The root causes of cancer disparities

Over the past several decades, astonishing advancements in the understanding of cancer biology have led to the development of smart therapies able to pinpoint and destroy cancer cells, contributing to longer lifespans and even cures for many cancer patients.

“Precision medicine allows patients to receive the most appropriate treatment for their specific needs by understanding the genomic base of cancer. The development of targeted drugs that are able to treat genetic abnormalities that cause cancer cells to grow is one of its greatest breakthroughs,” Dr Leonard Lichtenfeld, acting chief medical officer of the American Cancer Society, told Global Health and Travel back in 2016.

One powerful example of precision medicine is the drug imatinib, which has completely rewritten the script for treating chronic myelogenous leukaemia (CML), a type of blood cancer.

“When the drug first came out in the early 2000s, standard treatments for CML at the time were only able to help some patients for a certain period of time,” Dr Lichtenfeld said. “But with the development of imatinib the vast majority of patients were able to go into remission and live normal lives with limited side effect.”

Similarly, the drug trastuzumab, which acts on the protein HER-2 found on some breast cancer cells, increased the overall survival rate of women with HER-2 positive breast cancer by 33 percent. This was “a magnitude unprecedented in the history of chemotherapy for HER-2 positive cancer,” Siddhartha Mukherjee, a cancer specialist, wrote in The Emperor of All Maladies: A Biography of Cancer.

Trastuzumab has also proven to be effective in certain subtypes of stomach and oesophagus cancers where HER-2 contributes to the growth of malignant cells.

Coupled with the ability to diagnose some types of cancer at an early stage, these new medications explain why, by and large, more people are surviving a disease that was previously considered a death sentence.

“Cancer survival trends are generally increasing, even for some of the more lethal cancers. In some countries, survival increased by up to five percent for cancers of the liver, pancreas, or lung,” according to Global surveillance of trends in cancer survival 2000-14 (CONCORD-3), a study which analysed data from more than 37.5 million patients diagnosed with cancer in 71 countries around the world.

Unsurprisingly, female breast cancer is now one of the most curable. Between 2010 and 2014, 90.2 percent of women in the US, 89.2 percent of patients in Australia, and 88.2 percent in Canada achieved survival five years after diagnosis.

While medication has played a major role, prevention has also made a significant dent in cancer mortality rates. 

In the US, cancer deaths fell by 26 percent between 1991 and 2015, resulting in 2.4 million lives saved, according to the Cancer Progress Report 2018 by the American Association for Cancer Research. Public education initiatives have been a major driver in the decline of cancer deaths by raising awareness of preventable risk factors, such as smoking. Responsible for nine out of ten lung cancers, smoking also increases the risk of developing almost any other type of cancer, according to the US Centers for Disease Control and Prevention.

While the overall trends are positive, the increase in survival rates is also patchy, with high-income countries significantly outperforming middle-and-low-income ones. Many patients are also not reaping the full benefits of improved cancer therapies, even in rich nations. There are many reasons for  this disparity, including socio-economic status, education, and geographical constraints.

“Cancer is a disease of inequality,” declared Dr Christopher P. Wild, director of the International Agency for Research on Cancer, at the World Cancer Congress in Kuala Lumpur last October. In fact, patients diagnosed with the exact same type of cancer experience a wide range of treatment outcomes based on where they live.

For instance, the five-year survival rate of female breast cancer patients plunges to 68.7 percent in Thailand and 66.1 percent in India, according to CONCORD-3.

Overall, cancer deaths in Asia and Africa account for 64.6 percent of the global number despite having an incidence of just 54.2 percent, a trend that reflects the higher chances of dying of cancer in those regions compared to Europe and America.

What these numbers clearly show is that we are not making the most of past developments in cancer care. If more people are to benefit from our sophisticated understanding of cancer, it’s paramount that we figure out why medical advancements are not reaching some patients.

“When people talk about cancer, they always focus on treatment,” Dr Saunthari Somasundaram, President of the National Cancer Society Malaysia, told Global Health and Travel. “If someone gets sick, we need to get her better. However, we don’t look at it in terms of how that person got there in the first place.”

She believes that more research on the specific obstacles faced by cancer patients in each social and geographical setting is crucial to understanding the root causes of cancer disparities.

Who bears the brunt of cancer?

Though there are wide differences among nations, stark cancer disparities exist within each country as well, and unsurprisingly people with limited financial resources or treatment options come off worse.

In the US, the death rate for breast cancer is 39 percent higher in non-Hispanic black women compared to non-Hispanic white women, while “non-Hispanic black men have a prostate cancer death rate that is more than double that for men in any other racial or ethnic group,” according to the Cancer Progress Report 2018.

Overall, racial and ethnic minorities tend to be poorer and more medically underserved than white Americans, which is a major contributing factor to cancer disparities, according to the US National Cancer Institute.

Because those with limited or no disposable income can’t afford to see a doctor and undergo screening, they are typically diagnosed late when cancers are at an advanced stage. Even if a malignancy is diagnosed, they often have to skip treatment or go into debt to get medical help, especially those with no health insurance. A study presented at the American Society of Clinical Oncology in September analysed 1,000 women with advanced breast cancer and showed that 54 percent had to stop or refuse treatment for financial reasons, according to STAT.

Similar trends in other parts of the world reflect the fact that cancer treatment is unaffordable for many patients.

In 2012, the ACTION study assessed the impact of cancer treatment among more than 9,000 patients across Southeast Asia and found that, one year after diagnosis, 29 percent had died, while 48 percent survived but experienced financial catastrophe, defined as out-of-pocket medical bills amounting to or exceeding 30 percent of their annual household income. Only 23 percent of patients were still alive and were able to avoid financial hardship.

“In Malaysia and Southeast Asia, we are struggling with cancer because we deal with a lot of late diagnoses. Therefore, it’s hard to have optimal outcomes,” said Dr Somasundaram. “Late-stage cancers are harder to treat than those at an early stage and require aggressive treatment, which leads to lack of compliance, with patients dropping out of treatments because they are extended and more likely to involve side effects and huge cost. All these things are incredibly important to outcomes and that’s where disparities come in.”

Geography is another powerful and common driver of inequality that puts people living in rural areas or at a great distance from cancer care facilities at a disadvantage.

“There’s no question that access to healthcare is the most important health disparity,” Dr Stefan Ambs, a cancer researcher with the US National Cancer Institute, told Global Health and Travel. “In those states of the US where long travel times are needed to go for screening, people often don’t go for it and as a result there’s no early detection of cancer and cancer patients don’t survive well.”

With healthy lifestyles and early detection playing a big role in decreasing cancer risk, it’s natural that a variety of factors is helping fuel disparities, thus compounding the problem.

In Australia, there’s been a significant slump in cancer mortality rates among non-Indigenous people, while the opposite trend is afflicting Indigenous Australians. Between 1998 and 2015, the death rate decreased from 194 to 164 for every 100,000 non-Indigenous Australians, while it ranged from 195 to 246 for every 100,000 Indigenous individuals, according to the Australian Institute of Health and Welfare.

Socio-economic factors, such as lower employment and education rates, unhealthy behaviours, like higher smoking rates, and poor access to healthcare services are major reasons why Indigenous Australians, who make up a large portion of the country’s population living in remote areas, are at a disadvantage compared to non-Indigenous people.

Having cancer services available within easy reach is crucial, said Dr Somasundaram, but that’s not going to close the gaps in cancer care. “When you talk about access, it doesn’t only mean having the bricks and mortar available, it’s also ensuring that people can get to those bricks and mortar or want to get there. So, access covers a lot of issues,” she said.

In urban Kuala Lumpur, for instance, there’s an abundance of facilities, with 12 to 17 cancer centres for about eight million people, but treatment outcome disparities are rife, explained Dr Somasundaram.

One study comparing survival rates among patients with invasive breast cancer treated at either the public or private wings of the University of Malaya in Kuala Lumpur found that a greater number of private patients survived five years after diagnosis compared to public patients, with the first group achieving a survival rate of 86.8 percent while the second only reached 71.6 percent. The key contributing factor for such a divergence in survival rates was the increased late-stage presentation among public patients, concluded the authors of the study.

According to Dr Somasundaram, the well-to-do, who can afford to visit private hospitals and are more aware of cancer risks, tend to take a more proactive approach to cancer screening and treatment than low-income individuals who struggle to recognise potential cancer symptoms.

“Health literacy makes a huge difference in terms of whether someone is going to come for treatment at an early stage or not,” she said.

She also believes that poor understanding of cancer screening among some primary care providers in Malaysia creates additional obstacles to equal cancer care.

The different treatment experiences of Dr Somasundaram’s mother and her niece poignantly illustrate the uneven level of cancer care in countries such as Malaysia.

A physician who had always gone for regular breast screening, her mother was diagnosed with breast cancer at an early stage and successfully treated with surgery and oral medication. Her niece, however, never went for breast cancer screening and, after feeling a lump on her breast, consulted a primary care doctor who, instead of following the recommended diagnostic process involving imaging and biopsy, assumed the tumour was benign due to the patient’s young age and rushed her to surgery. Post-op the lump was found to be cancerous, and Dr Somasundaram’s niece had to undergo another surgery along with chemotherapy and radiotherapy to treat it.

“Because due process wasn’t followed, her optimal treatment was delayed,” said Dr Somasundaram. “When we talk about access to treatment, we need to make sure that all the steps before that are taken properly.”

Widening access to cancer best practice

One of the more obvious solutions for addressing the issue of cancer inequality is to reverse the current global shortage of cancer specialists.

A study published in the Journal of Global Oncology highlighted the serious shortage of oncologists in several parts of the world, with many countries in Africa having only one oncologist to cater to more than 1,000 patients.

This is easier said than done, however, and requires long-term planning and massive investments in human capital as well as facilities and equipment. It also runs against worldwide trends where specialists are choosing to practice in urban areas over rural settings for better pay and opportunities.

One promising solution is Project ECHO (Extension for Community Healthcare Outcomes), which is helping plug some of the gaps in regional specialist treatment by maximising the expertise of existing specialists.

Launched in 2003 in the US state of New Mexico to improve access to treatment for hepatitis C across the state, the programme aims to “democratise medical knowledge and get best-practice care to underserved people all over the world,” as Dr Sanjeev Arora, its founder, put it at the World Cancer Congress.

Project ECHO does this through virtual weekly meetings where specialists in academic hubs share their knowledge with clinicians practising in communities with limited or no access to specialist care.

A study of the pilot project in New Mexico showed that primary care physicians who participated in ECHO managed to become well versed in treating hepatitis C and were able to deliver care that was as effective and safe as that provided in a university clinic, while also broadening treatment access for New Mexico’s minorities, said Dr Arora.

Since its inception, the model has been applied to many other areas of medicine, from psychiatry and cardiology to dementia care and oncology.

In India, a country plagued by a dearth of medical specialists and where The Times of India estimated that in 2016 there were only 2,000 oncologists for about 10 million patients, the NGO Karuna Trust joined forces with the country’s National Institute of Cancer Prevention and Research and used the ECHO model to train primary care providers to screen for cervical, breast, and oral cancers.

“These are the most common types of cancer in India, and people are rarely screened for them,” Dr Sudarshan Hanumappa, founder and secretary of Karuna Trust, told Global Health and Travel. “This is the reason we wanted to do the screening for those three cancers.”

Karuna Trust currently manages 70 primary healthcare centres across five states in India, including a centre in Chamarajanagar where the cancer screening project took place, offering care to almost one and a half million patients.

“We are using the ECHO model extensively in our primary care centres to empower medical officers with the help of obstetricians and paediatricians, for instance,” said Dr Sudarshan. “It’s a tool that can lead to wonderful results if you make the primary healthcare system functional first, which is what we are doing in many medically underserved areas in India.”

Systemic changes for better integrating cancer prevention into primary care are needed, especially in low- and middle-income countries like Malaysia and India, because nations with cancer screening programmes are those that fare better in terms of treatment outcomes, said Dr Somasundaram. However, there are also little steps that are easier to take and can alleviate disparities.

In a hospital in the Malaysian city of Klang, for instance, social workers help breast cancer patients make appointments or address non-medical issues like transportation to the hospital. “This project, called Patient Navigation, has dropped treatment non-compliant rates by 20 percent,” she said. “These are low-hanging fruits, but they make a huge difference.”

In Tower Hamlets in London, a series of customised measures targeting women with some of the lowest breast cancer screening rates in the UK increased participation by 14 percent between 2006-07 and 2009-10, reducing the gap with the national average, according to An Inquiry into Geographical Inequalities and Breast Cancer. All it took was the adoption of various simple techniques, such as marketing campaigns, pre-appointment phone calls, and text message reminders.

In other circumstances, however, what’s needed to help eliminate disparities is more fundamental -- better research and better treatments.

“Although in most disparities they are not relevant factors, genetics and tumour biology can explain some cancer disparities, in particular with regards to breast and prostate cancer” said Dr Ambs, who’s researching the biology of breast and prostate cancers.

For example, one reason why African American women haven’t benefitted from improvements in breast cancer treatment to the same extent as white women has to do with black patients being more likely to have triple negative breast cancer. This subtype of the malignancy is harder to treat than others due to a lack of targeted therapies that act to disrupt the biological mechanism leading to cancer growth, he explained. African American breast cancer patients are also more likely to have untreated co-morbidities like diabetes, leading to increased breast cancer death rates.

“Unlike other types of the disease, triple negative breast cancer doesn’t express hormone receptors [proteins involved in cell growth], therefore we don’t have any target to treat it effectively,” said Dr Ambs. “We can only use standard chemotherapy, which doesn’t elicit any response in many patients, while those women who respond to this treatment often relapse. While women with triple negative breast cancer may initially respond better to chemotherapy than women with other breast cancers, long-term survival remains poor.

“There are ongoing trials targeting important pathways of triple negative breast cancer – like deficiencies in repairing our DNA - that look promising, so hopefully we’ll have more effective treatments for it soon.”

Dr Ambs believes this will help reduce disparities in treatment outcomes for women with triple negative breast cancer, but it won’t eliminate them because social factors, like access to care, remain important drivers of inequality.

Cervical cancer: a textbook example of inequity and a ray of hope towards cancer eradication

With cancer being a genetic disease whose risk inevitably increases with age, the idea of wiping it off the face of the earth is still wishful thinking, especially among advanced countries with growing ageing populations.

In his enlightening book The Emperor of All Maladies: A Biography of Cancer, Siddhartha Mukherjee writes about the almost inevitability of cancer as a natural part of human biology.

“Oncogenes [human genes that promote cancer] arise from mutations in essential genes that regulate the growth of cells. Mutations accumulate in these genes when DNA is damaged by carcinogens, but also by seemingly random errors in copying genes when cells divide. The former might be preventable, but the latter is endogenous. Cancer is a flaw in our growth, but this flaw is deeply entrenched in ourselves. We can rid ourselves of cancer, then, only as much as we can rid ourselves of the processes in our physiology that depend on growth - ageing, regeneration, healing, reproduction.”

While ridding ourselves of the very processes of life may seem impossible, in terms of cancer eradication there is now one potential notable exception hovering on the horizon.

“Cervical cancer affects over half a million women each year, and kills a quarter of a million. One woman dies of cervical cancer every two minutes, making it one of the greatest threats to women’s health. Each one is a tragedy, and we can prevent it […] That’s why today I am calling for coordinated action globally to eliminate cervical cancer,” Dr Tedros Adhanom Ghebreyesus, the Director-General of the World Health Organization, said last May in a forceful call to action.

Such optimism is grounded in the fact that we already have powerful tools to prevent cervical cancer through vaccination against the human papilloma virus (HPV), which is responsible for most cases of the malignancy. We also have the ability to detect it early, mostly via pap smear or HPV testing, which often leads to complete cure.

As a result, many countries with functional healthcare systems have seen both incidence and mortality rates tumble to minimal levels, with Australia predicted to eradicate cervical cancer by 2028, according to a study published in The Lancet.

This resounding success, however, stands in stark contrast to the still high mortality rates in many areas of the world with no systematic vaccination and screening programmes in place. Regions such as East Africa have death tolls from cervical cancer that exceed Australia’s and New Zealand’s by more than 20 times. Overall, about 85 percent of the women diagnosed with cervical cancer and 87 percent of those who die from it live in low- and middle-income countries, according to the report The global burden of women’s cancers: a grand challenge in global health.

“Cervical cancer is a disease of social disparities” because it mostly affects developing countries or low-income women who often don’t go for screening, Dr Woo Yin Ling, Professor of obstetrics and gynaecology at the University of Malaya, told Global Health and Travel.

Having dedicated much of her academic life to studying HPV, Professor Woo has been deeply distressed by regularly seeing young Malaysian women die from such a preventable disease.

“Everyday we have six new cases of cervical cancer in Malaysia and 50 percent of them will die from it because they present at an advanced stage,” she said. “When I spoke to the women and looked at the data, I realised that women were not getting regular screening.”

Although pap smear testing for cervical cancer is accessible in both public and private clinics across the country, uptake rates are low, with the latest national figures showing that only 12.8 percent of eligible women had a pap test, according to the National Health & Morbidity Survery done in 2011.

Professor Woo attributes this low uptake rate to the lack of an organised cervical screening programme and socio-cultural barriers.

“In countries like the UK or Australia, family doctors send their patients reminders about cervical cancer screening, while in Malaysia it’s up to women to go for pap smear. Malaysian women are also scared and embarrassed at the idea of doing a pap test because they feel it’s a painful inconvenience,” she said, noting that some women require their husband’s approval before being examined by a gynaecologist.

While cultural barriers are formidable enough, other factors also discourage women from having a pap smear. For example, most dread the uncomfortable experience of having a metal instrument, called a speculum, inserted into their vagina to enlarge it while the doctor uses a brush to collect cells from the cervix, the lower part of the womb.

Eager to help Malaysian women overcome these obstacles and encourage them to undergo proper screening, in 2017 Professor Woo partnered with VCS Foundation, an Australian not-for-profit organisation with expertise in cervical cancer screening, to develop a programme suitable for Malaysian women. Called Project Rose, the programme was piloted in five public clinics in urban Kuala Lumpur with the hope of creating a fundamental paradigm shift in the way the country conducted its cervical cancer screening.

Under the charity project, which is led by the University of Malaya in collaboration with the Malaysian Ministry of Health, women who visit the clinics can choose to get screened for HPV by placing a small brush into the vagina to take some random cells – all by themselves. And within three days they get the results on their mobile phones.

“In a clinic where about five pap smears are performed every day, we are now screening 50 women daily through HPV testing, with more than 4,000 patients already screened,” said Professor Woo. “Nurses advise female patients who attend the clinics to do the test, but we also see people coming for it because the word has spread.”

The feedback has been extremely positive, with 99 percent of participants willing to undergo the test again because it’s simple, quick, self-performed, and its results are sent through text message.

“With Project Rose, we have designed a solution for cervical cancer screening that is scientifically robust and can be used in a busy clinic because it doesn’t require lots of paperwork as the registration is done through the phone and won’t take up the healthcare professionals’ and the women’s time,” said Professor Woo.

Usually performed as an alternative to or in combination with pap smear, HPV testing outperformed the standard pap test as a screening method in a recent Canadian study.

“The HPV virus is the cause of 99 percent of cervical cancers. By focusing on detecting the virus, we are then better able to determine which women have developed precancerous lesions and treat those earlier,” Dr Gina Ogilvie, lead author of the study, told CNN.

The WHO recommends both tests as viable screening options.

Professor Woo agrees that HPV testing is the way to go and believes it will eventually replace pap smear. “Women who are 30 or older and test negative for HPV don’t need to be screened for the next five years, but I am confident protection from cancer could extend to ten years for many of them” she said.

In contrast, pap smear needs to be repeated at shorter intervals, with the US Preventive Services Task Force recommending it every three years for women between 21 and 65 years of age.

The success of Project Rose has spurred the Malaysian Ministry of Health to embrace HPV testing for cervical cancer, notes Professor Woo. And she is currently working with the Ministry to lay the groundwork for a new screening programme based on self-sampling.

“It will take some years before we can implement the new system because the Ministry of Health has to create a national registry of women to ensure that the correct woman gets screened at the correct time. For example, a registry will ensure women don’t go for HPV screening every year,” she said.

With Malaysia already having a successful HPV vaccination programme for all schoolgirls aged 13, one whose uptake rates exceed 80 percent of all eligible girls, Professor Woo is confident that a national screening programme based on HPV testing will pave the way for the elimination of cervical cancer in Malaysia.

This article was originally published in print in January 2019.