Expert Addresses Global Cervical Cancer Disparity

Ophira Ginsburg, MD

Of the more than 250,000 women who died of cervical cancer across the globe in 2017, 90% of them lived in low- or middle-income countries, according to Ophira Ginsburg, MD. She added that the tools to address this disparity in cancer care exist, but more work needs to be done to eliminate this preventable malignancy.

While the World Health Organization (WHO) has parameters in place for screening women for cervical cancer, Ginsburg said that it will require a collaborative effort from civil society organizations, academia, and medical societies to address the burden of cervical cancer mortality in low- and middle-income countries. Alleviating this obstacle means improving the health system for cancer care more broadly, including introducing technology, infrastructure, and resources used in high-income countries that are appropriate for the resource level of a given low-income country.

OncLive: What is the current state of cervical cancer prevention, globally?

In an interview with OncLive, Ginsburg, director of the High Risk/Cancer Genetics Program at NYU Langone's Perlmutter Cancer Center, discussed cervical cancer prevention, screening, and elimination on a global scale.Ginsburg: Cervical cancer has been largely addressed in many high-income countries that have had upwards of 40 years of experience of population-based screening programs with cytology, Pap tests, and appropriate access to treatment for precancer. In low- and middle-income countries—what some call developing countries—we are still seeing a tremendous number of women dying unnecessarily of this very preventable disease. Over 250,000 women died last year of cervical cancer, and 9 in 10 of those women were living in a low- or middle-income country. It is the epitome of cancer disparity.

We have the tools, and we know how to prevent and cure cervical cancer in all settings now. The good news is that we know what to do; the question is, “How do we get there?” When I was working at WHO prior to NYU Langone’s Perlmutter Cancer Center, one of my tasks was to work with other agencies involved in a joint program for cervical cancer control. Together, along with civil society organizations, academia, medical societies, and others, we are trying to help countries address this burden by finding pragmatic, tailored solutions that are appropriate for their resource level and would fit within their health system.

One of the opportunities in tackling cervical cancer prevention and control in low- and middle-income countries is that it can actually help to do a few other things that are not necessarily obvious. First is to improve the health system for cancer control more broadly. You have to bring to the mix the importance of radiotherapy, brachytherapy, and other therapies for invasive cervical cancer—these technologies, resources, infrastructure, and training are really important to address the cancer burden more broadly. Cervical cancer is what many in global health call the "low-hanging fruit" of cancer control because we have all of these tools, including cost-effectiveness data and WHO recommendations that are very clear to help advise countries. We can demonstrate what can be done in cancer more broadly in the poorer countries of the world.

Until now, many countries were reluctant, and quite understandably resistant, to allocating any resources toward cancer. This is because it is usually thought of as an expensive disease to treat, impossible to prevent, and requiring of major vertical investments in infrastructure. If you think about how long it takes to train a medical oncologist and how expensive it is to purchase a linear accelerator or a brachytherapy unit, you can see why countries might be put off by that. With cervical cancer control, so much can be done upfront through primary prevention through vaccination. Treatment of precancer by more pragmatic, less expensive, and more effective strategies, such as visual inspection with acidic acid (VIA) are opportunities to prevent and treat cervical cancer without an oncologist even being involved.

You mentioned the importance of vaccination in prevention. Can you expand on that?

Can you discuss VIA in more depth?

This is a great opportunity for us now. The time is right and there is political will at the highest level, including the new director general of WHO and the former UN Secretary General Ban Ki-moon, who called for the elimination of cervical cancer as a public health concern on World Cancer Day in 2016. This is a task that we believe in and we feel can be addressed—it is just going to take a lot of partnerships.Ten years after the introduction of the quadrivalent and bivalent HPV vaccines that target HPV subtypes 16 and 18—which accounts for about 70% of the cervical cancer burden in most countries where we have data—47 million girls had been vaccinated. First, it was a strategy of 3 doses, then 2, as recommended by WHO. Of those 47 million girls, fewer than 3% were living in low- or lower middle-income countries. These are countries where there is no effective population-wide cervical screening program. What that means is, even though we have the tools, including a 9-valent vaccine that would eliminate [a high percentage] of HPV infections, we have a long way to go in terms of rolling this out to all countries. HPV vaccination is absolutely essential, but it must be done hand-in-hand with increased access to effective screening and treatment programs. VIA is not new, but a number of years ago WHO recommended it after a large demonstration project in a number of sub-Saharan African countries showed that it was effective, acceptable, and feasible to implement, especially in the hands of non-gynecologists and even non-physicians, such as nurses and midwifes. During a pelvic examination, you apply 3% to 5% of acidic acid vinegar solution to the cervix. You then take a look under a light source after 1 minute, and the areas of white that appear can indicate an abnormality in the cervical epithelium. There are certain criteria by which the health workers are trained to identify those women who have those changes and are also suitable for treatment, even during the same visit, with cryotherapy. [Cryotherapy] is basically carbon dioxide or nitrogen gas that can be used in a community setting. This is one of the 3 strategies that WHO recommends and is considered a very cost-effective intervention in global health that can be implemented in a rural setting where no physicians are available. VIA, in addition to HPV DNA testing and Pap testing, are the 3 recommended strategies.

Now, you might ask, "why not Pap tests?" Pap tests have been working so effectively and have helped to decrease the incidence and mortality of cervical cancer in numerous countries, but they require a lot of infrastructure. The availability of cytopathology and the number of visits required to complete that process of screening is inhibitive. Women have to come in for the Pap test, return at a later date to learn of their abnormal results, and perhaps have another visit elsewhere for treatment. This has proven ineffective in many settings. This is, to an extent, why we are not recommending it if it does not already exist in a country. We tend to suggest starting with VIA, get those skills up, maintain those qualifications, and then introduce HPV-based DNA testing. The price of these is still too high, but the point-of-care diagnostic capacity is in trials now to make sure you can do that test and have a patient wait less than 2 hours for her diagnosis. She can then go home, and in many cases, may not have to come back for 5 years.

For women who are HPV-positive, there is still a role for VIA as a secondary screen. The question now is, “What is the best algorithm for managing those cases that are HPV positive?” There are still some areas of research, but by and large we have those strategies that we understand well enough to recommend the basics, depending on what environment you are in. In some countries, you may have a tertiary care facility [with] a lot of gynecologists. That needs to be in place for women who are suspected on VIA to have an invasive cervical cancer—those women should not have cryotherapy but be referred to a place where they can have a colposcopy and LEEP procedure.

Is there anything else that you really want to drive home?

In the meantime, you can introduce VIA and offer that opportunity to at least learn whether she is HPV positive for one of the oncogenic subtypes. That can be done in a tertiary center or a high-resource facility. There are a lot of ways to go. I would encourage people who are interested to look up the WHO website under cervical cancer, and you will see very good resources that are updated fairly regularly.In spring 2018, NYU Langone’s Perlmutter Cancer Center hosted the 6th Annual Symposium for Global Cancer Research with the National Cancer Institute Center for Global Health. At that meeting, we had more than 200 participants from over 30 countries. We announced the New York Challenge, which is challenging the global health community and countries to try to meet a 70% target for girls and boys to be vaccinated against HPV by 2030. This is one of the steps on the way toward cervical cancer elimination. We are in a way pressuring groups to challenge one another to see how they can do in their own country—including the United States. We have a long way to go here to reach that target of 70%. Metrics are being developed for how we will measure elimination. Keep your eye on Australia—they are getting close to elimination.

People often say, "This is an aspirational target, but how are we going to finance it?" I would encourage people to look at a 10-part series with a call-to-action at the beginning and a paper at the end that summarizes the findings. The International Journal of Gynecology and Obstetrics did a whole series just on cervical cancer elimination in low- and middle-income countries. In that document, there are data outlining how much it would cost. Over 10 years, it would cost $3.2 billion globally to vaccinate every girl, and screen and treat every woman aged 30 to 49 as needed in the 50 poorest countries. This would avert more than 3 million deaths, so that is something to consider. You can't put a price on that. There are cases to be made to invest in this effort and to assist countries that do need additional resources to tackle this burden.