Cervical cancer represents a severe and persistent public health crisis in South Africa. It is the second most frequent cancer among women in the country and, alarmingly, the leading cause of cancer-related death. Each year, an estimated 10,702 women are diagnosed with the disease, and 5,870 die from it. This high mortality-to-incidence ratio is a stark indicator of profound, systemic challenges in the country's ability to perform early detection and provide timely access to effective treatment.

The burden of this preventable disease is not distributed evenly across the population. It falls disproportionately on Black women, who account for over 80% of new cases and deaths, reflecting deep-seated socioeconomic inequalities and disparities in healthcare access. The high death rate is not an inevitability but a direct consequence of a screening system struggling with low coverage, diagnostic limitations, and fractured patient referral pathways. This combination of factors means that too many cancers are discovered at a late stage, when treatment is less effective and more costly, directly contributing to the high mortality figures.

The failure of South Africa's current cervical cancer screening system is multi-faceted, stemming from limitations in technology, policy, and implementation. The national policy, last updated in 2017, is anchored in cytology (the Pap smear), a technology with well-documented limitations in both sensitivity (the ability to correctly identify disease) and specificity (the ability to correctly identify its absence).

Beyond the test's inherent limitations, the implementation of the screening program is weak. Despite the provision of free tests, national screening coverage remains critically low and has recently been in sharp decline. After a brief recovery from the COVID-19 pandemic, screening rates fell by over 40% in 2022, dropping to a coverage level of just 21.4%. The system is further crippled by widespread operational failures, including shortages of trained personnel and equipment, long turnaround times for cytology results, and dysfunctional referral pathways for women with abnormal results. These breakdowns lead to a significant number of women being lost to follow-up; in some districts, only half of the women diagnosed with a high-grade lesion receive a follow-up colposcopy within six months, representing a critical gap between diagnosis and care.

This outdated policy stands in stark contrast to the evolving scientific consensus. Leading expert bodies in South Africa, such as the South African Society of Gynaecologic Oncology (SASOG), now advocate for a fundamental shift away from cytology and toward primary HPV DNA testing as the standard of care. This growing disconnect between national policy and evidence-based best practice underscores the urgent need to modernize the South African approach and address the systemic inefficiencies that generate avoidable costs and patient harm.

South Africa's unique epidemiological context, defined by the world's largest HIV epidemic, acts as a powerful risk multiplier that severely complicates cervical cancer screening. With nearly 25% of women aged 15-49 living with HIV, this co-epidemic dramatically elevates the background risk within the population and places immense pressure on the healthcare system.

Women living with HIV (WLWH) face a six-fold increased risk of developing cervical cancer compared to their HIV-negative counterparts. They are more susceptible to persistent infection with high-risk strains of the Human Papillomavirus (HPV), experience more rapid disease progression, and are often diagnosed at a younger age.

This biological reality creates an "extreme overload" on the screening system. The prevalence of high-risk HPV and abnormal cytology is significantly higher in WLWH. Critically, the diagnostic specificity of primary screening tests is substantially lower in this population. For example, the specificity of an HPV DNA test can fall to as low as 42.7% in WLWH, compared to over 80% in HIV-negative women. This combination of high disease prevalence and poor test performance results in a massive influx of women into the diagnostic pipeline, overwhelming the scarce colposcopy and pathology resources and making a high-specificity triage tool not just beneficial, but essential for the program's viability.

The OncoE6™ Cervical Test is a novel, point-of-care triage technology designed to bring greater accuracy and efficiency to cervical cancer screening. Its primary function is not to replace initial screening, but to rationalize the next steps. After a woman receives a positive primary screen (from either a Pap smear or an HPV DNA test), the OncoE6™ test is used to determine if she is at genuine, immediate risk of her infection progressing to cancer and therefore truly requires an invasive and costly follow-up procedure like a colposcopy.

The test achieves this by directly detecting the E6 oncoprotein, a specific molecular marker that is expressed only during the active, cancer-causing phase of an infection with HPV type 16 or 18. These two HPV types are the primary oncogenic drivers, responsible for an estimated 64.2% of all invasive cervical cancers in South Africa. By identifying this precise molecular signal, the test provides a clear indication of genuine cancer risk, allowing healthcare providers to focus resources on the women who need them most.

The OncoE6™ test represents a fundamentally different approach to screening by answering a more clinically relevant question. The key differences are:

• HPV DNA Test: This test detects the mere presence of high-risk HPV DNA. While highly sensitive, it has low specificity, meaning it flags many women who have transient infections that their immune system will clear without causing any harm. It can identify that a risk factor is present, but not whether that risk is actively causing disease.
• Pap Smear (Cytology): This test involves a microscopic search for visual changes in the appearance of cervical cells. Its accuracy is highly variable and depends on the quality of the sample, the skill of the cytologist, and biological factors in the patient, such as postmenopausal atrophy, which can make interpretation difficult.
• OncoE6™ Test: This test looks for neither the virus itself nor visual cell changes. Instead, it detects the malignant activity of the virus by identifying the E6 oncoprotein. This protein is a direct molecular marker that the virus has hijacked the cell's machinery and is actively driving it toward a cancerous state. This provides a much more precise and immediate signal of genuine cancer risk, filtering out the noise of clinically insignificant infections.

The OncoE6™ pathway effectively functions as a "molecular colposcopy," representing a paradigm shift from subjective, skill-based diagnostics to objective, technology-based diagnostics.

A traditional colposcopy is a visual examination where a specialist physician uses a magnifying instrument to look for suspicious-looking areas on the cervix and then takes a small tissue sample (a punch biopsy). This method is inherently subjective and prone to sampling error; if the biopsy misses the small, specific area containing the most advanced pre-cancerous cells, the diagnosis can be dangerously inaccurate. This process requires significant training, expensive equipment, and specialist time, creating a major bottleneck in the healthcare system.

The OncoE6™ pathway replaces this subjective visual search with an objective molecular one. The process begins with a simple swab that collects cellular material from the entire surface of the cervix, ensuring a comprehensive and representative sample. The test then performs a highly specific molecular analysis to detect the E6 oncoprotein. This approach minimizes the risk of a missed diagnosis due to sampling error, a critical failure point in the current system, particularly for postmenopausal women where the pre-cancerous lesion may be hidden from view. This shift democratizes a key diagnostic step, reducing reliance on scarce specialist infrastructure and increasing the reliability and consistency of diagnoses across the healthcare system.

No. While the OncoE6™ test adds an intermediate, upfront cost for women who have a positive primary screen, the comprehensive health economic analysis conclusively demonstrates that the overall pathway is a dominant, cost-saving strategy compared to the current Standard of Care.

The savings are generated because the test acts as a powerful and effective gatekeeper to the most expensive and invasive parts of the care pathway. By leveraging its exceptional specificity to accurately filter out the large majority of women with harmless, transient HPV infections, the OncoE6™ test drastically reduces the number of unnecessary referrals for colposcopies, biopsies, and Loop Electrosurgical Excision Procedures (LEEPs). The model shows that the cost of these avoided downstream procedures far outweighs the initial cost of the triage test itself. This illustrates a core principle of modern health economics: a strategic upfront investment in a more precise diagnostic can yield disproportionately large downstream savings by ensuring that high-cost resources are allocated only to the patients who will truly benefit from them.

Yes. To ensure the economic findings were robust and not dependent on a single price, a scenario analysis was conducted using three different price points for the OncoE6™ test: R1,500, R2,000 (the base case), and R3,000. The analysis confirmed that the OncoE6™ pathway remains the dominant, cost-saving strategy across this entire price range.

The results of the analysis, detailed in the table below, provide a clear picture of the economic benefits. Even at the highest modeled price of R3,000—double the lowest tested price—the pathway still generates a substantial 10% reduction in total system costs. This robust cost-saving profile de-risks the adoption decision for health financiers and policymakers, providing significant flexibility in pricing negotiations and demonstrating the powerful economic efficiency gained by improving diagnostic precision at the triage stage.

Note: Figures are illustrative based on model outputs for a cohort of 100,000 women screened.

The OncoE6™ test addresses the first of two primary failures of the current screening system: the over-investigation and over-treatment of young women. The defining clinical challenge in women under 30 is the extremely high prevalence of HPV infection, with some South African studies showing rates as high as 81%. However, the vast majority of these infections are harmless and transient, meaning the immune system will clear them without intervention.

Current low-specificity tests, particularly HPV DNA tests, cannot distinguish these transient infections from the tiny fraction that will persist and progress toward cancer. This leads to a high rate of positive results that trigger a cascade of costly, anxiety-inducing, and often unnecessary interventions. The OncoE6™ test solves this problem directly. Its high specificity of 98% and its unique ability to detect only the E6 oncoprotein from actively transforming infections means it correctly identifies most women with harmless infections as low-risk. This prevents them from being funneled into the diagnostic pipeline for unnecessary colposcopies and LEEP procedures, saving both direct costs and patient harm.

The term "biological costs" refers to the significant downstream economic consequences of iatrogenic harm—that is, harm caused by medical treatment itself. This concept reframes the economic debate from a simple accounting of immediate procedural costs to a more holistic evaluation of total health system liability, including the cost of preventable harm.

The LEEP procedure, which is often performed unnecessarily on young women in the current system, is not a benign intervention. It is associated with a significantly increased risk of adverse pregnancy outcomes in the future, with a comprehensive meta-analysis finding that women with a prior LEEP have more than double the odds of preterm delivery. The health economic model translates this clinical risk into a tangible financial cost. It quantifies this "biological cost" by multiplying the number of avoidable LEEP procedures by the increased risk of preterm birth, and then by the South Africa-specific cost of managing a low birthweight infant requiring neonatal intensive care (R31,800 per event).

By preventing the vast majority of these unnecessary LEEPs (an illustrative 10,500 procedures saved per 100,000 women screened), the OncoE6™ pathway almost entirely eliminates this significant downstream expenditure. In the model, this amounts to avoiding R33.4 million in future preterm birth management costs alone. This demonstrates that the current system is not just wasteful in the present; it is actively creating future costs and human suffering that the health system must then pay to manage.

For women over 50, the OncoE6™ test addresses the second primary failure of the current system: the dangerous under-diagnosis of disease. This age cohort faces a diagnostic paradox: while their overall HPV prevalence is lower, their rates of cancer incidence and mortality are high, peaking between the ages of 50 and 59.

A key reason for this is the dramatic failure of cytology (the Pap smear) in postmenopausal women. Hormonal changes lead to cervical atrophy, which makes obtaining an adequate sample difficult and interpreting the cells challenging. As a result, the sensitivity of a Pap smear can plummet from 75% in non-atrophic cases to as low as 17%. This catastrophic diagnostic failure means that pre-cancerous lesions and early-stage cancers are frequently missed, only to be discovered years later when they present at an advanced, symptomatic, and often incurable stage.

The OncoE6™ test's value here is its ability to prevent this diagnostic failure. Its mechanism—detecting the E6 oncoprotein—is not compromised by cervical atrophy. Furthermore, its clinical performance is exceptionally strong for detecting high-grade lesions, showing 100% sensitivity for those caused by HPV 16/18. By accurately detecting these high-risk lesions that cytology misses, the pathway enables treatment at an earlier, more curable, and far less expensive stage. The economic value is therefore driven by averting the immense financial and human costs of late-stage cancer treatment (an estimated R176,207 per case), representing a life-saving and cost-averting intervention.

For the high-risk population of Women Living with HIV (WLWH), the OncoE6™ test is not just a cost-saving tool but a critical instrument for maintaining the operational viability of the entire screening program. The screening challenge in this cohort is one of "extreme overload," caused by a perfect storm of very high HPV prevalence (up to 74%), high rates of abnormal cytology (up to 55%), and the poor specificity of primary screening tests.

This combination creates a massive and unmanageable influx of women into the diagnostic pipeline, overwhelming the limited colposcopy and pathology resources available in the health system. A system under such strain is prone to collapse, leading to longer waiting times, increased patient loss-to-follow-up, and staff burnout.

The OncoE6™ test's primary value for this group is its ability to manage this overwhelming volume. By applying its high specificity, it acts as a powerful filter, reliably identifying the majority of screen-positive women who do not have actively transforming infections and thus do not need an immediate referral to a specialist. This drastically reduces the number of referrals for colposcopy and LEEP, alleviating the bottleneck on specialist services and enhancing the resilience of the health system itself. It allows finite resources to be focused on the WLWH who are at the highest, most immediate risk, ensuring that care can still be delivered effectively.

Based on the robust clinical and economic evidence, there are clear, actionable recommendations for the National Department of Health (NDoH). It is strongly recommended that the NDoH revises the 2017 National Cervical Cancer Prevention and Control Policy to align with current evidence and expert consensus.

The revised policy should formally adopt two key changes. First, it should designate primary HPV DNA testing as the standard primary screening modality, moving away from the limitations of cytology. Second, and crucially, it should integrate the OncoE6™ test as the standard, reflex triage test for all women who screen positive on their primary HPV test. This strategic policy shift would modernize the national program, maximize the efficiency of the health system by optimizing resource allocation, and ultimately lead to improved clinical outcomes for the women of South Africa.

A practical, phased national rollout of the OncoE6™ test is recommended, designed to address existing system weaknesses and maximize impact. The rollout should prioritize high-burden districts and facilities with limited access to specialist colposcopy services, where the need for an efficient triage tool is greatest.

A key advantage that facilitates this strategy is the test's simple, dipstick-like format, which requires minimal training and no complex laboratory equipment. This makes it ideal for deployment in primary healthcare settings. Empowering primary care nurses to perform this point-of-care triage can help overcome existing health system barriers, reduce the high rates of patient loss-to-follow-up between screening and diagnosis, and ensure that only the highest-risk women are referred to the next, more resource-intensive level of care. This approach strengthens the primary healthcare system and improves access for women in underserved and rural communities.

The adoption of the OncoE6™ test should be viewed not simply as a cost-containment measure, but as a critical strategic investment in South Africa's public health future and its ability to meet global targets. The World Health Organization has issued a global call to action to eliminate cervical cancer by 2030, setting ambitious targets of 90% HPV vaccination coverage, 70% screening coverage with a high-performance test, and 90% treatment coverage for pre-cancerous and cancerous lesions.

Currently, South Africa struggles to meet these targets, particularly for screening and treatment, due to a strained and inefficient system. By making the screening pathway more accurate, efficient, and cost-effective, the integration of the OncoE6™ test can free up vital financial and human resources. These liberated resources can then be reinvested to expand screening coverage to underserved populations, strengthen referral and follow-up systems, and improve access to timely treatment. In this way, the OncoE6™ test can serve as a powerful catalyst, helping to transform the WHO's 2030 elimination goals from a distant aspiration into an achievable reality for the women of South Africa.