Cervical Cancer Resolution Overlooks Critical Treatment Disparities

WHO logo. Wikimedia Commons.

New Delhi, 4 February ( Chetali Rao and KM Gopakumar) –  The resolution on cervical cancer, which seeks to designate 17 November as the World Cervical Cancer Elimination Day, while reinforcing the global commitments and actionable steps of a 2020 World Health Assembly resolution, does little to address the inequities in the treatment.

The 156th meeting of the Executive Board of the World Health Organization (3 -11 February) is set to discuss the resolution focused on cervical cancer.

Resolution WHA73.2 adopted in 2020, established the Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem, aiming to reach and maintain an incidence rate of below 4 cases per 100,000 women in every country. This strategy sets clear targets for 2030, focussing on three key pillars i.e. vaccination: 90% of girls to be fully vaccinated; screening: 70% of women to be screened at 35 years and 45 years of age; and treatment: 90% of women diagnosed with cervical precancer or cancer to receive treatment or care.

Despite WHO’s strategic initiatives, the inclusion of cancers in UN Political Declaration on Universal Health Coverage  and its mention under the UNGA prevention and control of non-communicable diseases, the achievement of the third pillar of WHOs Global Strategy –  “90% of women diagnosed with cervical precancer or cancer to receive treatment” – remains a distant vision for many countries. This challenge is exacerbated by the limited affordability and accessibility of treatments, particularly advanced biologics, which have become the cornerstone of management and treatment of women affected by cervical cancer.

The Resolution’s operational paragraph (OP) 1(2) “Urges Member States …

To enable sufficient/ adequate resources to expand healthcare services for cervical cancer elimination efforts, in accordance with national priorities and contexts, and in the context of achieving universal health coverage; …”

Further, OP3 (1) “Recommends that stakeholders and or partners …

To enhance multilateral and international collaboration in the promotion of knowledge, safe, affordable and quality services, health care products and interventions for all to accelerate the elimination of cervical cancer as a public health problem in line with the achievement of UHC (universal health coverage), and other related regional commitments, taking into account any conflict of interests; …”

References in the current resolution to enabling resources to expand health services and promoting affordable health care products cannot be realized without prioritizing actionable strategies and commitments to ensure equitable access to treatments. With just five years remaining to meet the targets set in the Global Strategy, addressing inequities in treatment is paramount – as failure to do risks derailing the vision of eliminating cervical cancer as a public health problem.

The Global Burden of Cervical Cancer

The global burden of cervical cancer is a stark reflection of broader health disparities and represents a significant divide between developed and developing countries. In 2022, an estimated 660,000 new cases were detected and around 350,000 deaths were reported, of which 94% occurred in low- and middle-income countries (LMICs). The highest proportion of cervical cancer incidence and mortality were reported from sub-Saharan Africa, Central America and South-East Asia, where access to healthcare services is often limited or non-existent.

Progress in reduction and mortality of cervical cancer has predominantly been observed in high-income countries due to the high vaccination coverage, organized high quality population-based screening programs and availability of newer biologic therapies. Despite being preventable, the high mortality rate of cervical cancer in LMICs reflect the deep inequities that exist largely due to differences in the availability and uptake of Herpes Papilloma Virus (HPV) vaccination, the implementation of screening programs, and access to effective treatment. In these countries, trends are likely to continue increasing over the next decades unless significant improvement is done to scale-up preventive interventions, including screening and HPV vaccination coupled with increase access to treatment.

HPV Vaccination and Screening: Preventive Measures with Limited Reach in the Absence of Treatment

As a priority, WHO recommends HPV vaccines be administered to all girls aged 9-14 years, before they become sexually active. The introduction of vaccination programs has been pivotal in the prevention of cervical cancer as it has the potential to prevent more than 90% of cancers caused by HPV. There has been an extensive coverage of HPV vaccination in national immunization programs. By end of 2023, one hundred forty-three Member States had included HPV vaccine in their national immunization schedule and services.

However, evidence suggests that while HPV vaccination is crucial, it cannot solely achieve the elimination targets in countries with high incidence of cervical cancer. Specifically countries where incidence exceeds 25 cases per 100,000, cervical cancer cannot be eliminated with HPV vaccination alone, according to WHO’s proposed threshold of cervical cancer elimination (4 cases per 100,000 women). For example, in sub-Saharan Africa, the current approach will only eliminate cervical cancer in 27% of the countries.

Screening of pre-cancerous lesions is also a cost effective way to prevent cervical cancer. Successfully implemented screening strategies should focus on detecting early lesions before their progression to cancer. WHO recommends women aged 30 to 49 years to undergo screening through any of the three triage i.e. visual inspection with acetic acid in low-resource settings, pap tests every 3 to 5 years, or HPV testing every 5 years.

In countries like India, HPV testing has offered substantive protection against invasive cervical cancer than either visual inspection with acetic acid or cytology.  However, successful implementation of screening programs is severely lacking in LMICs. Lack of organized screening programs impedes the effectiveness of these programs. Furthermore lack of awareness and insufficient healthcare infrastructure make it difficult to establish and maintain organized screening programs.

Despite substantial evidence confirming the effectiveness of both these interventions, inequities in HPV vaccinations and screening uptake persist.

Treatment Access: The Challenge of High-Cost Biologics

Cervical cancer screening must be complemented with availability of treatment of detected lesions, as screening women without access to treatment is unethical. Over the last two decades, the advent of many groundbreaking therapies has transformed the treatment landscape for many cancers, including cervical cancer.

Biologics are advanced medicinal products created by biological processes rather than chemical synthesis. In the context of cervical cancer, innovative biologic treatments including immunotherapy drugs Pembrolizumab, Ceplimumab and antibody-drug conjugate like Tisotumab-vedotin have shown promising results in advanced cases, offering potential for prolonged survival and improved quality of life. These drugs are designed to target specific components of the cancer cells or the body’s immune system to fight the disease more effectively. Combination therapies like integrating chemotherapy with these advanced therapies have also emerged as an effective tool for managing the disease.

Despite the ability of these transformative therapies to revolutionise cervical cancer treatments and significantly improve patient outcomes, their introduction in developing countries has been very limited. Significant gaps exist between the health care spending in developed and developing countries. Steep price tags associated with these drugs makes them unaffordable to be absorbed in resource limited settings of developing countries, where resources are spent on competing needs like food, education and security. Hence, much of the drug costs are covered by out-of-pocket expenditures. Out-of-pocket expenditure accounts for 37%-50% of the total health expenditure in LMICs. Data suggests that patients in high income countries (HICs) can access drugs including high value and novel cancer medicines without incurring any out-of-pocket expenditure while in stark contrast for patients in LMICs, even access to drugs in WHO’s essential medicine list is limited, with out-of-pocket expenditure. 

For instance, the drug Pembrolizumab, despite its proven efficacy for patients with persistent, recurrent, or metastatic cervical cancer faces significant access challenges in developing countries. The table below lists the price per vial in US dollar of Pembrolizumab in a few countries:

The total course of treatment for the drug is prohibitive for patients relying on public health systems and worse for those who pay through out-of-pocket. According to World Bank statistics, per capita expenditure on health is $92 in LMICs compared with $5205 in HICs. Consequently, even though the prices of these medicines are less in developing countries as compared to developed countries, affordability remains a critical issue due to much lower per capita income.

Treatment access, particularly when it comes to high-cost biologics, is a significant challenge that underscores the inequality in global health. Women diagnosed with cervical cancer often face significant challenges in timely and appropriate treatments, resulting in higher mortality as compared to their developed country counterparts. Consequently, the disparity in mortality of women between developed and developing countries has widened over time.  Without timely access to effective treatments, this disparity is expected to worsen as cancer incidence is projected to increase much faster in LMICs, driven by demographic changes such as ageing population and increasing risk exposure associated with a growing economy.

Addressing Cost Challenges

To address the challenges of lack of affordable treatment, there is a pressing need to reduce the cost of these biological therapies and improve access. This includes using scientific evidence-based regulatory decision making to bring down the cost of these drugs. As patents on biologics expire it provides opportunities for generic versions of biologics known as “biosimilars” to be launched in the market. The availability of biosimilars in the market have ensured lower healthcare costs and increased accessibility for patients.

Research suggests that biosimilars have the potential to reduce spending on biologics and save between $38 and $124 billion from 2021 to 2025, thus exhibiting the potential to reduce health inequities particularly for patients in developing countries. Despite their potential to reduce the cost of treatment, biosimilars uptake has remained low in many regions. This mostly stems from lack of competition driven by high research and development costs, stringent regulatory barriers and questionable and predatory patent practices.

Strategies for Improving Access

A. Streamlining Regulatory Barriers

Bringing a biosimilar product to market is estimated to cost $100-300 million and clinical efficacy studies typically account for half of the research and development costs. The approval process for biosimilars is stringent, requiring extensive data to demonstrate comparability to existing treatments, which can add to the development costs. The growing body of scientific evidence against the role of comparative efficacy trials has been underway for a few years now, prompting global regulatory bodies like the United Kingdom’s Medicines and Healthcare products Regulatory Agency and WHO to revise their existing biosimilar guidelines.

Regulatory frameworks must prioritize the development of biosimilars based on scientific evidence to allow removal of unnecessary requirements like clinical efficacy studies rather than adhering strictly to traditional testing paradigms. By streamlining approval processes with focus on efficacy through rigorous analytical assessments and reducing unscientific barriers, regulatory bodies can facilitate quicker access to biosimilars that have demonstrated safety. Removing regulatory barriers will expedite the approval of affordable treatments for patients globally.

B. Addressing Abusive Patent Practices

Encouraging local production for vaccines and drugs can reduce costs and improve access. This requires technology transfer and capacity building in local manufacturing. In certain cases, countries can use flexibilities provided under the Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement and issue compulsory licenses to allow generic manufacturers to produce biosimilars without the consent of the patent holder. Additionally, enhancing patent examination guidelines is crucial for improving access to biologics, as it ensures that patents are only granted for clear, consistent criteria while considering public health implications.

The Ripple Effect of Cervical Cancer

The ripple effect of cervical cancer extends beyond the individual woman to the entire family unit and to communities. Women play a central role as caregivers and their cancer diagnosis perpetuates multifarious socioeconomic, cultural, health care based and psychological challenges. The loss of a woman to cervical cancer can lead to increased poverty and hardship for her dependents. It has been estimated that in resource-poor settings every 100 deaths of mothers due to cervical or breast cancer leads to the premature death of 14 to 30 children, thus underscoring the substantial social consequences of women cancers.

While significant emphasis is being placed on vaccination and screening to combat cervical cancer, it is crucial for countries to improve access to treatments to achieve reduction in cervical cancer mortality and ensure equitable access. While engaging in negotiations countries must be cognizant that vaccinations against HPV and screenings are vital preventive measures, but these efforts must be complimented with improvements in increasing access to treatments. Without equitable access to treatments,  the overall impact of these strategic initiatives remains very limited. – Third World Network