Vivien Tsu, Ph.D., M.P.H., and José Jerónimo, M.D.
N Engl J Med 2016; 374:2509-2511 June 30, 2016 DOI: 10.1056/NEJMp1604113

No woman should die of cervical cancer in this day and age, yet each year more than 260,000 women do, mostly in low- and middle-income countries (LMICs). The dramatic disparity in incidence rates between high- and low-income countries is due primarily to differential access to effective screening and precancer, or preventive, treatment; similar disparities also exist within countries. International gaps will widen further if use of the human papillomavirus (HPV) vaccine continues to lag in LMICs. Even with relatively low rates of use in the United States, we are already seeing dramatic benefits from vaccination in terms of reductions in rates of HPV infection and early cervical disease. Thanks in part to herd immunity for people not yet reached by the vaccine, and new vaccines that include more HPV types, there’s a good chance that, in the not-too-distant future, current and future generations of adolescent girls will be largely spared from cervical cancer. Eventually — after several decades — cervical cancer screening may no longer be warranted.

But that is not yet the case. Hundreds of millions of women are already beyond the age of vaccination, and without screening and preventive treatment, some 19 million will die from cervical cancer over the next 40 years. We know from experience that the successful methods used to reduce incidence in high-income countries (Pap smear, colposcopy, biopsy) aren’t feasible at scale in low-resource settings. The basic tools for effective cervical cancer screening already exist and are getting better each year, but they are still out of reach for millions of women living in LMICs. Yet we believe that innovative approaches and emerging international commitment make it possible to ensure that all women have access to these lifesaving cancer-prevention tools.

One notable advance in screening methods is visual inspection with acetic acid (VIA), which allows trained health workers to spot cervical abnormalities with just a speculum exam. We now also have highly sensitive molecular tests that detect HPV infection or its consequences — the precursors to cervical cancer. Molecular testing technology continues to progress, and though some of these tests require sophisticated laboratory infrastructure, others are closer to the point-of-care or lower-infrastructure models that can be implemented in LMICs. Both VIA and molecular testing are now recognized as acceptable screening methods by the World Health Organization (WHO), with HPV testing preferred wherever possible.

In recent years, we also have seen improvements in preventive treatment using technologies, such as CryoPen and thermal coagulation, that are not dependent on the hard-to-obtain compressed gases needed for conventional cryotherapy. Advances in the use of mobile phones for tracking health information and reaching patients, and the explosive growth of their availability in LMICs, represent another opportunity to improve cervical cancer prevention.

In order to take full advantage of these technological innovations, countries need the political will to support extensive deployment and training. Fortunately, attention to cervical cancer has increased substantially in recent years. The recognition of the growing importance of noncommunicable diseases (NCDs) led to a United Nations (UN) summit on NCDs in 2011 and the listing by the WHO of “screening and treatment of precancerous lesions to prevent cervical cancer” as a “best buy” intervention.4 In a recent commentary, the UN secretary-general described global cervical cancer prevention as an imminently feasible proposition.

Even in this age of pandemic diseases such as Ebola and Zika, the looming threat of NCDs has become too big to ignore. The new Sustainable Development Goals explicitly recognize that attention to NCDs is urgent, since failure to implement preventive measures now ensures that the burden will continue to mount. Energy and funding similar to those that have been mobilized for other health issues — enabling the eradication of polio, widespread treatment of HIV–AIDS, and a 50% reduction in childhood mortality over the past two decades, for example — are now needed in order to control cervical cancer. Only a few LMICs have the kind of strong national champions for cervical cancer that are needed. But signs of a global commitment are emerging: for example, a broad range of stakeholders gathered in London in November 2015 at a meeting organized by the Cervical Cancer Action coalition to help launch a 5-year-initiative called “Taking Cervical Cancer Prevention to Scale: Protecting All Women and Girls.”

Given these positive developments, what is holding us back? Countries can build on existing primary health care platforms to create efficient screening services, but they still face hurdles such as chronic shortages of health workers, weak referral processes, and inadequate health information systems that make it difficult to track individual patients or monitor program performance. To address these constraints, even as we await a new generation of screen-and-treat options that will allow us to incorporate both steps of care into a single visit, we can take a comprehensive approach to scaling up the current tools that we know can work in low-resource settings, and we can support further strengthening of health systems. Otherwise, we risk failing to reach women across the full range of countries and socioeconomic classes, even with VIA.

To start with, we can adopt innovative protocols and increase domestic and international investment to support them. In our view, molecular testing using vaginal samples collected by women themselves in their homes or communities and then conveyed to a processing site, combined with preventive treatment provided at an accessible location for women who have screened positive for HPV infection, will be most effective in closing the current prevention gap. This approach could mitigate the burden placed on weak health systems, reduce cultural barriers for women, and enhance the accuracy, yield, and efficiency of screening. Though it may raise some concerns about potential overtreatment, extensive experience in multiple countries and WHO guidelines suggest that the balance of benefits and harms supports such a screen-and-treat approach. Deployment of new ablative technologies that do not involve the use of external gas supplies can ensure the affordable treatment of precancerous lesions, preventing progression to invasive cancer.

By focusing on implementing sustainable, population-based screening on a national scale, rather than establishing limited pilot efforts based on unrealistic strategies and unsuitable technology such as Pap smears, we believe that LMICs can change the current pattern, leapfrog old technologies, ensure equitable access for rural and poor women, and reduce related mortality by half. Countries that can afford to do more than implement this basic approach, such as screening more than once or screening older women, can expect even greater disease reduction.

It’s also important to build service delivery systems that can incorporate even better technologies as they become available. Argentina, El Salvador, Guatemala, Honduras, and Nicaragua have already taken steps in this direction, using self-collected specimens for HPV testing. Some countries are now testing community tracking mechanisms that can ensure that women who have screened positive return for treatment, as well as incorporating relevant indicators in national health information systems.

The next steps for taking full advantage of this convergence of technological innovation and political commitment seem clear. First and foremost, the approach now being introduced in several Latin American countries, as described above, can be scaled up, applied in a few countries in Africa and Asia, and evaluated rigorously. The results would indicate what adaptations are needed in different environments to serve current generations of women, and the evaluation could provide essential data on costs and outcomes. Second, a virtual learning network could be developed for rapid sharing of lessons, enabling other countries and funders to apply them. Third, concerted and coordinated advocacy can spur greater investment at both national and global levels. Finally, continued technological innovation may well drive down the costs of rapid molecular tests.

Every year that we delay, we squander the scientific advances we have made, lose ground on building the evidence for effective strategies, and tragically, lose women who could have been saved.

SOURCE INFORMATION: From PATH (formerly the Program for Appropriate Technology in Health), Seattle.