In the global fight to prevent and cure cancer, there are few cancers that inspire more hope of eradication than cervical cancer. It has a well understood and vaccine-preventable aetiology, screening tests with proven success, and numerous treatment options if detected early. Indeed, in a landmark commitment in November 2020, 194 countries agreed to adopt the World Health Organisation (WHO)’s Global Strategy to Accelerate the Elimination of Cervical Cancer, the first global commitment to eliminate a cancer, with targets to achieve the following by 2030[1]: 

• 90% of girls fully vaccinated with the HPV vaccine by 15 years of age
• 70% of women screened using a high-performance test by age 35 and again by 45
• 90% of women identified with cervical disease receive treatment

It is anticipated that achieving these targets could result in a reduction of more than 40% of new cases of cervical cancer and 5 million related deaths by 2050.

However, it is crucial to examine the significant disparity in feasibility of these targets between countries with different disease prevalence and resource availability, particularly in the face of the COVID-19 pandemic.

Global HPV and cervical cancer burden and prevention initiatives

Cervical cancer is a well understood disease, with 99% of cases attributable to human papillomavirus (HPV) infection. HPV is the most common anogenital sexually transmitted infection globally, peaking in prevalence within the first decade of sexual debut.[2] It affects 10% of women worldwide and the rates are highest in Africa, where 22% of females have evidence of HPV infection. This already uneven distribution of infection is amplified in the rates of cervical cancer; in 2018, 85% of disease burden and almost 90% of deaths occurred in low- and middle-income countries (LMICs) [3], with all but one of the top 20 countries with the highest burden of cervical cancer being in Africa.[4] This uneven global distribution of morbidity and mortality can be linked to disparities at all three levels of the disease prevention model (figure 1). 

Starting with primary prevention, the prevention of initial HPV infection, vaccines against HPV have existed since 2006 and now protect against 90% of cancer-causing strains of the virus.[3] Between 2006 and 2017, vaccination programmes were commenced in 65% of countries (Australia being first in the world), and over 100 million adolescent girls received a dose of the vaccine.5 However, 95% of these doses were administered in high-income countries (HICs), with LMICs facing obstacles such as the cost of vaccines, and a lack of governmental and/or local commitment to instituting such programmes.[6] There have been some success stories among LMICs, for example, Rwanda was the first to implement a free national HPV vaccine programme in 2011.[3,7] This initiative resulted from a deal with a large pharmaceutical company to supply free vaccines, and required significant local efforts to bring the programme to schools and educate people about its importance. 

Moving to secondary prevention, the detection and treatment of early disease, numerous countries have successfully introduced cervical cancer screening programmes. Australia’s has been in place since 1991, and since 2017 has used highly sensitive DNA screening. Such programmes are crucial; when pre-cancerous lesions or early-stage cervical cancer are detected, cure rates are over 90%.[5] Sadly, as with vaccination programmes, many LMICs have faced obstacles to instituting screening programmes, leading to women having significantly more progressed disease at the time of presentation. These obstacles include lack of funding, lack of community awareness, cultural beliefs, and stigma around screening, particularly for unmarried women.[6] There are some nations such as Nigeria and Guinea that have had some success instituting programmes in partnership with the WHO or non-profit organisations[4], but even when such funds are available nations consistently face further barriers to screening remote communities.[6]

Finally, in terms of tertiary prevention, the treatment of established disease, there are numerous effective treatments for cervical cancer, particularly if caught early. However, these treatments are far more costly than primary or secondary prevention, thus accessing them in LMICs can be even more difficult. In 2019, only 30% of LICs reported having the required diagnostic and treatment infrastructure for early cervical cancer available in the public health system[5], and radiotherapy, a key component of treatment, is entirely unavailable in over 80% of LICs and over 50% of MICs.[8] Further, treatment can be complicated in LMICs by higher rates of comorbidities, and particularly by the prevalence of cervical cancer associated with HIV infection.[6] 

Clearly there are significant disparities between nations in the obstacles faced to eradicate cervical cancer, and in the context of the COVID-19 pandemic, these challenges have only grown. 
 
The Effects of COVID-19

COVID-19 has derailed efforts to eradicate cervical cancer globally by disrupting funding, access to vaccines and screening programmes, and availability of supplies.[1] HPV vaccination is typically performed at schools but globally in 2020, 1.6 million girls missed out on HPV vaccinations compared to 2019 due to school closures.[9] In the USA the HPV vaccination rate in April 2020 was 25% of the rate in 2019[10], and in Kenya over 400,000 girls missed out on their vaccine.[3] Rates of women presenting for HPV screening or receiving treatment for established disease have also fallen due to people increasingly staying at home, and health resources being reallocated in the face of the pandemic.[11]

While there are examples of disruption to cervical cancer prevention in all nations, there are disparities in how significantly they have affected LMICs compared to HICs, and in how easy it will be to bounce back from these setbacks. Many HICs are beginning to see a return to life as normal, and have taken measures to stay on track to eradicate cervical cancer;  as of 2021 Australia still sits poised to be first nation in the world to eliminate cervical cancer as a public health issue, as soon as 2028.[12] Meanwhile, <1% of the African population are fully vaccinated against COVID-19 amidst the Delta variant taking hold.[13] This means that the obstacles to cervical cancer prevention described above will be exacerbated further as these nations’ already stretched health budgets are consumed by the pandemic. 
 
Looking Forward

Pre-pandemic, LMICs were able to make gains towards eradicating cervical cancer when they did so through global partnerships and significant commitments at the levels of international bodies, pharmaceutical companies, governments, and local initiatives. These must continue in the face of the pandemic if there is any hope of achieving the targets in WHO’s Global Strategy to Accelerate the Elimination of Cervical Cancer. Adaptations will likely be required, for example, single doses of HPV vaccines being distributed when supply is low as these achieve sufficient efficacy [14]. 

Additionally, it has been suggested that the recommencement of screening programs be delayed by 6-12 months to avoid some individuals missing an entire cycle of screening, as this has harmful outcomes.[11] It is also hoped that advancements in public health messaging and infrastructure made during the COVID-19 pandemic could be utilised in increasing awareness and initiation of HPV vaccination and screening programmes in the future.[8] With a global approach and an understanding of public health prevention measures, there remains hope that cervical cancer could become a thing of the past.

By Rosie Kirk
 
References

1.     World Health Organisation. A cervical cancer-free future: First-ever global commitment to eliminate a cancer [Internet]. 2020 Nov. 17. Available from https://www.who.int/news/item/17-11-2020-a-cervical-cancer-free-future-first-ever-global-commitment-to-eliminate-a-cancer
2.     Palefsky JM, Hirsch MS, Bloom A. Human papillomavirus infections: Epidemiology and disease associations [Internet]. UpToDate. 2021. Available from https://www.uptodate.com/contents/human-papillomavirus-infections-epidemiology-and-disease-associations
3.     Shinkafi-Bagudu Z. Global Partnerships for HPV Vaccine Must Look Beyond National Income. JCO Glob Oncol. 2020;6
4.     World Health Organisation. Building a future free of cervical cancer in Africa [Internet]. 2021 Jun. 10. Available from https://www.who.int/news-room/feature-stories/detail/building-a-future-free-of-cervical-cancer-in-africa
5.     Simelela PN. WHO global strategy to eliminate cervical cancer as a public health problem: An opportunity to make it a disease of the past. Int J Gynecol Obstet. 2020;152(1):1-3
6.     Hull R, Mbele M, Makhafola T, Hicks C, Wang SM, Reis RM, Mehrota R, Mkhize-Kwitshana Z, Kibiki G, Bates DO, Dlamini Z. Cervical cancer in low and middle-income countries. Oncol Let. 2020;20(3):2058-74
7.     Bishumba N. Rwanda: Covid-19 – Pandemic Halts HPV Vaccination in Kigali [Internet]. All Africa. 2021. Available from https://allafrica.com/stories/202102180144.html
8.     Ginsburg O, Basu P, Kapambwe S, Canfell K. Eliminating cervical cancer in the COVID-19 era. Nat Cancer. 2021;2(2):133-4
9.     World Health Organisation. COVID-19 pandemic leads to major backsliding on childhood vaccinations, new WHO, UNICEF data shows [Internet]. 2021 Jul. 15. Available from https://www.who.int/news/item/15-07-2021-covid-19-pandemic-leads-to-major-backsliding-on-childhood-vaccinations-new-who-unicef-data-shows
10.  Daniels V, Xaxena K, Roberts C, Kothari S, Corman S, Yao L, Niccolai L. Impact of reduced human papillomavirus vaccination coverage rates due to COVID-19 in the United States: A model based analysis. Vaccine. 2021;39(20):2731-5
11.  Castanon A, Rebolj M, Pesola F, Sasieni P. Recovery strategies following COVID-19 disruption to cervical cancer screening and their impact on excess diagnoses. Br J Cancer. 2021;124(8):1361-5
12.  NHMRC Centre of Research Excellence in Cervical Cancer Control. 2021 Cervical Cancer Elimination Progress Report: Australia’s progress towards the elimination of cervical cancer as a public health problem. Melbourne; 2021 Mar. 26. Available from https://www.cervicalcancercontrol.org.au
13.  The Lancet. COVID-19 in Africa: a lesson in solidarity. Lancet. 2021;389(10296):185
14.  Center for Vaccine Innovation and Access. Single-Dose HPV Vaccine Evaluation Consortium [Internet]. Path. 2021. Available from https://www.path.org/programs/center-for-vaccine-innovation-and-access/single-dose-hpv-vaccine-evaluation-consortium/