- Cervical cancer remains one of the leading causes of cancer mortality among women in Latin America, despite prevention and screening efforts.
- Latin American countries must invest in multipronged, multifaceted approaches that include cervical cancer education, health promotion, vaccination, and screening programs.
- The HPV vaccine is best administered in school settings and, if possible, given at the same time as other mandatory vaccines.
- VIA screening must be available in any country where the gross national income per capita is less than $3,000 and in remote or rural areas where cytology-based programs have been unsuccessful.
Oh, what a circus, oh, what a show! Argentina has gone to town over the death of an actress called Eva Perón.”
In the opening scenes of Andrew Lloyd Webber’s musical Evita, the narrator cynically describes the national commotion after Argentinean first lady Eva Perón died following a relatively short fight against cervical cancer in 1952.1 Reality was even stranger than fiction. In real life, Eva Perón never knew she had cancer and was led to believe that she had a minor gynecologic problem requiring a simple procedure. In the midst of a campaign for re-election, her husband did not want to risk any negative press and, unbeknownst to her and the public, flew in a surgeon from New York City.
Eva’s experience cannot be treated simply as a testament to history. Cervical cancer may not be quite as shrouded in secrecy or so commonly referred to as “that disease” as was the case a half-century ago, but it continues to be highly stigmatized. Although mortality rates have fallen dramatically, cervical cancer is still one of the leading causes of death, especially of women below the poverty line, and continues to kill tens of thousands of women in Latin America every year.
HPV and Cervical Cancer Control
Cervical cancer remains one of the leading causes of cancer mortality among women in Latin America despite prevention and screening efforts.2 Over the last 3 decades, cervical cancer has become less common in some Latin American countries (Brazil, Colombia, Costa Rica, and Ecuador), but its incidence in the region remains 2- to 4-fold higher than in high-income countries like the United States and Spain.3 Cervical cancer cases and deaths are becoming increasingly concentrated in low-income countries and in the poorest regions within those countries.
In 2015, an estimated 74,488 women were diagnosed with cervical cancer in Latin America, and 31,303 died of the disease in Latin America.2 Between 2015 and 2035, cervical cancer mortality is projected to increase by 39% unless there is dramatic improvement in screening and vaccination.2
We, the authors, are involved in ongoing efforts to advocate for better cervical cancer control.4-6 Part of our work is to identify deficiencies in prevention and screening efforts that could be acted upon to further reduce cervical cancer incidence and mortality in Latin America.4-6
Cervical Cancer Prevention and Screening
Most cervical cancer is caused by HPV, a sexually transmitted infection that affects cervical cells and, given enough time, can cause cervical dysplasia (a precancerous lesion) and invasive cancer. There are two major interventions that can prevent cervical cancer: HPV vaccination and screening, which involves the detection and treatment of cervical dysplasia and early-stage cervical cancer. To date, more than 100 types of HPV have been identified. Two subtypes, HPV 16 and 18, cause up to 70% of cervical cancer cases in Latin America and are covered in all available vaccines.4 There are three HPV vaccines currently on the market:
- The bivalent vaccine (Cervarix from GlaxoSmithKline) covers HPV 16/18 only.
- The quadrivalent vaccine (Gardasil from Merck & Co.) covers HPV 16/18 and HPV 6/11, which cause genital warts.
- The 9-valent vaccine (Gardasil 9 from Merck & Co.) covers seven HPV types related to cervical cancer, including HPV 16/18 and HPV 6/11.
Experts on cervical cancer prevention agree that HPV vaccination programs should be large scale and should target young girls and teenagers before their first sexual encounter to have the greatest impact on HPV infection, cervical dysplasia, and cervical cancer incidence. If health resources allow for it, young women, boys, and young men can also be vaccinated.
Barriers to Large-Scale Vaccination Persist in Latin America
Since the first HPV vaccine became available in 2006, there has been tremendous enthusiasm to introduce it in low- and middle-income countries. Initially, the main barrier to introduction was cost. As a result of global and regional price negotiations, the bivalent vaccine is now available for purchase at a discounted price through the Pan American Health Organization, costing $8.50 per dose in 2016.7
In contrast to 2011 when only four Latin American countries (Argentina, Mexico, Panama, and Peru) had included the HPV vaccine in their national vaccination schedule, the vaccine is now available in the majority of Latin American countries. Despite the discounted price of the vaccine itself, a few countries—namely Bolivia, Nicaragua, Venezuela, and Honduras—have been unable to implement national coverage because of limited infrastructure and support staff, as well as a lack of political will and effective mobilization of civil society.4
Even in countries where the vaccine has been introduced nationally, the proportion of girls who have completed the three-dose injection series is disappointingly low.4 For example, in Argentina, 80% of girls age 12 received the first dose, but only 50% completed the series. In Brazil, one report noted that 97% of girls age 11 to 13 received the first dose, which was administered at school, but only 53% received the second dose, which was administered at health centers.4
Sustainability is also an issue, and there is some evidence that vaccination is falling off over time. Early reports from Brazil found that from January to May 2014, 83% of the target population (girls age 11 to 13) had received the first dose of the HPV vaccine. However, over the same period in 2015, only 40% of the target population had received the first dose of the vaccine, largely because vaccination shifted from schools to health care units.4
Need for a New Cervical Cancer Screening Strategy
The goal of cervical cancer screening is to identify and treat cervical dysplasia and/or early-stage invasive cervical cancer. Currently, there are three main methods of cervical cancer screening that are either used alone or in combination: cytology-based screening (the Pap test), visual inspection with acetic acid (VIA), and HPV DNA screening. All of these approaches are actively employed in Latin America.
Cytology-based screening has been used with success in high-income countries since the 1950s, but it is a complex test requiring significant infrastructure and health personnel to collect, prepare, process, and interpret the results in a timely manner. Although cytology-based screening is available in most Latin American countries, these programs have not been as successful as intended. Data from health surveys estimate that less than 55% of eligible women in Latin America have had recent Pap screening.4,8
Unfortunately, cytology-based screening programs have been underfunded; have encountered difficulties in delivery to low-income, rural, and remote populations; and have had issues with quality and/or delayed follow-up care. As an example of this, a study from Brazil showed that 10% of all Pap samples were of low quality and could not be interpreted—and this rate was as high as 60% in the rural state of Amazonas.4,9
Future Strategies to Reduce Cervical Cancer Incidence and Mortality in Latin America
Cervical Cancer Screening
VIA screening, also known as the “see and treat” approach, has many potential advantages over cytology-based screening programs in resource-constrained settings. VIA screening involves the application of acetic acid or Lugol’s iodine to the cervix, which allows precancerous lesions to be viewed with the naked eye. This allows cervical dysplasia to be detected in the clinic (without needing a laboratory), and when paired with cryotherapy, women can receive screening and treatment in one visit. As a result, unlike cytology-based screening, VIA is inexpensive, requires less staff and resources, avoids delays and errors that may occur when processing Pap samples, and has less loss to follow-up. VIA screening is effective, and a trial performed in India found that this intervention reduced cervical cancer mortality by 31% in a 12-year period.10
VIA is currently available in the public sector in Argentina, Colombia, Costa Rica, El Salvador, Guatemala, Guyana, Haiti, Nicaragua, Suriname, Trinidad and Tobago, Uruguay, and Venezuela.11 A cost-effectiveness analysis from Honduras estimated that VIA would cost $3,198 per cancer case avoided versus $36,802 per cancer case avoided with cytology-based screening.12 We recommend VIA screening to be available in any country where the gross national income (GNI) per capita is less than $3,000 and in remote or rural areas where cytology-based programs have been unsuccessful.
HPV DNA testing
HPV DNA testing is often used in combination with cytology-based screening in high-income countries, but HPV testing as a stand-alone method is gaining traction. A study from India showed that HPV DNA testing alone could also reduce cervical cancer mortality to a greater effect than either VIA or cytology-based screening.
HPV DNA testing can also be performed on self-collected samples, and a study from Jujuy, Argentina, found that women were more likely to participate in cervical cancer screening if self-sampling was arranged.13 In this study, women were randomly assigned to either a control-arm educational intervention, where they were advised to seek
cytology-based screening at their local health center, or self-sampling performed at home, which was coordinated by community health workers that arranged for HPV DNA testing. The differences in the two arms were stark: 86% of women participated in self-sampling and HPV DNA testing, but only 20% of women in the control arm pursued cytology-based screening at their local health center.
Although HPV DNA testing, through self-sampling at home or in health care centers, is a promising cervical cancer–screening strategy, it is unclear whether women identified to be HPV DNA–positive will follow up at their local health centers in a timely manner for treatment. Furthermore, HPV DNA testing is expensive. Until the cost decreases, HPV DNA testing for cervical cancer screening is not affordable on a national scale in the Latin American region. To date, only Mexico has included HPV testing as a service financially covered and provided by the public sector in conjunction with cytology-based screening, which parallels the approach used in the United States.4
Not all Latin American countries have introduced the HPV vaccine at a national level. Belize, Bolivia, Costa Rica, Cuba, the Dominican Republic, El Salvador, Guatemala, Haiti, Honduras, Nicaragua, and Venezuela have not introduced HPV vaccination and should be encouraged to do so.4,11
In Latin American countries where HPV vaccination has been introduced, these programs deserve and require more support for staff, infrastructure, research, and collection of quality-assurance data on who was vaccinated, where they were vaccinated, and whether the vaccine series was completed.
At $8.50 per dose, the price of the bivalent vaccine is still too high for many low-income Latin American countries. The Global Alliance for Vaccines and Immunization (GAVI) has negotiated a lower price of $4.60 for the bivalent vaccine for low-income countries (GNI/capita below U.S. $1,580). Haiti is currently the only country in the region that qualifies to purchase the vaccine at this price.
We believe that lower-middle–income countries should be considered for reduced vaccine price. At the time that GAVI began to negotiate this discounted price, it was predicted that Bolivia, Honduras, Guyana, and Nicaragua would also qualify for the reduced price, but recent economic development has put them above the GNI per capita threshold.4 Furthermore, it should be possible to negotiate an even lower price for the region, and many stakeholders and advocacy groups are currently working to do so through price negotiations and/or volume discounts.
The HPV vaccine was developed and tested to be administered on a three-dose schedule over a 6-month period. New data from the World Health Organization suggest that an alternative two-dose schedule provides adequate immunity in girls younger than age 15.4,14 Because this two-dose approach is cost saving, we support this approach in all Latin American countries for girls younger than age 15.
To reach all young girls and women who qualify for vaccination, the vaccine is best administered in school settings and, if possible, given at the same time as other mandatory vaccines. If school-based programs are not feasible, the vaccine should be given during a routine or required clinic visit.4 Antipoverty programs such as Oportunidades in Mexico can also encourage HPV vaccination in young girls.
Finally, because many logistical issues can arise that may affect a vaccination program, it is important to monitor the performance of a vaccination program to evaluate its success or shortcomings. Collecting data on how well a vaccination program works will allow policymakers to work on improving vaccination programs.
Cervical cancer screening
Continued high incidence and mortality from cervical cancer reflects a need to build capacity for cervical cancer screening, as well as vaccination. In recent years, the focus in Latin America has been on vaccination; however, cervical cancer screening should not be de-emphasized. Millions of women have already been exposed to HPV before vaccination was introduced, and those who are most vulnerable (low-income, underserved, and minority/indigenous populations and/or those who live in rural or remote areas) will not necessarily be reached by vaccination. In this setting, each Latin American country must review their current screening programs on a population level with regard to their effectiveness at screening the target population, the quality of the program, and their efficacy at detecting and treating cervical dysplasia and early-stage cervical cancer. These reviews should be conducted considering the cost of the program and whether alternative strategies to a traditional cytology-based program, such as VIA and/or HPV DNA testing, should be introduced, bearing in mind their cost effectiveness and feasibility.
Considering how challenging it can be to implement a successful cytology-based screening program in a low- or middle-income country, we believe that there is a role for VIA screening in every Latin American country, especially in remote and/or low-income regions. Currently, VIA screening is not available in the public sector in Belize, Brazil, Chile, Cuba, the Dominican Republic, Ecuador, Honduras, Panama, Paraguay, Peru, or Uruguay. This approach should be considered in these countries, especially for their lower-income regions.11
In the future, as more data emerge on cervical cancer incidence in the era of HPV vaccination, cervical cancer screening protocols should evolve. For example, there may be more of an emphasis on screening women who did not receive the HPV vaccination. Currently, we cannot recommend this approach because women who received the HPV vaccine against the 16/18 subtype are still at risk of cervical cancer from other HPV subtypes. Furthermore, from an epidemiologic standpoint, HPV 16/18 vaccination may impact the evolution of the HPV virus so that other HPV subtypes that cause cervical cancer may become more prevalent.
Educational efforts focused on cervical cancer prevention, screening, and treatment should also be supported in Latin American countries. Many patient surveys from the region demonstrate a lack of awareness about HPV and cervical cancer. Studies from low- and middle-income countries have shown that inexpensive educational interventions can improve participation and adherence rates to cervical cancer prevention and screening efforts.4
Patient navigator programs
Studies from Latin America have also shown that many patients with a positive Pap test are lost to follow-up. In this context, we advocate that health systems support patient navigator and/or community health worker programs. Such programs have been shown to improve cancer prevention and screening efforts. These programs help to engage indigenous minorities and low-income and rural populations. This is particularly important for countries such as Bolivia, Ecuador, Guatemala, and Peru that have large indigenous populations where race, language, and sociocultural differences can create barriers to vaccination and screening. Antipoverty programs in these countries, like Mexico’s Oportunidades, are particularly important because they improve participation in vaccination programs and cancer screening efforts.
The real-life story of Eva Perón has a final twist. Tormented by excruciating pain in her last few weeks of life, at a time when even doctors were uncomfortable using morphine and its derivatives, she had a lobotomy for pain control (without ever being told she had cancer).15 This cautionary tale reminds us to always strive to generate the best-quality data to inform clinical practice, public health efforts, and prevention programs. Today, we do have the tools to prevent women, the world over, from undergoing the same ordeal as Eva Perón. It is high time we implement them.
Providing optimal pain and palliative care to patients with cancer in Latin America is an ongoing challenge and must be prioritized by health care policymakers.5,16 Access to opioids and providers with palliative care training is limited in many low- and middle-income countries. Efforts to improve pain and palliative care in Latin America are ongoing but need continued support.17
A Call to Action
Although preventable, cervical cancer remains a major problem in Latin America. In the last decade, many Latin American countries have introduced the HPV vaccine, which is an exciting and highly effective intervention. However, vaccination alone will not control cervical cancer in the region, and in the next 2 decades, cervical cancer mortality is expected to rise by almost 40%. Hence, there is a need for Latin American countries to invest in multipronged, multifaceted approaches that include cervical cancer education, health promotion, vaccination, and screening programs (sidebar). Each country should review their current cervical cancer prevention and screening efforts, identify issues that can be improved upon, and implement changes in order to reduce cervical cancer incidence and mortality.
About the Authors: Dr. Bychkovsky is with the Dana-Farber/Harvard Cancer Center and Harvard Medical School. Dr. Knaul is with the University of Miami Institute for the Americas. Dr. Lopes is the medical director for international programs and associate director for global oncology at the Sylvester Comprehensive Cancer Center and associate professor of clinical medicine at the University of Miami. He is the editor-in-chief of the Journal of Global Oncology.