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Ed. Note: This post is part of Innovate4Health, a joint project of GMU’s Center for the Protection of Intellectual Property and the Information Technology and Innovation Foundation providing case studies on how IP-driven innovation is tackling some of the world’s toughest health issues.
Cervical cancer is a completely preventable disease, yet it remains the leading cause of cancer-related death and morbidity among women in the developing world, with approximately 85 percent of the disease burden occurring in low- and middle-income countries. To address this challenge, countries need to use testing as part of population-based screening for human papillomavirus (HPV), which is the principal cause of cervical cancer. Screening for HPV is particularly important in developing countries given the large numbers of people with HIV/AIDS, who are more susceptible to HPV due to their weakened immune systems. Previously, there were few HPV tests well suited to developing countries, but a new product—Xpert HPV—changes this by offering an accurate, real-time, self-contained, and easy to use molecular testing mechanism that can be used at the point-of-care.
Developing countries face a number of unique challenges in screening and testing for cervical cancer. Pap smear (cytology) screening has been successful in reducing the rates of cervical cancer in developed countries; however, logistical and resource requirements (such as trained personnel) make this difficult for developing countries. In contrast, “see-and-treat” screenings using visual tests are simple, affordable, and scalable to primary health care facilities in developing countries. However, this comes with the disadvantage of higher potential for false-positive results.
The World Health Organization recommends testing for high-risk HPV (hrHPV) infection be incorporated into cervical screening programs worldwide. Large-scale studies have shown the efficacy of molecular tests for hrHPV, leading to recommendations in Europe, Australia, the United States, and elsewhere to incorporate hrHPV DNA tests into population-based screening programs. Molecular cervical cancer screening—the detection of HPV DNA, RNA, or oncoproteins—has the potential to overcome the shortcomings of visual inspection. However, molecular testing was initially thought to be cost- and resource-prohibitive for developing countries, but newer tests such as Xpert HPV are cheaper, simpler, and more accessible for use at the point of care.
The Xpert HPV test is a rapid (around 60 minutes), fully automated, and easy-to-use test for hrHPV infections that is as accurate as laboratory-based testing. Xpert HPV was developed as molecular tests are more sensitive than existing detection methods for high-grade cervical intraepithelial neoplasia (a precancerous condition on the uterus). Xpert HPV uses disposable cartridges to hold the reagents, primers, and probes for the simultaneous detection of 14 hrHPVs, including HPV types 16, 18, and 45. Detecting HPV genotypes 16 and 18 is critical as they are associated with approximately 71 percent of all cases of cervical cancer, while HPV genotype 45 is associated with approximately 6 percent of additional cases of cervical cancer. Quick and accurate testing allows for same-day screening and treatment, which has advantages for patients and providers by reducing attrition of care (a particular problem with non-communicable diseases) and by reducing health care costs for patients and providers (given costs associated with multiple visits).
Xpert potentially makes screening and treatment more accessible as it has proven to be an effective point-of-care HPV DNA test, while using patient-provided specimens (as compared to clinician-provided). A 2016 study in Papua New Guinea (PNG) was the first to use a point-of-care hrHPV test for clinical cervical cancel screening in a high-burden, low-income country. The study showed that Xpert HPV worked well and that patient-collected specimens for the detection of hrHPV are comparable to clinician-collected specimens. Low-income countries may be able to use this feature (patient-provided samples and easy to use technology) to expand cervical screening, as a similar program that relies on clinician-collected samples will require substantially more resources. PNG is a good test for Xpert HPV: PNG has among the world’s highest estimated burdens of cervical cancer (incidence rates 6.3 times higher than those of Australia and New Zealand and a mortality rate that’s 13.5 times higher), with cervical cancer being the most common cancer among women in PNG.
Another study in Zambia—which has the world’s second highest annual cervical cancer incidence and mortality rate—showed that Xpert HPV matched or exceeded traditional visual identification methods. The study took place at the Cervical Cancer Prevention Program (CCPPZ) in Lusaka, Zambia and included 200 women. The results of this study supported existing research which showed that Xpert HPV performs well with women with HIV. Incorporating it into a clinic like the CCPPZ shows the potential for its broad impact as CCPPZ, since its inception in 2006, has played a major role in Zambia’s efforts to screen and treat people with HIV as part of the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) program.
Cepheid, which developed Xpert HPV, is a leading molecular diagnostics company based in the United States. The development of Xpert HPV is typical of the time, money, and effort needed to improve healthcare in developed and developing countries alike. In the early- to mid-2000s, Cepheid invested hundreds of millions to research and develop the foundational technology behind the GeneXpert system (which Xpert HPV is part of) and cartridges. This was in addition to supplementary funding provided through public-private partnerships with the National Institute of Allergy and Infectious Diseases and other organizations.
Cepheid has relied on intellectual property to secure patents for its GeneXpert platforms and cartridges and to protect its proprietary chemistry and manufacturing processes. It now holds an extensive patent portfolio. Cepheid is able to reap the rewards from its intellectual property portfolio and re-invest it in new technology that will be critical to improving healthcare in developing countries, such as the Xpert HPV.
Cepheid is ideally placed to help developing countries fight cervical cancer as it has the largest installed base of molecular detection systems (as compared to other HPV DNA tests) in developing countries. Cepheid’s GeneXpert platform is widely used for the diagnosis of tuberculosis and TB drug resistance in developing countries around the world. Cepheid could potentially integrate the Xpert HPV test as part of its Infinity system, which includes dozens of individual tests in a single automated system. In a 2013 presentation on Xpert HPV, Philip Castle, chairperson and CEO of the Global Coalition Against Cervical Cancer and executive director of the Global Cancer Initiative, highlighted this potential: "The excitement [around] this is [that] where there is TB, there are undoubtedly higher rates of cervical cancer….The fact that GeneXpert is placed in many of these high-burden, high-risk populations offers the opportunity to deliver cervical cancer prevention in these places … One can imagine almost a field kit at the smallest configuration [of the GeneXpert] … [as well as] high-throughput, centralized testing."
Cepheid also engages with developing countries as part of a specific program to help them use their products to improve healthcare services. In 2013, Cepheid sold 5,509 GeneXpert systems, with around 1,800 of these being in the company’s high-burden developing country program, where the company subsidizes the placement of thousands of GeneXpert systems and cartridges in various non-profit NGOs (mainly to test tuberculosis and TV drug resistance). Furthermore, Cepheid license its intellectual property with particular partners to minimize or in some cases eliminate royalty payments associated with its GeneXpert platforms in these developing countries. Intellectual property allows companies like Cepheid the flexibility and control to pursue a strategy of price and market entry differentiation depending on the individual market.
Xpert holds the potential to greatly improve the number of people being screened for HPV in developing countries. But again, as in previous Innovate for Health posts, the technology behind Xpert HPV (and the intellectual property embedded in it) is addressing only one part of the broader policy environment that affects healthcare outcomes in developing countries. Cervical cancer screening illustrates this, as despite numerous demonstration projects showing that simple and cost-effective methods for prevention (particularly visual inspection with acetic acid and immediate cryotherapy) are viable and effective, screening coverage rates remain very low in developing countries. This has been known for some time, yet rarely have such methods been adopted and scaled up by governments in developing countries. Xpert HPV offers a potentially better tool for improving screening in the future, but this highlights the underlying point that Xpert HPV’s impact will ultimately depend upon the broader healthcare system it is used in.