Download Screening in different age groups

Oppdatert februar 2008
Decision Making in General Practice
Women’s Health
Early Diagnosis – Preventive Treatment
Vignette 1
Linda Ulvang is 18 years old. She comes for a consultation because she wants to start
using contraception. The last half-year she has had a steady relationship with a man
and her sexual debut was two months ago. She hasn’t had sexual contact with anyone
other than her partner. You clarify that she has been healthy, has regular menstruation
and no gynaecological problems. BP is normal; there are no genetic disorders in the
family. She wants a prescription for birth control pills. “Is it necessary that I have a
gynaecological examination?” she asks.
What is your answer?
Which tests would you perform in this situation?
Do you have any doubts about taking these tests?
Vignette 2
Marit Bremseth is 48 years old. She is married and has three children. She hasn’t been
seriously ill before and there hasn’t been any family history of particular diseases. In
connection with contraception check-ups she has taken cervical cytological tests at 2-3
years intervals. The test results haven’t shown any abnormalities. She has not
menstruated during the past two years. Today, she has come to have her IUD removed
and asks for a “cancer test”. “I’m finally done with all this nonsense,” she exclaims.
“Now it’s not necessary with these kinds of check-ups anymore?”
How do you answer her?
How necessary are these types of tests?
Is there a difference if you detect mild dysplasia in an 18 year old as opposed to a 48
year old?
Chlamydia
Chlamydia screening
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Chlamydia testing is widespread, but how reliable is the test and how useful is it for
the different age groups? Norwegian epidemiological data (1) shows a prevalence in
teen age girls of 10% and among married women in their 30s, it is 0.5%. Let us
assume that the test you use has a sensitivity of 95% and specificity of 98%. Use the
table below to answer the questions that follow.
Prevalence 10%
Chlamydia infection
+
+
-
Test
1000
How many test results are false positive?
How likely is it that a positive test result is due to infection (percentage)?
Prevalence 0.5%
Chlamydia infection
+
+
-
Test
1000
How many of the test results are false positive?
What percentage of positive test results is due to infection?
What do you say to a 30 year old woman who you routinely take Chlamydia tests and
you find the test result is positive?
There are now many different tests for Chlamydia (cf. NEL). Several of these have a
specificity of 97-100%, while the sensitivity is 70-90%.
Cervical cytology
Vignette 2 continued
The cytological result for Marit Bremseth showed mild dysplasia. It was
recommended that she comes in for a check-up in one year.
Would you discuss the test results with Ms. Bremseth now or call her in for a check-up
in a little less than a year? Discuss.
If you choose to tell her about the test results now, what will you say to her?
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What is the chance that it is a false positive?
Is it likely that the test results indicate a serious dysplasia and that treatment is
necessary?
Which sources of error can create uncertainty about cytological test results?
In a meta-analysis (2) about the validity of cervical cytology, it was reported that the
sensitivity of different studies varied from 11% to 99% and specificity from 14% to
97%. The gold standard in these studies was histology. The analyses showed, as
expected, an inverse relationship between sensitivity and specificity. When sensitivity
increased, specificity decreased. An example of this inverse relationship is a
sensitivity of 20-35% which corresponds to a specificity of 90-95%.
What properties should a cervical cytological screening test have? High specificity or
high sensitivity?
Using the table below, calculate the number of false negatives and false positives if
the prevalence of dysplasia is 10%, sensitivity 80% and specificity 50%.
Dysplasia histology
+
Dysplasia
cytology
+
1000
How do you interpret a positive cytology from this?
Scientific data
It is assumed that most cervical cancers have a premalignant and reversible stage,
cervical intraepithelial neoplasia (CIN), which is graded CIN I-III. With a normal
course of development, the maximum incidence rate for cervical cancer is
approximately 45 years. However, due to screening, the incidence is today the same
with women in their 50s and 60s – yet, the incidence is highest at 65 years of age.
Grade of dysplasia is the most important prognostic factor. It is assumed that 20% of
women with CIN III will develop cancer 16 years (mean) later (3). It has been found
that 10-15% of the cases with CIN I progress to CIN II-III and 0.3% progress to
cancer.
Is cervical cancer screening worth the cost?
Swedish data (4) shows that the detection of carcinoma in situ does not lead to
decrease in incidence of cervical cancer, and indicates that many women will receive
unnecessary treatment of lesions that would otherwise spontaneously regress.
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British data (5) also demonstrates uncertainty about the usefulness of screening for
cervical cancer: In a defined area, 30-40 women die each year of cervical cancer. Over
a five year period 225,974 women were tested. New cytological changes were found
in 15,551 and of these nearly 6,000 were referred to cholposcopy. The other 9,500 had
either normal cytology at a new test or they still had moderate cell changes. A
considerable number of healthy women received an “incorrect” diagnosis of suspected
cell changes – with the consequences that has.
Early Diagnosis
Objective
The objective of early diagnosis is to prevent or hinder the development of disease,
perhaps improve the patient’s life situation and lengthen her life. If this is to be useful,
then it must be documented that early intervention improves treatment results better
than intervention at the time of disease manifestation (symptoms, signs or findings).
The objective of early diagnosis, or uncovering risk factors, can also be risk
assessment for a life insurance company or to prevent health risks for others (ex.
communicable disease like TB and HIV).
Method
There are three types of methods for early diagnosis:
1. Screening – an invitation sent to the entire population or selected groups of the
population (ex. women, people over 50, etc.) in order to test them regarding a
disease or risk factor
2. Periodical health examinations/check-ups – where a battery of examinations
and tests are systematically performed
3. Case-finding – the doctor uses the opportunity to perform a certain test (ex. a
blood pressure reading) when the patient has come for another reason
What characteristics of the disease decide whether early diagnosis is useful?
What characteristics of the screening test decide whether early diagnosis is useful?
What characteristics of the screening programme decide whether early diagnosis is
useful?
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As the figure above shows, the natural course of disease can be seen as divided into
different phases: Biological start, a point in time where early diagnosis is possible, a
point in time where diagnosis normally occurs and an end phase with different
possible outcomes. A deciding factor is if the illness has a lead time; this is a critical
period where treatment is more effective or easier to give. It must be documented by
scientific studies.
The gold standard is to perform randomized, controlled studies where a randomly
selected group of the population is offered early testing and the control group receives
standard health care services (they contact the doctor when they feel the need to). The
two groups are then followed through a period of time in order to decide if it is cost
effective.
Breast cancer
Breast cancer is the most frequently occurring form of cancer among women and is
the cause of most lost years of life. Can mammography screening help reduce the
mortality rate of breast cancer? What is the validity of mammography in identifying
women in an early stage of breast cancer?
Mammography
The clinical benefit of mammography is not in doubt. It is unlikely to detect a tumour
under 15-20 mm with a regular clinical examination, while mammography reveals
tumours as small as 5 mm. Different studies have shown that mammography has a
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sensitivity of 85-95% and a specificity of 86-98%. The values are clearly lower for
younger women as they have denser breast tissue that can camouflage tumours. It is
therefore the benefits haven’t been documented for women under 35.
Prevalence of breast cancer is approximately five per 1000 in the age groups that are
relevant for mammography screening. Use a sensitivity of 90% and a specificity of
95% and fill in the table below.
Confirmed breast cancer diagnosis
+
Mammography
+
100,000
How many women with breast cancer will go undetected?
How many women with pathological findings tested by mammography do not have
breast cancer?
What is the probability that a positive mammography is due to breast cancer?
Weigh the advantages and disadvantages of mammography screening against each
other.
Scientific data about the effect of mammography screening from The Norwegian
Doctors Electronic Manual (Norsk Elektronisk Legehåndbok)
Topics in dispute, different research community are in disagreement.
Screening in different age groups
 Screening among women 50-69 years old.
o Has been shown in meta-analyses to be useful, those screened have an
approximately 25% lower mortality rate
o Newer studies and analyses indicates uncertainty regarding this, the
situation has not yet been clarified, cf. below
o For example, there is no difference in breast cancer mortality between
patients who had yearly clinical examinations compared to clinical
examinations + mammography after 13 years follow-up
 Screening among women under 50 years old
o Are recently documented in meta-analyses, survival is longer in the
screened group
o Still, more women under 50 years must be screened in order to save one
woman from dying of breast cancer (their cancer type is more aggressive)
compared with women over 50 years
o Because of this it is uncertain if women under 50 years should be
recommended for screening (especially those under 45)
 Screening for the age group 70-79
o Could be marginally useful and cost effective for women in the three upper
quartiles of bone mass density, but harmful for those with the lowest bone
mass density
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Not in favour of screening
 Critical review of original studies and new meta-analyses has recently yielded
results that dispute that there is documentation for reduced mortality as a result of
screening
National screening program (2003)
Mammography screening was introduced in all counties for women who are between
the ages of 50-69 years old. The particular age groups will be offered the examination
every third year. The experience from the counties that have test run the screening, has
been positive. The establishing of different centres for breast cancer diagnostics in all
Norwegian counties is expected to improve primary diagnostics and treatment.
In addition to diagnostic precision and the effect of early intervention on prognosis,
the cost aspect is central to the discussion about the usefulness of screening
programmes. Large-scale examinations like cervix screening and mammography
screening is expensive and uses resources that could have been better used in another
area.
The dilemma with extending screening to include women who are in their 40s, has
recently been shown in a meta-analyse from the Norwegian Knowledge Center in
Health Care. They concluded that the programme showed an NNT of 3000 – that is,
3000 women must be screened in order to save one of them. Another aspect of this is
that 10 in 3000 will be incorrectly diagnosed as having breast cancer. If the screening
programme is to be extended, there is reason to ask the following questions:
Is society willing to accept that some healthy people are falsely claimed to have a
suspicuous lesion in order to give others this benefit? Does the usefulness of
mammography justify the resources it uses as opposed to the alternative ways these
resources could be used? Should scarce resources be used on the healthy instead of the
diseased? Will early diagnosis by screening result in less invasive and less costly
treatment?
Pitfalls of screening
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Lead time bias – An impression of improved survival is given because the disease is
diagnosed earlier with the help of screening even though the disease’s natural course
is not altered by treatment or intervention. This inflicts upon the patient more years as
ill without gaining total living years.
Length time bias – Apparent improved survival because the most slowly growing
cancers are overrepresented. These “more benign” cancer forms have longer lead time.
Requirements for screening programmes
Requirements of the disease and treatment
1. The disease must be a serious health threat
2. The disease must have an adequately known natural course
3. The disease must have a reasonably long asymptomatic or preclinical phase
4. An acceptable diagnostic method must be available that gives correct indication
for treatment
5. The treatment results must be considerably better for those who receive an early
diagnosis than for those who are diagnosed late in the course of the disease
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6. Recourses for follow-up with diagnostics and treatment for those test-positive
must be available
Requirements of the screening test
7. The test must have adequate validity (sensitivity and specificity)
8. The test must imply a small risk for those who are examined and not cause any
injuries
Requirements of the screening programme
9. The cost of the screening programme must be reasonable compared to alternative
health care initiatives and the effect must be documented in randomized studies
10. The programme as a whole should be accepted by the general public concerning
travel time and waiting time
11. The screening programme must be set up to run continually and should fit together
with other health care services
Long term hormone treatment for women
Vignette 3
Siri Kullseng is 49 years old, married and has two adult children. She hasn’t
menstruated during the last year and comes to talk with you about hormone treatment.
She doesn’t have any previous illnesses or present illnesses or health complaints.
Several of her friends have started taking oestrogen and she has been told that she
should also take oestrogen, the sooner, the better.
What is your attitude toward hormone treatment for menopausal women?
Which factors would you focus on in evaluating hormone replacement therapy
(HRT)?
What are the advantages of hormone treatment?
What are the disadvantages of hormone treatment?
Indications for hormone treatment
Most of the women who consider hormone treatment are attracted by the immediate
benefits and concerned about the possible disadvantages of this type of treatment
taken for a short period of life. The main reason that women want to take oestrogen, is
to relieve the unpleasant menopausal symptoms such as hot flashes, depression,
irritability, etc. Sometimes it is urinary incontinence that brings the topic forth.
Quality of life aspects such as sex life improvement and slowing down aging are
important issues for some, but it isn’t always these topics that are discussed with the
patient. When choosing the type of medication, most women immediately prefer plain
oestrogen or a continuous combined hormone replacement therapy (no breaks for
menstruation).
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Why would you recommend combination therapy?
Are there women who you would recommend that they take oestrogen alone therapy?
Possible disadvantages of long term hormone therapy
Today’s knowledge is mostly based on observational studies. In a systematic review
article (7) and according to US American guidelines (8) the conclusions are as
follows:
Endometrial cancer
The risk for a woman in her 50s is 2.6% for cancer and 0.3% for not surviving this
type of cancer. The risk for developing endometrial cancer is considerably increased
among women who use oestrogen alone therapy (RR = 8.2, CI 6.3-10.8). The risk
increases with the duration of treatment. Using combination therapy (oestrogenprogestin) does not increase the risk of cancer.
Breast cancer
The risk for a woman in her 50s is 10% for cancer and 3% for not surviving this type
of cancer. Oestrogen alone therapy increases to the risk for breast cancer only slightly
(RR = 1.3, CI 1.0-1.5). It is not certain as to whether combination therapy increases
the risk, perhaps a slightly higher risk (RR = 1.5 ?).
Vignette 3, continued
Signe Kullseng wants to know what kind of side effects long term treatment with
oestrogen has.
What is the probability, the absolute risk that she will develop uterine cancer
(endometrial cancer) with long term treatment with:
Oestrogen alone therapy?
Combination therapy?
What is the probability, absolute risk, for developing breast cancer with long term
treatment with:
Oestrogen alone therapy?
Combination therapy?
Possible advantages of long term hormone replacement therapy
From the same article (7) the following:
Coronary heart disease (CHD)
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CHD is the most common cause of death among postmenopausal women. The risk for
a woman in her 50s is 46% and mortality of CHD is 31%. Earlier studies suggested
that oestrogen therapy reduced the risk of cardiovascular disease. Newer studies
disproved this; even suggested the opposite that there was perhaps an increase in this
risk with oestrogen therapy.
Osteoporosis
The risk for a woman in her 50s for developing osteoporosis is 15% and the
probability is 1.5% for not surviving as a result of upper femur fracture. Incidence of
upper femur fracture is reduced for those who take oestrogen (RR = 0.75, CI 0.680.84). The effect increases with duration of treatment, but quickly decreases after the
treatment ceases. This benefit is greatest for women with osteoporosis. Combination
therapy seems to be equally effective.
Other effects
Oestrogen seems to have little influence on stroke/heart attack. It doesn’t influence
risk of thrombosis. In general, it has been estimated that oestrogen treatment can
increase length of life by 0.9 year.
Summary question
What factors will you emphasize when you advise a 50 year old woman about long
term hormone treatment?
Scientific literature
1. Skjeldestad FE. Chlamydia-tall.
2. Fahey MT, Irwig L, Macaskill P. Meta-analysis of Pap Test Accuracy. Am J
Epidemiol 1995; 7: 680-9.
3. Forsmo S, Buhaug H, Skjeldestad FE and Haugen OA. Treatment of pre-invasive
conditions during opportunistic screening and its effectiveness on cervical-cancer
incidence in one Norwegioan county. Int. J. Cancer 1997; ?: ?
4. Bergström R, Adami HO, Gustafsson L, Pontén J, Sparén P. Detection of
Preinvasive Cancer of the Cervix and the Subsequent Reduction in Invasive
Cancer. J Natl Cancer Inst 1995; 85: 1050-7.
5. Raffle AE, Alden B, Mackenzie EFD. Detection rates for abnormal cervical
smears: what are we screening for? Lancet 1995; 345: 1469-73.
6. Andersson I, Aspegren K, Janzon L et al. Mammographic screening and mortality
from breast cancer: the Malmö mammographic screening trial. BMJ 1988; 297:
943-8.
7. Grady D, Rubin SM, Petitti DB et al. Hormone Therapy to Prevent Disease and
Prolong Life in Postmenopausal Women. Ann Intern Med 1992; 117: 1016-37.
8. American College of Physicians. Guidelines for Counseling Postmenopausal
Women about Preventive Hormone Therapy. Ann Intern Med 1992; 117: 1038-41.
9. Østrogener og osteoporose. SLK’s terapiverksted 1994; nr. 2.
10. Behandling av osteoporose. SLK’s terapiverksted 1997, supplement 1.
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