In the JournalsPerspective

Cervical cancer elimination ‘could be achieved’ by 2120

High HPV vaccination coverage for girls and scaled-up screening and treatment may lead to the elimination of cervical cancer in most lower-middle-income countries over the next 100 years, according to results of two modeling studies published in The Lancet.

The models projected that more than 74 million cervical cancer cases and 60 million deaths could be averted, researchers noted.

“For the first time, we’ve estimated how many new cases of cervical cancer could be averted if WHO’s triple intervention strategy is rolled out and when elimination could be achieved,” Marc Brisson, PhD, associate professor at Laval University in Canada, said in a press release. “Our results suggest that to eliminate cervical cancer by the end of the century it will be necessary to achieve both high HPV vaccination coverage and high uptake of screening, especially in countries with the highest rates of the disease.”

The WHO strategy, developed after the organization issued a global call in 2018 to eliminate cervical cancer as a public health problem, included coverage targets of 90% for HPV vaccination, 70% for twice-lifetime cervical screening, and 90% for treatment of pre-invasive lesions and invasive cancer.

Vaccine, screening impact

In the first study, Brisson and colleagues modeled progress that could be made toward eliminating new cases of cervical cancer by introducing or increasing HPV vaccination coverage or by combining high levels of vaccination with screening for cervical cancer in low-income and lower-middle-income countries. The researchers also sought to estimate the number of cervical cancer cases averted while working toward elimination.

The WHO Cervical Cancer Elimination Modelling Consortium, consisting of three independent transmission-dynamic models according to WHO predefined criteria, estimated decreases in cervical cancer over the next century in 78 lower-middle-income countries under three different scenarios: girls-only vaccination; girls-only vaccination with one screening per lifetime; and girls-only vaccination with two screenings per lifetime.

Vaccination for girls would occur at age 9 years, with a catch-up to age 14 years. The model then assumed 90% coverage and 100% lifetime protection against HPV types 16, 18, 31, 33, 45, 52 and 58.

Cervical screening included HPV testing once or twice during the woman’s lifetime, at ages 35 years and 45 years, with uptake rising from 45% in 2023 to 90% starting in 2045.

Results showed that girls-only HPV vaccination would reduce the median-age standardized cervical cancer incidence in lower-middle-income countries from 19.8 (range, 19.4-19.8) cases to 2.1 (range, 2-2.6) cases per 100,000 women-years over the next century, representing a decrease of 89.4% (range, 86.2-90.1) and 61 million (range, 60.5-63) cases averted.

Adding two lifetime screenings reduced cervical cancer incidence to 0.7 (0.6-1.6) cases per 100,000 women-years, representing a 96.7% (range, 91.3-96.7) reduction and an additional 12.1 million (range, 9.5-13.7) cases averted.

The model also predicts that girls-only vaccination will result in elimination of cervical cancer in 60% (range, 58-65) of lower-middle-income countries based on a threshold of four or fewer cases per 100,000 women-years; in 99% (range, 89-100) of these countries based on the threshold of 10 or fewer cases per 100,000 women-years; and in 87% (range, 37-99) of these countries based on the 85% or greater reduction threshold.

Vaccination plus twice-lifetime screening led to 100% (range, 71-100) elimination in lower-middle-income countries for each of the thresholds.

Cervical cancer elimination could occur between 2059 and 2102 with girls-only vaccination in regions where all countries can achieve elimination. This would be accelerated by 11 to 31 years with twice-lifetime screening, according to the study.

Incorporating treatment

The second study modeled the impact of vaccination, screening and treatment on reducing deaths.

“One of our main findings is that although achieving cervical cancer elimination per se will take many decades, the benefits of scaling up to the WHO elimination coverage targets will start to be realized within a decade,” Karen Canfell, DPhil, chair of Cancer Council Australia's Cancer Screening and Immunization Committee, and colleagues wrote. “Key to this insight is an understanding of the timing of the effects of each intervention.”

Canfell and colleagues estimated reductions in cervical cancer mortality in 78 low-income and lower-middle-income countries under three different scenarios: girls-only vaccination at age 9 years with catch-up through age 14 years; girls-only vaccination with one screening per lifetime plus cancer treatment scale-up; and girls-only vaccination with two screenings per lifetime plus cancer treatment scale-up.

The model assumed lifetime protection against the same HPV types as the first model and 90% coverage in 2020. Cervical screening would be scaled up to 45% coverage by 2023, 70% coverage by 2030 and 90% coverage by 2045.

Researchers also assumed that 50% of women with invasive surgical cancer would undergo appropriate surgery, radiotherapy and chemotherapy by 2023, with an increase to 90% by 2030.

Results showed an estimated cervical cancer mortality rate across all 78 countries of 13.2 (range, 12.9-14.1) per 100,000 women in 2020.

By 2030, vaccination alone would lead to a 0.1% (0.1-0.5) reduction in cervical cancer compared with the status quo. However, adding two screenings and the appropriate cancer treatment would reduce mortality by 34.2% (range, 23.3-37.8), or 300,000 deaths, by 2030. Researchers observed similar results with one screening per lifetime.

By 2070, scaling up vaccination alone would lower mortality by 61.7% (range, 61.4-66.1), which equates to 4.8 million (range, 4.1-4.8) deaths averted. Adding one screening and scaling up cancer treatment would reduce mortality by 88.9% (84-89.3), with 13.3 million (range, 13.1-13.6) deaths averted. Adding two screenings plus scaled-up treatment would reduce mortality by 92.3% (range, 88.4-93), with 14.6 million (14.1-14.6) deaths averted.

By 2120, vaccination alone would reduce mortality by 89.5% (86.6-89.9), with 45.8 million (44.7-46.4) deaths averted; one screening and scaled-up treatment would reduce mortality by 97.9% (range, 95-98), with 60.8 million (60.2-61.2) deaths averted; and two screenings and scaled-up treatment would reduce mortality by 98.6% (96.5-98.6), with 62.6 million (range, 62.1-62.8) deaths averted.

Based on the WHO triple-intervention strategy, about half (48%) of deaths averted over the next 10 years would be in sub-Saharan Africa, whereas nearly a third (32%) would be in South Asia. Over the next 100 years, almost 90% of deaths averted would be from these regions. The strategy also would reduce rates of premature death (ages 30-69 years) by 33.9% (range, 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 emphasize the importance of acting now on three fronts to scale up HPV vaccination, screening and treatment for cervical cancer,” Canfell and colleagues wrote. “The findings [also] have informed the draft of the WHO global strategy for cervical cancer elimination, which will be presented to the WHO Executive Board in [this month] and thereafter considered at the World Health Assembly in May 2020.”

“If this 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,” Brisson said in the press release. – by John DeRosier

Disclosures: Brisson reports grants from WHO. Canfell reports grants from National Health and Medical Research Council Australia. Please see the studies for all other authors’ relevant financial disclosures.

High HPV vaccination coverage for girls and scaled-up screening and treatment may lead to the elimination of cervical cancer in most lower-middle-income countries over the next 100 years, according to results of two modeling studies published in The Lancet.

The models projected that more than 74 million cervical cancer cases and 60 million deaths could be averted, researchers noted.

“For the first time, we’ve estimated how many new cases of cervical cancer could be averted if WHO’s triple intervention strategy is rolled out and when elimination could be achieved,” Marc Brisson, PhD, associate professor at Laval University in Canada, said in a press release. “Our results suggest that to eliminate cervical cancer by the end of the century it will be necessary to achieve both high HPV vaccination coverage and high uptake of screening, especially in countries with the highest rates of the disease.”

The WHO strategy, developed after the organization issued a global call in 2018 to eliminate cervical cancer as a public health problem, included coverage targets of 90% for HPV vaccination, 70% for twice-lifetime cervical screening, and 90% for treatment of pre-invasive lesions and invasive cancer.

Vaccine, screening impact

In the first study, Brisson and colleagues modeled progress that could be made toward eliminating new cases of cervical cancer by introducing or increasing HPV vaccination coverage or by combining high levels of vaccination with screening for cervical cancer in low-income and lower-middle-income countries. The researchers also sought to estimate the number of cervical cancer cases averted while working toward elimination.

The WHO Cervical Cancer Elimination Modelling Consortium, consisting of three independent transmission-dynamic models according to WHO predefined criteria, estimated decreases in cervical cancer over the next century in 78 lower-middle-income countries under three different scenarios: girls-only vaccination; girls-only vaccination with one screening per lifetime; and girls-only vaccination with two screenings per lifetime.

Vaccination for girls would occur at age 9 years, with a catch-up to age 14 years. The model then assumed 90% coverage and 100% lifetime protection against HPV types 16, 18, 31, 33, 45, 52 and 58.

Cervical screening included HPV testing once or twice during the woman’s lifetime, at ages 35 years and 45 years, with uptake rising from 45% in 2023 to 90% starting in 2045.

Results showed that girls-only HPV vaccination would reduce the median-age standardized cervical cancer incidence in lower-middle-income countries from 19.8 (range, 19.4-19.8) cases to 2.1 (range, 2-2.6) cases per 100,000 women-years over the next century, representing a decrease of 89.4% (range, 86.2-90.1) and 61 million (range, 60.5-63) cases averted.

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Adding two lifetime screenings reduced cervical cancer incidence to 0.7 (0.6-1.6) cases per 100,000 women-years, representing a 96.7% (range, 91.3-96.7) reduction and an additional 12.1 million (range, 9.5-13.7) cases averted.

The model also predicts that girls-only vaccination will result in elimination of cervical cancer in 60% (range, 58-65) of lower-middle-income countries based on a threshold of four or fewer cases per 100,000 women-years; in 99% (range, 89-100) of these countries based on the threshold of 10 or fewer cases per 100,000 women-years; and in 87% (range, 37-99) of these countries based on the 85% or greater reduction threshold.

Vaccination plus twice-lifetime screening led to 100% (range, 71-100) elimination in lower-middle-income countries for each of the thresholds.

Cervical cancer elimination could occur between 2059 and 2102 with girls-only vaccination in regions where all countries can achieve elimination. This would be accelerated by 11 to 31 years with twice-lifetime screening, according to the study.

Incorporating treatment

The second study modeled the impact of vaccination, screening and treatment on reducing deaths.

“One of our main findings is that although achieving cervical cancer elimination per se will take many decades, the benefits of scaling up to the WHO elimination coverage targets will start to be realized within a decade,” Karen Canfell, DPhil, chair of Cancer Council Australia's Cancer Screening and Immunization Committee, and colleagues wrote. “Key to this insight is an understanding of the timing of the effects of each intervention.”

Canfell and colleagues estimated reductions in cervical cancer mortality in 78 low-income and lower-middle-income countries under three different scenarios: girls-only vaccination at age 9 years with catch-up through age 14 years; girls-only vaccination with one screening per lifetime plus cancer treatment scale-up; and girls-only vaccination with two screenings per lifetime plus cancer treatment scale-up.

The model assumed lifetime protection against the same HPV types as the first model and 90% coverage in 2020. Cervical screening would be scaled up to 45% coverage by 2023, 70% coverage by 2030 and 90% coverage by 2045.

Researchers also assumed that 50% of women with invasive surgical cancer would undergo appropriate surgery, radiotherapy and chemotherapy by 2023, with an increase to 90% by 2030.

Results showed an estimated cervical cancer mortality rate across all 78 countries of 13.2 (range, 12.9-14.1) per 100,000 women in 2020.

By 2030, vaccination alone would lead to a 0.1% (0.1-0.5) reduction in cervical cancer compared with the status quo. However, adding two screenings and the appropriate cancer treatment would reduce mortality by 34.2% (range, 23.3-37.8), or 300,000 deaths, by 2030. Researchers observed similar results with one screening per lifetime.

PAGE BREAK

By 2070, scaling up vaccination alone would lower mortality by 61.7% (range, 61.4-66.1), which equates to 4.8 million (range, 4.1-4.8) deaths averted. Adding one screening and scaling up cancer treatment would reduce mortality by 88.9% (84-89.3), with 13.3 million (range, 13.1-13.6) deaths averted. Adding two screenings plus scaled-up treatment would reduce mortality by 92.3% (range, 88.4-93), with 14.6 million (14.1-14.6) deaths averted.

By 2120, vaccination alone would reduce mortality by 89.5% (86.6-89.9), with 45.8 million (44.7-46.4) deaths averted; one screening and scaled-up treatment would reduce mortality by 97.9% (range, 95-98), with 60.8 million (60.2-61.2) deaths averted; and two screenings and scaled-up treatment would reduce mortality by 98.6% (96.5-98.6), with 62.6 million (range, 62.1-62.8) deaths averted.

Based on the WHO triple-intervention strategy, about half (48%) of deaths averted over the next 10 years would be in sub-Saharan Africa, whereas nearly a third (32%) would be in South Asia. Over the next 100 years, almost 90% of deaths averted would be from these regions. The strategy also would reduce rates of premature death (ages 30-69 years) by 33.9% (range, 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 emphasize the importance of acting now on three fronts to scale up HPV vaccination, screening and treatment for cervical cancer,” Canfell and colleagues wrote. “The findings [also] have informed the draft of the WHO global strategy for cervical cancer elimination, which will be presented to the WHO Executive Board in [this month] and thereafter considered at the World Health Assembly in May 2020.”

“If this 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,” Brisson said in the press release. – by John DeRosier

Disclosures: Brisson reports grants from WHO. Canfell reports grants from National Health and Medical Research Council Australia. Please see the studies for all other authors’ relevant financial disclosures.

    Perspective
    R. Wendel Naumann

    R. Wendel Naumann

    Cervical cancer was the leading cause of cancer-related mortality for women prior to the development of effective screening and treatment for preinvasive disease. Unfortunately, cervical cancer still ranks as the fourth most common cancer and cause of cancer mortality worldwide. 

    However, this statistic alone does not tell the entire story. Cervical cancer typically occurs in young women, often with children. Because of the age at which women develop cervical cancer, death of this disease results in significantly more years of life lost per case than any other common cancer. This is tragic given that there is effective cervical cancer screening and even prevention by vaccination.

    Approximately 15% of cancers are caused by viral infections. HPV is one of the leading causes of virally induced cancers and is responsible for virtually all cervical cancers, as well as a significant proportion of vaginal, vulvar, rectal, and head and neck cancers. We now have a highly effective vaccine that will prevent approximately 90% of the types of HPV responsible for cervical cancer. For those types not prevented by the vaccine, screening with cytology or HPV will eliminate most cases.

    Cervical cancer remains a major worldwide public health crisis in low- and middle-income countries. Although high-income countries have significantly reduced rates of cervical cancer through screening and vaccination, low- and middle-income countries still have disproportionally high incidence of and mortality from this disease.

    The numbers are staggering. Although global incidence of cervical cancer is 15 per 100,000 women, incidence in sub-Saharan Africa is almost twice as high, at 25 per 100,000 women. There are approximately 570,000 new cases of cervical cancer and over 300,000 deaths globally each year from this preventable disease. If we maintain the status quo, it is projected that there will be over 93 million cases and 60 million deaths of cervical cancer in the next 100 years.

    Given the disproportionate burden of cervical cancer in low- and middle-income countries, it is important to optimize the available resources, and WHO has developed a roadmap for the most efficacious path forward. The WHO 90-70-90 plan calls for vaccination of 90% of women, screening of 70% of women twice in their lifetime and adequate cancer care for 90% of women who develop cervical cancer.

    Modeling studies — which are important to determine the efficacy of this strategy — suggest that vaccination alone will eliminate a significant proportion of cervical cancer, but adding twice-lifetime screening at age 35 and 45 years is important in rapidly reducing cervical cancer incidence and mortality.

    The WHO plan is ambitious but achievable. Low- and middle-income countries have achieved vaccination rates greater than 90% for poliomyelitis and measles. High rates of vaccination also have been seen for HPV. For instance, the HPV vaccination campaign in Rwanda led by Agnes Binagwaho, MD, M(Ped), PhD, resulted in a vaccination rate of 97%. Low-cost and effective screening can be organized, as well. HPV detection can be self-collected and mass screening can be centralized at a very low cost.

    If the 90-70-90 plan is implemented successfully, it is projected that the incidence of cervical cancer will be reduced from 15 per 100,000 women to less than 1 per 100,000, with cervical cancer morality reduced to 0.2 per 100,000 in the next 100 years.

    The benefits of this program are astounding. Models project that successful implementation of the 90-70-90 strategy will result in the prevention of 74 million cases of cervical cancer and 60 million deaths in the next 100 years. Thus, there is no doubt that this is an important endeavor. Now that we have a roadmap going forward, it is important that we align resources to achieve this goal.

    References:

    Binagwaho A, et al. Bull World Health Organ. 2013;doi:10.2471/BLT.12.116087.

    Bray F, et al. CA Cancer J Clin. 2018;doi: 10.3322/caac.21492.

    Gultekin M, et al. Papillomavirus Res. 2019;doi:10.1016/j.pvr.2019.03.002.

    Plummer M, et al. Lancet Glob Health. 2016 Sep;4(9):e609-16. doi: 10.1016/S2214-109X(16)30143-7.

    Ries LA, et al. SEER Cancer Statistics Review, 1975-2002. NCI. Available at: seer.cancer.gov/csr/1975_2002/. Accessed Feb. 18, 2020.

    Senkomago V, et al. MMWR Morb Mortal Wkly Rep. 2019;doi:10.15585/mmwr.mm6833a3.

    Siegel RL, et al. CA Cancer J Clin. 2019;doi:10.3322/caac.21551.

    Tsu VD. Lancet. 2020;doi:10.1016/S0140-6736(20)30219-1.

    • R. Wendel Naumann, MD
    • Levine Cancer Institute at Atrium Health

    Disclosures: Naumann reports consultant roles with GlaxoSmithKline and Merck, and research funding from Bristol-Myers Squibb, GlaxoSmithKline and Merck.