Transcript Prevention/Screening in Adults

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:
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Definitions
Breast cancer
Cervical cancer
Colorectal cancer
Prostate cancer
Skin cancer
Chemoprevention
Controversies

Vaccinations
Definitions
Screening:
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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

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diagnostic intent
usually higher than average disease prevalence
Operating characteristics
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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

breast
ovary
colon
prostate
male breast?
breast
ovary
colon?
prostate?
male breast
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
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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.
B 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” 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 selfexamination (BSE).
“I” recommendation
Breast Cancer: other
considerations
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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
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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)
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–
–
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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
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Sensitivity 82%
Specificity 78%
Benefits untested
8 ongoing studies
Cervical Cancer - timing
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Interval: every 3 years after 2-3 normals
–
–
–
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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.
A 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 .
D recommendation
Cervical Cancer

The USPSTF recommends against routine
Pap smear screening in women who have
had a total hysterectomy for benign disease.
D 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” 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” recommendation
ASC-H = atypical squamous
cells suspicious for HSIL
Colorectal Cancer
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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
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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%
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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.

1USPSTF
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
– Flexible sigmoidoscopy
– Colonoscopy
$7-10
$176-299
$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.
A 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)
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FOBT: yearly
Sigmoid: every 5 years
DCBE: every 5 years
Colonoscopy: every 10 years
(One-in-a-lifetime after age 55)
Prostate Cancer
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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):
–
–
–
–
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Asian/Pacific Islanders:
Latino/Hispanic
White
Black
1.0
1.08
1.67
3.33
Black men have higher incidence rate
Most men will not die of their disease (3% out of 15%)
Prostate Cancer
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Considerations:
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DRE, PSA accuracy
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–
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Early detection
Mortality benefit?
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–
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DRE: <60% sensitivity, operator-dependent
PSA: 60-80% sensitive using 4.0 as abnormal
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” 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” 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” recommendation
Chemoprophylaxis for
Neoplastic Diseases


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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
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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
No Family history
0.7
1.1
1.5
1.6
Family history
1.6
2.3
3.2
3.4
3-4
5-6
7-8
8
8
11-12
16
17
No Family history
1-2
2
2-3
2-3
Family history
2-3
3-4
4-5
5-6
<1
3
5
15
1-2
12
21
"22"
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
5-year risk of breast cancer, %
Benefits per 1,000 women of 5 y of tamoxifen
Cases of invasive breast cancer avoided, n
No Family history
Family history
Cases of noninvasive breast cancer avoided, n
Hip fractures avoided, n
Harms per 1000 women of 5 y of tamoxifen
Cases of endometrial cancer caused, n
Strokes caused, n
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.
D 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.
B recommendation
VACCINATIONS
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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 (7090%)
 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
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

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
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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
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

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