This document discusses cancer screening guidelines and tests. It covers: 1) The goals of cancer screening are early detection of malignancies to decrease morbidity and mortality by finding cancer at earlier, more treatable stages. 2) Screening programs for colorectal and breast cancer have contributed to decreases in cancer mortality rates in the United States. 3) Ideal screening tests are valid, reliable, sensitive, specific, low-cost, minimally invasive and provide accurate risk classification.

1. Cancer Screening
Presenter : Dr. Srikar Bharadwaj

2. • Screening is a means of early detection in asymptomatic individuals with a
goal of decreasing morbidity and mortality.
• The goal of cancer screening is to cure cancer by detecting the malignancy,
or its precursor lesion, at an early stage prior to the onset of symptoms,
when treatment of cancer is most effective.
• Overall cancer mortality has decreased by 25% from 1990 to 2015 in
United States, with even greater declines in the mortality rates for
colorectal cancer (47% among men and 44% among women) and, breast
cancer (39% among women)
• A portion of this decrease can be attributed to the introduction of high-
quality cancer screening for colorectal and breast cancer

3. • The most successful cancer screening programs lead to the
identification of precursor lesions e.g., cervical intra-epithelial
neoplasia (CIN) where the treatment of the precursor lesion leads to a
decrease in the incidence of invasive cancer over time.
• While screening can potentially reduce disease specific deaths, it is
also subjected to number of biases that may suggest benefit when
there is actually none.
• Because screening is done on asymptomatic healthy individuals, it
should offer substantial benefit that outweighs harm
• Hence, screening tests should be appropriately evaluated before their
use is widely encouraged in screening programs

5. • Potential negative outcomes of cancer screening :
 Overdiagnosis: When tumors are detected that would never become
symptomatic or lead to death
 Overtreatment: When tumors are detected that would never
become symptomatic or to death but are treated none-the-less

6. CHARACTERISTICS OF IDEAL SCREENING TEST
• Validity – Delivers correct result each time
• Reliability – Delivers same result each time
• Sensitivity – Correctly classify cases
• Specificity – Correctly classify non cases
• Low cost, minimally invasive and with less discomfort
• Performance

7. Accuracy of Screening tests
• Screening test accuracy or ability to discriminate disease is described
by four indices
 Sensitivity
 Specificity
 Positive Predictive Value
 Negative Predictive Value

8. • Sensitivity : Also called as true positive rate, is the proportion of
persons with the disease who test positive in the Screening test
• Specificity : Proportion of persons who do not have the disease and
test negative in the screening test
• Positive Predictive value : Proportion of person who test positive and
who actually have the disease
• Negative predictive value : Proportion of person testing negative and
who do not have the disease.

9. • Sensitivity and specificity of the tests are independent of the
underlying prevalence of the disease in the population screened
• Predictive values depend strongly on the prevalence of the disease
• Screening is most beneficial, efficient and economical when the target
disease is common in the population being screened

10. Potential biases of Screening test
• Common biases of screening tests are
a. Lead time
b. Length – based sampling
c. Selection
• These biases can make a screening test seem beneficial, when
actually it is not.

11. • Whether beneficial or not, screening can create false impression of
epidemic by increasing the number of cases diagnosed
• It can produce a shift in proportion of patients diagnosed at an early
stage and inflate survival statistics without reducing mortality
• In such cases, apparent duration of survival increases, without lives
being saved or life expectancy changed

12. • Lead time bias occurs whether or not a test influences the natural
history of the disease
• The patients are merely diagnosed at an earlier date
• Survival appears increased even if life is not prolonged
• The screening test only prolong time the subject is aware of the
disease and spends as a cancer patient .

14. • Length based sampling : It occurs because screening test more easily
detect slow growing, less aggressive cancers than fast growing
cancers
• Cancers diagnosed due to onset of symptoms between scheduled
screenings are on average more aggressive, and treatment outcomes
are not as favorable
• An extreme form of length bias sampling is called over diagnosis –
the detection of pseudo disease

15. • The reservoir of some undetected slow growing tumors is large.
• Many of these tumors fulfill the histologic criteria of cancer but will
never become clinically significant or cause death during patient’s
remaining life span
• This problem is compounded by the fact that most common cancers
appear most frequently at ages when competing cause of death are
more frequent.

16. • Selection bias : It occurs because the population most likely to seek
screening often differs from general population to which the
screening test might be applied.
• In general, Volunteers for studies are more health conscious and likely
to have better prognosis or lower mortality rate, irrespective of
screening result
• This is called as healthy volunteer effect.

17. DRAWBACKS OF SCREENING
• Risks associated with screening include
 Harm due to screening intervention itself
 Harm due to further investigation of person with positive tests
 Harm from treatment of person with positive result, whether or not
life is extended by treatment
• The diagnosis and treatment of cancers that would never have
caused medical problems can lead to harm of unnecessary treatment
and give patients the anxiety of cancer diagnosis

18. ASSESSMENT OF SCREENING TESTS
• Good clinical trial design can offset some biases of screening and
demonstrate the relative risks and benefits of a screening tests
• A Randomized control screening trial with cause – specific mortality
as the end point provides the strongest support for a screening
intervention
• Overall mortality should also be reported to detect an adverse effect
of screening and treatment on other disease outcome

19. • In a randomized trial, two like populations are randomly established
• One is given the usual standard of care and other receives screening
intervention being assessed.
• Efficacy for the population studied is established when the group
receiving the screening tests has a better cause – specific mortality
rate than control groups
• Studies showing a reduction in incidence of advanced – stage disease,
improved survival or stage shift are misleading evidence of benefit

20. • Although a randomized, controlled screening trial provides the
strongest evidence to support a screening test, it is not perfect
• Unless the trial is population based, it does not remove the question
of generalizability to the target population.
• Screening trials usually involve thousands of people and last for years
• Every non randomized study design is subjected to strong
confounders

21. SCREENING FOR SPECIFC CANCERS
• Screening for cervical, colon, and breast cancer has the potential to
be beneficial for certain age groups
• Depending on age and smoking history, lung cancer screening can
also be beneficial
• Special surveillance of those at high risk for specific cancer because of
a family history or a genetic risk factor may be prudent
• A number of organizations have considered whether or not to
endorse use of certain screening tests

22. • The American Cancer Society (ACS) and U.S. Preventive services Task
force (USPSTF) publish screening guidelines
• The American academy of Family Practitioners (AAFP) often
follows/endorses the USPSTF guidelines
• American college of Physicians (ACP) develop recommendations
based of Structural reviews of other organizations guidelines

23. BREAST CANCER
• Breast Self – examination, Clinical breast examination by a care giver,
mammography and magnetic resonance imaging (MRI) have all been
advocated as usual screening tools
• A number of trials have suggested that annual or biennial screening
with mammography in normal risk women older than age 50 years
decreases breast cancer mortality.
• In most trials, breast cancer related mortality rates decreased by 15 –
30 %

24. • The U.K. Age trial evaluated the impact of mammography in women
age 40 – 49 years, found no statistically significant difference in breast
cancer mortality for screened women vs controls after 11 years of
follow up
• Nearly half of women aged 40 – 49 years screened annually will have
false positive mammograms necessitating further evaluation, often
including biopsy.
• In United States, widespread screening over the past several decades
has not been accompanied by a reduction in incidence of metastatic
breast cancer suggesting over diagnosis at population level.

25. • In addition, substantial improvements in systemic therapy have likely
decreased the impact of mammography and early detection on falling
breast cancer mortality rates
• Digital breast tomo synthesis is a newer method of breast cancer
screening that reconstructs multiple x – ray images of breast into
superimposed three dimensional slices.
• Genetic screening for BRCA 1 and BRCA 2 mutations and other
markers of breast cancer has identified group of people at high risk
for breast cancer

26. • Mammography is less sensitive at detecting breast cancers in women
carrying BRCA 1 and BRCA 2
• It is because such cancer occur in younger women in whom
mammography is known to be less sensitive.
• MRI is more sensitive than mammography in women at high risk due
to genetic predisposition or women with dense breast tissue, but
specificity is lower.

27.  Self-examination :
• Women ≥20 years ,Breast self-exam is an option
 Clinical examination
• Women 20–39 years: Perform every 3 years
• Women ≥40 years: Perform annually
 Mammography
• Women ≥40 years: Screen annually for as long as woman is in good
health

28.  MRI
• Women >20% lifetime risk of breast cancer: Screen with MRI plus
mammography annually
• Women 15%–20% lifetime risk of breast cancer: Discuss option of
MRI plus mammography annually
• Women <15% lifetime risk of breast cancer: Do not screen annually
with MRI

29. CERVICAL CANCER
• Screening with Papanicolaou (pap) Smear decreases cervical cancer
mortality
• Cervical cancer mortality rate has fallen substantially since wide
spread use of pap smear.
• Screening guidelines recommend regular pap smear testing for all
women who have reached age of 21
• The recommended interval for pap screening is 3 years.

30. • In all cases, screening adds little benefit but leads to important harms
including unnecessary procedures and overtreatment of transient
lesions
• Beginning at age 30, guidelines include HPV testing with or without
pap smear
• The screening interval for women who test normal using this
approach may be lengthened to 5 years.

31. • An upper age limit at which screening ceases to be effective is not
known, but women age 65 years with no abnormal results in previous
10 years may choose to stop screening
• Screening should be discontinued in women who have undergone a
hysterectomy with cervical excision for non cancerous reasons.

32.  Pap Smear test (cytology)
• Women ages 21–29 years: Screen every 3 years
• Women 30–65 years: Acceptable approach to screen with cytology
every 3 years
 HPV test
• Women <30 years: Do not use HPV testing
• Women ages 30–65 years: Preferred approach to screen with HPV
and cytology co testing every 5 years
• Women >65 years: No screening following adequate negative prior
screening

33. COLORECTAL CANCER
• Fecal Occult blood testing (FOBT), digital rectal examination (DRE),
rigid and flexible sigmoidoscopy, colonoscopy, and computed
tomography colonography have been considered for screening
• A meta analysis of 5 randomized control trials demonstrated a 22 %
relative reduction in colorectal cancer mortality after 2 to 9 rounds of
biennial FOBT at 30 years of followup
• Annual screening was shown to result in greater reduction in
mortality in a single trial ( 32 % relative reduction )
• However, only 2 – 10 % of those with occult blood in the stool have
cancer

34. • Fecal immunochemical tests (FIT) have higher sensitivity for colorectal
cancer than FOBT tests.
• Fecal immunochemical tests may have lower ability to detect
proximal vs distal colonic tumors.
• Multi targeted stool DNA testing combines FIT with testing for altered
DNA biomarkers that are shed into stool,
• This test has higher single test sensitivity for colorectal cancer than
FIT alone but specificity is lower
• This result in higher number of false positive tests and follow up
colonoscopies

35. • A blood test for methylated SEPT9 gene associated with colorectal
cancer is available. Sensitivity of this test is low.
• Two meta analysis of 5 randomized control trials of sigmoidoscopy
found an 18 % relative reduction in colorectal cancer incidence and
28 % relative reduction in colorectal cancer mortality.
• Diagnosis of adenomatous polyp by sigmoidoscopy should lead to
evaluation of entire colon with colonoscopy.
• The most efficient interval for screening sigmoidoscopy is unknown,
but an interval of 5 years is often recommended

36. • One time Colonoscopy detects 25 % more advanced lesions – (polyps
> 10mm, villous adenoma, invasive cancer) than one time FOBT with
sigmoidoscopy.
• Observational studies suggest that efficacy of colonoscopy to
decrease colorectal cancer mortality is primarily limited to left side of
colon
• CT colonography, appears to have sensitivity for polyps > 6mm,
comparable to colonoscopy

37.  Sigmoidoscopy
• Adults ≥50 years: Screen every 5 years
 Fecal occult blood testing (FOBT)
• Adults ≥50 years: Screen every year with high sensitivity guaiac based
FOBT or fecal immunochemical test (FIT) only
 Fecal Immunochemical testing (FIT)
• Adults ≥50 years: Screen every year

38.  Colonoscopy
• Adults ≥50 years: Screen every 10 years
 CT colonography
• Adults ≥50 years: Screen every 5 years

39. LUNG CANCER
• Chest X – ray and sputum cytology have been evaluated in several
randomized lung cancer screening trials.
• The most recent largest screening trial Prostate, Lung, Colo rectal and
ovarian (PLCO) cancer screening trial found that xray did not reduce
the risk of dying from lung cancer
• However, it showed evidence of over diagnosis associated with chest
x ray
• Low – dose CT has also been evaluated in several trials

40. • National lung Screening trial (NLST) demonstrated a statistically
significant reduction of 3 fewer deaths per thousand people screened
with CT compared to X ray after 12 years.
• However, harms include potential radiation risk associated with
multiple scans, discovery of incidental findings of unclear significance
and high range of false positive results.

41.  Low Dose CT Scan
• Adults 55 – 80 years, with a > 30 pack year smoking history, still
smoking or have quit within the past 15 years
• Only perform screening in facilities with the right type of CT scanner
and with high expertise/specialists.

42. OVARIAN CANCERS
• Adnexal palpation, trans vaginal ultrasound (TVUS) and serum CA 125
assay have been considered for ovarian cancer screening
• A large randomized control trial has shown that annual screening
program of TVUS and CA 125 in average risk women did not reduce
death from ovarian cancer
• Adnexal palpation was dropped early in study because it did not
detect any ovarian cancers that were not detected by either TVUS or
CA 125
• In PLCO trial, 10 % of participants had a false – positive result from
TVUS or CA 125

43. PROSTATE CANCER
• The most common prostate cancer screening modalities are digital
rectal examination (DRE) and serum PSA assay
• An emphasis on PSA screening has caused prostate cancer to become
most common non skin cancer diagnosed in American males
• This disease is prone to length – bias, lead time bias and over
diagnosis
• Hence debate continues on whether screening should be offered
unless the patient specifically asks to be screened.
• Men older than 50 years have high prevalence of clinically
insignificant prostate cancer

44. • The major Randomized control trials of impact of PSA screening on
prostate cancer mortality are PLCO and European Randomized
Screening study for prostate cancer (ERSPC)
• European study found that 570 men would need to be invited for
screening and 18 cases of prostate cancer detected to avert 1 death
from prostate cancer
• Treatment for low stage prostate cancer such as surgery and radiation
therapy can cause substantial mortality including impotence and
urinary incontinence

45.  Prostate Specific Antigen (PSA)
• PSA level is 2.5 ng/mL or higher - Screening should be done yearly
• PSA of less than 2.5 ng/mL – Every 2 years
• Starting at age 50, men should talk to a doctor so they can decide if
testing is the right choice for them.
• If African American or have a father, brother who had prostate cancer
before age 65 – Can be started at age 45 years

46. SKIN CANCER
• Visual examination of all skin surfaces by the patient or by a health
care provider is used in screening for basal, squamous cell cancers
and melanoma
• Screening is associated with substantial rate of over diagnosis.
 Complete skin examination by clinician or patient
• Self-examination monthly;
• Clinical exam as part of routine cancer-related checkup

47. SUMMARY
• Cancer screening is looking for cancer before a person has any
symptoms.
• False positive and false negative tests are possible.
• Finding the cancer may not improve the person’s health or help the
person live longer.
• Screening studies are done to see whether deaths from cancer
decrease when people are screened

48. THANK YOU !!!