                [j ]Modelling and Economics Unit, Public Health England, London, UK
                [k ]School of Public Health, University of Hong Kong, Hong Kong, China
                [l ]Institut national de santé publique du Québec, Québec, QC, Canada
                [m ]Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
                [n ]Department for the Management of Noncommunicable Diseases, Disability, Violence and Injury Prevention, World Health Organization, Geneva, Switzerland
                [o ]Department of Immunization, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland
                [p ]Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland
                Author notes
                [* ]Correspondence to: Prof Marc Brisson, Centre de recherche du CHU de Québec, Universite Laval, Axe Santé des populations et pratiques optimales en santé, Québec, QC G1S 4L8, Canada marc.brisson@ 123456crchudequebec.ulaval.ca
                [†]

                Joint first authors

                Article
                S0140-6736(20)30068-4
                10.1016/S0140-6736(20)30068-4
                7043009
                32007141
                f3df08db-d3b6-4f6c-9a7d-91ee078c5e20
                © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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