Cancer Exam 2

gold standard (medical definition)

"Any standardized clinical assessment, method, procedure, intervention or measurement of known validity and reliability which is generally taken to be the best available, against which new tests or results and protocols are compared." --the definitive test is a biopsy of the suspected tumor.

randomized clinical trials for screening test efficacy

-Basic procedure: Eligible individuals are randomized to the group that receives periodic screenings or to the control group who are left to follow their usual level of medical care. --Patients are followed for cancer-free survival or cancer-specific mortality. -Key problem: once a screening test becomes the standard of care, it is unethical to evaluate it using a RCT, and deprive the control group of access to it

hpv subtype 16

- etiologically associated with oral cancers, and is thought to be transmitted through oral sex (horizontal transmission) -Different causal pathway to oral cancer than tobacco and alcohol associated tumors: --HPV associated tumors tend to occur on the tonsillar area, the base of the tongue and the oropharynx, whereas non-HPV associated tumors tend to involve the anterior tongue, floor of the mouth, the mucosa that covers the inside of the cheeks and alveolar ridges --HPV associated tumors also occur more frequently in younger ages than tobacco related oral cancer, with the highest rate in white male non-smokers

National Cancer Institute's definition of disparities:

-"Cancer health disparities are adverse differences between certain population groups in cancer measures, such as: --incidence (new cases), --prevalence (all existing cases), --morbidity (cancer-related health complications), --mortality (deaths), --survivorship and quality of life after cancer treatment, --burden of cancer or related health conditions, --screening rates, and stage at diagnosis."

group 1: Carcinogenic to Humans

-"Known Human Carcinogen" -This category is used when there is sufficient evidence of carcinogenicity in humans. In other words, there is convincing evidence that the agent causes cancer. -as of July 2020 there were 120 agents

Many separate variables may be used to capture SES including:

-% with High School Degree (or other measure of educational attainment) -Median household income - % in poverty -% in management occupations - % on public assistance income -% female head of household with dependent children - % vacant homes

follow up for HPV positive women

-CINtec® PLUS Cytology - Dual-stain test; FDA approved for women who have tested positive for HPV --Measures the presence of two specific proteins, p16 and Ki-67, in a sample of cervical cells --Expression of p16 is strongly linked with HPV infection, and Ki-67 is used as a biomarker for the rapid cell division seen in precancers and cancer -Women with positive dual-stain test result should get a biopsy to check for cervical precancer or cancer -Women with negative dual-stain test result can safely wait 3 years before getting screened again

HTLV-1 treatment

-Currently no cure or treatment for HTLV-1 -Considered a lifelong condition, but most (90-95%) infected people remain asymptomatic throughout lifespan -Only small proportion will develop ATLL

Time line of key public health measures related to tobacco/cigarette control, 1950 - 1998

-1950 First reports linking smoking with cancer (Doll and Hill's landmark report) -1964 U.S. Surgeon General's Report on Smoking and Cancer -1967 Fairness doctrine messages on TV and radio gave equal time for smoking prevention messages ; 1st World Conference on Smoking and Health held in New York -1970 Nixon signs laws banning cigarette ads on television and radio; and mandating warning -1977 Start of the non-smokers rights movement and first Great American Smoke-out -1980s Dramatic increase in federal and state cigarette tax; smoking begins to be banned in some federal worksites -1986 IARC declares tobacco smoke a Group 1 carcinogen; U.S. Surgeon General's Report on Environmental Tobacco Smoke -1988 Smoking banned on short domestic flights in the U.S. -1995 California is the first state to enact a statewide smoking ban - many more states would follow during the early to mid 2000s -1996 Nicotine medications available over the counter; smoking banned on U.S. international flights -1998 Tobacco Master Settlement agreement

First systematic assessment of mammography through randomized clinical trial

-1968 -found 35% decrease in breast cancer mortality among women 50-69 who received periodic screenings compared to non-screened women --many, but not all studies using RCTs show similar results --furthers upport: in US, mortality rate from breast cancer dropped from 1973-1990 --unclear how much due to mammography, earlier detection of palpable tumors and/or adjuvant systemic therapy -since 1968, mammography has become more widely used

landmark events that have given rise to how we currently approach cancer and other health disparities

-1973 Hensechke et al -1985 Dept. of Health and Human Services (Heckler report) -1989 Special report on cancer (Freeman)

example of cancer cluster

-1974 - occupational physician in B.F. Goodrich plant near Louisville, Kentucky reported four cases of a very rare cancer called angiosarcoma of the liver --Cases occurred during 1967-1973 --All four men had worked for at least 14 years in the section producing polyvinyl chloride using vinyl chloride monomer (VCM) --follow-up studies by epidemiologists confirmed the association between VCM and this rare cancer

Hepatocellular carcinoma in europe

-71% of newly diagnosed liver cancer cases are infected with HBV or HCV -This increase has been largely attributed to the increase of HBV in these populations, due to increased migration of people from highly endemic areas --Now, even countries with low endemicity are experiencing the burden of HBV

heliobacter pylori

-A Gram-negative spiral bacterium that can colonize in the human stomach --Unique ability to survive in gastric juices due to ability to produce an enzyme that locally reduces acidity, penetrate the stomach wall's protective mucous coating, and migrate to the epithelial surface where it anchors --Several distinct strains exist with different propensities to cause disease -H. pylori is believed to be the most common cause of chronic infection globally --Estimated to infect about half of world's population, with higher prevalence in economically developing countries (up to 80% of the population)

causal association with stomach cancer and H. pylori

-A large number of epidemiologic studies support it --Most strongly linked to virulent form of H. pylori that carries the CagA gene --Risk is highest for gastric cancer in the non-cardia areas of the stomach - 8 fold risk --Odds ratios range from 1.92 to 2.56 --Further evidence: individuals treated with antibiotics for H. pylori infection reduces the risk for stomach cancer

case control designs for screening test efficacy

-A useful design, but also present inherent methodological challenges when attempting to evaluate the efficacy of cancer screening. ◦Ideal for studying rare diseases - many forms of cancer are rare in general population -Often used for mortality studies --Cases died of cancer under study --Controls are drawn from general population and should be healthy --Then both are compared for use of screening --If control and case subjects have the same screening rate, the screening test has no effect on mortality (no efficacy) -Remember the principle of reciprocity: --A control must have had the opportunity to become a case --A case must have had the opportunity to become a control

Current recommendations for lung cancer screening

-Annual screening for lung cancer with low-dose computed tomography (LDCT) is recommended for adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years --Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery

The American Cancer Society recommends annual lung cancer screening with a low-dose CT scan (LDCT) for certain people at higher risk for lung cancer who meet the following conditions:

-Are aged 55 to 74 years and in fairly good health, and -Currently smoke or have quit within the past 15 years, and -Have at least a 30-pack-year smoking history, and -Receive smoking cessation counseling if they are current -Have been involved in informed/shared decision making about the benefits, limitations, and harms of screening with LDCT scans, and -Have access to a high-volume, high quality lung cancer screening and treatment center.

asian pacific islanders and cancer

-Asian/Pacific Islanders tend to have the lowest rates of our most common cancers, such as those of the lung, breast, prostate and kidney --May reflect differences in lifestyle, especially traditional diet and higher income in U.S. -They tend to have higher rates of infectious-origin cancers, however, particularly among the foreign born

Global outlook on prostate cancer screenings

-At present, the utility of mass screening for Prostate cancer using PSA remains highly controversial in many countries. -On the right, a summary presented at an international conference on Prostate Cancer in 2019 -Currently, more national professional groups or task forces recommend against PSA screening than are in favor of it

HCV prevention

-At present, there is no vaccine available, but research in this areas is ongoing -Other primary prevention strategies are strongly recommended to cut down on transmission, such as practicing safe sex and not sharing needles

Breast cancer by Stage at Diagnosis in Selected Countries

-Countries that detect more early stage disease (Stage 1, Stage II) have better resources and to conduct mass screening programs and public service campaigns than those detecting later Stage cases (Stage III, Stage IV) -Stage at diagnosis is strongly associated with 5-year survival

cohort studies for screening test efficacy

-Can offer stronger evidence of efficacy than case control studies, but the cancer in question must occur frequently enough in the population being followed to yield sufficient data for analysis -Basic design: begin by following a large group of healthy people then observed behaviors over time - compare who gets screened, who doesn't, with who dies of cancer -This design may not be practical, is very time consuming and costs a great of money to undertake -Not a good design for rare diseases!

-The associations between infectious agents and cancer may be best summed as follows:

-Cancer results from a complex and multistage process involving multiple factors --The infectious agent may play a role at different points in the pathogenesis in conjunction with other factors -Cancer is also multi-causal --Infectious agents, as well as toxins, chemicals or other causal factors may all be capable of initiating or promoting the processes that result in cancers with the same histologic features -Always remember that there is likely to be more than one multi-factor, causal pathway that can result in the development of the same type of cancer -- example: Consider oral cancer, which has been associated with tobacco exposure as well as HPV.

Who survives cancer?

-Cancer survival in a population is affected by a number of factors: --The types of cancer that occur --The stages at which they are diagnosed --The prevalence of screening/early detection services --Whether treatment is available -Survival rates are also affected by disease awareness and data quality in countries -There can also be survival differences within a country that reflect differences in access to screening and treatment -- Example: 5-year survival for cervical cancer in the United States in 2004-2009 was 64% among Whites vs. 56% among blacks -Globally this varies by country and health system --National health systems help to reduce disparities within their populations for diagnosis and treatment --Differences in risk by SES, race/ethnicity, sex, urban/rural location, etc.

HTLV-1 has been associated with Adult T-Cell Leukemia/Lymphoma (ATLL)

-Cancer thought to be a rare outcome of a fairly common viral infection -Striking feature of ATLL is the geographic clustering of cases in Japan -ATLL is also found in other parts of the world, notably among Japanese migrants

lead time bias

-Cancers detected by screening are diagnosed earlier and would have longer apparent survival than clinically detected cases, even if treatment is ineffective -The perception that screening lengthens survival, but in reality it doesn't

Current recommendations for cervical cancer screening

-Cervical cancer screening (testing) should begin at age 21. Women between ages 21 and 29 should have a Pap test every 3 years. HPV testing should not be used in this age group unless there is an abnormal Pap test result. -Women between the ages of 30 and 65 should have a Pap test plus an HPV test every 5 years OR have a Pap test alone every 3 years -Women over age 65 who have had regular cervical cancer testing with normal results should not be tested for cervical cancer, as long as they have not had any serious pre-cancers found in the last 20 years.

parasites and cancer

-Chronic parasitism involving Schistosoma and liver flukes are associated with an increased risk of certain cancers

cigars

-Cigar smoke, like cigarette smoke, contains toxic and carcinogenic substances --Cigars actually contain a higher level of some cancer-causing substances than cigarettes, such as nitrosamines and tar --The longer burning time of a cigar results in greater exposure to carbon monoxide, hydrocarbons, ammonia, cadmium and other substances --The porous wrapper makes the burning of the cigar more complete, also results in greater exposure to toxins than in cigarette smoke -Cigar has been found to cause cancers of the oral cavity cancers (cancers of the lip, tongue, mouth, and throat) and cancers of the larynx (voice box), esophagus, and lung --Whether or not they inhale, cigar and cigarette smokers directly expose their lips, mouth, tongue, throat, and larynx to smoke and its toxic and cancer-causing chemicals. --The esophagus also becomes exposed and at higher risk for cancer when saliva containing the chemicals in tobacco smoke is swallowed

cigarette consumption in the US

-Cigarette consumption has changed considerably during the past century in the U.S. -1880 to about 1915: Cigarettes are a very small proportion of tobacco consumption. Cigars, roll-your-own, and chewing tobacco account for most tobacco use during this period -1915 to 1945: There is a steady increase in cigarette consumption per capita -1945 - 1965: Cigarette consumption levels off -1965 - 1995: Cigarette consumption declines dramatically

association of EBV with burkitt's lymphoma

-Clear geographic association between infection and the disease -Endemic in tropical Africa --Restricted to areas of sub-Saharan Africa ---Cases tend to occur in areas of low altitude, high annual rainfall, high temperature, and humidity ---Distribution matched endemic Malaria (important cofactor) --Most cases EBV+ -Occurs with intermediate frequency in Egypt, Brazil, turkey, Mexico --80% of cases are EBV+ -Occurs sporadically occurs in western Europe and North America --20% of cases are EBV+

cofactors of EBV and Nasopharyngeal cancers

-Cofactors may include genetic susceptibility and dietary exposures --Rare among North American and European whites --More common among Chinese, Malaysians, Greenland Inuit, and native Hawaiians

cohort studies on HBC

-Cohort studies have found consistent, elevated risks for HBV+ males compared to HBV- males --One large cohort study conducted among Taiwanese males with an internal comparison group found a relative risk of 98.4 ---Huge relative risk, but actually thought to underestimate the true risk ---Other studies using rates in the general population for comparison reported relative risks ranging from 5.6 to 10.4, which are thought to greatly underestimate the actual risk ---Clear temporal relationship; infection with HBV preceded the onset of disease -◦Case control studies report similar findings, with odds ratios ranging from 7.0 to 58.2

When comparing one group to another (Group Disparities), which group should be the referent?

-Comparison to largest group frequently examined, but should they be the referent if they don't have the lowest rates? -Or, should the group with the lowest rates be the referent?

virtual colonoscopy

-Computerized tomographic colonography (X_ray) image of entire colon -Efficiency: sensitivity of virtual colonoscopy to detect lesion was 97.4% and specificity was 100% (optical colonoscopy being the Gold Standard had a sensitivity and specificity of 100%)

HPV treatment

-Currently there is no cure for an existing HPV infection -However, your immune system will try to clear it - it usually clears in most people -Treatments available for symptoms caused by HPV (genital warts in particular)

inequality

-Differences in health status or the distribution of health determinants between different populations groups. -These differences may be unnecessary, avoidable, considered unfair and unjust. -Differences may also be due to biological variation or free choice or due to conditions in the external environment mainly outside the control of the individuals concerned and/or larger society

why are there differences?

-Disparities in race/ethnicity and sex can involve biological, environmental and behavioral factors. --There are also many within-group differences such by age, SES, ancestry, and sexual orientation that these numbers obscure -- Patterns at state or local level may also be substantially different ---Often lots of regional differences such as those between rural and urban areas, depending on the cancer -foreign born populations often have much higher rates for cancers with an infectious component than native born populations such as for liver/bile duct stomach cancers -higher rates of mortality, particularly where incidence is lower, often indicated individuals are getting diagnosed later or have cancers that are more aggressive, both of which are less amenable to treatment

Hepatitis B virus

-Double stranded DNA virus of the hepadnaviruses family --Viruses in this family have the same gene structure and replicate in the same way -Have an affinity for hepatic cells and cause liver infections -Epidemiologic and experimental evidence supports a strong causal association between HBV and hepatocellular carcinoma (primary liver cancer) -Vertical transmission leads more often to persistent lifelong infection than horizontal transmission -Hormones appear to be related to cancer risk --Males and females are equally likely to become infected with HBV at birth, but infected males are 3 times more likely than infected females to develop hepatocellular carcinoma --Evidence from animal studies also support this: HBV+ female rats treated with male hormones develop disease rates close to the rates observed in HBV+ male rats

vaping

-E-cigarettes heat nicotine (extracted from tobacco), flavorings and other chemicals to create an aerosol that you inhale -Current research clearly indicates vaping is not a safe or healthy alternative to smoking --May be more socially acceptable, but not the same as safe -Long-term health effects of vaping not well understood yet --Do know that nicotine is a highly addictive substance with known dangerous side effects -Vaping among young adults who never smoked cigarettes is a particular concern

Evidence for the association of EBV with B-Cell lymphoma:

-EBV is a double stranded DNA virus that multiplies in B lymphocytes -Once infected B lymphocytes can grow continually in a cell culture, where they lose contact inhibition and develop new surface antigens -Virus has been shown to cause malignant lymphoma in several primate species -EBV can cause a number of host responses, including subclinical infections and infectious mononucleosis, after which the virus can remain in a latent state within epithelial cells -◦EBV is not a complete carcinogen Appears to be part of a multistep carcinogenic process -Infection with the virus is widespread, but the associated cancers are rare --Important cofactors involved for lymphomas --Immunosuppression appears to be very important ---immunosuppression can lead to reactivation of latent EBV ----An excessive number of lymphoma cases have been observed in renal transplant patients, patients with inborn immunodeficiency disorders, and patients with immunodeficiency due to AIDS who are EBV+

two important evens in early 2000s health disparities

-Eliminating disparities set as a national goal by the U.S. Surgeon General --Target goals of Healthy People 2010 -Center to Reduce Cancer Health Disparities was established as part of the National Cancer Institute -Key goals: --Understand the causes of disparities in cancer --Work on reducing and eliminating them Lots of reports, data, etc. --Used as resource in preparing this lecture

Regular, or standard, optical colonoscopy

-Entire colon is examined using , including upper part that sigmoidoscopy misses

association of HPV with other cancers

-Epidemiologic and laboratory data strongly support that HPV is etiologically related to anal cancer --Evidence of increased risk with increasing levels of anal intercourse (horizontal transmission) ---HPV DNA detected in 93% of women and 69% of males with anal cancer ---84% of anal cancer specimens were positive for high risk HPV, especially subtype #16

efficacy in uterine cervix cancer screening

-Evidence for efficacy comes from the large drop in mortality after Pap test began being used in the U.S.: --1950-1970: 70% drop in mortality from invasive cervical cancer --1970-1990: an additional 40% drop in mortality -Other studies also support the efficacy of the Pap test: ◦In the U.S., half of all invasive cervical cancers occur in women who never had a Pap test. -An additional 10-20% occur in women that did not have a Pap test in previous 5 years -25% of cervical cancers in the U.S. were in women with an abnormal Pap test result, who either did not return for care or where the clinician did not perform recommended follow-up tests or treatment

general patterns for who survives cancer

-For cancers that are more amenable to screening and/or treatment, such as breast, colorectal, cervical, stomach and certain childhood cancers, there are large survival differences by HDI level --5-year survival rate for breast cancer in 2010-2014 was 90% in the U.S. and Australia vs. 65% in Malaysia -For cancer sites without early detection or effective treatment, such as liver, lung, or pancreas, survival rates vary less by HDI

prostate cancer

-For many - perhaps most men - prostate cancer is a slow growing, 'indolent' cancer --Would not progress to clinically meaningful disease in their lifetime --In non-aggressive form, low risk of death from disease --More likely to die from another health issue --Screening is not of value to these men, and on a population level this results in many unnecessary medical procedures ---Biopsy of prostate is painful ---May elect to get unnecessary treatment, with consequences: ----Radical prostatectomy can have many serious side effects including loss of continence, impotency, and even risk of death ----Radiotherapy carries risk from radiation, may increase risk of second cancers in the pelvic area --Psychological stress (even with 'watchful waiting" )

Numerous populations may be affected by disparities including, but not limited to

-racial and ethnic minorities -residents of rural areas -persons with disabilities -persons of low socioeconomic status

Current recommendations for prostate cancer screening

-For men aged 55 to 69 years, the decision to undergo periodic prostate-specific antigen (PSA)-based screening for prostate cancer should be an individual one --Men should be informed of uncertainties, risks and potential benefits --African Americans and men with family history of prostate cancer, are at higher risk for prostate cancer -For men aged 70 years and older: The USPSTF recommends against PSA-based screening for prostate cancer -Age 50 for men who are at average risk of prostate cancer and are expected to live at least 10 more years. -Age 45 for men at high risk of developing prostate cancer. This includes African Americans and men who have a first-degree relative (father or brother) diagnosed with prostate cancer at an early age -Age 40 for men at even higher risk (those with more than one first-degree relative who had prostate cancer at an early age). -After this discussion, men who want to be screened should get the prostate-specific antigen (PSA) blood test. The digital rectal exam (DRE) may also be done as a part of screening

prostate cancer screening

-For some men, prostate cancer can be deadly --In U.S., second only to lung cancer in male cancer mortality ---In aggressive form, a fatal disease ---Once metastasized, likes to spread to the bones ---Early detection and treatment is important ----Radical prostatectomy and/or radiotherapy often used ---Screening helps identify these men within a window of cure, before the cancer invades/spreads beyond the prostate capsule

S. mansoni

-Geographic distribution: Widespread in Africa and the only species in the Western Hemisphere, endemic in Brazil, Surinam, and Venezuela and on some Caribbean islands -Currently not classified by IARC (inadequate evidence)

Global Outlook on Cancer Disparities

-Globally, the incidence, mortality and survival from cancer varies by HDI --

colorectal cancer screening

-Goal is to detects cancer as well as polyps and nonpolypoid lesions (areas of abnormal cell growth) that may --Polyps often take 10-15 years --Finding and removing polyps or other areas of abnormal cell growth is an effective way to prevent colorectal cancer development -Colorectal cancer is generally more treatable when it is found early, before it has had a chance to spread. -Several screening options, all have advantages and disadvantages --Tests may be used alone or in combination, depending on various factors

prevention for H. pylori

-H. pylori bacteria may be passed from person to person through direct contact with saliva, vomit or fecal matter, so improved hygiene; H. pylori may also be spread through contaminated food or water -A vaccine would be ideal, but there have been obstacles to development- currently no advanced vaccine candidate is in development -Improved hygiene, such as washing hands may help

How does HBV infection increase the risk for cancer?

-HBV causes chronic inflammation, fibrosis and immune responses --Leads to hyperproliferation of cells in the liver, which may introduced mutations that eventually escape DNA repair systems -May foster genetic instability in DNA repair process -Other areas currently being researched

basic causal mechanisms for HPV

-HPV encodes for two trans-scripting genes that create proteins that interact with tumor suppresser genes and cause these products not to function

implications for defining disparities

-How data are collected and interpreted -How results are measured and applied to overall goal of eliminating disparities

HDI

-Human Development Index -The HDI is a composite index, also constructed based on multiple variables like the deprivation index introduced earlier -HDI includes a wider range of variables, not just measuring SES -Used in reports to evaluate cancer disparities

Global outlook on cervical cancer screenings

-IARC's World Cancer Report indicates that only 18% of countries that currently provide screening for cervical cancer reached the recommended target of more than 70% coverage --An estimated 55% of low-income countries that reported offering cervical cancer screening generally lack accessible radiotherapy or surgery services -At this pace, global elimination of cervical cancer is not predicted until 2120 -More than one prevention strategy is needed --HPV vaccination + two cervical screenings in her life would accelerate elimination by 11 - 31 years, depending on the country --WHO predicts that if no action is taken, cervical cancer deaths will rise globally by 50% by 2030

"Black-White" differences

-In the U.S., we often compare the rates between Blacks and Whites◦ --Historically, differences were even greater than we observe today -In mid 2000s, started to narrow due to downward trends in tobacco use by African American males --We see evidence of this in declines in the rate of lung cancer

pap test results

-In the United States, about 3 million abnormal Pap test results are found each year. --In a low-risk population, most Pap test results are normal. -abnormal results are reported according to the Bethesda system and include --low-grade squamous intraepithelial lesion --high-grade squamous intraepithelial lesion --squamous cell carcinoma

low-resource countries

-In these countries, the majority of cancer patients are diagnosed with advanced-stage disease --Only effective treatment options are pain relief and palliative care ---Relies on use of inexpensive oral pain medications ranging from aspirin to opiates ---Sufficient access to opioid drugs for use in palliative care resource countries is often not available ---- Due to regulatory or pricing obstacles, lack of training and knowledge among health workers, and weak health care systems

What differences in our main outcome measures may indicate

-Incidence --Reflects differences in risk factors for disease --Stage at diagnosis reflects -Survival --Reflects differences in treatment, stage at diagnosis --Reflect differences in tumor type or other biological factors associated with the progression of the disease -mortality --Reflects factors contributing to survival (see above) --Mortality rates may be lower (or higher) due to death from competing risks ---Competing risks = other causes of death -Low incidence coupled with high mortality may be particularly indicative of disparities in screening and treatment

High-grade squamous intraepithelial lesion (HSIL)

-Indicates moderate or severe cervical intraepithelial neoplasia or carcinoma in situ -About 20% will progress to cancer if not treated

Low-grade squamous intraepithelial lesion (LSIL)

-Indicates possible cervical dysplasia, typically caused by a human papillomavirus infection -Usually resolves spontaneously within two years and managed by watchful waiting. -Chance of progression to more severe dysplasia, so colposcopy with biopsy may -If the dysplasia progresses, treatment may be necessary.

SES & Disparities: key findings

-Individuals in more SES deprived areas or lower education and income groups had higher mortality and incidence rates than their more affluent counterparts --Excess risks being particularly marked for lung, colorectal, cervical, stomach, and liver cancers. --Inequalities in mortality from all-cancers, lung, prostate, and cervical cancer increased during 1979-2011 in the U.S. --Cancer patient survival was significantly lower in more deprived neighborhoods and among most ethnic- minority groups --Risk taking behaviors, obesity, screening/treatment rates often differ by SES

inequities

-Inequities are inequalities that are deemed to be unfair or result from some form of injustice. -What constitutes an inequity relies on moral or ethical judgment and is not always unambiguously measurable or observable.

vertical transmission of HBV

-Infection from infected mother to child may occur in utero or during neonatal period --The younger the age of HBV acquisition, the higher the probability of chronicity and associated problems

horizontal transmission of HBV

-Infection may also occur between adults through contaminated blood supply

liver fluke infection association with cholangiocarcinoma, or bile duct cancer

-Infection with flukes also involves chronic inflammation process as well as cellular and structural changes in the biliary ducts -Latency between infection and malignancy is typically decades long

HCV treatment

-Intended to clear the virus from your body -May be done using one medication or a combination of two to three medications to be taken for 12 - 24 weeks or longer -Successful in over 90% of people with hepatitis C, reducing the risk of death from liver cancer and cirrhosis

HPV and cofactors

-Interaction between immune suppression and HPV --HIV+ women have higher rates of cervical intraepithelial neoplasia -Smokers are more likely than nonsmokers to have mutagenic cervical fluids --Smoking may have an immunologic effect that allows HPV to persist in cervical cells --Smoking may contribute to chromosomal instability -Nutrition and HPV --Some support that low levels of vitamin C and carotenoids are at increased risk for cervical neoplasia --Low foliate consumption may also be related

International Agency for Research on Cancer (WHO)

-International expert working groups evaluate the evidence of the carcinogenicity of specific exposures -The data is drawn from fields including epidemiology, toxicology and genetics; evidence from human studies, animal studies, metabolic and mechanistic experiments are all considered -Each substance that is evaluated receives a classification reflecting IARC's assessment of its carcinogenicity -The assessment is published as a report:, entitled: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, published 1971 to present --Since 1971, more than 1000 agents have been evaluated, of which more than 400 have been identified as carcinogenic, probably carcinogenic, or possibly carcinogenic to humans

key problem to prostate cancer screening

-It is not possible to know how the cancer will proceed based on screening tests --Biopsy provides confirms if cancer is present and provides more information, but it is not definitive in terms of prognosis --And once diagnosed, can cancer ever been ignored? -Currently, it is very controversial if PSA should be used as a mass screening tool on all men

occupation and cancer

-It's estimated that between 4 --10% of all cancer deaths in the U.S. each year may be due to occupational exposures --The workers at highest risk tend to be in manufacturing, mining, construction, mechanical, maintenance, or other blue-collar occupations --Among these high-risk groups, it is estimated that up to 20% of all cancer deaths may be work-related -Globally, the burden of occupation-related cancers is likely to be higher in countries where industry controls were only recently instituted or have yet to be --A disproportionate number of occupation-related cancers will occur in economically developing countries in future years

hepatocellular carcinoma globally

-Large differences by sex --For males worldwide - 2nd most common cancer in mortality -Half of all cases and deaths occur in China -In economically developing/non-Western countries --Infection with Hepatitis B or Hepatitis C common --Exposure to aflatoxin B1 (grain/crops) --Cholangiocarcoma - rare subtype- associated with Liver fluke infection -In Western countries, more often due to: --Obesity, --Type 2 diabetes --Alcohol-related disease (cirrhosis) --Fatty liver disease (obesity related) -Most cases can be prevented through vaccination, sanitary medical practices, healthy lifestyle choices, and environmental management strategies

Tobacco Master Settlement Agreement (MSA)

-Largest civil litigation settlement in U.S. history -Central purpose was to reduce smoking, and particularly youth smoking in the U.S. -Each of the 46 states gave up their legal claims that the tobacco companies had been violating state antitrust and consumer protection laws -The tobacco companies agreed to pay the states billions of dollars in yearly installments to compensate them for taxpayer money that was spent on patients and family members with tobacco-related diseases

cigarette smoking and premature death

-Life expectancy for smokers is at least 10 years shorter than for nonsmokers. -Quitting smoking before the age of 40 reduces the risk of dying from smoking-related disease by about 90% -Smoking still higher in some groups: males, lower education, below poverty level, disabled, LGBTQ, un/underinsured, mental health issues, and some race/ethnic groups

HBV treatment

-Most people diagnosed with chronic HBV need treatment for the rest of their lives --Reduces risk of liver disease including liver cancer --Prevents further spreading the virus to others -Treatment include a combination of antivirals and interferon injections; a liver transplant is another option, but this may not be available

challenges of determining if an infectious agent has etiologic association to cancer

-Like chemical carcinogens, viruses and other infectious agents only produce cancer in the host after a substantial incubation or latency period --Often many years, commonly in the range of 15 to 40 years -The initial infection with the infectious agent is often subclinical (a-symptomatic), so it is often difficult to determine how long an individual has been infected based on their clinical presentation -The virus or infectious agent may be common, even ubiquitous (widespread), whereas the related cancer may be uncommon (rare) --Host factors are likely to be of critical importance --Different strains of virus and different species of parasites may have different oncogenic potential --Also, there are likely to be differences in the geographic distribution of the infectious agent ---Particularly obvious for parasites, also true for viruses

S. japonicum

-Linked with cancer -Geographic distribution: Only in Asia, mainly in China and the Philippines -Considered by IARC to be a possible carcinogen (limited evidence) --Hepatocellular carcinoma (liver cancer) 2 to 10 fold increase in risk --Also limited evidence for association with colon and rectal cancer

Global outlook on lung cancer screening

-Lung cancer screening has been implemented in the United States, but at present, it is still under consideration in Europe - --So far, European study results indicate that LDCT can lead to a considerable shift to the diagnosis of early-staged lung cancers, this should reduce mortality ---Some European countries and medical societies have published recommendations for lung cancer screening using computed tomography --Key issue: health care systems differ between countries, even in higher income countries, and present issues both in cost and implementation and cost for this screening -In developing countries, organized screening programs for using LDCT are practically non-existent --Many challenges including cost, infrastructure, trained human resources, and issues raised by the likely over-diagnosis of lung cancer due to presence of pulmonary tuberculosis and other chest infections in many populations

Lung Cancer Screening

-Lung/bronchus cancer is the leading cause of cancer deaths for both men and women in the U.S. --Smoking accounts for up to 85-90% of lung cancer cases --Often diagnosed too late for treatment to be an effective --The five-year survival rate for lung cancer is 56% for early stage disease ---Only 16% of lung cancer cases are diagnosed at an early stage --For distant tumors (spread to other organs) the five-year survival rate is only 5% --Until very recently, the main option was for regular chest X-Rays/sputum cytology ---Evidence shows these do not reduce mortality from lung cancer. ---In particular, X-Rays have high-false positive rate and risks include exposure to radiation.

global outlook on breast cancer screenings

-Mammography screening is very costly and is cost-effective and feasible in countries with good health infrastructure that can afford a long-term organized population-based screening -Many low- and middle-income countries face a double burden of cervical and breast cancer --Combined cost-effective and affordable interventions to tackle these highly preventable diseases is needed -As per WHO, limited resource settings with weak health systems where breast cancer incidence is relatively low and the majority of women are diagnosed in late stages have the option to implement early diagnosis program based on awareness of early signs and symptoms and prompt referral to diagnosis and treatment

Global outlook on colorectal cancer screenings

-Many countries lack population-based colorectal screening programs despite having high colorectal incidence and mortality --Typically a problem in lower income countries --Due to limitations in resources including colonoscopy capacity, and the organization of structure of healthcare delivery -However, many countries without an existing screening program have this on the agenda and are expected to implement programs in coming years --Many will use non-invasive stool tests (FIT or gFOBT) for screening purposes

Workers in occupational settings are generally exposed to higher levels of chemical and physical agents than individuals in non-occupational settings

-Many of these chemical and physical substances are also found in smaller amounts in non-occupational settings --Examples: pesticides, solvents, metals, acids -If elevated risks are found at higher exposure limits, this serves as a warning that widespread community risk may exist --Occupation-related cancers are sometimes called sentinel events, which means they are an observed situation that serves to warn of a hazardous situation

◦Low dose CT (computerized tomography) or CAT scans

-More detailed images than X-Rays, lower dose of radiation -Randomized controlled trial evidence demonstrated a 20% relative lung cancer mortality benefit -This has led to endorsement of screening by several expert bodies in the US and funding by healthcare providers -As of 2019, however, cost-effectiveness of LDCT screening for lung cancer is a highly debatable issue

A large amount of time is spent at work and a growing number of chemical and physical substances or agents are found in workplace settings

-More than 80,000 substances are currently in use internationally, but estimates suggest that only 2% have been sufficiently tested for their potential carcinogenicity in humans -New substances, often associated with rapidly developing technologies, are likely to have unknown risks --Example: computer industry - exposure to solvents, acids, metals, lighting conditions, other environmental characteristics, some of which have not been adequately studied alone or in combination with each other -Evaluating the association between exposure to chemical and physical agents and the risk of cancer in workers is one way that epidemiologists help to identify previously unknown or suspected risks --Often the health effects of occupational exposures are not known until other host and/or environment factors are present, such as genetic susceptibility, combined exposure with other agents, smoking, alcohol use, etc. --The latency between exposure and the onset of symptoms is also a particular problem when identifying occupation-related cancers. In numerous cases it can be years, even decades, between exposure and the onset of clinical disease --The risk or hazard of workplace exposure to potentially carcinogenic substances is typically investigated using a retrospective cohort design and is based on employment records

prevalence and cancer

-Most major cancers have a preclinical prevalence that is less than 10% and the sensitivity and specificity of their screening tools are lower than those presented in our examples. --How can we get a better yield and have a higher positive predictive value? --Answer: target the groups with the highest preclinical prevalence -Recommendations for cancer screening tests always specify the population they are to be used on: --Specific age groups, often aged 50 + --Frequency often depends on presence of other well-established risk factors, such as a family history of the disease or race/ethnicity

Prevalence of cancer screening in U.S.

-National data is based on the Health Interview Survey 2015 (Smith et al. 2019): --Colorectal cancer screening in adults aged 50 years or more: ---Colonoscopy or sigmoidoscopy: 60.3% ---stool based test: 7.2% --Breast cancer screening in women aged 40 years or more: ---Mammography in previous year: 50.2% ---Mammography in previous two years: 64.3% --Cervical cancer screening in women aged 21-64 years ---Pap test in previous three years: 81. 6 % --Lung cancer screening in high risk smokers aged 55- 80 years ---Low-dose CT scan: 3.9% --Additional variation by geographic region, race/ethnicity and other factors

natural history of cervical cancer

-Natural history of cervical cancer --Still being determined, but predominate hypothesis appears to be: ---Most CIN 1 lesions regress and affected tissues return to normal; Remaining lesions thought to progress from low grade to high grade in the face of persistent HPV infection; High grade lesions can progress to invasive carcinoma -Odds ratios (OR) for HPV infection and increasing levels of cytological abnormality are strongly correlated (dose response) --Infection or inflammation: OR 2.6 --Atypia: OR 3.0 --CIN I: OR 11.7 --CIN II/III: OR 21.6

lung cancer - US males

-Non- Hispanic Black males have the highest incidence in lung cancer as well as the highest mortality

colorectal cancer - US males

-Non-Hispanic Black males also have the highest incidence and mortality from colorectal cancer -Again, Asian & Pacific islanders have the lowest mortality

prostate cancer - US males

-Non-Hispanic Black males have the highest incidence and mortality -Asian & Pacific islanders have a significantly lower mortality from this cancer

lung cancer - US females

-Non-Hispanic White females have the highest incidence and mortality from Lung cancer -Rates are lower among females Hispanics and Asian & Pacific Islanders

Opisthorchis and Clonorchis in humans

-Once inside humans, immature flukes migrate up through the ampulla of Vater to the biliary tree, mature in the small intrahepatic ducts --Mature worms chronically infect the bile ducts and more rarely, the pancreatic duct and gall bladder --They also produce eggs, which are passed in the feces --Mature worms can survive in the body for a very long time (25 years has been recorded) -Infection with flukes also involves chronic inflammation process as well as cellular and structural changes in the biliary ducts

Advantages of regular, or standard, optical colonoscopy

-One of the most sensitive tests currently available for detecting small polyps and lesions; precancerous and cancerous growths can be found and either removed or biopsied during the procedure

2. Cancer resulting from workplace exposure should be preventable

-Our goal is to reduce cancer incidence and mortality by implementing primary and secondary preventative measures -Confirmed information should lead to the removal of agents or adequate protection of potentially exposed workers -In the U.S., the Occupational Safety and Health Administration (OSHA) is charged with developing and enforcing workplace safety and health regulation.This includes agents that are carcinogens:

US patterns of disparities

-Overall, Non- Hispanic Whites have the greatest all-cancer incidence, but non-Hispanic Blacks have the greatest cancer mortality -Asian-Pacific Islanders have the lowest all-cancer incidence and cancer mortality

Papanicolaou test

-Pap smear; an exfoliative biopsy for the detection of conditions that can be early indicators of cervical cancer -names for greek doctor, Georgios Papanikolaou, who developed test in 1927 -used to detect potentially pre-cancerous and cancerous processes in the endocervical canal in the female reproductive system -does not detect every form of uterine cancer, but not detect many common forms of disease

HPV prevention

-Practicing safe sex -Vaccination --Gardasil - protects against four HPV types (6, 11, 16, and 18); FDA approved for use by females aged 9-26 to help prevent cancer of the cervix, vagina, and vulva; genital warts, and anal cancer; also approved for males aged 9-26 to help prevent genital warts and anal cancer --Cervarix - targets HPV types 16 and 18; FDA approved for females aged 10-25 to help prevent cervical cancer

Opisthorchis and Clonorchis treatment

-Praziquantel is the drug of choice for treating both Opisthorchis and Clonorchis; other medications may also be available --Second round of treatment may be needed for some patients -Patients with severe or advanced sequelae of infection, such as ascending cholangitis, may require biliary drainage or surgery

HTLV-1 prevention

-Prevention of transmission by screening for HTLV-1 among blood donors -Women who are positive should not breastfeed -Preventing ATLL currently relies on the prevention of HTLV-1

breast cancer screening

-Prior to development of X-ray mammography, early detection of breast lesion was limited to periodic physical exams by physician/self-checks by women to feel for suspicious lumps -First attempts to use radiography to detect breast abnormalities were made in 1920s, but mammography as we know it today was not developed until the 1960s. -Further advancements and refinements in technology made from 1960-present

different strains of virus and different species

-Risk associated with infection depends upon the species

S. haematobium

-S. haematobium causes urinary tract disease -Geographic distribution: Widely distributed over the African continent with smaller foci in the Middle East and India -Considered by IARC to be a Group 1 Human carcinogen (sufficient evidence) -Linked to bladder cancer, 2-14 fold increase in risk --Induces chronic inflammation of the lower urinary tract, leading to obstruction, squamous metaplasia, urinary retention and secondary bacterial infections --Development of squamous cell carcinomas as opposed to more common transitional cell carcinomas, presence of mutagenic and carcinogenic materials in the urine, and p53 gene mutations

selection bias

-Screened vs. unscreened --Individuals who are motivated enough to participate in screening programs may also engage in other healthy behaviors and therefore have a different probability of getting disease than individuals who refuse to get screened.

evaluating colorectal screenings

-Screening colonoscopies have been evaluated through cohort studies --Screening colonoscopy was associated with a substantial and comparably decreased mortality risk for both right-sided and left-sided cancers within a large community-based population --In prospective cohort studies, colonoscopy has been associated with long-term (20-30 years) reduction in colorectal cancer mortality -The sigmoidoscopy has been more heavily evaluated --British multi-center RCT (2010): Findings; Reduces overall colorectal cancer incidence and mortality by 31 percent --Earlier RCT: no difference in diagnostic yield between sigmoidoscopy + FOBT vs. sigmoidoscopy alone

ages for colorectal screening

-Screening for average risk individuals for colorectal cancer should start at age 50 years and continuing until age 75 years. The risks and benefits of different screening methods vary; options include: --annual screening with FIT, or --screening every 10 years with flexible sigmoidoscopy and annual screening with FIT, or --screening every 10 years with optical colonoscopy, or screening every 5 years with CT colonograph -The decision to screen for colorectal cancer in adults aged 76 to 85 years should be an individual one, taking into account the patient's overall health and prior screening history --Greatest benefit is to adults who have never been screened. --Most appropriate among those health enough to undergo treatment without comorbid conditions that significantly limit their life expectancy

evaluating potential carcinogens

-Several organizations have programs to evaluate the potential carcinogenicity of specific chemical and physical agents found in the workplace --International Agency for Research on Cancer (WHO) --National Institute for Occupational Safety and Health (U.S.) --National Toxicology Program (U.S.) -

issues concerning how to measure and compare exposure (screening) between cases and controls:

-Should we measure and compare the frequency of screening? --Problem: the control group is likely to consist of non-diseased individuals who are more likely than cases of having had one or more negative tests and thus a higher rate of screening. -Should we measure and compare how recent the screening test was conducted? --Problem: incident cases will be more likely to have had a recent screening test than controls, when the date of case diagnosis is used as the index date for both. -Should we measure and compare ever vs. never screened? --Problem:Although this may be the best option, it still raises the issues of participation bias discussed on the previous slide

the screening test should be:

-Simple to administer -Efficient, with both accuracy and reliability -Socially and politically acceptable to the population being screened -Cost effective -Effective in reducing morbidity or mortality from the disease

Social/Group Disparities vs. Total Disparity

-Social/Group Disparities - Reflects differences between groups based on an identified parameter such as race/ethnicity, education, etc. -Total Disparity - Reflects the overall distribution of health among all individuals in a population, without regard to group membership.

Human T-Cell Lymphotropic Virus (HTLV-1)

-Spread both horizontally from husband to wife (through transmission in semen) and vertically from mother to children (through transmission in breast milk) -Also spread through blood transfusions and sharing needles -Low rate of seroconversion after age 40 suggests that infection at an early age is etiologically important

recommendations for colorectal screening

-Stool-based tests --Highly sensitive fecal immunochemical test (FIT) --Highly sensitive guaiac-based fecal occult blood test (gFOBT) every year --Multi-targeted stool DNA test (MT-sDNA) every 3 years -Visual (structural) exams of the colon and rectum --Colonoscopy every 10 years --CT colonography (virtual colonoscopy) every 5 years --Flexible sigmoidoscopy (FSIG) every 5 years

LGBTQ & disparities in U.S.

-Studies suggest that some gay/bisexual males may be at higher risk for prostate, testicular, anal, and colon cancer, while lesbian/bisexual females may be at higher risk of breast, ovarian, and endometrial cancers --Some cancer may be associated with greater risk-taking behaviors, including substance use or abuse, depression, greater exposure to infectious agents such as HPV, or homelessness due to family rejection -For females in particular, fewer full-term pregnancies, fewer mammograms -LGBTQ youths in particular tend not to disclose sexual orientation to their physicians -In general, non-disclosure and/or avoidance of health professionals can result in inadequate screenings and/or late stage diagnosis of cancer

Association of EBV with Nasopharyngeal cancers

-Substantial evidence from both Epidemiologic and experimental data support an etiologic association --In a large prospective study, the incidence of nasopharyngeal cancers in the EBV+ group was 18 times higher than in the entire screened population --Experimental studies have found EBV in all tumor cells, indicating that the cancer arises from clonal expansion of a single infected cell --Clones of EBV infected cells have been identified in premalignant lesions, and in one study 5 out of 8 cases with premalignant lesions develop nasopharyngeal cancer within a year

HBV vaccination studies

-Taiwan implemented a HBV vaccination program in 1984. Started with immunizing neonates with HBV+ mothers, extended afterwards to all neonates, primary school children, middle school children and finally to adults --With vaccination, the prevalence of the disease dropped from 10.6% to 0.8% --Liver cancer incidence rates among vaccinated children dropped dramatically by 74%

global tobacco smoking

-The World Health Organization's Report on the Global Tobacco Epidemic, currently estimated that smoking is currently responsible for 30% of all cancer deaths in developed countries --Recall that smoking causes even more deaths from vascular, respiratory and other diseases than cancer --Consumption of tobacco products is increasing globally, though it is decreasing in some high-income and upper-middle-income countries. -WHO estimates that tobacco smoking is estimated to account for more than 7 million deaths a year worldwide from direct tobacco use (all health conditions, including cancer) --More than HIV/Aids, TB and Malaria combined -This is projected to reach 27.5 million new cases and 16.3 million deaths by 2040 based on growth and aging of world population --Projections likely to be underestimates given adoption of unhealthy lifestyles and behaviors associated with rapid growth in economically transitioning countries --More than 75% of tobacco-attributed deaths are among people living in low- and middle-income countries

conditions for mass screening programs

-The condition should be an important public health problem. This is typically presented as incidence, mortality, disability, years of life lost, etc. -There should be an accepted effective treatment of the disease being screened, with adequate facilities for diagnosis and treatment. -The disease should have a recognized latent or early pre-symptomatic stage, and its natural progression from latent to declared disease should be well understood. -The screening program should be ongoing - a continuing process rather than a temporary program.

current trends and issues with tobacco

-The deaths attributable to tobacco smoking remains a top public health concern in the U.S. -in addition to lung and other cancers, tobacco smoking also contributes heavily to heart disease, chronic obstructive pulmonary disease and stroke - this also includes the damage done by secondhand smoke. -Focusing on lung cancer, note that the incidence and mortality of the disease is much higher among African-American males than their White or female counterparts. Also note that since the early to mid 1990s the rates are finally starting to decline. This is a direct reflection of the decrease in tobacco smoking that began around in 1965.

tobacco and cancer

-The etiological relationships between various tobacco products and numerous cancers is well established in the scientific literature -Exposure to tobacco through cigarette smoking has played a major role - primary focus or remainder of this lecture --The cigarette has had the greatest population impact of any tobacco product --It has also been most heavily studied --Other products such as cigars, chewing tobacco and snuff are also associated with increased risk of cancer and will be reviewed in this lecture to a lesser extent

Things we look for in order to infer a causal association between an infectious agent and cancer:

-The geographic distribution of the infection should be similar to that of the tumor with which it is associated, after adjusting for the age and other cofactors that known to be important in tumor development --Presence of viral or other serum markers such as high antibody titers should be higher in cases than in non-cases within the same geographic setting (strength of association) --Presence of the viral or other serum marker should precede the development of the tumor ---In other words, exposure must precede the onset of disease (temporality) -Prevention of the infection or control of the host's response to it should decrease the incidence of the tumor (experimental evidence

breast cancer - US females

-The incidence of breast cancer is close in Non- Hispanic Whites (highest) and Blacks -Mortality is much higher among Blacks, however

geographic and socio-economic variation in incidence for H. pylori

-There is a strong geographic correlation between areas with high stomach cancer mortality rates and high prevalence of H pylori infection -Highest incidence is seen in areas and populations of low socio-economic development; becoming a little less common in the Western world -Currently thought to affect 20% of the population in developed countries and 90% in developing countries

Current evidence for Tobacco Smoking as a Group 1 Carcinogen

-There is sufficient evidence in humans for the carcinogenicity of tobacco smoking. --Tobacco smoking causes cancers of the lung, oral cavity, naso-, oro- and hypopharynx, nasal cavity and accesory sinuses, larynx, oesophagus, stomach, pancreas, colorectum, liver, kidney (body and pelvis), ureter, urinary bladder, uterine cervix and ovary (mucinous), and myeloid leukaemia. --Also, a positive association has been observed between tobacco smoking and cancer of the female breast. --For cancers of the endometrium (post-menopausal) and of the thyroid, there is evidence suggesting lack of carcinogenicity. -There is sufficient evidence in humans for the carcinogenicity of parental smoking. --Parental smoking causes hepatoblastoma in children. Also, a positive association has been observed between parental smoking and childhood leukemia (particularly acute lymphocytic leukemia). There is sufficient evidence in experimental animals for the carcinogenicity of tobacco smoke and of tobacco smoke condensates

group 3: Not classifiable as to its carcinogenicity to humans

-This category is used most commonly when the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. -as of July 2020, there were 499 agents

group 2b: Possibly Carcinogenic to Humans

-This category is used when there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. -as of July 2020, there were 313 agents

group 2a: Probably Carcinogenic to Humans

-This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals -as of July 2020, there were 88 agents

1950, Doll and Hill study on "Smoking and Carcinoma of the Lung"

-This study used a Case-Control design, which compared 1465 cases with lung cancer with 1465 controls without the disease and examined how much exposure (e.g., cigarette smoking history) each study subject had -Main findings: --Smokers had increased lung cancer death rates compared to non-smokers ---Heavy smokers 50 were times as likely than nonsmokers to have contracted lung cancer, demonstrating strength of association --The risk of death increased proportionate to the amount of cigarettes smoked, demonstrating a dose-response relationship

The fecal immunochemical test (FIT), also called an immunochemical fecal occult blood test (iFOBT)

-This test reacts to part of the human hemoglobin protein, which is found in red blood cells -This is a newer kind of stool test that also detects occult (hidden) blood in the stool -This detection is important because hidden blood can be a sign of precancerous polyps -Efficiency: Detects about 79 percent of colon cancers

treatment for h. pylori

-Triple regimens containing two antimicrobial agents have been the standard therapies against H. pylori infection for more than 15 years --Once had eradication efficacy of 90%, now closer to 70% due to antibiotic resistance --Subsequent/adjuvant therapies being explored to increase efficacy

HPV subtypes

-Two subtypes #16 and #18 are associated with 70% of cervical cancer and pre-cancerous lesions -HPV also associated with cancers of the anus, vulva, vagina, penis and oropharynx

1775 Percival Pott

-first to demonstrate that a specific type of occupational exposure was causally associated with cancer -Observed a high death rate from cancer of the scrotum in boys/young men who worked as chimney sweeps -Much later, shown to be dermal exposure to polycyclic aromatic hydrocarbons (PAHs) found in coal tar

National Institute for Occupational Safety and Health (NIOSH)

-U.S. agency created by the Occupational Safety and Health Act of 1970 - the same act that created OSHA -NIOSH conducts scientific research, develops guidance and authoritative recommendations, disseminates information, and responds to requests for workplace health hazard evaluations -Known in the workplace for their NIOSH Pocket Guide to Chemical Hazards and other resources -Some of the substances that NIOSH has investigated and considers carcinogenic or possibly carcinogenic includes: Asbestos, Asphalt fumes, Benzene, Beryllium, Cadmium, Chromium, Ethylene oxide, Formaldehyde, Hexavalent Chromium, Silica and Trichlorethylene

National Toxicology Program (NTP)

-U.S. interagency program whose mission is to evaluate the toxicity of agents of public health concern -Their goals include strengthening the science base for risk assessment, providing needed scientific data as well as guidance in the interpretation of that data for regulatory agencies and other groups involved with health-related research -Report on Carcinogens publication --This is a congressionally mandated, science-based, public health document that is prepared for the Health and Human Services Secretary by the National Toxicology Program --The most recent report is 14th Report on Carcinogens, issued in June 2016 --The report identifies agents, substances, mixtures, and exposure circumstances that are known or reasonably anticipated to cause cancer in humans. Each edition is cumulative and consists of a substance profile, including information on cancer studies and possible mechanisms of action as well as current federal regulation to limit exposures.

squamous cell carcinoma

-Usually a slow growing cancer, but can progress and spread -Diagnosis is made through biopsy

Who Is at Risk of Developing Cancer?

-Very high and high HDI countries have more cancer cases than medium or low HDI countries -Many behaviors that increase cancer risk, such as smoking, unhealthy eating, and a sedentary lifestyle, are more common in higher-HDI countries and contribute to higher cancer rates -Also, cancer risk increases with age; an estimated 80% of all cancers in the world are diagnosed in people 50 years of age or older. --the proportion of cancers diagnosed at age 65 or older increases with HDI --this difference is largely due to the young age distribution of economically developing countries

host factors

-When present, risk associated with infectious agent may be greatly increased -Some of these could include age at the time of infection, immune status, and/or genetic susceptibility

making comparisons by race/ethnicity:

-White Americans are often the largest group --But they don't always have the lowest incidence rates depending on the cancer -Asian Americans often have incidence rates that are considerably lower for certain --But their low rates could be due to in part to interplay of diet/genetics/other factors we don't yet understand or may change over time (i.e., loss of traditional diet)

synergistic effects of smoking

-Why would the risk be increased? --Smoking draws other particles or agents in the environment deeper into the lungs --A lit cigarette may increase the temperature of the particles or agents entering the body, further activating them or increasing their toxicity --Epidemiological studies have found: ---Interactions between smoking and asbestos, ionizing radiation, and arsenic may increase the risk of lung cancer - in some cases, 50x to 90x the risk of smokers without the occupational exposure ---Interactions between smoking and exposure to aromatic amines may increase the risk of bladder cancer

ages for breast cancer screening in US

-Women ages 40 to 44 years= annual screening is optional -Women ages 45-49 years: annual screening -Women aged 55 and older= screening every 2 years or annually -Women should continue screening mammography as long as their overall health is good and they have a life expectancy of 10 years or longer.

European ages for breast cancer screening

-Women ages 40 to 44 years= no screening -Women ages 45-49 years= screening every 2 or 3 years -Women aged 50-69 years= screening every 2 years -Women aged 70-74 years= screening every 3 years

Human Papillomavirus (HPV)

-a DNA virus that has been causally linked to cancers of the uterine cervix, anal and oral cancers -Association with cervical cancer most heavily studied to date: --Epidemiologic studies conducted during the 1950s to 1970s suggested that uterine cancer was caused by an agent that passed from men to women during intercourse (horizontal transmission) --Experimental studies during the 1970s and 1980s demonstrated the presence of HPV in dysplastic, in situ, and invasive cervical lesions ---Shown to have capability of transforming human epithelial cells in vitro -HPV can infect males as well as females --transmitted to partners through intercourse

3-D mammography

-a new technology -- still under evaluation --appears to improve detection in women over 65 years old age and in women with dense breast tissue --also appear to have fewer false positives

infectious agents and cancer

-a number of infectious agents are etiologically related to various types of cancer, principally certain viruses, bacteria, and parasitic organisms -Current research suggests that in the developing world, approximately 20% of all cancers are associated with an infectious agent; Some data suggests this percentage will increase in the future as causal mechanisms become better understood -When mapped, cancers associated with an infectious agent often display clear geographic patterns or clustering, which reflects where the infectious agent is endemic

body burden

-aggregated estimate of the exposure an individual has through all routes into the body (i.e., inhalation, dermal, ingestion, ocular, etc.) as well as the metabolic rate resulting in the biologically relevant dose --Example: worker in chlorine manufacture industry may be exposed to chlorine through both inhalation (from chlorine gas) and dermal contact (chlorine in a solid or liquid form) --Both routes must be considered in order to properly estimate an individual's exposure level -This data may not be possible or is very difficult to obtain, but the lack of it must be considered when evaluating study results

H. pylori gastritis

-almost all hosts develop it, usually asymptomatic or leading to dyspepsia --More severe illness develops in some hosts --There is substantial evidence for the etiologic relationship between H. pylori and duodenal and gastric ulcers --Association between H. pylori with gastric cancer is a rare outcome of this common infection --Certain type of lymphoma has also been associated with it (very rare)

secondhand smoking/ETS

-also referred to as involuntary smoking, passive smoking -typically defined as non-smokers who breathe over people's smoke; more generally discussed as environmental tobacco smoke (ETS) -more than 50 studies have evaluated secondhand smoking/ETS --most show an increased risk, especially for individuals with high exposure -non-smokers inhale the same carcinogens as smokers, but at lower doses --the urine of non-smokers exposed to ETS contains concentrations of tobacco specific carcinogens such as N-nitroso that are 1% to 5% of the concentrations found in the urine of active smokers -non-smokers have a statistically significant increased risk of lung-cancer if their spouses smoke than if their spouses were non-smokers --risk is 25% greater for women and 35% greater than for men

Hepatitis B and C viruses (HBV and HCV)

-among the world's most common infectious pathogens --Currently estimated that 1 in 12 of the global population) are chronically infected with one or both of these viruses --An estimated 257 million people living with chronic hepatitis B and 71 million people living with chronic hepatitis C worldwide --Majority of these people live in the developing countries --Many are unaware that they are infected --IARC has classified that both HBV and HCV are Group 1 carcinogens -Chronically infected patients are at increased risk of developing cirrhosis, hepatic decompensation and hepatocellular carcinoma (primary liver cancer), which together account for over than 1 million deaths annually

hepatitis C virus

-an RNA virus with a molecular structure similar to the family of flaviviruses that cause yellow fever or Dengue fever -Horizontal transmission through contaminated blood products is the most common route of transmission --Intravenous drug users, hemodialysis patients, recipients of blood transfusions are at highest risk --Sexual transmission may also occur --Common for infected individuals to fall outside these high risk groups --Prevalence is higher in developed countries than in developing countries

In 2000, United States Public Law 106-525 was enacted: "Minority Health and Health Disparities Research and Education Act,"

-authorized the national center for minority health and health disparities -purpose is to coordinates activities among NIH institutions -law provides us with a general legal definition -"A population is a health disparity population if there is a significant disparity in the overall rate of disease incidence, prevalence, morbidity, mortality or survival rates in the population as compared to the health status of the general population. "

Overall lifetime risk of ATLL

-between 2-6% in persons who are persistent carriers of HTLV-1 -Large percentage of patients with ATLL have relatives with ATLL, other lymphomas or hematopoietic neoplasms -Genetic susceptibility suggested -Given the rarity of disease in the presence of a common exposure, it is likely that HTLV-1 is part of a multistep carcinogenic process

Opisthorchis and Clonorchis

-biologically similar parasitic flatworms, which are also known as liver flukes -Like Schistosomes, they are Trematodes (flattened oval or wormlike animals) that spend part of their lifecyle in mammals, including humans --Also have a complex life cycle --These worms are hermaphrodites, capable of self-fertilization -Infection is acquired by eating raw or undercooked freshwater fish which contain the infective stage (metacercariae) of flukes (food-borne infection)

1989 Special report on cancer (Freeman)

-black-white differences in health primarily linked to lower socioeconomic status; also, poorer Americans have a 10-15% lower 5 year cancer survival than more affluent Americans

Prostate specific antigen (PSA)

-blood is drawn and checked for concentrations of this molecule in the bloodstream. --Test introduced in the mid-late 1980's --Easy to perform, many men get it done annually

global trends in incidence and mortality by HDI - females

-breast --highest incidence highest mortality in in very high HDI, but relatively high/equal among all -cervix --highest incidence and mortality among low HDI -colorectal --highest incidence and mortality in very high HDI -lung --highest incidence and mortality among very high and high HDI

Deprivation Index

-can be used to estimate SES -an index constructed from numerous variables to better characterize SES --does better job than any one variable or using a handful separately --also more stable over time -increasingly popular choice for US cancer researchers using SEER or other surveillance data

schistosoma

-caused by an infection with blood flukes of the genus Schistosoma, which are a type of trematode worm --They are multi-cellular parasites with complex lifecycles --The definitive hosts are mammals, including humans --The intermediate hosts are freshwater snails --Transmission to humans is by contact with larvae in contaminated water ---The larvae are capable of penetrating human skin and enter the bloodstream ---Migrate and mature in the veins that drain the bladder, liver or the intestine depending on the species --Several species have been associated with cancer ---The geographic distribution differs by species

global second-hand smoking

-causes more than 1 million premature deaths per year -heart disease, respiratory disease, cancer and other conditions --About 63% of the world's population is now covered by at least one comprehensive tobacco control measure - up from 15% in 2008 --But only 20% of world live in smoke free environments and 10% are covered by an effective tobacco tax policy -Children are particularly at risk, either from adopting smoking at an early age or from exposure to environmental tobacco smoke --About 50% of children between ages of 13 and 15 were exposed to secondhand smoke both inside and outside the home --In 2004, children accounted for 31% of the deaths attributable to second-hand smoke

highest HBV prevalence

-china, southeast asia, sub-saharan africa -the annual incidence of hepatocellular carcinoma is highest in areas with males born in Asia --May be countries in Asia or countries with high immigration from those countries --Prevalence is highest in developing countries

Cirrhosis

-chronic degenerative disease of the liver -Cirrhosis may be caused by: --Alcohol abuse (the most common cause in the United States) --Autoimmune diseases of the liver --Hepatitis B or C virus infection --Inflammation of the liver that is long-term (chronic) --Iron overload in the body (hemochromatosis)

sidestream smoke

-produced at the burning end of the cigarette during intervals when the smoker is not actively drawing smoke through the cigarette

current trends and issues with tobacco in the US

-cigarette smoking rates are highest among those with less education (top image) -Although rates have largely converged among adults under 65 over time, individuals aged 25-44 have had higher rates of smoking than other age groups -Among high school seniors, currently Whites tend to smoke more than Hispanics or African-Americans (bottom image)

global trends in incidence and mortality by HDI - males

-colorectal --highest incidence and mortality in very high and high HDI -lung --highest incidence and mortality in very high and high HDI -prostate --highest incidence and mortality in very high HDI followed by low HDI

epstein-barr virus (EBV)

-common infection -best known for causing mononucleosis, but less often it can lead to other diseases -EBV ranges from mild to more severe, chronic form of disease -EBV is linked to B-cell lymphomas, nasopharyngeal cancer, and Burkitt's lymphoma -also associated with development of Hodgkin's disease/lymphoma

early 1700s: Bernardino ramazzini

-comprehensive treatise called De Morbis Artificum Diatriba [The Diseases of Workers] -Each chapter contains a description of the disease associated with a particular work activity followed by a literature analysis, workplace description, questions for workers, disease description, remedies, and advice -Appears to be have been largely ignored by medical authorities of that age

IARC Monograph No. 38 (1986)

-concluded that there was sufficient evidence that active tobacco smoking was carcinogenic in humans (Group 1 carcinogen) causing cancers not only of the lung, but also lower urinary tract including renal pelvis and bladder; upper aero-digestive tract including oral cavity, pharynx, larynx, esophagus and pancreas --The report specifically cited the hazards of these constituents of tobacco smoke, including: ---Acetaldehyde, Acetone, Acrolein, Acrylonitrile and methyl acrylate, Ammonia, Benzene, Benzo[a]pyrene, Bicyclohexyl, Cyclohexane, Ethylamine, Dimethylamine, Formaldehyde, Furfural, Hydrazine, Hydrogen cyanide, Methylamine, Methyl chloride, Nicotine, Nitric oxide, Nitrogen dioxide, 2-Nitropropane, N-Nitrosamines, PAH, Propionaldehyde, Pyridine, Pyrrolidine, Tar, Trimethylamine, Vinyl chloride

2002, update to tobacco monograph

-concluded that tobacco smoke is a multiple organ site carcinogen: --Adding to the list of cancers associated with smoking: cancer of the nasal cavity, paranasal sinuses and nasopharynx, stomach, liver, kidney, cervix uteri, adenocarcinoma of the esophagus, and leukemia -IARC has also concluded that secondhand tobacco smoke is also carcinogenic to the human lung

HPV prevalence surveys

-conducted in various countries suggest that HPV is likely to be a major cause of cervical neoplasia in all parts of the world in a wide range of diverse populations --Prevalence survey using samples from 32 hospitals in 22 countries found: ---HPV DNA in 93% of all invasive cervical cancers ---50% of these were type #16 ---Type #18 is more common in Indonesia

2013: The Cochrane Collaboration

-conducts review of 7 screening trials conducted on over 600,000 women aged 39-74 --authors concluded that traditional mammograms reduce mortality from breast cancer by 15% after 13 years of follow up, however over diagnosis and overtreatment is at 30% --◦"For every 2000 women invited for screening throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress including anxiety and uncertainty for years because of false positive findings."

mammogram

-contemporary mammograms use low-energy X-rays and digital detectors -results are read by radiologists --examine images for masses/micro-calcifications -women with suspicious mass typically called back for diagnostic mammography, followed by a biopsy of the mass in question -adjuncts to mammography include ultrasound, ductography, positron emission mammography, and magnetic resonance imaging

basic premise of screening

-detecting disease early in its natural history leads to: --prompt diagnosis and treatment --resulting in a significant reduction in mortality -Disease must have a natural history that includes a clearly defined preclinical phase that allows for early detection -The preclinical phase must be of sufficient length to permit detection with periodic screenings -Length between screenings must also be reasonable --Often one or more years between screenings --Frequency depends on the disease and your level of risk

adult schistosomes

-do not multiply in the human body but live there for years producing eggs --Eggs may leave the body in urine or feces --Eggs remaining in the human body get trapped in tissues, where they elicit hypersensitivity granulomas (a small area of inflammation due to tissue injury) that cause disease in the urogenital system, liver or intestines depending on the species of schistosomes -latency period may last for years

1973 Hensechke et al

-documented increasing cancer mortality among African Americans over previous 25 years

mainstream smoke

-drawn from the burning end of the cigarette through the tobacco directly into the smoker's mouth

1985 Dept. of Health and Human Services (Heckler report)

-drew national attention to significant differences in health care outcomes for African Americans, Native Americans, Hispanics, and Asian/Pacific Islanders compared to Caucasians -poorer outcomes resulted in higher death rates -In 2000, United States Public Law 106-525 was enacted: "Minority Health and Health Disparities Research and Education Act,"

1964 report of the advisory committee to the US Surgeon General

-drew public attention to the mounting evidence of the carcinogenic effects of tobacco smoking. -On the basis of their extensive review of the biomedical literature, the Advisory Committee concluded that cigarette smoking is: --A cause of lung cancer and laryngeal cancer in men --A probable cause of lung cancer in women --The most important cause of chronic bronchitis -This report was just the first in a series. -Since that time, there have been more than 35 reports to the Surgeon General on tobacco.

digital rectal examination (DRE)

-examiner inserts a gloved, lubricated finger into the rectum to examine the adjoining prostate. --Problem: by the time you feel the tumor, it may be too advanced

females and smoking

-females adopted the practice of cigarette smoking several decades later than males in the U.S. These sex differences in smoking patterns is reflected in the rise in lung cancer mortality among females beginning in the 1970s

Longer-term follow-up of the European Randomized study of Screening for Prostate Cancer trial (2014) and 2019

-found that PSA-based screening for prostate cancer prevents 1.28 men from dying of prostate cancer for every 1000 men screened --Screening 1000 men aged 55 to 69 years may prevent approximately 3 men from developing metastatic prostate cancer

retrospective cohort studies

-frequently used by epidemiologists to research associations between occupational exposures and cancer --In a retrospective design, subjects are selected based on their past exposure status and followed through to the present to see if they developed or died of cancer ---This largely avoids the problem of latency encountered in prospective cohort designs, which starts with current exposure and follow subjects into the future ---Retrospective cohorts are different from case control studies, which select subjects based on their disease status and then investigate their past exposures -possible because employers retain employment records for individuals --Epidemiologists begin by grouping individuals by categories of exposure level or duration (i.e., high, medium, low), job title, work area, etc. ---Detailed and/or complete quantitative records on individual exposure are rarely available, however -Epidemiologists work with whatever data they can, including interviews with former employees, industrial hygienists, plant or area managers and supervisors

global concerns of occupation-related cancers

-greater than 80% of occupation-related cancers are estimated to occur in economically developing countries --the majority of these workers are not covered by occupational health and safety laws --in recent years, the risk has increased because some hazardous industries have moved from developed countries where regulations are often laxer and the cost of labor is less -relatively few epidemiologic studies on occupation-related cancers are performed in economically developing countries, where acute and infectious health problems dominate public health resources and scientific concerns --makes it difficult to assess the extent of the problem in many countries --some associations however have been identified, including: ---mesothelioma and lung cancer from asbestos mining in south Africa and china ---lung cancer among gold miners (South Africa), tin miners (China) and hematite (China) ---lung cancer among copper and arsenic smelting workers (China)

ideal screening test

-has a good yield and a high positive predictive value. In other words: --It identifies many cases of previously unknown disease --And, a high percentage of those who test positive actually have the disease

smoke less tobacco and snuff

-have also been found to be carcinogenic --Potent carcinogens include nitrosamines, polycyclic aromatic hydrocarbons, and radiation-emitting polonium --Relative risks observed for oral cancers and smokeless tobacco range from 6.0 to 12.0 --Snuff is associated with cheek and gum tumors, and long term use is associated with a 50% increase in risk of cancers of the gum and buccal mucosa --The surgery associated with oral cancers is particularly disfiguring, since it can involve removing the lower jaw and part of the tongue (see image at left) -Smokeless tobacco use is high in Asia and Africa --Asian and African countries have oral cancer incidence rates that are 10 times higher than countries in Europe or North America

Earlier RCTs of prostate cancer screening

-have not shown unequivocal benefit from PSA --One study showed significant improvement in cancer specific survival for men in the screened group but with a high risk of over-diagnosis and over-treatment. --Another study found no benefit in survival from screening

viruses that are etiologically associated with various types of cancer

-hepatitis B and C viruses -HPV -Epstein-Barr Virus -Human T-cell lymphotropic virus

evaluating efficacy

-ideally determined through randomized clinical trials -observational study designs sometimes used -case-control designs -cohort studies

cancer clusters

-increased number of cancer cases than expected in a geographic area -Caused by pollutant or carcinogen -Cancer cases may cluster among individuals with a history of high exposure levels.

exposure matrix

-is often created by the researcher -it uses a variety of available information to score and estimate an individual's cumulative index of exposure -It is commonly used in occupational epidemiology

2 types of smoke from cigarettes

-mainstream and sidestream --Both contain a wide variety of compounds, including carbon monoxide, benzene, N-nitroso compounds, and formaldehyde --There are different concentrations of carcinogenic chemicals in each --Sufficient evidence to classify many of them as human or animal carcinogens

defining disparities

-many definitions and terms are used in larger discussion of disparities --various terms and definitions have emerged because of program-related purposes and research interests --diff terms emphasize diff aspects and influence what questions are asked -most definitions focus on this: significant differences in health status or a health outcome between one population and another -

background of health disparities

-marked differenced between racial/ethnic socioeconomic groups in health status have been a concern since the rise of the public health movement in the 19th century --in general, the poor/disadvantaged experience more of certain diseases and die at a younger age than those with wealth/greater access to resources --differences in cancer incidence, survival and mortality have been well documented since the mid 20th century

H. pylori transmission

-may be passed person to person or through contaminated food --some research suggests it may be acquired very early in life, such as through vertical transmission from mother to infant

types of screening tests

-muti-phasic screening -mass screening -selective screening

testing for HPV

-now included in cervical cancer screenings --presence of subtypes is strongly associated with pre-invasive lesions called cervical intraepithelial neoplasia (CIN)

periodic

-occurring on a regular basis

Hepatocellular carcinoma

-primary liver cell carcinoma -Accounts for most liver cancers in the U.S. -Occurs more often in men than women, usually age 50 or older --Age varies in different parts of the world -Higher incidence in Africa and Asia than in North or South America and Europe -Not the same as metastatic liver cancer, which starts in another organ (such as the breast or colon) and spreads to the liver -causally associated with scarring of the liver (cirrhosis)

HCV and epidemiological studies

-range of findings is broad -associated with an increased risk for hepatocellular carcinoma with an odds ratio range from 1.7 to 92.4 --some studies do not show a statistically significant association --in general, not as studied as HBV and hepatocellular carcinoma

IARC has reviewed some workplace settings and occupations for cancer risk

-rating is for setting or occupation --may be due to multiple or collective exposures --in some cases, specific carcinogens have not been identified -sometimes, the setting or occupation is associated with more than one type of cancer -in terms of cancer prevention, workers should be protected from all exposures that can cause cancer at any site, not just the primary cancer site

breast cancer screening for women age 50-74 years

-recommends biennial (every 2 years) screening mammography -The decision to start screening mammography in women prior to age 50 years should be an individual one. -Of all of the age groups, women aged 60 to 69 years are most likely to avoid breast cancer death through mammography screening. -Women who place a higher value on the potential benefit than the potential harms may choose to begin biennial screening between the ages of 40 and 49 years. -Women with a parent, sibling, or child with breast cancer are at higher risk for breast cancer and thus may benefit more than average-risk women from beginning screening in their 40s

As you know from previous lectures, the overall cancer death rate peaked in the U.S. in the early 1990s. Since then it has gradually been decreasing due to:

-reduction in smoking = primary prevention -improved detection and treatment = secondary and tertiary prevention **but not all groups have benefited equally from these efforts --persistent gaps in cancer incidence and survival within race/ethnicity groups remain ---differences still span prevention, detection, treatment, survivorship, and death ---in some cases, the differences appear to be increasing

association between EBV with Hodgkin's lymphoma

-relationship is complex -Patients diagnosed with infectious mononucleosis, a disease caused by EBV, have 3x the risk for developing Hodgkin's disease -Serologic case control studies also support this -40% of Hodgkin's disease occurring in developed countries appears to be associated with EBV --Risk found to be greater among Hispanics than whites and greater among young males than females --Risk is also greater among children from poor countries than children from more economically developed nations --More likely to associated with mixed cellularity subtype than the nodular sclerosis type

disadvantages of sigmoidoscopy

-requires prior thorough cleansing, misses polyps in upper portion of colon, small risk of tearing/perforation, abnormalities may require colonoscopy; detects about 45% fewer cancers than colonoscopy

efficiency and related issues

-sensitivity and specificity --They measure the ability of a screening test to correctly classify individuals with and without the disease. -values for sensitivity and specificity each can range from 0-100% -an ideal screening test has both high sensitivity, but typically tradeoffs involved -efficiency measures the total or overall accuracy of a screening test

observational study designs for screening test efficacy

-sometimes used to assess efficacy of screening tests, but these are can be prone to forms of bias that are hard to control or correct. -ex:using an ecologic design: use cancer registry data to compare the incidence and mortality trends before and after the implementation of mass screening in a large population. --Mass screening tests for cervical cancer were implemented in the1950s and 1960s. The period after implementation saw an increase in the incidence of carcinoma in situ (early stage cancer) and a decrease in incidence of invasive carcinoma (later stage cancer), as well as decrease in mortality from this disease. --These shifts changes support the efficacy of cervical cancer screening --This is not absolute evidence, however, because of the possibility of the ecologic fallacy (which ecologic studies are prone to)

efficacy

-the ability of a screening test to produce the desired amount of the desired effect (i.e., save lives) --if early detection by the test results in increased survival or prolongs other health benefits

biological evidence specific to viruses and cancer includes:

-the virus should be able to transform human cells in vitro into malignant ones -The viral genome or DNA should be demonstrated in tumor cells and not in normal cells -The virus should be able to induce the tumor in a susceptible experimental animal and neutralization of the virus prior to injection should prevent the tumor --Note: this is not always possible. We are not always able to reproduce human cancers in experimental animals with the suspected virus

known risks of breast cancer screening

-unnecessary surgery and anxiety -more frequent mammograms include a small but significant increase in breast cancer induced by radiation

traditional mammogram

-up to 90% sensitivity but may be considerably lower due to factors including breast density --false negatives rate of 10% or more ---these women have breast cancer, but it is not caught by mammography ---the false-negative rate is twice, but is not caught my mammography --false positive rate of about 7% ---these women do not have breast cancer, but undergo biopsy

HBV prevention

-vaccine is most effective means to prevent infection -WHO recommendation: --All infants receive the hepatitis B vaccine as soon as possible after birth, followed by 2 to 3 additional shot --In many endemic areas, widespread infant vaccination programs have led to dramatic declines of new HBV cases

socioeconomic status

-very important to consider when assessing disparities, but is not usually collected on most national U.S. health surveys. --Americans typically do not like to disclose income information --Surveys typically get a better response on questions on occupation rather than income -Most cancer surveillance data that is commonly used to monitor disparities (i.e., SEER), does not have income or other SES data for individual patients --In research studies, area-based SES may be used instead -Estimated based on a person's area of residence (e.g., county or census tract) using freely available U.S. Census data -one common problem is that one variable is unlikely to capture SES

chronic active Epstein-barr virus infection (CAEBV)

-very rare complication of EBV infection -Disease is active for at least 3 months -Serious complications such as anemia, nerve damage, liver failure, and/or interstitial pneumonia can occur -The only well-documented, effective treatment for CAEBV is hematopoietic stem cell transplantation

Hepatocellular carcinoma in the US

-was once rare in North America and Western Europe throughout most of the 20th century -During 1973-1996, hepatocellular carcinoma increased 2.2% per year in the U.S. --Contributions from viral etiology doubled --Estimated that contributions from HCV infection rose from 11% to 21.2% , with a rapid rise in the 1990s --Estimates that contributions from HBV rose from 6.4% to 11% during this same period

group one occupational exposures examples

-work process or occupation --aluminum production --chimney sweeping --coal gasification --painter

group 2 occupational exposures examples

-work process or occupation --manufacture of art glass, glass containers, and pressed ware --carbon electrode manufacture

why study the occupational causes of cancer?

1.A large amount of time is spent at work and a growing number of chemical and physical substances or agents are found in workplace settings 2. cancer resulting from workplace exposure should be preventable 3. Workers in occupational settings are generally exposed to higher levels of chemical and physical agents than individuals in non-occupational settings

Four categories of cancer that may be detected through screening - but only one that actually benefits:

1.Cancers that are so easily treated that a later detection would have produced the same total cure. 2.Cancers so aggressive that even "early" detection is too late. 3.Cancers that would have receded on their own or are so slow-growing that the individual would die of other causes before the cancer produces symptoms. 4.Cancers that are detected by screening whose treatment outcome improves as a result of earlier detection. ****This is the only group that benefits from cancer screening.

how is pap test performed?

1.The doctor/nurse begins by inserting a speculum into the woman's vagina, which spreads the vagina open and allows access to the cervix. 2.The health care provider then collects a sample of cells from the outer opening of the cervix and from the central opening using a small spatula, brush or broom. 3.The cells are placed on a glass slide and taken to the laboratory to be checked for abnormalities. The sample is stained and read for abnormalities by specially trained individuals called cytotechnologists. In some areas, computers are used to prescreen the slides before they are read by specialists.

Black or African American

A person having origins in any of the black racial groups of Africa.

white

A person having origins in any of the original peoples of Europe, the Middle East, or North Africa.

Native Hawaiian or Other Pacific Islander

A person having origins in any of the original peoples of Hawaii, Guam, Samoa, or other Pacific Islands.

american indian or alaska native

A person having origins in any of the original peoples of North and South America (including Central America) and who maintains tribal affiliation or community attachment

asian

A person having origins in any of the original peoples of the Far East, Southeast Asia, or the Indian subcontinent including, for example, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and Vietnam.

hispanic or latino

A person of Cuban, Mexican, Puerto Rican, Cuban, South or Central American, or other Spanish culture or origin, regardless of race. The term, "Spanish origin," can be used in addition to "Hispanic or Latino."

Swedish RCT study for prostate cancer screening

After 20 years of follow-up, the rate of death from prostate cancer did not differ significantly between men in the screening group and those in the control group. - Used both DRE and PSA

colorectal cancer.- US females

Although the incidence in colorectal cancer has come down among Black females, they still have the greatest mortality

Opisthorchis and Clonorchis prevention

Avoid eating infected raw or undercooked freshwater fish.; lightly salted, smoked, or pic

length bias

Cancers are more likely to be detected by screening if they are slowly progressive/have a long preclinical phase

nearly two-thirds of the world's smokers live in 10 countries

China India Indonesia Russian Federation United States of America Japan Brazil Bangladesh Germany Turkey

country differences in ranking by sex for tobacco smoking

China is #1 for males and the U.S. is #1 globally for females

injustice

Denial or violation of economic, socio-cultural, political or civil rights by certain population groups within a society.

advantages of virtual colonoscopy

Less invasive than standard colonoscopy, no sedation needed, no risk of tearing/perforation

US Preventive Services Task Force

Recommends test for: - Cancer screenings - Heart & Vascular Disease - Infectious Disease - Endocrine conditions - Focus on individuals ** Usually discussed and carried out under primary care physician

Sigmoidoscopy

Rectum and lower colon are examined using sigmoidoscope

screening

The presumptive identification of unrecognized disease or defect by the application of tests, examinations, or other procedures which can be applied rapidly to sort out apparently well persons who probably have a disease from those who probably do not. A screening test is not intended to be diagnostic. Persons with positive or suspicious findings must be referred to their physicians for diagnosis and necessary treatment

Positive predictive value

The probability of having disease given a positive test

negative predictive value

The probability of not having disease given a negative test

top states with most smokers (over 19%)

West Virginia Kentucky Louisiana Missouri Tennessee Arkansas Alabama Ohio Indiana Mississippi Oklahoma Alaska

Income by Race and Ethnicity in U.S.

While income is only one part of SES, it varies widely by race/ethnicity in the U.S. -highest median household income to lowest --asian --white ,non hispanic --hispanic, any race --black

double contrast barium enema

X-rays of the entire colon and rectum are taken after the patient is given an enema with a barium solution and air is introduced into the colon

primary prevention

preventing disease formation

preclinical phase

prior to symptoms

carriers of HTLV-1

also found in central African blacks, blacks from Caribbean, Melanesians in Papua New Guinea, and natives of the Andean region in South America

secondary prevention

detecting unrecognized, pre-symptomatic disease -screening

disadvantages of the fecal immunochemical test (FIT), also called an immunochemical fecal occult blood test (iFOBT)

fails to detect some polyps and some cancers; if test is positive, other tests must be conducted for biopsy/removal

tertiary prevention

improving health outcomes for individuals with clinical disease

low resources

lack of screening and treatment facilities, medications, etc.

mass screening

large scale, total population groups

advantages of the fecal immunochemical test (FIT), also called an immunochemical fecal occult blood test (iFOBT)

low cost, easy prep, low risk

advantages to double contrast barium enema

no sedation needed, complications are rare

advantages to sigmoidoscopy

relatively quick, few complications, minimal discomfort; In many cases, Precancerous and cancerous growths can be found and either removed or biopsied

Disadvantages regular, or standard, optical colonoscopy

requires prior thorough cleansing, requires sedation, small risk of tearing/perforation

disadvantages to double contrast barium enema

requires prior thorough cleansing; may miss small polyps; if test is positive, other tests must be conducted for biopsy/polyp removal; detects about 30 to 50 percent of the cancers that can be found with standard optical colonoscopy

selective screening

target high risk populations

excess deaths

the difference between the number of deaths observed in a minority population and the number of deaths which would have been expected if they had the same age and sex-specific death rate as the non-minority population.

efficiency

the effects or end results achieved in relation to the effort expended in money, resources, and time

specificity

the probability of having a negative screening test result if disease is not present

sensitivity

the probability of having a positive screening test result if disease is present

referent

thing that a symbol represents

multi-phasic screening

using multiple tests, checking for multiple diseases

EBV treatment

◦Currently no treatment for EBV; Treatment is usually based on managing the symptoms ◦Virus can linger in the body for years, get re-actived, become infectious to others

Schistosoma Prevention

◦Currently no vaccine is available ◦Avoid swimming or wading in freshwater where schistosomiasis occurs ◦Drink safe water; boil other water before bathing ◦Control efforts in some countries have involved trying to eliminating the snails that are required to maintain the parasite's life cycle, but these measures often harm other species - requires ongoing treatment or snails likely to return

EBV prevention

◦Currently there is no effective vaccine ◦Prevention by avoiding contact with infected individuals is the only option

Schistosoma treatment

◦Praziquantel, a prescription medication, is taken for 1-2 days to treat infections caused by all schistosome species ◦Heavier infections can be harder to clear ◦Note: reinfection after re-exposure to Schistosoma is possible after treatment

disadvantages of virtual colonscopy

◦requires prior thorough cleansing, may not detect all small polyps, nonpolypoid lesions, and cancers; detection of abnormality typically requires standard colonoscopy; risk of radiation exposure