Cancer Prevention, Screening, and Early Detection
Summary of Key Points
Etiology and Pathogenesis
• The six hallmarks, or cardinal derangements, characterizing all epithelial cancers are sustained proliferative signaling, evasion of growth suppressors, activation of invasion and metastasis, replicative immortality, induction of angiogenesis, and resisting cell death. These six hallmarks tend to occur in a permissive context characterized by four features: suppressed immune surveillance, tumor-promoting inflammation, cellular dysregulation, and genome instability and mutation.
• Tobacco, which accounts for 30% of all cancers and 90% of lung cancers, is the greatest modifiable risk factor for cancer. The use of tobacco is on the rise in developing nations, and declines in smoking prevalence in the United States have recently begun to slow. Tobacco is likely to remain an important public health issue in the United States and globally for the foreseeable future unless tobacco control strategies can be more fully implemented and sustained.
• After tobacco, obesity has the highest attributable cancer mortality. Recent evidence suggests that obesity, resulting at least in part from excess caloric intake, is a key driver in cancer development. Diet, physical inactivity, infections, and sun exposure contribute to cancer risk as well.
• Data related to the role of nutrition in cancer risk is more persuasive for specific foods, rather than for specific nutrients or other food constituents. A few factors have been “convincingly” associated with an increased risk of cancer, as classified by the American Institute for Cancer Research, but none has been “convincingly” associated with a decreased risk.
Prevention
• Cancer incidence is set to double by 2030 as a result of a growing and aging population.
• Nearly two thirds of all cancer deaths are attributable to tobacco, poor diet, physical inactivity, and obesity.
• We can prevent approximately half of all cancers occurring today by implementing tools and knowledge we already have.
Chemoprevention
• Thirteen chemopreventive agents have been approved by the U.S. Food and Drug Administration for treatment of precancerous lesions or to reduce the risk of invasive cancer, nearly all of which are for accessible organs.
• The identification and eradication of a number of infectious, oncogenic agents can yield significant cancer preventive benefits as well. Globally, about 18% of cancers have an infectious etiology. In addition to the use of the human papillomavirus vaccines, vaccination for hepatitis B, “triple therapy” for Helicobacter pylori, and treatment of chronic hepatitis B and C can yield a marked reduction in the cancer burden in regions where these agents are endemic, although these medical interventions are not labeled for a cancer preventive indication.
• Because chemoprevention focuses on healthy individuals in whom cancer may never develop, balancing the risks and benefits of any chemopreventive intervention is central to their development.
• In the future, chemopreventive trials must be smaller, faster, cheaper, and focused on high-risk cohorts and drug combinations. Integrative assessments of the full range of benefits and risks of chemopreventive agents across cancer sites and diseases will also be important.
Screening
• Population-based screening tests are available for the following cancers: cervical (Papanicolaou test), colon (colonoscopy, fecal occult blood testing, flexible sigmoidoscopy, and double-contrast barium enema), breast (mammography), and prostate (prostate-specific antigen test).
• The National Lung Screening Trial study demonstrated that low-dose helical computed tomography screening can reduce lung cancer mortality by 20%.
• Numerous genomics-based and proteomics-based approaches are attempting to identify biomarkers that can aid in the risk assessment and early detection of various cancers.
1. Which of the following distributions best represents the most recent estimates of the relative contributions of individual risk factors to overall cancer mortality?
A Tobacco, 30%; diet 35%; physical inactivity, 5%; obesity, 20%
B Tobacco, 25%; diet, 25%; physical inactivity, 25%; obesity, 25%
C Tobacco, 30%, diet, 5%; physical inactivity, 5%; obesity, 20%
D Tobacco, 35%; diet, 15%; physical inactivity, 10%; obesity, 10%
2. Agents to treat precancerous lesions or reduce cancer risks (i.e., chemopreventive agents) are currently approved by the Food and Drug Administration for use in all of the following organs, except:
3. For which of the following stages of progression from human papillomavirus (HPV) infection to invasive cervical cancer do we not have interventions to reduce or prevent the risk of developing cervical cancer?
4. What is the impact of computed tomography (CT) screening on lung cancer–specific and overall mortality, as demonstrated by the National Lung Screening Trial (NLST)?
1. Answer: C. Tobacco is the single greatest contributor to cancer mortality, accounting for nearly one third of all cancer deaths. Obesity is the second greatest contributor, responsible for approximately one fifth of all cancer deaths. Diet and physical inactivity are also significant risk factors, each accounting for approximately 1 in 20 cancer deaths. These estimates are best represented by the distribution in C.
2. Answer: D. Chemopreventive agents are available for reducing the risk of breast cancer (Tamoxifen and Raloxifene) and cervical cancer (human papillomavirus vaccines—Gardasil and Cervarix), and for treatment of precancerous lesions of the esophagus (photodynamic therapy + Photofrin) and skin (fluorouracil, diclofenac sodium, 5-aminolevulinic acid + photodynamic therapy, and ingenol mebutate). Although Celecoxib was initially approved for use to reduce the burden of colonic adenomas in individuals with familial adenomatous polyposis in conjunction with usual surgical management, its approval was subsequently withdrawn in 2011 when confirmatory trials proved challenging.
3. Answer: C. Vaccines against the HPV can block or reduce the risk of HPV transmission between individuals, acute HPV infection after exposure to an infected individual, and the development of precancerous lesions and cancers of the cervix. However, once a person has been infected with HPV, we do not currently have interventions that are known to block the development of persistent HPV infections. Risk factors for persistent HPV infections include older age, certain HPV strains, and immunodeficiency.
4. Answer: B. Results of the NLST, as reported by Aberle et al., demonstrated a 20% reduction in lung cancer mortality in high-risk patients undergoing low-dose helical CT screening compared with those receiving chest radiography. Furthermore, the NLST demonstrated that mortality due to any cause was reduced by nearly 7% in the CT group compared with the radiography group.
