Cancer Prevention: Major Initiatives and Looking into the Future

Carolyn Cook Gotay

Disclosures

Expert Rev Pharmacoeconomics Outcomes Res. 2010;10(2):143-154. 

In This Article

Major Current Initiatives

In this section, we will discuss four areas where there is currently considerable activity that has significant implications for the future of cancer prevention research and practice.

Global Tobacco Control

The biggest challenge for future tobacco control lies in developing countries, where 85% of the world population resides and the prevalence of smoking is increasing. According to the WHO, unless urgent action is taken, there will be more than 8 million deaths every year by 2030, with more than 80% of tobacco deaths in developing countries, and 1 billion estimated deaths during the 21st Century. To counter these dismal and frightening projections, the WHO developed a tobacco-free initiative with the goal:[109]

"to reduce the global burden of disease and death caused by tobacco, thereby protecting present and future generations from the devastating health, social, environmental and economic consequences of tobacco consumption and exposure to tobacco smoke."

Activities include the WHO Framework Convention on Tobacco Control (WHO FCTC), the first treaty negotiated under the auspices of the WHO. This treaty was adopted by the United Nations' World Health Assembly in 2003 and has become one of the most widely endorsed treaties in UN history, with168 endorsements, representing countries and political entities (e.g., EU) that pledge their commitment to tobacco control. The WHO FCTC supports working groups, conferences and research, and provides a platform for the enactment of policies and legislation in its member countries. The WHO has developed an active program focused on initiating and sustaining comprehensive tobacco control programs globally. This initiative, MPOWER, is a package of the six most important and effective tobacco control policies proven to reduce tobacco use, developed to help countries fulfil their promises to the WHO FCTC.[21] The six strategies are:

  • Monitor tobacco use and prevention policies

  • Protect people from tobacco smoke

  • Offer help to people wanting to quit tobacco use

  • Warn about the dangers of tobacco

  • Enforce bans on tobacco advertising, promotion and sponsorship

  • Raise taxes on tobacco

While these principles provide helpful directions to guide tobacco control efforts, Warner raises the important issue that research is needed to develop and tailor approaches to reducing tobacco use that are culturally appropriate and make sense in the context of the environment in which they are applied.[43] This implies very different interventions will be needed in regions according to levels of literacy, preferred form of tobacco use (e.g., cigarettes compared with bidis often used in India) and beliefs and attitudes regarding smoking.

Vaccinations to Prevent Cancer

One of the highest profile cancer prevention programs in the past few years has been vaccination against the human papillomavirus (HPV) for young women. Invasive cervical cancer rates are low in developed countries that have effective Pap screening programs. However, most of the developing world does not have access to Pap screening. The consequences are that, worldwide, cervical cancer is the second most deadly cancer in women and causes 288,000 deaths per year. There are an estimated 510,000 new cases of cervical cancer, 80% in developing countries.[44] The vaccine, which has been shown to be very effective against the most common strains of HPV, offers considerable promise for eliminating much of cervical cancer, and vaccination programs have been initiated in both the developed and developing worlds. Immunization programs have been implemented in Australia, New Zealand and in other countries in North America, and Europe for young girls; the specific age recommendation varies from country to country, but most are between 10 and 12 years of age. Efforts are being made to extend HPV vaccination programs to developing countries. The Bill and Melinda Gates Foundation has provided considerable support for these activities, including funding demonstration projects in Ghana, India, Peru, South Africa and Thailand,[45] in cooperation with other partners in the Global Alliance for Vaccines and Immunization.[110]

Although the vaccination programs are new – since the HPV vaccines were not approved until recently (e.g., 2006 in the USA) – there is evidence that uptake of the vaccine thus far in developed countries has been lower than optimal. For example, in the USA, most recent data indicate that approximately 37% of young women have received at least one (out of the three recommended) vaccinations; this was similar to rates for other newly recommended vaccinations, including meningococcal conjugate vaccine (42%) and tetanus/diphtheria/acellular pertussis vaccine (41%), but lower than for established vaccinations, such as hepatitis B and measles/mumps/rubella (≥90%). Rates are considerably higher when the vaccination is done through the school system; rates of approximately 90% have been reported in areas of Scotland (UK) and Spain that have such programs.[46] Programs based on broad-based rather than targeted recommendations regarding who should be vaccinated, include enforcement (e.g., necessary for school admission) and provide government subsides to reduce the cost of vaccinations are likely to have the highest uptake in the population.

The burden of male HPV-associated diseases, such as anal, penile, and head and neck cancers is considerably less than that of cervical cancer in women. However, HPV infection is common in men and is transmittable,[27] influencing disease rates in both men and women and, therefore, creating a case for recommending vaccination to boys.[47] Additionally, HPV vaccination programs can contribute to reducing virus-related cancer morbidity and mortality in other ways: for example, by making contraceptives readily available. It seems quite possible that immunization programs will be extended to boys in the future.

The HPV vaccination programs have generated a fair amount of controversy through concerns regarding vaccine safety, concerns about promoting promiscuity (since HPV is a sexually transmitted virus) and cost–effectiveness,[48] particularly as Pap screening will continue to be needed since the vaccination does not prevent all strains of HPV. In addition, there is a clear need for an array of preventive strategies – vaccination being only one option – combined with screening and early detection, as shown for the infections listed in Tables 2 & 3. Experience with HPV vaccination provides important 'lessons learned' for future programs, such as extending programs for existing vaccines, such as HepB, and as more vaccines are developed. Although the reports of the HPV vaccination experience thus far has been reported primarily based on the developed world, the potential for cancer prevention is even greater in developing regions.

Chemoprevention

The use of natural and synthetic compounds to prevent cancer is referred to as chemoprevention. Chemoprevention studies can be subdivided in two categories, based on the type of agent: nutrient and related agents, and molecular-targeted agents.[49]

Nutrient & Related Agents While many compounds, such as certain vitamins, minerals, and naturally occurring phytochemicals, have looked promising for chemoprevention in epidemiological studies,[50] to date, there have been few positive impacts on cancer incidence.[1] For example, the recently completed Selenium and Vitamin E Cancer Prevention Trial (SELECT) involved 35,000 men in a study of placebo compared with selenium and vitamin E singly or in combination and found no effects on the target of prostate cancer prevention.[51]

In fact, randomized trials have shown that some supplements may increase the risk of cancer.[49] One of the best known examples is the The β-Carotene and Retinol Efficacy Trial (CARET), a randomized trial that built on epidemiological findings demonstrating that β-carotene was linked with lower rates of lung cancer. Trial participants were individuals at high risk of developing lung cancer, and were randomly assigned to receive β-carotene or placebo. The trial findings indicated a significant increase in lung cancer and death in the β-carotene group.[52]

While this trial indicates that caution is warranted in such studies, there is considerable ongoing research in this area. In a search of trials worldwide, Amin and colleagues identified 31 current clinical trials using natural compounds for cancer prevention.[53] Agents being studied include green tea, curcumin (found in turmeric powder), resveratrol (red wine), geninstein (soybeans), pomegranate, lycopene (tomatoes), and n-3 polyunsaturated fatty acids (cooking oils and dark, leafy vegetables). The results of these efforts will inform future intervention programs.

Molecular-targeted Agents Chemopreventive agents that affect hormone levels have been shown to prevent cancer. Tamoxifen is an estrogen receptor modulator and was the first US FDA-approved chemopreventive agent after it was found to reduce the risk of breast cancer incidence by 50% in high-risk women.[54–56] Another estrogen receptor modulator, raloxifene, which was developed as an osteoporosis drug, has recently been found to be as effective as tamoxifen in preventing breast cancer, but with fewer side effects.[57,58] Finasteride, a chemopreventive agent for prostate cancer, was found to reduce incidence by 25% in men at high risk.[59] However, the side effects of all of these agents can be considerable (e.g., uterine cancer, blood clots, stroke, menopausal symptoms for tamoxifen, erectile dysfunction, lowered sexual desire, impotence and gynecomastia for finasteride).[54,55,57–59] Such side effects limit the use of these chemopreventive drugs in healthy populations and may impede their uptake, even in high-risk groups. However, this research has provided 'proof of principle' that cancer can be prevented through molecularly targeted agents, which paves the way for the development of efficacious and acceptable approaches in the future.

Cohort Studies to Identify New Causes of Cancer

Although the causes of many cancers are known, and approximately half could be prevented through modification of behavioral risk factors, the causes and risk factors for some kinds of cancers (e.g., many brain tumors and lymphomas) remain largely unknown. Additional risk factors are also important to explain variation, even in cancers where significant causes have been identified, and research is needed to identify cancer causes. Cohort studies – in which individuals are assessed for behavioural and biological factors and followed prospectively for future health outcomes – provide important clues to cancer etiology. Much of our current knowledge of cancer risk factors is based on the associations that have been found between risk factors and diagnosed cancers in cohort studies. There is currently a stunning array of cancer cohort studies being conducted around the world. Many of these studies belong to the Cohort Consortium hosted by the US National Cancer Institute.[111] As of October 2009, the Cohort Consortium included 39 cohorts representing over 4 million individuals. Among the largest of these studies are the European Prospective Investigation into Cancer and Nutrition (EPIC) study,[112] which includes over 520,000 people in ten European countries (Denmark, France, Germany, Greece, Italy, The Netherlands, Norway, Spain, Sweden and the UK), the Multiethnic/Minority Cohort Study of Diet and Cancer,[113] which includes 215,000 men and women, primarily of African–American, Japanese, Latino, Native Hawaiian and Caucasian origin, from Hawaii and Los Angeles (CA, USA), and the American Cancer Society Cancer Prevention Study II,[114] which includes approximately 1.2 million US men and women in its baseline assessment.

All of the cohorts include risk factor assessment and biological specimens, and approximately half of the individuals (2 million people) have germline DNA banked. These data will enable the investigation of the interaction between genetic and environmental factors, currently an area at the cutting edge of oncology. The mission of the Consortium is to provide "a coordinated, interdisciplinary approach to tackling important scientific questions, economies of scale, opportunities to quicken the pace of research, and a collaborative network of investigators".[111] Some of the current initiatives using pooled data from multiple cohorts include studying genetic factors underlying breast and prostate cancer, identifying risk factors for pancreatic cancer, and assessing the role of vitamin D in cancer etiology. Pooled assessments enable the detection of effects not possible in a single study, and the ability to replicate findings in different subsamples. The results of such analyses are generally suggestive rather than definitive and provide leads to be followed-up in subsequent laboratory, clinical and population studies.

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