Preventive Medicine

(Cancer Screening &

Immunizations) in Adults
Michael Adams, M.D., FACP
Program Director
Assistant Professor of Medicine
Georgetown University Medical Center
 Outline
Cancer screening: Vaccinations
Definitions
Breast cancer
Cervical cancer
Colorectal cancer
Prostate cancer
Skin cancer
Chemoprevention
Controversies
 Definitions
Screening:
testing for disease in average (or low) risk,
asymptomatic population
may be considered a form of primary prevention
goals:
early detection
treating to reduce morbidity or mortality
no diagnostic intent
average prevalence (by definition)
 Definitions
Case-finding:
testing in patients at higher risk
patients seeking medical care because of a complaint
patients with familial risks / exposures / other diagnosis
may be a form of secondary prevention
disease present, reduce mortality / recurrence rate
diagnostic intent
usually higher than average disease prevalence
 Operating
characteristics
high sensitivity
low burden
early detection
ability to modify course of disease
higher prevalence = better positive predictive
value
 GUIDELINES
ACP, USPSTF, CTF, NCI, NIH, AMA,
ACC, AHA, AUA, ACOG, IOM
USPSTF
evidence-based
frequent updates
factor in net benefit, quality of the evidence
US Preventive Services
Task Force (USPSTF)
http://www.ahcpr.gov/clinic/uspstfix.htm
 USPSTF Ratings
Recommendation: A - routinely provide to eligible
patients.
The USPSTF found good evidence that [the service]
improves important health outcomes and concludes that
benefits substantially outweigh harms.

Recommendation: B - routinely provide to eligible

patients.
The USPSTF found at least fair evidence that [the service]
improves important health outcomes and concludes that
benefits outweigh harms.
 USPSTF Ratings
Recommendation: C - no recommendation for or against
routine provision of [the service]
At least fair evidence that [the service] can improve health
outcomes but concludes that the balance of the benefits and
harms is too close to justify a general recommendation.

Recommendation: D - recommends against routinely

providing [the service] to asymptomatic patients
The USPSTF found at least fair evidence that [the service]
is ineffective or that harms outweigh benefits.
 USPSTF Ratings

Recommendation: I - evidence is insufficient to

recommend for or against
Evidence that [the service] is effective is lacking, of
poor quality, or conflicting and the balance of
benefits and harms cannot be determined.
 Breast Cancer

North America: leading cancer in women, 2nd

leading cause of cancer death
2001: 192,000 diagnoses, 40,200 deaths
>50%: no known major predictors
Risk increases with age, atypical hyperplasia
BRCA-1 and -2 BRCA-1 BRCA-2
BRCA-1 BRCA-2
breast
breast breast
breast
ovary
ovary ovary
ovary
colon
colon colon?
colon?
prostate
prostate prostate?
prostate?
male
malebreast?
breast? male
malebreast
breast
pancreatic?
pancreatic?
 Breast Cancer:
mammography
Sensitivity 56-95%
Lower in younger, dense breasts, HRT
Specificity 94-97%
More false positives (less specific) in younger
women

Abnormal mammogram & chance of cancer:

40-49: 2-4% PPV
50-59: 5-9%
60+: 7-19%
 Breast Cancer:
Clinical Breast Exam
Sensitivity 40-69%

Specificity 86-99%

4% of patients with abnormal CBE diagnosed

with cancer in a large community trial

These trials compared CBE with mammography,

mortality trials use both CBE & mammogram
 Breast Cancer: age
considerations
Most screening trials 50-69
40-49: weaker evidence, delay in benefit (lower
prevalence in younger women)
Interval for screening is unknown
Over 70:
evidence generalized unless comorbid conditions reduce life
expectancy
Higher absolute risk of cancer
Mammography benefits (absolute) increase with age
Mammography risks (RELATIVE) diminish with age
 Breast Cancer

The (USPSTF) recommends screening

mammography, with or without clinical breast
examination (CBE), every 1-2 years for women
aged 40 and older.

BBrecommendation
recommendation
 Breast Cancer: CBE

The USPSTF concludes that the evidence is

insufficient to recommend for or against routine
CBE alone to screen for breast cancer.

I
Irecommendation
recommendation
 Breast Cancer:
Self Breast Exam
Sensitivity 26-41%

Specificity unknown

No known mortality difference

Risks of abnormal self exam (anxiety, testing,

biopsy)
 Breast Cancer: self-
exam
The USPSTF concludes that the evidence is
insufficient to recommend for or against
teaching or performing routine breast self-
examination (BSE).

I
Irecommendation
recommendation
 Breast Cancer: other
considerations
Patient preferences, clinical judgment
Family history
BRCA
Other organizations have varying
recommendations:
Yearly after age 40: AMA, ACOG, ACS, ACR
Yearly after 50: CTF, AAFP, ACPM
Interval varies (q1, q2 between 40-49)
BSE: ACOG, ACS, AMA, AAFP favor teaching
 Cervical Cancer

13,000 cases yearly

4,100 deaths (2002)
Risks:
early intercourse
increased # of sexual partners
smoking
HPV (95-100% of squamous cell CA of
cervix)
 Cervical Cancer
Natural history of HPV slow transition to cancer
orderly fashion from less severe to more severe dysplasia
Not faster in HIV+ women (prevalence higher)
Every 6-12 months
Younger women: HPV may be transient
Older women: higher chance of progression to cancer
PAP smear: 60-80% sensitive
New technologies (ThinPrep): no good data yet
 Cervical Cancer HPV
testing
Sensitivity 82%
Specificity 78%
Benefits untested
8 ongoing studies
 Cervical Cancer - timing
Interval: every 3 years after 2-3 normals
Sensitivity 60-80% for high grade lesions for a single PAP
test
ACS: wait until age 30 to extend screening interval
Annual screening: cervical neoplasia, HPV, other STDs, high
risk sexual behavior
Cessation of screening
Low predictive value for women over 65 (ACS: 70), no
abnormal PAP in past 10 years
Hysterectomy for benign disease (only cancer in 1995 study
of 10,000 PAP smears was vaginal squamous cell CA)
 Cervical Cancer

The USPSTF strongly recommends

screening for cervical cancer in women
who have been sexually active and
have a cervix.

AArecommendation
recommendation
 Cervical Cancer

The USPSTF recommends against

routinely screening women older than
age 65 for cervical cancer if they have
had adequate recent screening with
normal Pap smears and are not
otherwise at high risk for cervical
cancer .
DDrecommendation
recommendation
 Cervical Cancer

The USPSTF recommends against

routine Pap smear screening in women
who have had a total hysterectomy for
benign disease.

DDrecommendation
recommendation
 Cervical Cancer
The USPSTF concludes that the evidence is
insufficient to recommend for or against the
routine use of new technologies to screen for
cervical cancer.

I
Irecommendation
recommendation

The USPSTF concludes that the evidence is

insufficient to recommend for or against the routine
use of human papillomavirus (HPV) testing as a
primary screening test for cervical cancer.

I
Irecommendation
recommendation
ASC-H = atypical squamous
cells suspicious for HSIL
 Colorectal Cancer

4th most common cancer in US

2nd leading cause of cancer death
At age 50, 5% risk of being diagnosed
with colon cancer
Adenomatous polyps precursor
Hereditary polyposis syndromes (FAP,
HNPCC) 6% of all colon cancers
 Colorectal Cancer - DRE
Little evidence
Sensitivity much less than multiple
test cards
False negatives no stool in vault
False positives rectal trauma
Therefore, not recommended as a tool
for colorectal cancer screening
 Colorectal Cancer -
FOBT
sensitivity 26 - 92%, specificity 90-99%
3 samples, rehydrated cards improve sensitivity
(diminishes specificity)
Annual screening has detected 49% of incident
cancers
FOBT: 33% reduction in mortality over controls
inexpensive
 Colorectal Cancer -
sigmoidoscopy
Alone:
detects approximately 7 cancers and 60 large
polyps/1000 exams
estimated detection of significant colonic lesions of
80%
Sigmoid abnormalities often trigger colonoscopy
Combination with FOBT:
detects 65-75% of polyps and 40-65% of cancers
reduces mortality by 60%
detects an additional 7 cancers over FOBT alone
 Colorectal Cancer -
DCBE
Limited studies: sensitivity 86-90% for cancer /
polyps
Only 48% sensitive for polyps > 1cm in
National Polyp Study
Specificity 85%
No outcome data
 Colorectal Cancer -
colonoscopy
Sensitivity 90% for large polyps, 75% for small
polyps
Specificity difficult to define
Minority of patients who have polypectomy
would have developed cancer
PROS: view entire colon, ability to biopsy/treat
during procedure
CONS: cost, complications, prep/discomfort
 Colorectal Cancer -
colonoscopy
The effectiveness of colonoscopy to prevent
colorectal cancer or mortality has not been tested
in a randomized clinical trial.1
Comparisons with historical controls: estimates
76-90% reduction in cancers.

1
USPSTF website:
http://www.ahcpr.gov/clinic/3rduspstf/colorectal/colorr.htm
 Colorectal Cancer CT
colography (virtual
colonoscopy)
Non-invasive
10-15 minutes
85-90% sensitive in research setting
Prep still necessary
No outcome data
New software?
 Colorectal Cancer -
costs
Costs for screening, 2002
Stool hemoccult $7-10
Flexible sigmoidoscopy $176-299
Colonoscopy $670-981 excluding
facility fee

Among 6 high-quality cost-effectiveness analyses examining only

direct costs, the average cost-effectiveness ratio values for screening
adults older than 50 with each of the major strategies were under
$30,000 per life-year saved (Year 2000 dollars). Studies varied as to
which strategy was most cost-effective, however. (USPSTF)
 Colorectal Cancer

The USPSTF strongly recommends that

clinicians screen men and women 50
years of age or older for colorectal
cancer.

AArecommendation
recommendation
 Colorectal Cancer

Other considerations:
Family history of colon cancer <60: test earlier
The choice of screening strategy should be based on
patient preferences, medical contraindications,
patient adherence, and resources for testing and
followup. (USPSTF)
Timing (American Cancer Society)
FOBT: yearly
Sigmoid: every 5 years
DCBE: every 5 years
Colonoscopy: every 10 years
(One-in-a-lifetime after age 55)
 Prostate Cancer
2nd leading cause of cancer death among men
in US
2002: 189,000 new cases
Risk increases with age (6.5% by age 60)
Ethnic differences (mortality):
Asian/Pacific Islanders: 1.0
Latino/Hispanic 1.08
White 1.67
Black 3.33
Black men have higher incidence rate
Most men will not die of their disease (3% out
of 15%)
 Prostate Cancer
Considerations:
DRE, PSA accuracy
DRE: <60% sensitivity, operator-dependent
PSA: 60-80% sensitive using 4.0 as abnormal

Early detection
Mortality benefit?
Scant evidence, some showing reduced deaths
from prostate cancer after prostatectomy but
complications not considered
Complications of treatment
Age of patient
Screening is most likely to benefit the
following:
50-70 year old men at average risk
Men over 45 with risk factors (Black men, Family hx)
 Prostate Cancer -
USPSTF
Despite the absence of firm evidence of
effectiveness, some clinicians may opt to
perform prostate cancer screening for
other reasons. Given the uncertainties
and controversy surrounding prostate
cancer screening, clinicians should not
order the PSA test without first discussing
with the patient the potential but
uncertain benefits and the possible harms
of prostate cancer screening. Men should
be informed of the gaps in the evidence,
and they should be assisted in considering
their personal preferences and risk profile
before deciding whether to be tested.
 Prostate Cancer
Prostate cancer guidelines
USPSTF: do not recommend screening
ACS, AUA, AAFP, AMA: consider DRE at age
40, PSA over 50 (40 for Black men)
CTF: recommend against PSA, do not
recommend discontinuation of DRE
ACP: do not recommend screening
All groups advise physicians to give
information to patients about screening,
risk/benefit, treatment & individualize testing
 Prostate Cancer

The U.S. Preventive Services Task Force

(USPSTF) concludes that the evidence is
insufficient to recommend for or against routine
screening for prostate cancer using prostate
specific antigen (PSA) testing or digital rectal
examination (DRE).

I
Irecommendation
recommendation
 Skin Cancer

The U.S. Preventive Services Task Force

concludes that the evidence is insufficient to
recommend for or against routine counseling by
primary care clinicians to prevent skin cancer.

I
Irecommendation
recommendation
 Skin Cancer

The U.S. Preventive Services Task Force

(USPSTF) concludes that the evidence is
insufficient to recommend for or against routine
screening for skin cancer using a total-body skin
examination for the early detection of cutaneous
melanoma, basal cell cancer, or squamous cell
skin cancer.

I
Irecommendation
recommendation
 Chemoprophylaxis for
Neoplastic Diseases
tamoxifen and raloxifene may prevent some
breast cancers in women at low or average risk
for breast cancer
tamoxifen can significantly reduce the risk for
invasive ER-positive breast cancer in women at
high risk for breast cancer and that the
likelihood of benefit increases as the risk for
breast cancer increases
raloxifene consistent evidence (fewer studies)
 Chemoprophylaxis
side effects
VTE
Symptomatic side effects (hot flashes)
Endometrial cancer (tamixofen only)
Need to balance harms vs benefits
Variable Age 45 Age 55 Age 65 Age 75
5-year risk of breast cancer, %

No Family history 0.7 1.1 1.5 1.6

Family history 1.6 2.3 3.2 3.4
Benefits per 1,000 women of 5 y of tamoxifen

Cases of invasive breast cancer avoided, n

No Family history 3-4 5-6 7-8 8

Family history 8 11-12 16 17
Cases of noninvasive breast cancer avoided, n

No Family history 1-2 2 2-3 2-3

Family history 2-3 3-4 4-5 5-6
Hip fractures avoided, n <1 3 5 15
Harms per 1000 women of 5 y of tamoxifen

Cases of endometrial cancer caused, n 1-2 12 21 "22"

Strokes caused, n 1 3 9 20
Pulmonary emboli caused, n 1-2 4-5 9 18
Cases of DVT caused, n 1-2 1-2 3 4
 Chemoprophylaxis for
Neoplastic Diseases
The U.S. Preventive Services Task Force
(USPSTF) recommends against the routine use
of tamoxifen or raloxifene for the primary
prevention of breast cancer in women at low or
average risk for breast cancer.

DDrecommendation
recommendation
 Chemoprophylaxis for
Neoplastic Diseases
The USPSTF recommends that clinicians
discuss chemoprevention with women at high
risk for breast cancer and at low risk for adverse
effects of chemoprevention. Clinicians should
inform patients of the potential benefits and
harms of chemoprevention.

BBrecommendation
recommendation
 VACCINATIONS
Td
pneumovax
influenza
Hepatitis B
Varicella
Hepatitis A
Meningococcus
MMR
Polio
Pneumococcal Vaccine
Contains capsular polysaccharides of 23
common strains
underused (only 45% of patients over age 65)
>65, chronic disease (CHF, COPD, liver
disease, alcoholism, DM), HIV, splenectomy
Revaccinate: nephrotic syndrome, renal
failure, transplant, (ab titer wanes)
maybe revaccinate elderly after 6 years
Vaccinate preganant women if high risk: after
first trimester
safe
 Influenza vaccine
Only 65% of patients over 65 receive
flu shots
2 type A strains, 1 type B strain
reduces illness in healthy patients
(70-90%)
reduces mortality & hospitalizations
in elderly (despite only 30-40%
effectiveness)
 Influenza vaccine
Eligible:
>50
nursing home/long-term
care facility
chronic illness (DM, renal,
Hb-opathies,
cardiopulmonary disease,
immunosuppressed, long
term ASA use)
health care / home care /
day care
 Influenza vaccine
Adverse reactions:
soreness at site
febrile illness (24-48 hours) - not
influenza
immediate hypersensitivity (rare, even
in egg allergic patients)
Guillain-Barre (1976 with Swine flu
vaccine, 1990-91 a few cases, very rare
now)
 Influenza vaccine
Contraindications
Severe egg allergy
Active neurologic disease
 Hepatitis B vaccine
Safe, effective (90% immunity in healthy patients - less
if older, obese, smokers, chronic disease
liver/renal/DM, HIV)
0,1,6 months
Indications:
sexual exposure - multiple, homosexual
health care workers
IVDA
HIV (50-70% seroconversion)
infants born to HBsAg positive women
post-exposure prophylaxis
depends on type of exposure, patient risk
high: HBIG + Hep B series
low: Hep B series or booster
 Hepatitis B vaccine
Adverse reactions: local
Pregnancy is not a contraindication
Non-responders:
3 additional doses, check titers (30-50%
response)
Revaccination or checking titers
not recommended for immunocompetent
people
recommended for hemodialysis patients
 Td
Tetanus rare, but fatality rate high (31-42%)
Primary series: 3 doses at 0,1,6 months
toxoid every 10 years
local erythema common
Arthus reaction uncommon
anaphylaxis, urticaria, angioedema,
neurologic complications - very rare
wound prophylaxis (high risk,
unvaccinated): immune globulin + Td at
different sites
 MMR

Measles (live, attenuated vaccine):

resurgence 1990
Resurgence in inner city, college
campuses
Vaccine produces noncommunicable
disease
Single dose is 95% effective, life long
immunity
 MMR
all adults born after 1956 & no h/o
disease revaccinate
travelers to endemic areas, high
risk of natural disease
Postexposure prophylaxis: vaccinate
immediately (protective within 72
hours) OR immune globulin
 MMR
fever, rash common side effects
do not give 14 days before or 5 months
after I.G., blood, or ab-containing blood
products
do not give to the following:
acute leukemia, lymphoma
malignancy
steroid, chemotherapy, alkylating agents
HIV unless stable/well
Pregnant women, considering within 3 mos.
 MMR
Mumps:
orchitis, meningitis, nerve deafness
live, attenuated vaccine
90% effective after single dose
all adults born after 1956
parotitis, encaphalitis rare
same timing as measles, same
contraindications
Egg/neomycin allergy
 Rubella
Main issue is prevention of congenital
rubella
Vaccinate women of child bearing age
MMR - 95% effective
joint pains 40%, but arthritis rare
Arthralgias may persist up to 3 weeks
Rare neurologic side effects (neuritis)
avoid in pregnancy, neomycin allergy
Same contraindications as measles
 Polio vaccine
OPV, IPV - both trivalent, 95% effective
IPV preferred (higher risk of paralysis with OPV
- 1/1.2 million)
Single booster for travelers to endemic areas
who were immunized
travelers not previously immunized complete
primary series (3 doses: 0,1,6 months)
No need to vaccinate adults otherwise
IPV: hypersensitivity only
avoid in pregnancy, immunocompromised
 Hepatitis A
Inactivated vaccine
Indications: endemic areas, homosexual
men, IVDA, liver disease, occupational
risk
95% effective after 3 weeks, 99%+
after 2nd dose
immune globulin if travel within 2
weeks or if food borne outbreak/close
contact (diaper/sexual contact/day care)
 Varicella
Live, attenuated vaccine
85% effective in children, reduces
severity of illness if contracted
well tolerated
 Meningococcus
High risk only:
household contacts
>4 hours spent with patient for 5 of 7 days prior
dorms, barrack roommates, day care
mouth-to-mouth
prophylaxis:
rifampin (600mg q 12h x 4) - resistance
cipro 750 mg x 1
ceftriaxone 250 mg IM x 1