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Three-pronged approach could eliminate cervical cancer within 100 years

More than 74m cervical cancer cases and 62m deaths could be averted in the next 100 years if 78 of the world’s poorest countries rapidly deploy HPV vaccinations, cervical screening and cancer treatment, two studies have projected. Medical News Today reports that the studies – conducted by researchers affiliated with The WHO Cervical Cancer Elimination Modelling Consortium – outline the measures that they advise different countries to apply when it comes to preventing cervical cancer.

The consortium was co-led by Professor Marc Brisson from Université Laval’s faculty of medicine in Québec, Canada.

In one study, the researchers predict that vaccinating girls from low- and middle-income countries against the human papillomavirus (HPV) could lead to an 89.4% reduction in cervical cancer cases over the next century. Usually, HPV infections pass on their own, without any significant effects on a person’s health. In more severe cases, the virus can cause genital warts and cancer – and it is the top risk factor for cervical cancer. However, getting vaccinated against HPV can prevent these possibilities.

In the first study, Brisson and his colleagues argue that with adequate vaccination, low- and middle-income countries could avert an estimated 61m cases of cervical cancer up to 2120. They also say that getting screened for this type of cancer twice in one’s lifetime can reduce its incidence by 96.7%, and avert 2.1m new cases.

The team also predicts that in countries that successfully put into effect an HPV vaccination policy, it may be possible to achieve the full elimination of cervical cancer at some point between 2055–2102. Furthermore, “introducing twice-lifetime screening” into the mix could hasten the eradication of cervical cancer by as much as 11–31 years.

“For the first time, we’ve estimated how many cases of cervical cancer could be averted if the World Health Organisation (WHO) strategy is rolled out and when elimination might occur,” says Brisson.

In their second study, the WHO consortium researchers estimate that in low- and middle-income countries – the regions whose populations are most affected by cervical cancer – the mortality rate for cervical cancer will be 13.2 per 100,000 women in 2020. Yet, they say, if those countries implement effective twice-lifetime screening policies, as well as deliver appropriate treatment where needed, this action could lower the mortality rate by 34.2% by 2030.

This would mean averting as many as 400,000 deaths related to cervical cancer within just 10 years. Even getting people to undergo once-lifetime cervical cancer screenings could achieve similar results, they note.

Brisson and his colleagues also predict that improving vaccination rates could lower mortality rates by 61.7% by 2070. He also notes that adding better screening and cervical cancer treatment practices into the mix could reduce death rates by 88.9%.

In 100 years from now, the researchers argue that appropriate HPV vaccination could lower death rates by 89.5%, preventing 45.8m deaths related to cervical cancer. And applying better screening practices and cancer treatment on top of that could lead to a 97.9% lower mortality rate by 2120. Once-lifetime screening could prevent 60.8m deaths in this timeframe, while twice-lifetime screening could avert 62.6m deaths related to cervical cancer.

The researchers have used the findings of their two studies to put together WHO’s cervical cancer elimination strategy, which they will present at the 73rd World Health Assembly to be held in Geneva, Switzerland, in May 2020.

“If the strategy is adopted and applied by member states, cervical cancer could be eliminated in high income countries by 2040 and across the globe within the next century, which would be a phenomenal victory for women’s health,” argues Brisson. “However,” he cautions, “this can only be achieved with considerable international financial and political commitment, in order to scale up prevention and treatment.”

Abstract 1
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.

Abstract 2
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: World Health Organisation (WHO), UNDP, UN Population Fund, UNICEF, World Bank Special Programme 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.

Authors
Karen Canfell, Jane J Kim, Marc Brisson, Adam Keane, Kate T Simms, Michael Caruana, Emily A Burger, Dave Martin, Diep T N Nguyen, Élodie Bénard, Stephen Sy, Catherine Regan, Mélanie Drolet, Guillaume Gingras, Jean-Francois Laprise, Julie Torode, Megan A Smith, Elena Fidarova, Dario Trapani, Freddie Bray, Andre Ilbawi, Nathalie Broutet, Raymond Hutubessy

[link url="https://www.medicalnewstoday.com/articles/could-we-say-goodbye-to-cervical-cancer-by-2120#Call-for-international-commitment"]Full Medical News Today report[/link]

[link url="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30068-4/fulltext"]The Lancet abstract 1[/link]

[link url="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30157-4/fulltext"]The Lancet abstract 2[/link]

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