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CLINICAL PRACTICE GUIDELINES
Health Screening
Ministry
of Health
NMRC
July 2003
National Medical
Research Council
MOH Clinical Practice Guidelines 6/2003
Levels of evidence and grades of recommendation
Levels of evidence
Level
Type of Evidence
Ia
Evidence obtained from meta-analysis of randomised controlled
trials.
Ib
Evidence obtained from at least one randomised controlled trial.
IIa
Evidence obtained from at least one well-designed controlled study
without randomisation
IIb
Evidence obtained from at least one other type of well-designed
quasi-experimental study.
III
Evidence obtained from well-designed non-experimental descriptive
studies, such as comparative studies, correlation studies and case
studies.
IV
Evidence obtained from expert committee reports or opinions and/or
clinical experiences of respected authorities.
Grades of recommendation
Grade
Recommendation
A
(evidence levels Ia,
Ib)
Requires at least one randomised controlled trial as part
of the body of literature of overall good quality and
consistency addressing the specific recommendation.
B
(evidence levels IIa,
IIb, III)
Requires availability of well conducted clinical studies
but no randomised clinical trials on the topic of
recommendation.
C
(evidence level IV)
Requires evidence obtained from expert committee
reports or opinions and/or clinical experiences of
respected authorities. Indicates absence of directly
applicable clinical studies of good quality.
GPP
(good practice
points)
Recommended best practice based on the clinical
experience of the guideline development group.
CLINICAL PRACTICE GUIDELINES
Health Screening
MOH Clinical Practice Guidelines 6/2003
Copyright © 2003 by Ministry of Health, Singapore
Available on the MOH website: http://www.gov.sg/moh/pub/cpg/cpg.htm
Statement of Intent
These guidelines are not intended to serve as a standard of medical care.
Standards of medical care are determined on the basis of all clinical data
available for an individual case and are subject to change as scientific
knowledge advances and patterns of care evolve.
The contents of this publication are guidelines to clinical practice, based on
the best available evidence at the time of development. Adherence to these
guidelines may not ensure a successful outcome in every case, nor should
they be construed as including all proper methods of care or excluding
other acceptable methods of care. Each physician is ultimately responsible
for the management of his/her unique patient in the light of the clinical data
presented by the patient and the diagnostic and treatment options available.
Foreword
Health screening aims to identify diseases in apparently well people through
the application of tests, examinations or other procedures which can be easily
applied.
Screening must be based on evidence that it is associated with improved
clinical outcomes. For mass screening, there should also be evidence of costeffectiveness.
While there is a general perception that screening will improve clinical
outcomes, this may not be so. This is because no screening test is 100%
sensitive and specific. False positive tests will inevitably generate anxiety
and require further testing, with attached risks and costs, while false
negatives may give the patients a false sense of security. Hence there is a
need for recommendation on health screening based on a rigorous review of
evidence.
I would like to commend the Committee on Health Screening for their hard
work and commitment in producing the guidelines on health screening. I
hope that these guidelines will assist medical professionals in their clinical
practice.
PROFESSOR TAN CHORH CHUAN
DIRECTOR OF MEDICAL SERVICES
Contents
Page
Executive summary of recommendations
1
1 Introduction
19
2 Screening for blood cholesterol
23
3 Screening for hypertension
29
4 Screening for diabetes mellitus
35
5 Screening for obesity
41
6 Screening for lung cancer
45
7 Screening for hepatocellular carcinoma (HCC)
49
8 Screening for colorectal cancer
55
9 Screening for prostate cancer
67
10 Screening for breast cancer
75
11 Screening for cervical cancer
95
12 Screening for uterine cancer
101
13 Screening for ovarian cancer
105
14 Screening for tuberculosis
109
15 Screening for hepatitis B
119
16 Screening for renal diseases
123
17 Screening for osteoporosis
131
18 Screening for visual acuity for the elderly
143
19 Screening for sexually transmitted infection
145
20 Clinical audit
163
Summary chart
165
Self-assessment (MCQs)
169
Workgroup members
177
Acknowledgements
179
List of Endorsing Agencies
181
Executive summary of recommendations
Details of recommendations can be found in the main text at the pages indicated.
Screening for blood cholesterol
C In screening for cholesterol, the optimal test is a full lipid profile
including LDL-cholesterol, fasting triglyceride and HDL cholesterol.
(pg 25)
Grade C, Level IV
GPP If the results are optimal based on the current recommendations for
Singapore, we recommend repeat screening at 3 yearly intervals. (pg 24)
GPP
B Screening should be carried out in all individuals above the age of 40
years on an opportunistic basis. (pg 24)
Grade B, Level IIb
A All patients with pre-existing coronary heart disease, stroke or
peripheral vascular disease should be screened irrespective of age. (pg 24)
Grade A, Level Ia
A All patients with diabetes mellitus should be screened irrespective of
age. (pg 24)
Grade A, Level Ib
B All individuals with impaired fasting glycaemia or impaired glucose
tolerance should be screened at any age. (pg 24)
Grade B, Level III
B All individuals with a family history and/or clinical evidence of familial
hyperlipidaemia should be screened after the age of 2 years. (pg 24)
Grade B, Level IIa
GPP Earlier screening from age 30 should be considered for individuals
with other risk factors for CHD e.g. smoking, hypertension, family history
of premature CHD. (pg 24)
GPP
1
B Earlier screening from age 30 years should be considered for those of
Indian ethnicity. (pg 24)
Grade B, Level III
Screening for hypertension
C Blood pressure should be measured at least once every 2 years for
adults aged 21 years and above with diastolic pressure below 85 mmHg
and a systolic pressure below 130 mmHg (i.e. normal BP). (pg 30)
Grade C, Level IV
A Measurements are recommended annually for persons with a diastolic
blood pressure of 85-89 mmHg or systolic blood pressure of 130-139
mmHg (i.e. high normal BP). Persons with higher blood pressures or
major coronary risk factor such as diabetes mellitus require more frequent
measurement. (pg 30)
Grade A, Level Ib
C Any person aged 21 years and above should have their blood pressure
measured during any visit to a physician ("case finding"). (pg 31)
Grade C, Level IV
A Sphygmomanometry is the recommended method for blood pressure
measurement, and it should be performed in accordance with the
recommended technique. (pg 31)
Grade A, Level Ia
A Pregnant women should have their blood pressure checked routinely as
part of the prenatal care. (pg 32)
Grade A, Level Ia
A Routine counselling to promote physical activity and a healthy diet for
the primary prevention of hypertension is recommended for all adults.
(pg 31)
Grade A, Level Ia
Screening for diabetes mellitus
C Screening of asymptomatic individuals at high risk for type 2 diabetes
mellitus should be carried out on an opportunistic basis. (pg 35)
Grade C, Level IV
2
C Screening should begin at age 40 years, and be considered at an earlier
age (e.g. 30 years) if risk factors for diabetes are present. (pg 35)
Grade C, Level IV
B Fasting plasma glucose (FPG) is the recommended test for screening in
the clinical setting because it is easy to perform and convenient.
Individuals with a FPG ≥ 7.0 mmol/L should have a repeat testing on a
different day to confirm the diagnosis of diabetes. Individuals with FPG of
6.1-6.9 mmol/l on screening should undergo a 75g oral glucose tolerance
test (OGTT) to determine precisely the degree of glucose intolerance.
(pg 38)
Grade B, Level III
B OGTT is also a suitable test for screening. (pg 38)
Grade B, Level III
C Individuals found to have normal glucose tolerance on screening and
who do not have risk factors for developing diabetes should have repeat
screening at 3 yearly intervals. For those with diabetes risk factors, repeat
screening may be performed more frequently e.g. at annual interval.
(pg 39)
Grade C, Level IV
B Those detected to have impaired fasting glycemia (IFG) or impaired
glucose tolerance (IGT) should have repeated screening on an annual
interval in view of the high rate of conversion to diabetes. (pg 39)
Grade B, Level III
Screening for obesity
B Body mass index (BMI) and waist circumference can be used to classify
obesity and assess risk. (pg 41)
Grade B, Level III
C All individuals ≥18 years of age should be screened. (pg 42)
Grade C, Level IV
GPP Screening should be done once a year for all individuals ≥ 18 years.
(pg 42)
GPP
3
Screening for lung cancer
A Neither chest X-ray nor sputum cytology is recommended for
screening. (pg 46)
Grade A, Level Ib
C The screening efficacy of low-dose spiral CT is unknown at present.
(pg 46)
Grade C, Level IV
Screening for hepatocellular carcinoma (HCC)
GPP There is no evidence to support population-based surveillance for
HCC. However, HCC surveillance should be offered to patients with
chronic hepatitis B infection, hepatitis C liver cirrhosis and liver cirrhosis
from other etiologies. HCC surveillance should be performed periodically
with alpha-fetoprotein 3 to 6 monthly and ultrasound of the liver at 6 to 12
monthly interval. There is no definite recommended age to start
surveillance. However, it is noted that the local statistics showed that HCC
detection starts to increase from the age of 30 years. (pg 52)
GPP
C Current accepted tests used for HCC surveillance include ultrasound of
the hepato-biliary system and alpha feto-protein level. (pg 49)
Grade C, Level IV
Screening for colorectal cancer
A Asymptomatic individuals above the age of 50 years should undergo
screening for colorectal cancer. This would include asymptomatic
individuals with a family history limited to non-first degree relatives. The
screening options would be faecal occult blood testing annually. (pg 62)
Grade A, Level Ia
B Alternatively, other methods that could be employed in this group
include flexible sigmoidoscopy every 5 years; (pg 62)
Grade B, Level IIa
4
B or colonoscopy every 10 years. (pg 62)
Grade B, Level IIb
(Those with a positive faecal occult blood test would undergo colonoscopy
or when technically not possible, a barium enema.)
B In individuals with a history of colorectal cancer in a first degree
relative aged 45 years or younger or with a family history of two or more
affected first degree relatives, colonoscopy is recommended every 3 years
performed 10 years prior to the youngest case in the family. (pg 62)
Grade B, Level IIa
B In individuals who have a history of colorectal cancer in a first degree
relative over the age of 45 years, colonoscopy is recommended every 10
years. The age of commencing colonoscopy is 10 years prior to the
youngest case in the family or age 50 years whichever is earlier. (pg 62)
Grade B, Level IIb
A In individuals with a personal past history of colorectal polyps,
colonoscopy is recommended one year after polypectomy in the presence
of high risk features (polyp > 1cm, multiple, villous architecture) or three
years after polypectomy in the absence of high risk features (solitary,
tubular architecture). (pg 62)
Grade A, Level Ib
B In individuals with a personal past history of colorectal cancer,
colonoscopy is recommended one year after resection provided that total
imaging of the bowel was achieved prior to surgery. (pg 62)
Grade B, Level IIa
B In individuals with a family history of familial adenomatous polyposis,
flexible sigmoidoscopy is recommended annually from the onset of
puberty. (pg 62)
Grade B, Level IIb
Genetic counselling should be considered.
5
B In individuals with a family history of Hereditary Non-polyposis
Colorectal Cancer, colonoscopy is recommended every two years 10 years
prior to the diagnosis of colorectal cancer in the youngest family member.
(pg 62)
Grade B, Level IIb
Genetic counselling should be considered.
B In individuals with left-sided ulcerative colitis, colonoscopy is
recommended every 1-2 years from the 15th year after diagnosis. For
individuals with pan-colitis, colonoscopy is recommended every 1-2 years
from the 8th year after diagnosis. (pg 62)
Grade B, Level IIb
C Plasma CEA (carcinoembryonic antigen) levels are not recommended
for use in the screening of asymptomatic, average risk individuals. (pg 61)
Grade C, Level IV
Screening for prostate cancer
A Population screening for prostate cancer should not be recommended at
present among Asians. (pg 68)
Grade A, Level Ia
GPP High-risk men, such as men above 50 years of age with a history of
a first degree relative with prostate cancer at a young age (<60 years),
should be offered screening. (pg 68)
GPP
B Combined use of prostate specific antigen (PSA) and digital rectal
examination (DRE) has a higher detection rate for prostate cancer than
either test alone. (pg 68)
Grade B, Level IIb
B Transrectal ultrasound (TRUS)-guided biopsy for raised PSA and/or
abnormal DRE is recommended. (pg 69)
Grade B, Level IIb
6
Screening for breast cancer
A All normal risk, asymptomatic women 50-64 years of age should be
screened with mammography only, every 2 years. Ultrasound and breast
examination are not routinely required. (pg 80)
Grade A, Level Ia
A In Western nations, the evidence supports mammographic screening
every 2 years for all normal risk women 65-75 years of age. However, for
Singaporean women the much lower incidence of breast cancer in this age
group suggests that screening mammography may be less beneficial. If
individual screening is performed, it should be at two-yearly intervals.
Ultrasound and breast examination are not routinely required. (pg 80)
Grade A, Level Ia
A Women with breast implants are recommended to have routine
screening mammography once every 1-2 years, depending on their age.
(pg 87)
Grade A, Level Ia
A Normal risk, asymptomatic women under 40 years should not undergo
breast screening with any imaging modality. (pg 81)
Grade A, Level Ib
A Clinical breast examination has been proven to confer no mortality
benefit in a screening population. (pg 83)
Grade A, Level Ib
B Breast ultrasound and MRI can both detect cancers that are occult on
mammography. However, they should not be used for routine breast
screening outside of clinical trials. (pg 84)
Grade B, Level IIa
B Nuclear scintimammography shows promise as an adjunct technique for
detection of breast cancer in limited circumstances, usually in conjunction
with mammography. Its use for breast screening is unwarranted. (pg 85)
Grade B, Level III
7
C Women at normal risk aged 40-49 years should be encouraged to have
annual screening mammography. Ultrasound and breast examination are
not routinely required. (pg 81)
Grade C, Level IV
C Women on conventional hormone replacement therapy have a very
slightly increased risk of breast cancer. They should have regular
screening mammography. Those aged 40-49 years should be screened
annually, and those aged 50-65 years biannually, for up to 5 years after
cessation of HRT. (pg 81)
Grade C, Level IV
C Women who are at very high risk of breast cancer by virtue of being a
BRCA gene carrier, or a very strong first-degree family history of breast
cancer, should perform monthly breast self examination, 6-monthly
clinical breast examination and ultrasound, and annual mammography.
Screening should start as early as 5 years before the age of onset of breast
cancer in the youngest family member. Breast magnetic resonance
imaging should be considered, but only if cost is not problematic and the
expertise and equipment for MRI-guided breast needle biopsy and
localisation are available. (pg 82)
Grade C, Level IV
C Thermography and Electrical Impedance Scanning must be regarded as
investigational techniques. Their use for breast screening is not warranted.
(pg 86)
Grade C, Level IV
GPP Women with prior breast cancer should receive annual screening
mammography of the remnant and contralateral breasts. At 5 years
disease-free post-surgery, they may return to the standard screening
interval for asymptomatic women of the same age. (pg 86)
GPP
GPP Despite evidence that it has no survival benefits, BSE is generally
recommended as it is felt to improve women’s awareness of their own
breasts and breast cancer. As the incidence of breast cancer is extremely
low before the age of 30 years, BSE is only recommended from the age of
30 years for normal risk women. (pg 84)
GPP
8
GPP When encountered, women with free silicone or paraffin oil
injections in their breasts should be clinically examined and counselled as
to the futility of screening using any currently available test. MRI may be
useful in highly selected cases where there is a strong suspicion of breast
cancer. (pg 87)
GPP
Screening for cervical cancer
B Well-run population-based cervical cancer screening programme with
good coverage reduces the incidence and mortality of cervical cancer.
(pg 96)
Grade B, Level IIa
B All women who have ever had sexual intercourse should have a Pap
smear by the age of 25 years. (pg 96)
Grade B, Level III
B Pap smear screening should be performed every 3 years. (pg 96)
Grade B, Level IIa
B Screening can be discontinued at age 65 years if the smear taken at age
65 years was negative and the previous smears were negative. (pg 96)
Grade B, Level III
B HIV positive women should be screened earlier and more frequently,
preferably annually. (pg 97)
Grade B, Level III
Screening for uterine cancer
B There is no indication that screening is warranted for women who are at
average or increased risk* for endometrial cancer. (pg 102)
Grade B, Level IIb
*Women may be regarded as being average risk, increased risk or high risk for
endometrial cancer.
C Hereditary Non-Polyposis Colorectal Cancer is a syndrome in which
there is an inherited tendency to develop colorectal cancer. Women with or
9
at risk for hereditary non-polyposis colorectal cancer (HNPCC) are
considered high risk and should be offered annual screening for
endometrial cancer with endometrial biopsy by age 35 years. (pg 102)
Grade C, Level IV
Screening for ovarian cancer
B Routine population screening for ovarian cancer by ultrasound, the
measurement of tumour markers, or pelvic examination is not
recommended. (pg 105)
Grade B, Level IIa
GPP There is insufficient evidence to recommend for or against the
screening of asymptomatic women at increased risk of developing ovarian
cancer. Experts suggest referral of these women to tertiary centres for
multimodal screening. (pg 106)
GPP
Screening for tuberculosis
A Tuberculin Skin Test (TST) screening for latent TB infection is
recommended only for identifying candidates for treatment of latent TB
infection (generally with isoniazid, INH). Therefore, it is recommended
only in persons at high risk of breakdown to TB disease. (pg 113)
Grade A, Level Ib
(Indiscriminate screening or erroneous selection of subjects could lead to
the needless administration of INH and the unnecessary exposure of these
subjects to the risk of drug-induced hepatitis which in some cases may be
fatal.)
B As a rule, mass chest X-ray screening for TB is not recommended.
(pg 114)
Grade B, Level III
Screening for hepatitis B
A All pregnant women should be tested for HBsAg during the early
antenatal visit. The test may be repeated in the third trimester if acute
10
hepatitis is suspected, an exposure to hepatitis has occurred or the woman
practices a high-risk behaviour such as intravenous drug abuse. (pg 120)
Grade A, Level Ib
A Serological screening for HBsAg and anti-HBs should be performed
pre-vaccination for all except newborn. (pg 121)
Grade A, Level Ib
A Persons who remain at risk of HBV infection such as health care
workers and dialysis patients should be screened using HBsAg and antiHBs and vaccinated against hepatitis B if the test is negative. Such
individuals should then be tested for response to the vaccination. (pg 121)
Grade A, Level Ib
B Screening high risk individuals like those with a family history of
hepatitis B infection, liver cancer or those at high behavioural risk should
be performed. They should be tested at baseline and whenever exposure is
suspected. (pg 121)
Grade B, Level IIa
C Routine screening for HBV infection in the general population is not
recommended but recommendations for screening may be made based on
cost-effectiveness analyses. Such analyses suggest that screening can be
cost-effective in groups with an HBV marker prevalence >20%. (pg 121)
Grade C, Level IV
Screening for renal diseases
C A healthy asymptomatic individual may undergo opportunistic
screening with urine dipstick examination. (pg 125)
Grade C, Level IV
C Specific individuals at increased risk (e.g. age over 50 years,
hypertension, smoking, diabetes and family history of renal disease) of
chronic renal disease should undergo annual dipstick testing for
proteinuria. (pg 125)
Grade C, Level IV
11
C Individuals at increased risk of developing chronic renal disease should
undergo testing of serum creatinine in order to estimate the level of
glomerular filtration rate. (pg 126)
Grade C, Level IV
C Individuals with a positive dipstick proteinuria should have a spot
urinary protein-creatinine ratio test to quantitate their proteinuria. (pg 125)
Grade C, Level IV
Screening for osteoporosis
C All individuals with prior fragility fractures during adulthood should be
considered for BMD measurement and osteoporosis treatment. (pg 133)
Grade C, Level IV
C Population screening using BMD is not recommended for
postmenopausal women. A case-finding strategy is preferred, measuring
BMD in individuals at highest risk for osteoporosis identified using
clinical evaluation tools such as OSTA or NOF guidelines, and clinical
risk factor evaluation. (pg 138)
Grade C, Level IV
C Women with osteoporosis, who are being monitored for progression or
who are being treated, should have a follow-up bone density measurement,
usually at an interval of at least one year. In women with osteopenia, a
reasonable interval might be 1 to 2 years, while in those with normal
BMD, a more reasonable interval may be 2 to 5 years. (pg 138)
Grade C, Level IV
C Screening is not recommended for premenopausal women and men.
BMD measurement should be considered in those at high risk for fracture.
(pg 138)
Grade C, Level IV
C BMD measurement should be considered in patients with high risk for
steroid-associated fractures, who are initiating or already on long-term
higher-dose corticosteroid therapy. (pg 138)
Grade C, Level IV
12
Screening for visual acuity for the elderly
B The population to be screened includes any person 65 years and above,
and the screening test involves using a Snellen chart to test each eye.
(pg 143)
Grade B, Level III
B Any person screened and found to have vision worse than 6/12 can be
referred for assessment and treatment. (pg 144)
Grade B, Level III
C The optimal frequency for screening is not known and is left to the
discretion of the screener. (pg 144)
Grade C, Level IV
C Besides visual acuity testing using the Snellen chart, there is
insufficient evidence to recommend for or against routine screening with
ophthalmoscopy by the primary care physician in asymptomatic elderly
patient. (pg 144)
Grade C, Level IV
Screening for other sexually transmitted infections
Chlamydia trachomatis infection
A Sexually active women with the following risk factors may be at higher
risk of chlamydial infection and should be considered for screening: those
aged 25 years and younger, who have a new sexual partner, who have
partners with symptoms of an STI or who have had two or more partners
in the past 12 months and lack the use of barrier contraception. (pg 147)
Grade A, Level Ib
A Women undergoing termination of pregnancy with risk factors (as
above) should be screened. (pg 147)
Grade A, Level Ib
B Pregnant women aged 25 years and younger and other pregnant women
at higher risk for infection (i.e. women who have had two or more sexual
partners in the past 12 months, or partners with symptoms of an STI)
should be considered for screening. (pg 147)
Grade B, Level IIb
13
C Women undergoing instrumentation of the uterus should be considered
for screening on an individual case basis because even in low prevalence
groups, there may be a resultant risk of ascending infection. (pg 147)
Grade C, Level IV
C Asymptomatic men with high-risk behaviour such as frequent partner
change, lack of use of barrier protection or sex with prostitutes can be
considered for screening. These patients should be referred to specialist
centres for counselling, and investigation. (pg 148)
Grade C, Level IV
A Screening can be performed using cultures or enzyme immunoassays
(EIA) on endocervical swabs in women and urethral swabs in men.
(pg 148)
Grade A, Level Ia
A Nucleic acid amplification tests (NAAT) using polymerase chain
reaction (PCR) or ligase chain reaction (LCR) can also be used in
screening on endocervical or urethral swabs, and have the advantage of
being used on non-invasive specimens such as urine. (pg 148)
Grade A, Level Ia
C Serological tests based on genus-specific complement fixation test are
not useful in the diagnosis of chlamydial genital infections, with the
possible exception of lymphogranuloma venereum. (pg 149)
Grade C, Level IV
GPP In men, a Gram-stained urethral smear taken 4 hours from the last
void of urine showing presence of 5 or more leukocytes per high-power
field indicates urethritis. This may be due to Chlamydia trachomatis or
other organisms, as well as other factors that may not be sexually
transmitted. These patients should be assessed by specialist centres for
counselling and advice. (pg 148)
GPP
GPP The optimal frequency of screening is a matter of clinical
discretion. Screening for chlamydia infection should be performed about 1
week after high-risk exposure or change of sex partner. (pg 149)
GPP
14
Syphilis
C All women and men at increased risk for infection, including sex
workers, persons who exchange sex for money or drugs, persons with
other STIs (including HIV) and genital ulceration, and sexual contacts of
persons with active syphilis should be screened. (pg 150)
Grade C, Level IV
B Pregnant women should be screened at their first antenatal visit.
(pg 151)
Grade B, Level III
C Pregnant women at higher risk of infection (i.e. women who have
partners with symptoms of an STI, or continue to engage in sexual activity
with multiple partners, or a partner who has sex with multiple partners)
should have screening repeated in the third trimester. (pg 151)
Grade C, Level IV
C Screening for syphilis is performed using nontreponemal tests such as
RPR or VDRL. Positive results should be confirmed with a specific test
such as TPPA or TPHA. Both nontreponemal and treponemal tests can be
combined for use in screening, although this would be more costly and
labour-intensive. (pg 152)
Grade C, Level IV
C Follow up serologic tests should be obtained to document declines in
titres after treatment. They should be performed using the same test
initially used to document infection (e.g. VDRL or RPR) to ensure
compatibility. (pg 153)
Grade C, Level IV
GPP The optimal frequency of screening is a matter of clinical
discretion. Screening for syphilis should be performed 1 month after
exposure, and repeated again after 3 months. (pg 152)
GPP
15
Gonorrhoea
C Women at high risk of infection – including sex workers, women with a
history of repeated episodes of gonorrhoea, and women with two or more
sex partners in the previous year should be screened. (pg 154)
Grade C, Level IV
GPP Homosexual men with frequent partner change or other high-risk
behaviour (i.e. those who have sex with partners with symptoms of an STI,
those who do not use barrier protection including unprotected receptive
and insertive oral and anal intercourse) should be considered for screening.
(pg 154)
GPP
C The ideal screening test is isolation of Neisseria gonorrhoeae by culture
from the appropriate sites. (pg 154)
Grade C, Level IV
GPP Sites to be sampled will be determined by the history of sexual
contact – urethra, cervix, rectum or pharynx. (pg 155)
GPP
GPP The optimal frequency of screening is a matter of clinical
discretion. Screening for gonorrhoea should be performed about 1 week
after exposure. (pg 155)
GPP
Genital Herpes Simplex
GPP Routine screening for genital herpes simplex virus (HSV) infection
by viral culture, serology or other means is not recommended for
asymptomatic men or women, including asymptomatic pregnant women.
(pg 155)
GPP
HIV
C Clinicians should assess risk factors for HIV infection in all persons by
obtaining a careful sexual history and inquiring about drug use. (pg 156)
Grade C, Level IV
16
C Counselling and testing for HIV should be offered to all persons at
increased risk of infection. These include those seeking treatment for STI;
men who have sex with men; past or present injecting drug users; persons
who exchange sex for drugs or money and their sex partners; persons
whose past or present sex partners were HIV-infected, and persons who
have had a blood transfusion or an organ transplant that had not previously
been screened. (pg 156)
Grade C, Level IV
GPP Pregnant women should be offered the test in the first trimester.
(pg 157)
GPP
C Screening for HIV is performed using ELISA. A positive result requires
2 reactive ELISA tests and confirmation with the Western Blot (WB)
assay, performed by experienced laboratories that receive regular external
proficiency testing. (pg 157)
Grade C, Level IV
C Persons who continue to exhibit high-risk behaviour should have
screening tests on a regular basis. The frequency at which these
individuals are screened is a matter of clinical discretion. Screening for
HIV should be performed 6-monthly in a person who continues to exhibit
high-risk behaviour. (pg 157)
Grade C, Level IV
C Persons with recent high-risk behaviour should be screened at 1 month,
3 months and 6 months after the last high-risk exposure to rule out a
possible initial false negative result. (pg 157)
Grade C, Level IV
Genital Human Papillomavirus (HPV) infection
C Women with a history of STI may be at increased risk for cervical
cancer, which is linked to certain HPV types. However, the HPV types that
frequently cause anogenital warts do not cause cancer. The Pap smear is a
screening test for cervical carcinoma and not a screening test for STIs, and
women who have external genital warts do not need to have Pap smears
more frequently than women who do not have warts. (pg 158)
Grade C, Level IV
17
C Clinical examination with the unaided eye is the oldest diagnostic
technique in detection of genital warts. However, subclinical genital HPV
infection, a term used to refer to manifestations of infection in the absence
of genital warts, may still exist. No screening tests for subclinical infection
are available, and there are no recommendations for routine screening.
(pg 158)
Grade C, Level IV
18
1
Introduction
1.1
Guideline Objectives and Target Group
The health screening guidelines are intended to assist medical
practitioners, especially those in the primary health care sector, advise
their patients on the screening to be conducted for various diseases
based on the patient’s age, gender and presence of risk factors.
These guidelines provide current evidence-based clinical practice
recommendations on screening for a range of disease conditions found
across various medical disciplines. The individuals for whom these
guidelines are recommended are average-risk asymptomatic adults.
High-risk individuals have also been identified.
1.2
Guideline Development
The health screening guidelines were developed by a workgroup
appointed by the Ministry of Health. Its members comprised experts
in their area of specialty. The workgroup formulated these guidelines
by reviewing published international screening guidelines and current
evidence available in the research literature, and taking into
consideration the local population’s characteristics. Feedback from
relevant professional organisations was also sought in the process.
1.3
Principles for Screening
Screening people who are apparently well in order to pick up
asymptomatic disease can be beneficial to the individual if early
treatment is available to improve the prognosis. It is beneficial to
society at large if identification leads to primary prevention in
protecting others from becoming affected. However, there are other
considerations for screening. Wilson and Junger1 cited the following
principles of screening for early disease detection:
a) The condition sought should be an important health problem
b) The natural history of the disease should be adequately
understood
1
Wilson MG, Junger G. Principles and practice of screening for disease.
Public Health Paper 34. Geneva. WHO. 1968.
19
c) There should be a recognisable latent or early symptomatic stage
d) There should be a suitable and acceptable screening test or
examination
e) There should be an accepted treatment or useful intervention for
patients with the disease
f) Facilities for diagnosis and treatment should be available
g) There should be an agreed policy on whom to treat as patients
h) The cost of case-finding (including diagnosis and treatment of
patients diagnosed) should be economically balanced in relation
to possible expenditure on medical care as a whole
i) Case finding should be a continuing process and not a once and
for all project.
Whether or not a screening policy results in improved health
outcomes depends on a number of factors viz. the characteristics of
the disease, the screening test, and the patient population.
Screening may be considered where there is a high prevalence of the
disease with potential serious consequences, the disease condition has
a natural history with a latent stage during which symptoms of disease
are either not present or early; and when detected and managed, is
beneficial in improving the likelihood of favourable health outcomes
(viz. reduced disease-specific morbidity or mortality). The screening
test should be acceptable to the public, simple, fairly readily applied,
and valid. With regard to diagnosis, the condition must be treatable
and treatment and care available for those who need it. Early
treatment should improve the outcome compared to treating patients
when they present with signs and symptoms of the disease.
There is also a need for screening on a continuing basis rather than
single-occasion screening. Single-occasion screening is of limited
value because only a small proportion, often those at least risk, is
likely to be screened, and screening picks up those persons in the
population who just happen at that particular time to have that
condition being checked for. It therefore does not affect the future
incidence of disease. Continuing examinations have greater advantage
as they cover more of the population at risk including, by reexamination, persons presenting with new disease.
20
1.4
Screening tests characteristics
Sensitivity and specificity are important characteristics of the validity
of a screening test. The validity of a screening test is the ability of the
test to separate those who have the disease condition from those who
do not. The result of the screening test is confirmed by an acceptable
diagnostic procedure (“gold standard”) which distinguishes between
“true” or “false” results. Sensitivity is the ability of the test to
correctly identify those who truly have the disease. It is the ratio,
expressed as a percentage, of the number of individuals with the
disease whose screening tests are positive to the total number of
individuals with the disease. Specificity is the ability of the test to
correctly identify those who do not have the disease. It is the ratio,
expressed as a percentage, of the number of individuals without the
disease whose screening tests are negative to the total number of
individuals without the disease.
A highly sensitive test will have a low proportion of false negative
results, that is, there will be few missed cases. Few screened people
who have the disease will be told incorrectly that they are free of the
disease and have a false sense of security. A highly specific test will
have a low proportion of false-positive results, that is, there will be
few screened people free of the disease who are incorrectly told that
they have the condition. False-positives could generate anxiety and
unnecessary additional tests which may have potential adverse effects
and cost. Ultimately, the medical practitioner would have to weigh the
benefits and disadvantages for screening an individual.
The positive predictive value (PPV) is the screening test’s ability to
identify those who have the disease (true-positives) among all those
whose screening tests are positive. PPV is affected by disease
prevalence. For example, PPV increases with increasing prevalence of
a disease in a high risk population.
Reliability is the ability of the test when reproduced, to have the same
result. A poorly reliable test is likely to have high interobserver
variation (e.g. between different laboratories) or intraobserver
variation (i.e. between the same observer).
21
1.5
Assessing the evidence
In assessing the evidence, different study designs were considered
including randomised controlled trials, cohort studies, case-control
studies and uncontrolled cohort studies. Recommendations to screen
average and/or high risk individuals are influenced by multiple factors
including scientific evidence of effectiveness, costs and policy
concerns.
It is often considered that picking up diseases by screening will be
economical for a community as a whole. To diagnose and treat all
patients would however, also add considerably to the total screening
cost. Hence, only prospective studies which determine if morbidity or
mortality has been reduced and life improved when compared to a
non-screened population can demonstrate the savings in cost to a
community. However, there are often limitations to such studies
including the difficulty in practice in randomising people into
screened and control groups, ethical issues to conduct randomised
trials when screening using a test is already regarded as normal
practice, and significant losses over time in both the intervention and
control groups during the study.
22
2
2.1
Screening for blood cholesterol
Introduction
The treatment of hyperlipidaemia to reduce the risk of coronary heart
disease (CHD) is supported by a wealth of good clinical trial data.
The benefits of treatment in those with high coronary risk have been
clearly demonstrated1-4. The recently released Heart Protection Study
has further shown that benefits of treatment are seen regardless of
gender, age and baseline LDL cholesterol levels5. However, it is also
true that knowledge of benefits do not necessarily translate into
clinical practice6. This treatment gap is seen in both primary care as
well as hospital-based practice. The National Health Survey in 19927
and 19988 had shown that substantial proportions of individuals with
hyperlipidaemia are undiagnosed. Before treatment can be initiated,
those with hyperlipidaemia must be identified and hence the need for
guidelines on screening individuals in our population for
hyperlipidaemia.
This guideline on cholesterol screening is closely patterned after the
Clinical Practice Guidelines on Lipids which was released by the
Ministry of Health in 20019 but with minor modifications based on
further data being made available. In preparing these
recommendations, we have also taken into consideration the Ministry
of Health recommendations for screening for diabetes mellitus in
asymptomatic subjects10 to facilitate better use of resources and
identification of those at risk of dyslipidaemia.
23
2.2
Who should be tested
The following individuals should be screened for blood cholesterol:
Individuals to be screened
Grade of
recommendation,
level of evidence
All individuals aged 40 years and above*.
Grade B, Level IIb
All patients with pre-existing CHD,
cerebrovascular or peripheral artery disease
irrespective of age1,3,5.
Grade A, Level Ia
All patients with
irrespective of age5.
mellitus
Grade A, Level Ib
All individuals with impaired fasting
glycaemia or impaired glucose tolerance†
irrespective of age11.
Grade B, Level III
All individuals with a family history and/or
clinical
evidence
of
familial
hyperlipidaemia12,13 after the age of 2
years14.
Grade B, Level IIa
Earlier screening from age 30 years should
be considered for individuals with other risk
factors for CHD, e.g. smoking, hypertension,
family history of premature CHD.
GPP
Earlier screening from age 30 years should
be considered for those of Indian ethnicity15.
Grade B, Level III
diabetes
* Based on the steep rise of prevalence of diabetes after the age of 40 years and that
96% of diabetic patients had elevated LDL cholesterol (LDL-C) at diagnosis in the
National Health Survey 1998. As patients will be screened for diabetes every 3 years,
the lipids should be screened concurrently.
†
91% of impaired glucose tolerance (IGT) patients had elevated LDL-C.
It is also reasonable to screen lipids in individuals undergoing a
general health screening.
GPP If the results are optimal based on the current recommendations
for Singapore9, we recommend repeat screening at 3 yearly intervals.
GPP
24
2.3
What should be tested
C In screening for cholesterol, the optimal test is a full lipid profile
including LDL cholesterol (LDL-C), fasting triglyceride (TG) and
HDL cholesterol (HDL-C)9,16,17.
Grade C, Level IV
Serum total cholesterol and HDL-C concentration can be measured at
any time of the day in the non-fasting state. However, TG levels must
be obtained after 10-12 hours of fasting. Total cholesterol (TC), HDLC and TG are measured directly. LDL-C is usually calculated using
the Friedwald formula18 which is as follows:
LDL-C (mmol/l) = TC – (HDL-C + {TG / 2.2})
This formula cannot be used if the TG is >4.5 mmol/l (400 mg/dl).
Direct measurement of LDL-C is now available in certain laboratories
in Singapore.
References
1.
Randomised trial of cholesterol lowering in 4444 patients with coronary
heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet
1994;344:1383-9.
2.
Prevention of cardiovascular events and death with pravastatin in patients
with coronary heart disease and a broad range of initial cholesterol levels.
The Long-Term Intervention with Pravastatin in Ischaemic Disease
(LIPID) Study Group. N Engl J Med 1998;339:1349-57.
3.
Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on
coronary events after myocardial infarction in patients with average
cholesterol levels. Cholesterol and Recurrent Events Trial investigators.
N Engl J Med 1996;335:1001-9.
4.
Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease
with pravastatin in men with hypercholesterolemia. West of Scotland
Coronary Prevention Study Group. N Engl J Med 1995;333:1301-7.
25
5.
MRC/BHF Heart Protection Study of cholesterol lowering with
simvastatin in 20,536 high-risk individuals: a randomised placebocontrolled trial. Lancet 2002;360:7-22.
6.
Pearson TA, Laurora I, Chu H, et al. The lipid treatment assessment
project (L-TAP): a multicenter survey to evaluate the percentages of
dyslipidemic patients receiving lipid-lowering therapy and achieving lowdensity lipoprotein cholesterol goals. Arch Intern Med 2000; 160:459-67.
7.
Tan CE, Emmanuel SC, Tan BY, et al. Prevalence of diabetes and ethnic
differences in cardiovascular risk factors. The 1992 Singapore National
Health Survey. Diabetes Care 1999;22:241-7.
8.
Cutter J, Tan BY, Chew SK. Levels of cardiovascular disease risk factors
in Singapore following a national intervention programme. Bull World
Health Organ 2001;79:908-15.
9.
Clinical Practice Guidelines. Lipids. Singapore: Ministry of Health;
2001.
10. Clinical Practice Guidelines. Diabetes Mellitus. Singapore: Ministry of
Health; 1999.
11. Ministry of Health. Epidemiology and Disease Control Department,
National Health Survey 1998, Singapore.
12. Kane JP, Malloy MJ, Ports TA, et al. Regression of coronary
atherosclerosis during treatment of familial hypercholesterolemia with
combined drug regimens. JAMA 1990;264:3007-12.
13.
Tomochika Y, Okuda F, Tanaka N, et al. Improvement of atherosclerosis
and stiffness of the thoracic descending aorta with cholesterol-lowering
therapies in familial hypercholesterolemia. Arterioscler Thromb Vasc
Biol 1996;16:955-62.
14. Wray R, Neil H, Rees J. Screening for hyperlipidaemia in childhood.
Recommendations of the British Hyperlipidaemia Association. J R Coll
Physicians Lond 1996;30:115-8.
15. Lee J, Heng D, Chia KS, et al. Risk factors and incident coronary heart
disease in Chinese, Malay and Asian Indian males: the Singapore
Cardiovascular Cohort Study. Int J Epidemiol 2001;30:983-8.
26
16. Executive Summary of The Third Report of The National Cholesterol
Education Program (NCEP) Expert Panel on Detection, Evaluation, And
Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel
III). JAMA 2001;285:2486-97.
17. Wood D, De Backer G, Faergeman O, et al. Prevention of coronary heart
disease in clinical practice: recommendations of the Second Joint Task
Force of European and other Societies on Coronary Prevention.
Atherosclerosis 1998;140:199-270.
18. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the
concentration of low-density lipoprotein cholesterol in plasma, without
use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
27
28
3
Screening for hypertension
3.1
Introduction
Hypertension is defined as a diastolic blood pressure of 90 mmHg or
higher, or a systolic pressure of 140 mmHg or higher1,2. It is an
important risk factor for coronary heart disease, congestive heart
failure, stroke, ruptured aortic aneurysm, renal disease, and
retinopathy. Milder forms of hypertension predict progression to more
severe elevations and development of cardiovascular disease. In
Singapore, ischemic and other heart disease is the second while
cerebrovascular disease is the fourth leading cause of death,
respectively. Together both accounted for nearly 36% of all deaths in
20012,3,10. The 1998 Singapore National Health Survey showed that
the percentage of adults aged 30-69 years old with high blood pressure
(defined as BP > 140/90 mmHg) had risen from 22.2% in 1992 to
27.3% in 19983. Only a third of the treated hypertensives reached the
recommended target level. Among those who were found to have
hypertension at the survey, 53% had not been previously diagnosed3.
Fifty-four percent of patients suffering from acute myocardial
infarction in Singapore had underlying hypertension (unpublished
data, Myocardial Infarct Registry, National Heart Centre of
Singapore). Coronary heart disease mortality begins to increase at
systolic blood pressure above 110 mmHg and at diastolic pressure
above 70 mmHg4. Successful efforts to lower blood pressure could
thus have substantial impact on population morbidity and mortality.
Hence, primary prevention, early detection and adequate treatment of
hypertension are essential in order to prevent complications and death
from the disease.
3.2
Definition
A person with blood pressure > 140/90 mmHg is considered
hypertensive, while those with systolic blood pressure ranging from
130-139 mmHg or diastolic blood pressure 85-89 mmHg belong to the
high normal range1,2,6.
Sphygmomanometry remains the most appropriate screening test for
hypertension in the asymptomatic population. Although the apparatus
is highly accurate when performed correctly, false-positive and falsenegative results do occur in clinical practice. Self-measured (home)
29
blood pressure and ambulatory blood pressure monitoring may
provide useful information in special circumstances such as “whitecoat” or “resistant” hypertension, but there is insufficient evidence at
present to warrant their routine use in screening5,7. Other nonmercury, non-invasive devices might be used provided that they are
accurate and are periodically calibrated with the standard, mercury
sphygmomanometer.
Sphygmomanometry should be performed in accordance with
recommended technique5,6. Hypertension should not be diagnosed on
the basis of a single measurement. Elevated readings should be
confirmed on more than one reading at different visits1,6.
3.3
Effectiveness of Early Detection
There is a direct relationship between the magnitude of blood pressure
elevation and the benefit of lowering pressure. Over the past three
decades, many randomized clinical trials on hypertension have
demonstrated benefits in morbidity and/or mortality in adult patients
(>21 years of age) either for severe, moderate and even mild
hypertension. The efficacy of treating hypertension is clear. An
average diastolic blood pressure reduction of 5-6 mmHg in anyone
with hypertension could reduce the incidence of coronary heart
disease by 14% and the incidence of strokes by 42%. Treatment of
hypertension is associated with multiple benefits, including reduced
coronary heart disease and vascular deaths, but meta-analyses suggest
it produces the largest reductions in cerebrovascular morbidity and
mortality8,9.
3.4
Screening
The optimal interval for blood pressure screening has not been
determined and is left to clinical discretion.
C Blood pressure should be measured at least once every 2 years for
adults aged 21 years and above with diastolic pressure below 85
mmHg and a systolic pressure below 130 mmHg6,10 (i.e. normal BP).
Grade C, Level IV
A Measurements are recommended annually for persons with a
diastolic blood pressure of 85-89 mmHg or systolic blood pressure of
30
130-139 mmHg (i.e. high normal BP). Persons with higher blood
pressures or a major coronary risk factor such as diabetes mellitus
require more frequent measurement6,10.
Grade A, Level Ib
C Any person aged 21 years and above should have their blood
pressure measured during any visit to a physician (“case finding”)6, 10.
Grade C, Level IV
The Canadian Task Force on the Perodic Health Examination found
insufficient evidence to recommend for or against routine blood
pressure measurement in persons under 21 years of age11.
It is important for clinicians to minimize the potential harmful effects
of under or over diagnosing hypertension. For example, if performed
incorrectly, sphygmomanometry can produce misleading results,
resulting in some hypertensive patients thereby escaping detection
(false negatives) and some normotensive persons receiving
inappropriate labeling and treatment (false positives). This will cause
certain psychological, behavioral, and financial consequences.
Treatment of hypertension may also have undesirable side effects,
especially from drug therapy.
A Sphygmomanometry is the recommended method for blood
pressure measurement, and it should be performed in accordance with
the recommended technique5, 6.
Grade A, Level Ia
In adults, blood pressure criteria for the diagnosis of hypertension are
an average diastolic pressure of 90 mmHg or greater and/or an
average systolic pressure of 140 mmHg or greater. Once confirmed,
patients should receive appropriate counseling regarding physical
activity, weight reduction, dietary sodium intake, and alcohol
consumption. Antihypertensive drugs should be prescribed in
accordance with recent guidelines.
A Routine counseling to promote physical activity and a healthy diet
for the primary prevention of hypertension is recommended for all
adults10.
Grade A, Level Ia
31
3.5
Other relevant information
A Pregnant women should have their blood pressure checked
routinely as part of prenatal care10.
Grade A, Level Ia
Prospective cohort studies have shown that children with high normal
blood pressure are more likely than their normal counterparts to have
hypertension as adults12. There is no trial, however, to show that
treating high blood pressure in childhood will result in reduced blood
pressure in adulthood. Moreover in children, the criteria defining
hypertension vary with age. There is insufficient evidence to
recommend for or against routine, periodic blood pressure
measurement to detect essential hypertension in this age group,
although measurement of blood pressure during office consultation is
recommended for children and adolescents in specific situations, e.g.
children with recurrent urinary tract infections, with features of
polycystic disease, Cushing’s syndrome or unequal peripheral
pulses10, 12.
3.6
Summary
Periodic screening for hypertension is recommended for all adults
aged 21 years or older. It is suggested that the interval for blood
pressure screening should be at least once every two years for initial
BP < 130/85 mmHg (i.e. normal BP), and annually if the diastolic
blood pressure is 85-89 mmHg or systolic blood pressure is 130-139
mmHg (i.e. high normal BP) or if patient has major coronary risk
factor such as diabetes mellitus. Currently, sphygmomanometry is the
recommended method for blood pressure measurement, and it should
be performed in accordance with the recommended technique. Other
non-invasive, non-mercury devices might be used provided that the
devices are accurate and are periodically calibrated with values
obtained simultaneously from the mercury sphygmomanometer.
Hypertension should not be diagnosed on the basis of a single
abnormal blood pressure reading but an average of at least two
abnormal readings at different visits. Once hypertension is confirmed
on repeated sittings, patients should receive appropriate counseling
(e.g. dietary salt intake, alcohol consumption, weight reduction,
physical activity). Other cardiovascular risks should be vigorously
32
sought and appropriately managed if indicated. Drug therapy should
be started using clinical judgement and currently available guidelines.
References
1.
Singapore Hypertension Treatment Guidelines 2000. Ministry of Health,
Singapore.
2.
The Guidelines Subcommittee of the World Health Organization –
International Society of Hypertension (WHO-ISH). Mild Hypertension
Liaison Committee: 1999 WHO-ISH Guidelines for the Management of
Hypertension. J. Hypertension 1999; 17:151-83.
3.
Ministry of Health, Singapore. Epidemiology and Disease Control
Department. National Health Survey 1998 Report.
4.
Neaton JD, Wentworth D. Serum cholesterol, blood pressure, cigarette
smoking, and death from coronary heart disease. Overall findings and
differences by age for 316,099 white men. Multiple Risk Factor
Intervention Trial Research Group. Arch Intern Med 1992; 152:56-64.
5.
American Society of Hypertension. Recommendations for routine blood
pressure measurement by indirect cuff sphygmomanometry. Am J
Hypertens 1995; 9:1-11.
6.
Joint National Committee on Detection, Evaluation and Treatment of
High Blood Pressure. The sixth report of the Joint National Committee on
Prevention, Detection and Treatment of High Blood Pressure (JNC VI).
Arch Intern Med 1997; 157:2413-46.
7.
Pickering TG, James GD, Boddie C, et al. How common is white coat
hypertension? JAMA 1988; 259:225-8.
8.
Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke, and
coronary heart disease. Part 2, short-term reductions in blood pressure:
Overview of randomized drug trials in their epidemiological context.
Lancet 1990; 335:827-38.
9.
Hebert PR, Moser M, Mayer J, et al. Recent evidence on drug therapy of
mild to moderate hypertension and decreased risk of coronary heart
disease . Arch Intern Med 1993; 153:578-81.
33
10.
Summary of Policy Recommendations for Periodic Health
Examination. Kansas City, Mo: American Academy of Family
Physician; 1997.
11.
Canadian Task Force on the Periodic Health Examination. Canadian
guide to clinical preventive health care. Ottawa:Canada
Communication Group. 1994; 636-48, 944-51.
12.
Gillman MW, Cook NR, Rosner B, et al. Identifying children at high
risk for the development of essential hypertension. Pediatrics 1993;
122:837-46.
34
4
Screening for diabetes mellitus
4.1
Introduction
Diabetes mellitus is a common and growing healthcare problem in
Singapore, affecting 9.0% of the adult population according to the
1998 National Health Survey1. There is also epidemiological evidence
that type 2 diabetes is appearing at a younger age, with diabetes being
diagnosed in youths and even in children. In the 1998 health survey,
the prevalence of diabetes was 0.8% in persons aged 18-29 years and
3.3% in persons aged 30-39 years, and rising to more than 10% in
those 40 years and older.
Chronic hyperglycaemia is associated with damage and failure of
various organs. Long-term complications of diabetes are the leading
cause of blindness, renal failure and lower limb amputation.
Individuals with undiagnosed diabetes are also at significantly higher
risk for coronary heart disease, stroke and peripheral artery disease
than the nondiabetic population. They also have a greater likelihood of
having hypertension, hyperlipidaemia and obesity2.
Type 2 diabetes is often asymptomatic in its early stages, and can
occur 4-6 years prior to clinical presentation3. The 1998 health survey
found that 62% of Singaporeans found to have diabetes were
previously unaware of the diagnosis. The purpose of screening is to
identify asymptomatic individuals who are likely to have diabetes.
Opportunistic screening for diabetes is appropriate under certain
circumstances.
4.2
Who should be screened
C Screening of asymptomatic individuals at high risk for type 2
diabetes mellitus should be carried out on an opportunistic basis2,4,5.
Grade C, Level IV
C Screening should begin at age 40 years, and be considered at an
earlier age (e.g. 30 years) if risk factors for diabetes are present.
Grade C, Level IV
35
This recommendation is based on the steep rise of diabetes prevalence
in Singapore after age 40 years.
B Risk factors for diabetes include:
•
•
•
•
•
•
•
•
Overweight/ obesity (body mass index ≥ 25 kg/m2)*
Hypertension (≥ 140/90 mmHg)
A first degree relative with diabetes mellitus
Previous gestational diabetes mellitus
Coronary artery disease
Polycystic ovary disease
Dyslipideamia (HDL cholesterol <1.0 mmol/l, and /or triglyceride
level ≥ 2.82 mmol/l) †
Previously identified impaired fasting glycaemia (IFG) or
impaired glucose tolerance (IGT).
Grade B, Level III
4.3
*
Based on prevalence of diabetes mellitus of ≥10% in those obese individuals aged
30-40 years (data from the 1992 National Health Survey). Note that the value has
been lowered from BMI 27, the recommendation stated in the 1999 MOH Clinical
Practice Guideline6
†
New recommendation, not in the 1999 MOH Clinical Practice Guideline6
Screening test and effectiveness
Early diagnosis of diabetes and treatment can prevent or delay the
progression of the major diabetic complications and reduce the burden
of diabetes4,5.
Three recent large randomized clinical trials in subjects with impaired
glucose tolerance7-9, had demonstrated that treatment with lifestyle
intervention, metformin or acarbose, reduced the incidence of type 2
diabetes mellitus by 58%, 31% and 36% respectively, compared to
those who were in the non-intervention groups. These studies showed
that it should be possible to delay or prevent the development of type
2 diabetes and its related complications and suggest that more
widespread screening to detect high risk individuals with prediabetes
(IGT or IFG) may be justified.
36
Figure 1: Algorithm for screening for type 2 diabetes mellitus
in asymptomatic individuals
Asymptomatic subject
Fasting plasma
glucose ≥ 7.0
mmol/l
No
Yes
Repeat fasting
plasma glucose
Fasting plasma
glucose 6.1-6.9
mmol/l
No
≤ 6.0
mmol/l
Fasting plasma
glucose ≥ 7.0
mmol/l
Yes
Yes
DIABETES
MELLITUS
No
6.1-6.9
mmol/l
Oral Glucose Tolerance Test
(2-h post challenge)
7.8 – 11.0
mmol/l
<7.8
mmol/l
No diabetes
mellitus
(repeat
screen
at 3 years)
Impaired fasting
glycaemia
(repeat screen at
1 year )
Impaired glucose
tolerance
(repeat screen at
1 year)
37
≥ 11.1
mmol/l
Diabetes
Mellitus
4.3.1 Fasting plasma glucose
B Fasting plasma glucose (FPG) is the recommended test for
screening in the clinical setting because it is easy to perform and
convenient*10. Individuals with a FPG ≥ 7.0 mmol/L should have a
repeat testing on a different day to confirm the diagnosis of
diabetes10,11. Individuals with FPG of 6.1-6.9 mmol/l on screening
should undergo a 75g oral glucose tolerance test (OGTT) to determine
precisely the degree of glucose intolerance11.
Grade B, Level III
*Venous blood samples should be collected in appropriate tubes for plasma glucose
measurement which should be performed by a laboratory reference method.
4.3.2
Oral glucose tolerance test (OGTT)
B OGTT is also a suitable test for screening10,11.
Grade B, Level III
A 2-hour plasma glucose value of ≥ 11.1 mmol/l on OGTT is a
positive test for diabetes.
Criteria for definition of IFG and IGT11 are shown in Table 1.
Table 1: Intermediate categories of glucose tolerance.
Fasting plasma
glucose
(mmol/l)
2-hour plasma glucose
during OGTT
(mmol/l)
Impaired Fasting
Glycaemia (IFG)
6.1-6.9
And
<7.8
Impaired Glucose
Tolerance (IGT)
<7.0
And
7.8-11.0
Fingerprick capillary blood glucose testing measured by a glucose
meter is better used for self-monitoring of blood glucose rather than as
a screening tool, because of the imprecision of this method 12,13.
The HbA1c test is currently not recommended for the screening of
diabetes12,13.
38
4.4
Frequency of Screening
C Individuals found to have normal glucose tolerance on screening
and who do not have risk factors for developing diabetes should have
repeat screening at 3 yearly intervals13. The rationale for this interval
is that there is little likelihood of an individual developing any
complications of diabetes to a significant degree within 3 years of a
negative screening test result. For those with other diabetes risk
factors, repeat screening may be performed more frequently, e.g. at
annual intervals13.
Grade C, Level IV
B Those detected to have IFG or IGT should have repeated screening
at annual intervals in view of the high rate of conversion to diabetes1416
.
Grade B, Level III
References
1.
Ministry of Health. Epidemiology and Disease Control Department,
National Health Survey 1998, Singapore.
2.
Harris MI. Undiagnosed NIDDM: clinical and public health issues.
Diabetes Care 1993; 16:642-52.
3.
Harris MI, Klein R, Welborn TA, et al. Onset of NIDDM occurs at
least 4-7 yr before clinical diagnosis. Diabetes Care 1992; 15:815-9.
4.
Pyorala K, Pedersen TR, Kjekshus J, et al. Cholesterol lowering with
simvastatin improves prognosis of diabetic patients with coronary
heart disease. A subgroup analysis of the Scandinavian Simvastatin
Survival Study (4S). Diabetes Care 1997; 20:614-20.
5.
The Diabetes Control and Complications Trial Research Group. The
effect of intensive treatment of diabetes on the development and
progression of long-term complications in insulin-dependent diabetes
mellitus. N Engl J Med 1993; 329:977-86.
6.
Clinical Practice Guidelines. Diabetes Mellitus. Singapore: Ministry
of Health; 1999.
39
7.
Diabetes Prevention Program Research Group. Reduction in the
incidence of type 2 diabetes with lifestyle intervention or metformin.
N Eng J Med 2002; 346:393-403.
8.
Tuomilberto J and the Finnish Diabetes Prevention Study Group.
Prevention of type 2 diabetes mellitus by changes in lifestyle among
subjects with impaired glucose tolerance. N Eng J Med 2001;344:134350.
9.
Chiasson J and the STOP-NIDDM Trial Research Group. Acarbose
for the prevention of type 2 diabetes mellitus: the STOP-NIDDM
randomised trial. Lancet 2002 ;359 : 2072-7.
10.
The Expert Committee on the Diagnosis and Classification of
Diabetes Mellitus. Report of the Expert Committee on the Diagnosis
and Classification of Diabetes Mellitus. Diabetes Care 1997; 20:118397.
11.
Alberti, KGMM, Zimmet PZ. Definition, diagnosis and classification
of diabetes mellitus and its complications. Part 1: diagnosis of
classification of diabetes mellitus. Provisional report of a WHO
consultation. Diabetic Medicine 1998;15:539-53.
12.
American Diabetes Association: Tests of glycemia in diabetes
(Position Statement). Diabetes Care 2003; 26: S106-8.
13.
American Diabetes Association: Screening for type 2 diabetes
(Technical Review). Diabetes Care 2000; 23: 1563-80.
14.
Chou P, Li CL, Wu GS, et al. Progression to type 2 diabetes among
high-risk groups in Kin-Chen, Kinmen. Exploring the natural history
of type 2 diabetes. Diabetes Care 1998; 21:1183-7.
15.
Alberti KG. The clinical implications of impaired glucose tolerance.
Diabet Med 1996; 13:927-37.
16.
Coutinho M, Gerstein HC, Wang Y, et al. The relationship between
glucose and incident cardiovascular events. Diabetes Care 1999;
22:233-40.
40
5
Screening for obesity
5.1
Introduction
Obesity and established cardiovascular risk factors such as
hypertension, hyperlipidaemia, hyperglycaemia and coronary heart
disease are positively associated1,2,3. The evidence for obesity as an
independent predictor of cancer is less well established, although
associations have been identified for cancers of the endometrium,
ovaries, breast, prostate and colon4. Obesity is also associated with
other medical problems such as gall bladder disease, sleep apnoea,
osteoarthritis, reduced fertility, social stigmatization and
discrimination.
The 1998 National Health Survey of residents in Singapore aged 1869 years found that overall 24.4% were overweight and 6.0% were
obese5.
5.2
Screening test and effectiveness
•
•
Body mass index [BMI = (weight in kg)/(height in m)2]
BMI is reliable and correlates well (r=0.7-0.8) with body fat
content in adults6,7.
Waist circumference is a reliable indicator of abdominal fat
mass8.
B Body mass index (BMI) and waist circumference can be used to
classify obesity and assess risk.
Grade B, Level III
41
Table 2: NHLBI classification of overweight and obesity by
BMI, waist circumference and associated disease risk
Disease risk relative to Normal weight and waist
circumference*
Men ≤102cm (≤40in)
Women ≤88cm (≤35in)
>102cm (>40in)
>88cm (>35in)
<18.5
-
-
18.5-24.9
-
-
25.0-29.9
Increased
High
BMI
(kg/m2)
Underweight
Normal
†
Overweight
Obesity
Extreme
Obesity
Obesity
class
30.0-34.9
I
High
Very High
35.0-39.9
II
Very High
Very High
≥ 40.0
III
Extremely High
Extremely High
* Disease risk for type 2 diabetes, hypertension, and cardiovascular disease
†
Increased waist circumference can also be a marker for increased risk even in persons of normal
weight
Source: Reproduced with permission from the National Heart, Lung, and Blood
Institute (NHLBI). The Practical Guide - Identification, Evaluation and Treatment of
Overweight and Obesity in Adults (Oct 2000), National Institutes of Health.
5.3
Age and gender for screening
C All individuals 18 years of age or older should be screened1,2.
Grade C, Level IV
5.4
Frequency of screening
GPP Screening should be done once a year for all individuals 18
years or older.
GPP
5.5
Other relevant information
A reduction of Body Mass Index and/or waist circumference leads to
a reduction in risk factors for cardiovascular disease1,2. Weight
reduction measures include dietary restriction and an increase in
physical activity. Adjunct behavioral modification like counseling
may also be of benefit.
42
The initial goal of weight loss is to reduce body weight by 10% from
the original. Weight loss should be about 0.5-1.0kg per week for a
period of 6 months. Studies also suggest that weight loss and
maintenance appear to be more successful in the long term with
greater frequency of patient-physician contact.
References
1.
National Institutes of Health, National Heart, Lung and Blood Institute.
Clinical Guidelines on the identification, evaluation, and treatment of
overweight and obesity in adults- the evidence report. Obes Res 1998;
6:51S.
2.
US Preventive Services Task Force. Screening for obesity. In: Guideline
for clinical preventive services. 2nd ed. Baltimore, Md.: Williams and
Wilkins, 1994; 41.
3.
World Health Organization. Obesity: Prevention and managing the global
epidemic.
Report of a WHO consultation on obesity.
WHO/NUT/NCD/98.1, Geneva 1998.
4.
International Agency for Research in Cancer. Handbook for Cancer
Prevention Volume 6: Weight Control and Physical Activity 2002.
IARC, WHO, Lyon.
5.
Ministry of Health. Epidemiology and Disease Control Department,
National Health Survey 1998, Singapore.
6.
Deurenberg P, Weststrate JA, Seidell JC. Body mass index as a measure
of body fatness: age- and sex-specific formulas. Br J Nutr 1991; 65:105.
7.
Gray DS, Fujioka K. Use of relative weight and body mass index for
determination of adiposity. J Clin Epidemiol 1991; 44:545.
8.
Lemieux S, Prud’homme D, Bouchard C, et al. A single threshold value
of waist girth identifies normal-weight and overweight subjects with
excess visceral adipose tissue. Am J Clin Nutr 1996; 64:685.
43
44
6
Screening for lung cancer
6.1
Introduction
Routine screening for asymptomatic early lung cancer is not
recommended for any subset of individuals at present. Previous
studies of screening high-risk individuals using chest X-ray and/or
sputum cytology have not confirmed a survival benefit1.
Anecdotal reports of favourable survival outcomes associated with
resection of early lung cancers discovered serendipitously have raised
the possibility, however, that more sensitive technologies than chest
X-ray or sputum cytology could be capable of detecting lung cancers
at a sufficiently early stage to confer a survival benefit. The advent of
low-dose spiral computed tomography (CT) is relevant here, since
two-thirds of CT-detected lung cancers in asymptomatic patients are
early stage2, consistent with a 3- to 10-fold greater sensitivity of CT
over chest X-ray3, 4. Whether the detection of such so-called early
stage lung cancers translate into improved outcomes, i.e. reduced
mortality, has not been demonstrated and is the subject of ongoing
controlled trials. At present, however, there are no controlled clinical
trial data available upon which to base any assessment of its efficacy
or cost-effectiveness as a screening tool5.
Given the current state of ignorance regarding the screening utility or
otherwise of low-dose spiral CT, it is imperative that at-risk
individuals are not misled into believing that any such screening
initiatives will necessarily reduce their odds of dying from lung
cancer. In this context it is essential that patients be informed that the
only proven strategy for reducing the probability of lung cancer
mortality is smoking cessation6.
Not withstanding this important caveat regarding possible abuses
involving the misleading promotion of low-dose spiral CT as a
screening tool for lung cancer, and given a mandate upon providers to
openly inform clients as to the lack of proven screening efficacy of the
latter intervention, individuals who perceive themselves to be at
heightened risk for lung cancer (and who are supported in that
perception by their doctor) may wish to undertake a low-dose spiral
CT examination, having been fully informed beforehand as to all costs
and potential risks of such a procedure7.
45
6.2
Definition
There is no general recommendation to screen any subset of
asymptomatic individuals for lung cancer at present. Individuals who
are perceived to be at low risk, e.g. non-smoking males with no other
risk factors, should be actively discouraged from undertaking routine
lung cancer screening.
6.3
Screening test and effectiveness
A Neither chest X-ray nor sputum cytology is recommended for
screening1.
Grade A, Level Ib
C The screening efficacy of low-dose spiral CT is unknown at
present.
Grade C, Level IV
6.4
Age and gender for screening
No subset of individuals is recommended to undergo routine
screening3.
6.5
Frequency of screening
Since no screening technology is of proven value, no optimal
frequency of screening is established3.
6.6
Other relevant information
At-risk individuals who seek low-dose spiral CT examination outside
of a clinical trial setting, having been fully informed of the
aforementioned limitations and risks, should be referred for such
examination via their primary care physician or specialist. Testing
should only occur in a multidisciplinary setting3.
6.7
Summary
There is no proven evidence for the efficacy of lung screening at
present. Emphasis should remain on smoking cessation, and such
counselling should be mandatory prior to undertaking any potential
46
screening intervention. The screening utility of low-dose spiral CT is
unknown at present and is currently being studied in ongoing trials.
References
1.
Marcus PM, Bergstralh EJ, Fagerstrom R, et al. Lung cancer mortality in
the Mayo Lung Project: impact of extended follow-up. J Natl Cancer Inst
2000; 92:1308-16.
2.
Aberle DR, Gamsu G, Henschke Cl, et al. Screening for lung cancer with
helical CT: Society of Thoracic Oncology consensus statement. J Thorac
Imaging 2001; 16:65-8.
3.
Henschke Cl, McCauley DI, Yankelevitz DF, et al. Early Lung Cancer
Action Project: overall design and findings from baseline screen. Lancet
1999; 354:99-105.
4.
Sone S, Takashima S, Li F, et al. Mass screening for lung cancer with
mobile spiral CT scanner. Lancet 1998; 351: 1242-5.
5.
Heffner JF, Silveshi G. CT Screening for Lung Cancer – Is Smaller
Better? Am J Respir Crit Care Med 2002; 165:433-4.
6.
Sobue T, Moriyama N, Kaneko M, et al. Screening for lung cancer with
low-dose helical computed tomography: anti-lung cancer association
project. J Clin Oncol 2002; 20:911-20.
7.
Smith RA, Cokkinides V, von Eschenbach AC, et al. American Cancer
Society. Guidelines for the early detection of cancer. CA Cancer J Clin
2002; 52: 8-22.
47
48
7
Screening for hepatocellular carcinoma (HCC)
7.1
Introduction
Hepatocellular carcinoma (HCC) is one of the common cancers seen
locally. It is the fourth most common cancer among Singaporean
males. The male to female ratio is 4:11. The main risk factors for
development of HCC include chronic hepatitis B infection and liver
cirrhosis secondary to chronic liver inflammation from various
etiologies (hepatitis C, alcohol and other chronic liver disease). In
Singapore, the age-standardized rate of HCC has declined slightly
from 1970 to 19951. However, the incidence is still considerably
higher than the western population with Singapore ranked fourth to
Japan, Shanghai and Hong Kong1.
7.2
Definition
The recommendations here are for HCC and not for other primary
(cholangiocarcinoma, hepatoblastoma, etc) or secondary malignancy
involving the liver.
7.3
Tests for hepatocellular carcinoma (HCC) surveillance
C Current accepted tests used for HCC surveillance include
ultrasound of the hepato-biliary system and alpha feto-protein (∝FP)
level.
Grade C, Level IV
7.3.1
Serum ∝FP levels
∝FP is secreted by hepatoma cells as well as regenerating
hepatocytes. A rise in the serum ∝FP level in the absence of
significant liver inflammation suggest HCC development. The
negative predictive value of ∝FP is 99% but its positive predictive
value ranges from 9% to 30% only2,3. ∝FP levels rising in a stepwise
manner strongly suggests the presence of HCC and a person with
persistent mildly elevated ∝FP (<200 ng/ml) is at higher risk of HCC
development compared to those with a single elevated level2.
49
∝FP can be elevated in patients with inflammation of the liver. The
levels may exceed thousands. Hence, ∝FP should never be used alone
to establish diagnose HCC.
7.3.2
Ultrasonography of the liver
This, together with ∝FP, are the commonest tests used in the
surveillance of HCC in at-risk population. The sensitivity of
ultrasound for small HCC (<5 cm diameter) ranges from 68% to 87%
and a false positive rate of 28% to 82%3-7. Regenerating nodules in a
patient with cirrhosis is the leading cause of false-positive ultrasound.
Upon detection of a nodule in the liver, the patient should be referred
to a referral center for further evaluation.
The combination, however, of ∝FP and ultrasound is superior to
either test alone for HCC surveillance8.
7.3.3
Others
i)
Liver function test.
Although liver function test is usually performed in patients with
chronic hepatitis B and C to detect flares and decompensation, it is not
an investigation performed for HCC surveillance because the liver
function test can be normal in early HCC. However, if there is a
decrease in serum albumin associated with a rise in the serum alkaline
phosphatase, this is suggestive of a space-occupying lesion and
warrants further investigations9.
ii)
des-γ-carboxy prothrombin10
iii)
Lens culinaris agglutinin a-reactive profiles of ∝FP10.
These are under evaluation and await further data for their accuracy.
They are currently not available in Singapore.
7.4
The evidence for HCC surveillance
To date, there is no data to support surveillance of HCC in the general
population. However, longitudinal prospective studies have shown
that patients with chronic hepatitis B infection and liver cirrhosis from
50
other etiologies are at higher risk of developing HCC. It is in this
population of at-risk individuals that HCC surveillance can be offered.
The aim of these surveillance programmes is to detect small (<5 cm
diameter) HCC which are more amenable to therapy with reports of
long-term tumour-free survival11,12. Four population-based screening
studies have been published on hepatitis B carriers2,13-15. Using ∝FP
as a screening method, small HCC were detected in 37% to 59% of
persons with HCC. Although there is evidence that long-term
survival can occur in some patients with resected small HCC, there is
currently no data available comparing survival outcome in chronic
hepatitis B infected persons who are surveyed for HCC versus no
HCC surveillance8. It is also important to note that the high false
positive rates of both ∝FP and ultrasound may result in expensive and
higher risk procedures like angiographic studies and liver biopsy.
Despite the lack of definite evidence for benefit in survival8, most
hepatologists do surveillance based on the expectations and
affordability of their patients.
The risk factors for development of HCC in chronic HBV infected
individuals are male gender, older age group (>45 years), family
history of HCC, presence of liver cirrhosis and co-infection with
hepatitis C16-20. While it is logical to target this group of individuals
for HCC surveillance, it is known that HCC can also develop in
young, asymptomatic, non-cirrhotic chronic HBV infected persons
with normal alanine transaminase. These younger individuals, many
without liver cirrhosis, showed a distinct survival advantage when the
HCC was detected and treated early2. In view of this, the optimal age
to initiate HCC surveillance is currently not defined. However, it is
noted that local cancer statistics showed that HCC detection increases
after 30 years of age.
Surveillance of a large population of chronic HBV infected
individuals need huge resources, which may not be feasible. Cirrhotic
patients have a higher risk of HCC but also a higher chance of being
unsuitable for liver resection21,22. Some patients at risk of HCC
development may not benefit from the HCC surveillance program. It
is important for the physician to discuss with the patient the aims, cost
and expected benefits from HCC surveillance before initiating the
program for the particular patient.
51
7.5
Summary
GPP There is no evidence to support population-based surveillance
for HCC. However, HCC surveillance should be offered to patients
with chronic hepatitis B infection, hepatitis C liver cirrhosis and liver
cirrhosis from other etiologies. HCC surveillance should be performed
periodically with alpha-fetoprotein 3 to 6 monthly and ultrasound of
the liver at 6 to 12 monthly interval. There is no definite
recommended age to start surveillance8. However, it is noted that the
local statistics showed that HCC detection starts to increase from the
age of 30 years.
GPP
References
1.
KS Chia, A Seow, HP Lee, et al. Cancer incidence in Singapore 19931997. Singapore Cancer Registry report no. 5: 82-3.
2.
McMahon BJ, Bulkow Lharpster A, Snowball M, et al. Screening for
hepatocellular carcinoma in Alaska Natives infected with chronic
hepatitis B: a 16-year population-based study. Hepatology 2000;
32:842-6.
3.
Sherman M, Peltekian KM, Lee C. Screening for hepatocellular
carcinoma in chronic carriers of hepatitis B virus: incidence and
prevalence of hepatocellular carcinoma in a North American urban
population. Hepatology 1995; 22:432-7.
4.
Sheu JC, Sung JL, Chen DS, et al. Early detection of hepatocellular
carcinoma by real-time ultrasonography. Cancer 1985; 56:660-6.
5.
Colombo M, de Franchis R, Del Ninno, et al. Hepatocellular
carcinoma in Italian patients with cirrhosis. N Engl J Med 1991;
325:675-80.
6.
Tanaka S, Kitamura T, Nakanishi K, et al. Effectiveness of periodic
checkup by ultrasonography for the early diagnosis of hepatocellular
carcinoma. Cancer 1990; 66:2210-4.
52
7.
Yuen MF, Cheng CC, Lauder IJ, et al. Early detection of
hepatocellular carcinoma increases the chance of treatment: Hong
Kong experience. Hepatology 2000; 31: 330-5.
8.
Lok ASF, McMahon BJ. Chronic Hepatitis B. Hepatology 2001;
34:1225-41.
9.
Teo EK, Fock KM. Hepatocellular Carcinoma: An Asian Perspective.
Dig Dis 2001; 19:263-8.
10.
Shimauchi Y, Tanaka M, Kurumatsu R, et al. A simultaneous
monitoring of Lens culinaris agglutinin. A reactive alpha-fetoprotein
and des-gamma-carboxy prothrombinas an early diagnosis of
hepatocellular carcinoma in the follow-up of cirrhotic patients. Oncol
Rep 2000; 7:249-56.
11.
Dusheiko GM, Hobbs KEF, Dick R, et al. Treatment of small
hepatocellular carcinomas. Lancet 1992; 340:285-8.
12.
Gazelle GS, Goldberg SN, Solbiati L, et al. Tumour ablation with
radio-frequency energy. Radiology 2000; 217:633-46.
13.
Tang ZY, Yang BH, Zhou ZD. Primary prevention of hepatocellular
carcinoma. J Gastroenterol Hepatol 1995; 10:683-90.
14.
Lee CS, Sheu JC, Wang M, et al. Long-term outcome after surgery for
asymptomatic small hepatocellular carcinoma. Br J Surg 1996;
83:330-3.
15.
Mima S, Sekiya C, Kanagawa H, et al. Mass screening for
hepatocellular carcinoma: experience in Hokkaido, Japan. J
Gastroenterol Hepatol 1994; 9:361-5.
16.
Beasley RP. Hepatitis B virus. The major etiology of hepatocellular
carcinoma. Cancer 1988; 61:1942-56.
17.
McMahon BJ. Hepatocellular carcinoma in viral hepatitis. In: Wilson
RA. Ed. Viral Hepatitis. New York: Marcel Dekker 1997; 315-30.
18.
McMahon BJ, Holck P, Bulkow L, et al. Serologic and clinical
outcomes of 1536 Alaska natives chronically infected with hepatitis B
virus. Ann Int Med 2001; 135:759-68.
53
19.
Fattovich G, Giustina G, Schalm SW, et al. Occurrence of
hepatocellular carcinoma and decompensation in western European
patients with cirrhosis type B. The EUROHEP Study Group on
Hepatitis B Virus and Cirrhosis. Hepatology 1995; 21:77-82.
20.
Liaw YF, Lin DY, Chen TJ, et al. Natural course after the
development of cirrhosis in patients with chronic type B hepatitis: a
prospective study. Liver 1989; 9:235-41.
21.
Ebara M, Ohto M, Shinagawa T. Natural history of minute
hepatocellular carcinoma smaller than 3 centimeters complicating
cirrhosis. Gastroenterology 1986; 90:289-98.
22.
Sherman M. Hepatocellular carcinoma. Gastroenterologist 1995; 3:556.
54
8
Screening for colorectal cancer
8.1
Introduction
Colorectal cancer has emerged as the cancer with the highest
incidence in Singapore1. Individuals face a moderate to high risk of
developing colorectal cancer which is comparable to developed
countries. Despite improvement in surgical technique and the
development of adjuvant therapy, mortality from colorectal cancer has
not declined appreciably. One of the major reasons for this is the
advanced stage of disease at the time of presentation2. This is in
contrast to the five-year survival rate of approximately 90% for
localized colon cancer2. Further, it has been demonstrated that most
colorectal cancers develop from adenomas. Endoscopic removal of
adenomas result in a reduced colorectal cancer risk3. The long premalignant period of this adenoma-carcinoma sequence makes it ideal
to screen for colorectal cancer.
8.2
Definition
8.2.1
Average-risk individuals
The lifetime probability of an individual developing colorectal cancer
is approximately 5%4. The risk rises with age, occurring sporadically
among younger individuals and rising sharply after the age of 501
years. For average-risk individuals, screening should begin at the age
of 50 years. This would include asymptomatic individuals and
individuals who have a family history of colorectal cancer limited to
non-first degree relatives and no other risk factors5-7.
8.2.2
High-risk individuals
Patients at high risk for colorectal cancer include those who have one
or more first-degree relatives with colorectal cancer8 or a personal
history of colorectal neoplasia9. Patients with prior endometrial,
ovarian or breast cancer and those who have had pelvic radiation may
have a slightly higher than average risk of colorectal cancer10.
55
8.2.3
Very high-risk individuals
Patients at very high risk for developing colorectal cancer are those
with a hereditary or genetic predisposition for colorectal cancer, that
is, a family history of familial adenomatous polyposis, other
hereditary gastrointestinal polyposis syndromes or hereditary nonpolyposis colorectal cancer11-14. Also at a high-risk are patients with a
long history of extensive inflammatory bowel disease15, 16.
8.3
Screening tools and effectiveness
Screening tools currently available in current practice include
Annual faecal occult blood test
Flexible sigmoidoscopy
Double-contrast barium enema
Colonoscopy
•
•
•
•
8.4
Faecal Occult Blood Tests (FOBT)
In this screening strategy, FOBT when positive is followed up by
colonoscopy or when technically not possible, a barium enema. Three
groups of tests are available: the guaiac test, immunochemical tests
and heme-porphyrin tests. The stool guaiac test works on the principle
of the pseudo-peroxidase activity of either heme in its free form or
bound to its apoprotein (as haemoglobin, myoglobin and certain
cytochromes). The test does not turn positive with degradation
products of heme which lack peroxidase activity. As the reaction is
not specific for blood, dietary peroxidase from plant or animal origin
will produce a positive test result. Drugs with reducing properties such
as vitamin C will produce a false negative result. Dietary restrictions
(red meat, horseradish, turnips) are necessary to reduce false-positive
results, although the need for dietary restriction has been recently
questioned17. The test does not localize the site of bleeding and may
also test positive in the presence of upper gastrointestinal ulcerinducing drugs like aspirin and NSAIDS. Other drugs such as
colchicine and oxidizing agents such as iodine and reserpine may give
false positive results.
In contrast, the immunochemical tests are the most chemically
selective and specific for human haemoglobin and some of its early
degradation forms. Non-human haemoglobin does not produce a false
56
positive result. Drugs related to gastrointestinal bleeding may result in
a positive test. Technologies used in these tests include enzymelinked immunosorbent assays (ELISA), radial immunodiffusion,
reverse passive haemagglutination and latex haemagglutination. Test
kits using these technologies are available.
The heme-porphyrin tests are specific for di-carboxylic porphyrins
and detect intact heme in any form and its porphyrin degradation
products. Fluorescent spectrometry is required and permits
quantification. This had not been used in population screening
because of the laborious testing process.
Test positivity is dependent on the site of the bleeding. Gastric and
proximal small bowel bleeding would result in greater heme
degradation products as opposed to distal colonic bleeding as there is
more time for degradation to occur. This allows for greater specificity.
However, there is a degree of overlap between blood loss in the
normal gastrointestinal tract (estimated to be up to 1.5 ml per day) and
patients with colorectal neoplasia. This mitigates against test accuracy
and accounts for false positives observed.
The amount of bleeding is dependent on site of bleeding and size of
the tumor. Proximal cancers bleed the most while adenomas bleed less
than cancers. Adenomas of less than 1 cm are unlikely to bleed. The
amount of bleeding varies resulting in the need to obtain multiple
samples over several days. It has been shown that greater than three
tests does not increase the sensitivity significantly18,19.
The Hemoccult II stool guaiac test is perhaps the most widely studied
FOBT. The crude sensitivity in individuals screened with guaiac
FOBT (Hemoccult II) is estimated to be in the region of 50% to 75%
and as high as 90% for hydrated Hemoccult II5-7. These results are
based on individuals who are known to have colorectal cancers. The
test when applied in a population setting is affected by compliance
and other factors19. The predictive values for cancers and adenomas in
the Nottingham5 and Funen6 trials were 53% and 59% respectively.
The results include a 2-year follow-up for interval or “screen-missed”
cancers detected after the initial screening tests. These trials including
one from Minnesota7 have also shown a significant reduction of
mortality from colorectal cancer following FOBT screening of
between 15% to 30%.
57
There has been no randomized, controlled population trials using an
immunochemical test. In Japan, a reverse passive haemagglutination
test (Hem-sp) was used in population screening from 1992 following
the passage of the Law of the Aged. The Japanese Ministry of Health
and Welfare targeted 2.5 million asymptomatic individuals aged 40
years and above for screening. Data was available for 1.1 million
individuals in a survey20. 76,323 (7.1%) tested positive. 70.1%
underwent further evaluation and 2,017 (0.2%) were found to have a
colorectal cancer, of these 56% were early cancers. These results are
comparable to the guaiac FOBT trials. Compared to the Nottingham
trial which has the highest FOBT positivity of the five randomised
trials (2.7 per 1,000 screened with rehydrated slides and 0.9 per 1,000
with unhydrated slides)5, the immunochemical test gave a cancer
detection rate of 1.9 per 1,000 screened. The rates are similar using
the “intention-to-screen” principle, taking into account compliance. It
would appear that with the immunochemical test, although more
sensitive than the guaiac test in detecting occult blood, the specificity
for cancer is only modestly better. Polyp detection rate is relatively
higher for the immunochemical tests21. Polypectomy and subsequent
surveillance may result in a reduction in the incidence of colorectal
cancer3.
8.5
Sigmoidoscopy
The rationale of using flexible sigmoidoscopy for screening lies in the
fact that up to two-thirds of the colorectal cancer are within the reach
of this procedure. Its secondary function in screening is the detection
of index polyps that will necessitate a subsequent colonoscopy.
Approximately 30% of cancers proximal to the splenic flexure have
an index lesion situated distally22. In countries such as the US and
UK, this procedure can be performed effectively and safely by trained
nurse practitioners23.
Early trials on sigmoidoscopy involved the rigid scope and were nonrandomised case controlled trials. In a pooled analysis of 14 studies
using flexible sigmoidoscopy for screening about 11,000 individuals,
30 cancers were detected and 24 of these were localized24. While
empirically, flexible sigmoidoscopy screening should reduce mortality
from colorectal cancer, its true effectiveness is still not clear until the
results of the MRC sponsored trial and the NCI trial involving
148,000 individuals over 50 years of age are known in 2006 and 2008
respectively.
58
As an alternative screening option, asymptomatic individuals above
the age of 50 years could undergo flexible sigmoidoscopy once every
5 years10,25-28. For individuals with a family history of familial
adenomatous polyposis, flexible sigmoidoscopy is recommended
annually from the onset of puberty10,28.
8.6
Double Contrast Barium Enema (DCBE)
There has been no trials using DCBE for population screening. The
benefits have been extrapolated from studies using endoscopy. DCBE
has a lower risk of perforation than colonoscopy but still requires
bowel preparation for accurate diagnosis of small lesions like polyps.
The American Society of Radiologists standard stipulates that the
enema must be of a quality to detect 90% of the colorectal cancer and
80% of the polyps greater than 1 cm in diameter29. Even with good
bowel preparation, DCBE is known to miss small polyps. This is less
likely with colonoscopy. There is also a need to perform a
colonoscopy if the DCBE is positive for confirmation and biopsy. As
a tool in population screening, its role is still unknown.
8.7
Colonoscopy
While colonoscopy is the “gold-standard” in screening for colorectal
cancer and has a widely accepted role in screening for high-risk
individuals, its use in population screening in an average risk setting is
still largely unknown. Two large studies have demonstrated that
colonoscopy will detect a substantial portion of asymptomatic
colorectal cancers and high risk polyps30, 31. A case control study has
found that patients with a diagnosis of colorectal cancer were less
likely to have had previous colonoscopy. The odds ratios for disease
incidence were 0.47 for colon cancer and 0.61 for rectal cancer. For
mortality, the odds ratio was also lower in patients with previous
colonoscopy (0.43)32. It requires bowel preparation and inconvenience
that will reduce compliance if used as a screening tool. Its major
concerns are the costs involved and associated complication including
death.
Perforation and bleeding after polypectomy are the major
complications observed.
In the Minnesota trial7, 12,246
colonoscopies were done with 4 perforations and 11 haemorrhages
(rate of 12 per 10,000). In a screening trial from Goteborg33, 2,298
59
endoscopies (mainly flexible sigmoidoscopy) and DCBE were
performed with a complication rate reported as 30 per 10,000. In the
Nottingham trial5, 1,774 colonoscopies were done with 7
complications, 6 requiring surgery giving a rate of 39 per 10,000. In
the Japanese series 20 of 53,536 examinations, 248 complications were
reported (rate of 46 per 10,000). Twelve deaths were reported. Whilst
colonoscopy is a relatively safe procedure, it is not devoid of
complications.
Asymptomatic individuals above the age of 50 years can undergo
colonoscopy once every 10 years as a screening option10, 25-27. For
individuals with a history of a colorectal cancer in a first degree
relative over the age of 45 years, colonoscopy, every 10 years is
recommended. For an individual with a family history of colorectal
cancer aged 45 years or younger or a family history of 2 or more
affected first degree relatives, colonoscopy every 3 years performed
10 years prior to the youngest case in the family is recommended10,2628
. For individuals with a personal past history of colorectal polyps,
colonoscopy is recommended one year after polypectomy in the
presence of high risk features (polyp > 1 cm, multiple, villous
architecture) or three years after polypectomy in the absence of high
risk features10,28.
For individuals with a personal past history of colorectal cancer,
colonoscopy is recommended one year after resection provided that
total imaging of the bowel was achieved prior to surgery7,35. For
individuals with a family history of hereditary non-polyposis
colorectal cancer, colonoscopy is recommended every 2 years
commencing 10 years prior to the age of diagnosis of colorectal
cancer in the youngest family member10,28. For individuals with left
sided ulcerative colitis, colonoscopy is recommended every 1-2 years
from the 15th year of diagnosis. For individuals with pan-colitis
colonoscopy is recommended every 1-2 years from the 8th year of
diagnosis20.
60
8.8
Comment on the use of carcinoembryonic antigen
(CEA) for screening
The determination of plasma CEA levels has been used to detect early
asymptomatic recurrence of colorectal cancer34. However, its use in
the screening of asymptomatic, average-risk patients is difficult to
justify. It can be elevated in other malignant conditions, benign
conditions such as ulcerative colitis and liver cirrhosis and among
smokers. The low specificity and sensitivity of the plasma CEA in the
diagnosis of colorectal cancer makes it a poor screening tool35.
8.9
Summary
Colorectal cancer is the most common cancer in Singapore according
to incidence. Screening for colorectal cancer should be performed
after risk stratification. There is good evidence that screening for
colorectal cancer will lead to reduction of mortality from the disease
in all risk groups.
8.10
Screening guidelines
Based on the forgoing discussion and review of international practice
parameters and guidelines10,25,26,27, the following recommendations are
made for the screening of colorectal cancer (see Table 3).
61
TABLE 3 : Recommendations for the Screening of Colorectal Cancer
RISK GROUP
A.
SCREENING TOOL
Average risk
Asymptomatic or family history limited to
non-first degree relatives
(screening tool alternatives in order of
supporting evidence)
B.
1.
High Risk
Colorectal cancer in first
degree relative age 45 years or
younger or two or more first degree
relatives
2.
ONSET
(Age, years)
FREQUENCY
LEVEL OF
EVIDENCE
GRADE OF
RECOMMENDATION
Faecal occult blood testing
50
Annually
Ia
A
Flexible sigmoidoscopy
50
Every 5 years
IIa
B
Colonoscopy
50
Every 10 years
IIb
B
Barium Enema
50
Every 5 to 10 years
IV
C
Colonoscopy
10 years prior to youngest case in the family or
age 45 years, whichever is earlier
Every 3 years
IIa
B
Colorectal cancer in first degree relative
over the age of 45 years
Colonoscopy
10 years prior to youngest case in family or age
50 years, whichever is earlier
Every 10 years
IIb
B
3.
Personal history of colorectal polyps
Colonoscopy
One year after polypectomy in the presence of
high risk features (>1cm, multiple, villous
architecture) three years after polypectomy
(solitary, tubular architecture)
Ib
A
4.
Personal history of colorectal malignancy
Colonoscopy
One year after resection
IIa
B
5.
Personal history of ovarian or endometrial
cancer
Colonoscopy
One year after resection
IV
C
C.
1.
Very High-Risk
Family history of familial adenomatous
polyposis
Flexible sigmoidoscopy;
consider genetic counselling
and testing
12 to 14 years (from puberty)
Annually
IIb
B
2.
Family history of hereditary non-polyposis
colorectal cancer
Colonoscopy; consider
genetic counselling and
testing
From 10 years prior to the diagnosis in the
youngest family member
Every 2 years
IIb
B
3.
Inflammatory bowel disease
a.
left-sided colitis
Colonoscopy
From 15th year of diagnosis onwards
Every 1-2 years
IIb
B
b.
pan-colitis
Colonoscopy
From 8th year of diagnosis onwards
Every 1-2 years
IIb
B
62
References
1.
Chia KS, Seow A. Lee HP, et al. Cancer incidence in Singapore 19931997. Singapore Cancer Registry Report No. 5 : 2000.
2.
Ries LA, Miller BA, Hankey BF, et al. eds. SEER cancer statistics review
1973-1991: tables and graphs. Bethesda National Cancer Institute, 1994.
3.
Winawer SJ, Zauber AG, O’Brien MJ, et al. Randomized comparison of
surveillance intervals after colonoscopic removal of newly diagnosed
ademonatous polyps. N Engl J Med 1993; 328: 901-6.
4.
Parker SL, Tong T, Bolden S, et al. Cancer statistics 1996. CA Cancer J
Clinic 1996; 46:5-27.
5.
Hardcastle JD, Chamberlain JO, Robinson MH, et al. Randomized
controlled trial of faecal occult-blood screening for colorectal cancer.
Lancet 1996; 348:1472-7.
6.
Kronborg O, Fenger C, Olsen J et al. Randomized study of screening for
colorectal cancer with faecal occult blood for colorectal cancer. Lancet
1996; 348:1467-71.
7.
Mandel JS, Bond JH, Church TR, et al. Reducing mortality from
colorectal cancer by screening for faecal occult blood. Minnesota colon
cancer control study. N Eng J Med 1993; 328:1365-71.
8.
Fuchs C S, Giovannuci EL, Colditz GA, et al. A prospective study of
amily history and risk of colorectal cancer. N Engl J Med 1994; 331:1669
– 74.
9.
Cali RL, Pitsch RM, Thorson AG, et al. Cumulative incidence of
metachronous colorectal cancer. Dis Colon Rectum 1993; 36:388-93.
10. Winawer SJ, Fletcher RN, Miller L, et al. Colorectal cancer screening:
Clinical guidelines and rationale. Gastroenterglogy 1997; 112:594-642.
11. Jang YS, Steinhasem RM, Heimam TM. Colorectal cancer in familial
adenomatous polyposis. Dis colon Rectum 1997; 40:312-6.
12. Haggitt RC, Reid BJ. Hereditary gastrointestinal polyposis syndromes.
Am J Sung Pathol 1986; 10:871-7.
63
13. Lovett E. Family studies in cancer of the colon and rectum. Br J Surg
1976; 630:13-8.
14. Lynch HT, Watson P, Smyrk TC, et al. Colon cancer genetics. Cancer
1992; 70:1300-12.
15. Bauer WM, Lashner BA. Inflammatory bowel disease and intestinal
cancer. Practical Gastroentrol 1998; 22:20-7.
16. Ekbom A, Helmick C, Zack M, et al. Ulcerative colitis and colorectal
cancer. A population based study. N Engl J Med 1990; 323:1228-33.
17. Rozen P, Knaai J, Samuel Z. Eliminating the need for dietary restrictions
when using a sensitive guaiac fecal occult blood test. Dig Dis Sci
1999;44:756-60.
18. Macrae FA, St John DJB. Relationship between patterns of bleeding and
Hemoccult sensitivity in patients with colorectal cancers or adenomas.
Gastroenterology 1982; 82:89-898.
19. Hardcastle JD, Chamberlain J, Sheffield J, et al. Randomised controlled
trial of faecal occult blood screening for colorectal cancer. Results of the
first 107349 subjects. Lancet 1989;27:1160-4.
20. Committee for a nationwide totaling of mass screening for
gastrointestinal cancers. J Gastroenterol Man Surv 1995; 33:200-18.
21. St John DJ, Young GP, Alexeyeff MA, et al. Evaluation of new occult
blood tests for detection of colorectal neoplasia. Gastroenterology,
1993;104:1661-8.
22. Selby JV. Targeting colonoscopy. Gastroenterology 1994; 106:1702-5.
23.
Wallace MB, Ho KY, Trnka Y, et al. Comparison of nurse
practitioners/physician assistants to gastroenterologists in performing
flexible sigmoidoscopy 1998; 114:A698.
24. Selby JV. Clinical trials in screening sigmoidoscopy. Cn: Colorectal
Cancer. Winawer SJ (ed). Raven Press 1985. New York 291-301.
25. American Cancer Society. Cancer Facts and figures, 1996. American
Cancer Society Publication no. 5008-96. 1996.
64
26. Preventive health care, 2001 update: colorectal cancer screening. CMA J
2001 24; 165:206-8.
27. United States Preventive Services Task Force. Screening for colorectal
cancer. US Preventive Service Task Force report 1996.
28. The Standards Committee. Practice Parameters for the detection of
colorectal Neoplasms. The American Society of Colon and Rectal
Surgeons. 2002.
29. Reston VA. Colon cancer diagnosis in an era of cost containment.
Council of the American College of Radiology, Reston, Virginia 1990.
30. Imperiale TF, Wagner DR, Lin CY, et al. Risk of advanced proximal
neoplasms in asymptomatic adults according to distal colorectal findings.
N Eng J Med 2000; 343:169-74.
31. Lieberman DA, Weiss DG, Bond JH, et al. Use of colonoscopy to screen
asymptomatic adults for colorectal cancer. N Eng J Med 2000; 343:162-8.
32. Müller AD, Sonnenberg A. Protection by endoscopy against death from
colorectal cancer.
A case-control study among veterans. Arch Intern
Med 1995; 155:1741-8.
33. Kewenter J, Brevirge H, Haglund E, et al. Screening, rescreening and
follow-up in a prospective randomized study for detection of colorectal
cancer by faecal occult blood testing. Scand J Gastroenterol 1994;
29:468-73.
34. Filella X, Molina R, Bedini JLA. Clinical usefulness of CRA as tumor
marker in patients with colorectal cancer. J Nucl Med Allied Sci 1990;
34:107-10.
35. Mc Gill DB, Ahlguist DA. Screening for colorectal disease in the large
intestine: Physiology, Pathophysiology and Disease.
Phillips SF,
Pemberton JH, Shorter RG eds. Mayo Foundation 1991. Raven Press
Ltd. New York.
65
66
9
Screening for prostate cancer
9.1
Introduction
Adenocarcinoma of the prostate is the sixth most common cancer
among men in Singapore with an incidence of 13 per 100,000 per
year1. Autopsy studies have shown that approximately 30% of men
over the age of 50 years have histologic evidence of prostate cancer2.
Many men will die, however, from competing medical hazards and
not prostate cancer. Prostate cancer is often a slowly progressive
disease, and as a consequence, men with newly diagnosed disease
often face difficult choices regarding appropriate treatment. Treatment
options include watchful waiting, radical prostatectomy, radiotherapy,
and hormonal therapy.
Cure of prostate cancer is only possible when the disease is localised
to the prostate. Current data supports the concept that Prostate
Specific Antigen (PSA) screening results in early diagnosis and stage
migration. The percentage of incurable prostate cancers has also
greatly decreased, and the death rates from prostate cancer declined by
nearly 5% per year since 19933. Recent publications from the National
Cancer Institute have attributed this decline, at least in part, to PSA
screening. However, other factors may also have contributed to this
decline. From the economic standpoint, the financial costs of treating
advanced prostate cancer are greater than those of treating early
disease.
Most of the tumours diagnosed in the PSA-era are not insignificant
tumours by traditional grade and Gleason criteria. Multiple studies
including the Surveillance, Epidemiology and End Results (SEER)
Program have shown that moderately differentiated or Gleason sum
5-7 tumours pre-dominate in the PSA-era. Most of the available data
are from Western populations and Asians are known to have lower
incidences of prostate cancer3-6.
9.2
Who to screen
Screening with PSA has the potential of diagnosing organ-confined
prostate cancer. Early detection with PSA should not be refused to any
man who is aware of the potential risks and benefits.
67
In America, where prostate cancer is the most common cancer
amongst men, the American Cancer Society and the American
Urological Association recommend that men aged 50 years and older
with at least 10 years life expectancy should be offered prostate cancer
screening each year7. In Asia, the incidence of prostate cancer is
much lower. Furthermore, scientific evidence to demonstrate a
decrease in cancer-specific mortality from screening is lacking. The
results of several large randomized studies on prostate cancer
screening are also not ready.
A Therefore, at present, population screening for prostate cancer is
not recommended among Asians.
Grade A, Level Ia
GPP High-risk men, such as men above 50 years of age with a
history of a first degree relative with prostate cancer at a young age
(<60 years), should be offered screening.
GPP
9.3
Screening test and effectiveness
Screening for prostate cancer involves the following:
•
Digital rectal examination (DRE)
Digital rectal examination provides a rapid clinical assessment
for the presence of any suspicious prostatic nodule. The rationale
for including DRE stems from the fact that 10-25% of cancers
have a normal PSA (<4 ng/ml)8.
B Combined use of DRE and PSA has a higher detection rate for
prostate cancer than either test alone8.
Grade B, Level IIb
While the DRE is a rapid examination, it demands the
involvement of an experienced investigator and is unpleasant for
the man being screened.
•
Prostate Specific Antigen (PSA) blood test
B The introduction of PSA testing has been instrumental to the
dissemination of wide-spread prostate cancer screening. It is the
68
single test with the highest positive predictive value for cancer.
A PSA cut-off point of 4 ng/ml detects 75% of prostate cancers9.
Grade B, Level IIb
The simplicity of the test makes it very attractive for most men
despite its low specificity and imperfect sensitivity.
Approximately 15% of prostate cancers are detected between 3
and 4 ng/ml, have extracapsular extension and therefore are
probably not curable10. However, lowering the PSA cut-off too
much will decrease its specificity. Efforts to enhance specificity
include the use of free PSA and free-to-total PSA ratio. A
concept of combining a decreased PSA cut-off (to 2.5 ng/ml)
with a low free-to-total PSA ratio (<0.20) could improve both
sensitivity and specificity11,12. The value of using age-specific
ranges of PSA to enhance the diagnosis of prostate cancer has
been controversial and there is, at present, no established agespecific ranges in Asians.
•
Transrectal ultrasound-guided biopsy (TRUS biopsy)
Transrectal ultrasound (TRUS) was developed 20 years ago to
detect prostate cancer.
B Several studies have shown that most hypoechoic lesions
found on TRUS are not cancers and 50% of non-palpable cancer
more than 1 cm are not visualized on TRUS13,14.
Grade B, Level IIb
The investigation is time-consuming and also less attractive for
men as a screening procedure. The place of TRUS at present, is
in guiding systematic core biopsies of the prostate. Prostate
biopsies can be performed with little pain under local anaesthesia
and with a serious complication rate of far less than 1%.
B TRUS-guided biopsy is currently recommended for patients
with abnormal PSA results and/or suspicious DRE8.
Grade B, Level IIb
Current biopsy strategies include obtaining more than six
biopsies in most patients, focusing biopsies laterally, taking
69
additional transitional zone biopsies in very large glands, and
adjusting number of cores by taking prostate volume and
patient’s age into consideration15. In patients with elevated PSA,
a second biopsy found cancer in up to 34% of men after an initial
negative biopsy16.
9.4
Frequency of screening
The optimal screening interval has yet to be determined. So far,
investigators have studied intervals ranging from 6 months to 4 years.
Lower PSA levels may be followed by a longer screening interval. A
PSA level below 1 ng/ml seems to imply little risk for disease
progression within 2-4 years13.
9.5
Other relevant information
Data from several ongoing randomized trials of screening for prostate
cancer are expected to be available in the near future. Regional mass
screening cohort studies are being conducted in the Austrian state of
Tyrol, where volunteers exposed to PSA testing are followed over
time17. The European Randomized Study of Screening for Prostate
Cancer (ERSPC) is conducted in 7 European countries18. The
Prostate, Lung, Colorectal and Ovary (PLCO) cancer screening trial is
in progress in the US; participants are recruited from 10 centres
across the country19. Meanwhile, the first analysis of the Laval
University Prostate Cancer Detection Program (LUPCDP) Canadian
trial compared prostate cancer mortality in screened and unscreened
men between 1988 and 199620. It indicated that the screening
intervention could well lead to a reduction of cause-specific mortality
that is larger and faster than expected.
The outcome of the ERSPC, PLCO and Canadian trials will help in
the modeling and recommendation of the screening policies, and in
the ultimate decision for nation-wide introduction of cost-effective
screening programs.
9.6
Summary
Despite the fact that population-based screening for prostate cancer
has yet to be definitively proven or disproved to affect the diseasespecific mortality, this summary explores changes in the PSA-era data
70
from areas where screening has been prevalent to support the working
hypothesis that disease-specific mortality can be decreased. It must be
kept in mind that uncertainty exists regarding the reasons for the
current declining mortality, from screening itself to aggressive
treatment of disease identified in the PSA-era. Without direct
evidence of decreased prostate cancer mortality from well conducted
randomized population screening trials, it then becomes a personal
choice for asymptomatic individuals to undergo testing for prostate
cancer perhaps to lower the risk of dying from metastatic prostate
cancer. This benefit has to be balanced against the burden of
morbidity from testing and over treatment of some individuals.
References
1.
Chia KS, A Seow, Lee HP, et al. Cancer incidence in Singapore 19931997. Singapore Cancer Registry Report No. 5, 2000.
2.
Scardino PT. Early detection of Prostate Cancer. Urol Clin N Amer 1989;
16:635.
3.
Hankey BF, Feuer EJ, Clegg LX, et al. Cancer surveillance series:
Interpreting trends in prostate cancer - Part I: Evidence of the effects of
screening in recent prostate cancer incidence, mortality and survival rates.
J Natl Cancer Inst. 1999; 91:1017-24.
4.
Stephenson RA. Population-based prostate cancer trends in the PSA era:
data from the Surveillance, Epidemiology, and End Results (SEER)
program. Monographs in Urology 1998; 3.
5.
Farkas A, Schenider D, Perotti M, et al. National trends in the
epidemiology of prostate cancer, 1973 to 1994: Evidence for the
effectiveness of prostate-specific antigen screening. Urology 1998;
52:444.
6.
McNeal JE, Redwine EA, Freiha FS, et al. Zonal distribution of prostateic
adenocarcinoma. Correlation with histological pattern and direction of
spread. Am J Surg Pathol 1998; 12:897.
7.
Smith RA, Cokkinides V, von Eschenbach AC, et al. American Cancer
Society guidelines for the early detection of cancer. CA Cancer Journal
for Clinicians 2002; 52:8-22.
71
8.
Catalona WJ, Richie JP, Ahmann FR, et al. Comparison of digital rectal
examination versus prostate-specific antigen in the early detection of
prostate cancer: Results from a multi-centre clinical trial of 6630 men. J
Urol 1994; 151:1283-90.
9.
Labrie F, Dupont A, Suburu R, et al. Serum prostate-specific antigen as
pre-screening test for prostate cancer. J Urol 1992; 147:846-52.
10. Lodding P, Aus G, Bergdahl S, et al. Characteristics of screening detected
prostate cancer in men 50-66 years old with 3 to 4 ng/ml Prostate Specific
Antigen. Urology 1998; 159:899-903.
11. Lilja H, Stenman UH. Successful separation between benign prostatic
hyperplasia and prostate cancer by measurement of free and complexed
PSA. Cancer Treat Res. 1996; 88:93-101.
12. Catalona WJ, Ramos CG, Carvahal GF, et al. Lowering PSA cutoffs to
enhance detection of curable prostate cancer. Urology 2000; 55:791-5.
13. Gustaffsson O, Norming U, Almgard LE, et al. Diagnostic methods in the
detection of prostate cancer: a study of randomly selected population of
2,400 men. J Urol. 1992; 148:1827-31.
14. Carter HB, Hamper UM, Sheth S, et al. Evaluation of transrectal
ultrasound in the diagnosis of prostate cancer. J Urol 1989; 142:1008-10.
15. Djavan B, Zlotta AR, Ekane S, et al. Is one set of sextant biopsies enough
to rule out prostate cancer? Influence of transition and total volumes on
prostate cancer yield. Eur Urol 2000; 38:218-24.
16. Djavan B, Zlotta AR, Remzi M, et al. Optimal predictors of prostate
cancer on repeat biopsy: a prospective study of 1,051 men. J Urol 2000;
163:1144-8; discussion 1148-9.
17. Bartsch G, Horninger W, Klocker H, et al. Tyrol Prostate Cancer
Screening Group. Prostate cancer mortality after introduction of prostatespecific antigen mass screening in the Federal State of Tyrol, Austria.
Urology 2001 Sep; 58:417-24.
18. De Koning HJ, Auvinen A, Berenguer Sanchez A, et al. Large scale
randomized prostate cancer screening trials: program performances in the
72
European Randomised Study of Screening for Prostate Cancer (ERSPC).
Int J Cancer 2002; 97:237-44.
19. Miller AB, Yurgalevitsch S, Weissfield JL. Prostate Lung Colorectal and
Ovarian Cancer Screening trial Project Team. Death review process in the
PLCO Cancer Screening Trial. Control Clin Trials 2000; 21:400S-6S.
20. Labrie F, Candas B, Dupont A, et al. Screening decreases prostate cancer
death: first analysis of the 1988 Quebec prospective randomized
controlled trial. Prostate 1999; 38:83-91.
73
74
10
Screening for breast cancer
10.1
Introduction
Breast cancer is now the most common cancer in women in
Singapore, and, according to the Singapore Cancer Registry1, the ageadjusted incidence over the last 30 years has approximately doubled,
from 20 per 100,000 in 1968-72 to 46.1 per 100,000 in 1993-97, a rise
of about 3-4% per annum. It should be noted that Australia has also
seen a rise in age-adjusted breast cancer incidence from 70 cases per
100,000 in 1983 to 98 cases per 100,000 in 1996, an average annual
rise of 3.4%2.
Breast screening may be sporadic (or opportunistic), where an
individual woman chooses to have intermittent screening
mammography at her discretion, or mass (or population-based
screening), where women are systematically invited to have screening
mammography at predetermined intervals.
Until recently, Singapore’s breast screening was entirely sporadic in
nature. That is, the quality of mammographic screening was variable,
an unknown number of cancers was missed, screening practice was
unregulated and unaudited, screening was expensive for the individual
woman, with a high proportion of negative surgical procedures, and
there was no measurable beneficial outcome.
10.2
Key concepts in breast screening
10.2.1 Odds of significant disease
Significant disease in the context of breast cancer screening is the
detection of either non-invasive in situ carcinoma, or invasive cancer.
The prior probability of significant breast disease is greatly influenced
by the clinical scenario:
•
In a symptomatic woman presenting with a breast lump, there is
perhaps a 1:20 (5%) chance that the woman will turn out to have
a malignancy. This statistic is fairly typical in symptomatic breast
clinics in Singapore [National University Hospital Breast Clinic
data, unpublished].
75
•
In an asymptomatic woman who is a BRCA gene carrier, any
single screening visit has about 0.5-1% per year cumulative
chance of detecting cancer. This is derived from the estimated
lifetime risk of breast cancer in such gene carriers of 50% to
75%3,4.
•
Risk increases with age; in Singapore, an asymptomatic, normal
risk 30-year old woman has a 19 in 100,000 chance of developing
breast cancer each year (0.019%), while one who is 50-55 years
old has an annual risk of 185 in 100,000 (0.185%), which is
almost 10 times higher5. More than 99.9% of normal risk,
asymptomatic women screened by mammography or any other
test will NOT have breast cancer.
10.2.2 Imperfection of mammography
Well-performed mammography in a formal screening program has a
fairly high sensitivity for breast cancer, but is not very specific. In
Singapore, a recall rate of 8% and a needle biopsy rate of 1% has been
shown to be effective for detection of breast cancer in 0.5% of
screened women6. The cancer detection rate does not significantly
increase when recall rates exceed about 5%7. Recall rates much higher
than this are typical in sporadic screening, and result in large numbers
of unnecessary additional tests.
It is established that reading screening mammograms with just a
single radiologist can miss up to 30% of breast cancers8. Some
radiologists miss as few as 3% of cancers on their own9, but they are
highly experienced in screening and are in the minority. In general,
adding a second reader increases the cancer detection rate over a
single reader substantially10,11. Nevertheless, it is recognised that the
interval cancer rate (cancers that appear between routine screening
episodes) will be about 10% of all the cancers detected, typically at a
level of about 10 per 10,000 screens at 2 years12-15; only about onethird of these will be detectable on retrospective review16. Therefore,
about 7% of breast cancers cannot be detected by screening
mammography, even in retrospect.
It should be noted that routine screening mammography should be
distinguished from diagnostic mammography, which is targeted at
analysing a specific abnormality such as a palpable mass, or screendetected microcalcifications.
76
10.2.3 Sojourn time and screening interval
The time between the development of frankly malignant cellular
behaviour to the point of detectability with a screening test is called
the sojourn time. The time between screens must be appropriate for
the tumour and the age of the client. The potential benefits of
increased screening frequency must also be balanced by
considerations of the attendant increases in cost, radiation exposure,
and risk of false positive recalls.
For breast screening, this optimal screening interval has empirically
been determined through analysis of breast screening trial data17 to be:
•
•
1 year for women aged 40 to 49, and
2 years for women aged 50 to 70
10.2.4 Mass versus Individual screening
The goal of breast screening on a mass, or population basis is to
produce a shift in cancer detection towards pre-invasive cancers, and
to eventually reduce the mortality from breast cancer for the female
population.
There is only one breast screening test that has been shown to do this,
and that is well-performed, dual-read X-ray mammography. No other
test (including poorly performed mammography) has been shown to
have the same results. In general, mass breast screening is performed
through structured, accredited and audited formal programmes where
women are systematically invited to participate, usually at a reduced
cost.
On an individual, or sporadic screening basis, the goal of the woman
is to exclude cancer as best as possible. In general, this is an elective
procedure and the entire cost of the process is borne by the woman. In
this situation, it is common practice to perform breast ultrasound and
clinical breast examination. This practice is not proven to reduce
patient mortality, even though it occasionally reveals a
mammographically occult tumour.
77
10.3
Detailed recommendations
10.3.1 Screening with X-ray mammography
X-ray mammography has been subjected to randomised controlled
trials (RCTs) and much controversy. It is the most well-studied yet
most commonly misunderstood screening test which is in widespread
use today.
The Swedish Two-County trial of mammographic screening is a
landmark study. There is long-term mortality data from this trial17,
showing a persistent and significant 29% reduction in breast cancer
mortality in the group invited to screening.
Garne et al. reported the mortality results from the Malmö breast
screening trial18, showing that between 1977 and 1992, breast
carcinoma mortality decreased in Malmö by 43% compared with 12%
in the rest of Sweden (P < 0.001).
In 1996, Larsson and colleagues19 reviewed 5 of the Swedish
screening RCTs and calculated the estimated reduction of breast
cancer related mortality to be 24%. Nyström et al.20 reviewed overall
and breast cancer-related mortality of four of the Swedish RCTs on
breast screening, with similar results.
It is notable that there has been a statistically significant reduction in
breast cancer mortality in some countries since 1990 despite an
increase in incidence21,22. However, it is unclear if this decline is due
to better treatment or to breast screening, or a combination of the two.
The accepted view that mass screening mammography reduced the
breast cancer mortality was disputed recently by Gøtzsche and
Olsen23,24, who concluded that all but two of the mammography
screening trials were significantly flawed and their results could not
be considered valid. In the two trials they deemed to be adequately
randomised (the Canadian trial and the Malmö trial), they found no
effect of screening on breast-cancer or total mortality, despite the
conflicting mortality data published in 199718 which showed a
significant reduction in mortality for women in Malmö who
underwent screening.
78
This conclusion has been rebutted strongly by several international
experts. Most recently, Nystrom et al. have reviewed the Swedish
trials in detail, with particular attention to the randomization
methodology, including previously unpublished data25. They
concluded that the Swedish trials did not show significant bias, and
they reconfirmed a relative risk reduction on mortality of 24% for
women who started screening at 50 and older.
For women under 50, the evidence for mortality reduction from breast
screening is less clear-cut. Only one trial, from Gothenberg in
Sweden, has shown a statistically significant survival benefit for
women screened under the age of 50. This randomised controlled trial
specifically enrolled women aged 39-49 to mammographic screening
every 18 months. There was a 44% reduction in mortality (P<0.05)
from breast cancer in the study group compared to the control group26.
By contrast, the Canadian National Breast Screening Study showed
improved detection but no survival benefit deriving from screening in
this age group27.
Using subgroup analysis, the Two-County trial data has been
calculated to show an overall reduction in breast cancer mortality of
13% for women aged 40-49 years at randomisation28. Pooled trial data
suggests a survival benefit for women screened under the age of 5029.
Pooled analysis of women enrolled from 40-49 years in four of the
Swedish screening trials showed a 23% reduction in the breast cancer
mortality30.
The potential survival benefit of breast screening has been calculated
to be much higher for younger than for older women, with a high
screening frequency resulting in more lifetime gained31. However, the
cost of saving years of life in this age group would be at least twice as
much for each cancer detected as for women from 50–69 years.
For Singaporean women aged 45-49, the breast cancer incidence of
166 per 100,0005 is very similar to the rate in the same age cohort in
Canada
[1992,
Australia
[1992-1996,
187.5/100,000]32,
21
170/100,000] , and the USA [1992-1996, 198.6/100,000]33.
Furthermore, the Singapore Breast Screening Project has confirmed
that the mammographic cancer detection rate for local women is the
same as is seen in Western programmes5.
79
There is great variation in recommendations for mammographic
screening for women aged 40-49. Guidelines from expert panels on
breast screening for normal risk women in this age group vary from
annual mammography at one extreme (US, American Cancer Society
34
) to no mammography at all at the other (New Zealand, Royal New
Zealand College of General Practitioners 35). The use of pooled
subgroup analysis does not have the same weight of evidence as a
meta-analysis of RCTs specifically investigating this subgroup.
Therefore, recommendations for Singapore are based on a balance
between the US guidelines and the relatively high incidence of breast
cancer for Singaporean women in this age group, while taking into
account the weaker evidence, higher costs and higher false positive
rate of detecting breast cancer in this age group using screening
mammography.
10.3.2 Mammography for normal risk, asymptomatic
women
Based on this discussion and review, a number of recommendations
can be made about screening mammography.
•
Asymptomatic women 50-64 years
A All normal risk, asymptomatic women 50-64 years of age
should be screened with mammography only, every two years.
Ultrasound and breast examination are not routinely required.
Grade A, Level Ia
•
Asymptomatic women >65 years
A In Western nations, the evidence supports mammographic
screening every 2 years for all normal risk women 65-75 years of
age. However, for Singaporean women the much lower incidence
of breast cancer in this age group suggests that screening
mammography may be less beneficial. If individual screening is
performed, it should be at two-yearly intervals. Ultrasound and
breast examination are not routinely required.
Grade A, Level Ia
80
•
Asymptomatic women 40-49 years
C Women at normal risk aged 40-49 should be encouraged to
have annual screening mammography. Ultrasound and breast
examination are not routinely required.
Grade C, Level IV
•
Asymptomatic women <40 years
There is no evidence that women under the age of 40 with no risk
factors for developing breast cancer will derive any mortality
benefit from screening mammography or any other imaging test,
even if they occasionally detect an early breast cancer.
A Normal risk, asymptomatic women under 40 should not
undergo breast screening with any imaging modality.
Grade A, Level Ib
•
Women on hormone replacement therapy
It is now accepted that there is a small but definite increase in risk
of breast cancer with increasing use of hormone replacement
therapy (HRT), resulting in a net increase in breast cancer of 0.2%
at 5 years, 0.6% at 10 years and 1.2% at 15 years of continuous
HRT. This very small absolute increase in risk appears to
disappear within 5 years of ceasing HRT36. There is no evidence
that this slight increase in breast cancer increases patient mortality.
It is reasonable to perform screening mammography regularly for
these women. There is no evidence that mammography is
significantly less effective in these women, though HRT does
increase the amount and degree of mammographic glandular
density. No RCT of screening mammography in these women has
been performed, and there is no consensus about the ideal
screening interval. However, there is definitely no evidence that
these women should have more frequent screening than women of
the same age who do not receive HRT.
C Women on conventional HRT have a very slightly increased
risk of breast cancer. They should have regular screening
mammography. Those aged 40-49 should be screened annually,
81
and those aged 50-65 biannually, for up to 5 years after cessation
of HRT.
Grade C, Level IV
10.3.3 Women at increased risk of breast cancer
•
BRCA gene carriers & strong family history
These women, and women with very strong first-degree family
histories of breast and/or ovarian cancer have a 5-10 times
increased risk of breast cancer (0.5-1% per year) than women
without these risk factors. In addition, they frequently have their
cancers diagnosed before the age of 40. In most respects, they fall
outside the normal guidelines for routine breast screening.
There have been no RCTs of screening in these women, mainly for
logistic reasons. Only one prospective non-randomised study has
been reported to date, comparing the use of mammography,
ultrasound (US) and clinical breast examination (CBE) to
magnetic resonance imaging (MRI)37. While breast MRI was
shown to be more sensitive and specific for early cancer detection,
the cost of detection for each cancer is very high, and there is
currently no evidence that this confers any mortality benefit.
Breast self-examination (BSE) has been shown to be of no value in
reducing mortality from breast cancer in a very large scale
randomised trial38. Its use should be recognised as being of value
mainly in increasing an individual woman’s awareness of the
normal feel of her own breasts at various times in the menstrual
cycle.
From these considerations, any recommendations for this group of
women are based on best practice and limited published data.
C Women who are at very high risk of breast cancer by virtue of
being a BRCA gene carrier, or a very strong first-degree family
history of breast cancer, should perform monthly BSE, 6-monthly
CBE and US, and annual mammography. Screening should start as
early as 5 years before the age of onset of breast cancer in the
youngest family member. Breast MRI should be considered, but
82
only if cost is not problematic and the expertise and equipment for
MRI-guided breast needle biopsy and localisation are available.
Grade C, Level IV
10.4
Screening with other tests
The paradox of mammography is that while it is excellent at detecting
very early breast cancer, sometimes large palpable tumours are simply
not visible, particularly in dense breast tissue. This has led to
recommendations that screening include CBE, BSE, US,
scintimammography, breast MRI, and other tests as an adjunct to
mammographic screening. US, MRI and scintimammography have all
been subjected to small clinical studies, but none of these have been
RCTs or had mortality used as an outcome measure. These tests are
discussed in detail below.
10.4.1 Clinical breast examination (CBE)
The New York Health Insurance Plan trial39 and the Canadian
National Breast Screening trials27,40 included clinical breast
examination (CBE) in their studies. Both failed to show any benefit
from clinical breast examination.
A CBE has been proven to confer no mortality benefit in a screening
population.
Grade A, Level Ib
10.4.2 Breast self-examination (BSE)
Breast self-examination (BSE) has been studied in a high quality
large-scale RCT as a screening test for breast cancer in Chinese
women38. This trial showed no mortality benefit from BSE when used
for screening. Nevertheless, its widespread availability, low cost,
continuous nature and lack of proven harm argue for its continued use
largely because it is felt to improve women’s awareness of their own
breasts and breast cancer in general. In Singapore, the breast cancer
incidence starts to rise significantly only for women over the age of
30. It can be argued that routine BSE for Singapore women should
start after 30 if it is to be used at all.
83
GPP Despite evidence that it has no survival benefits, BSE is
generally recommended as it is felt to improve women’s awareness of
their own breasts and breast cancer. As the incidence of breast cancer
is extremely low before the age of 30, BSE is only recommended from
the age of 30 for normal risk women.
GPP
10.4.3 Breast ultrasound (US) and breast magnetic
resonance imaging (MRI)
The addition of routine US does appear to increase the detection of
cancers in women with mammographically dense breasts slightly at
the cost of a high proportion of negative diagnostic biopsies41.
However, there is no evidence that this application of US reduces
breast cancer mortality.
It has been argued that if US can detect additional cancers, then it
should be routinely used for screening, particularly if the patient is
paying herself. However, it is difficult to know where to stop. For
example, MRI is proven to be more sensitive and specific for invasive
breast malignancy than either ultrasound or mammography42. In
prospective screening studies of women with a very high risk of breast
cancer, MRI may be the only modality to detect a breast cancer37,43.
Using the same logic as is sometimes used to advocate screening US,
it could then be argued that MRI should be used to routinely screen
for breast cancer instead. However, it must be remembered that both
tests are associated with an increase in false-positive needle biopsies.
The addition of either test on a routine basis definitely increases the
cost of cancer detection40,42, with no proven impact on survival.
Ultimately, adding any test routinely to screening mammography adds
cost and potential morbidity with no survival benefit. Using a test
such as an US simply because it is cheaper and more widely available
than breast MRI is not scientifically valid.
B Breast US and MRI can both detect cancers that are occult on
mammography. However, they should not be used for routine breast
screening outside of clinical trials.
Grade B, Level IIa
84
10.4.4 Nuclear scintimammography
Certain radioactive tracers have been able to detect
mammographically occult breast cancers using nuclear medicine
gamma cameras.
This procedure has been termed
scintimammography. In particular, the tracers Tc99m-sesta-MIBI and
Tc99m-Tetrofosmin, both developed for cardiac nuclear scanning, have
been reported to detect breast cancers with a high sensitivity and
specificity when compared to mammography44,45. However,
scintimammography achieves best results if combined with
mammography46, and has no significant advantage over breast MRI47.
A major disadvantage of scintimammography is its poor anatomic
localisation and inability to guide needle biopsy procedures. There
have been no prospective RCTs of scintimammography for early
breast cancer detection, and there is no mortality data.
B Nuclear scintimammography shows promise as an adjunct
technique for detection of breast cancer in limited circumstances,
usually in conjunction with mammography. Its use for breast
screening is unwarranted.
Grade B, Level III
10.4.5 Thermography
scanning
and
electrical
impedance
Thermography can detect invasive breast cancers on the basis of
increased blood flow due to tumour angiogenesis. This technique has
been shown to be insensitive and inaccurate as a screening tool for
breast cancer48. However, recent technical advances have led to reexploration of this technology as a method of breast cancer detection.
In small uncontrolled studies, thermography has been shown to detect
invasive breast cancers though either with limited sensitivity and
accuracy49,50, or else with a very high false positive rate51. However, it
is unproven for detection of ductal carcinoma in situ, and has not been
studied in any RCT.
Electrical impedance scanning has been recently developed as an
investigational technique for suspected breast cancer. Claims for
increased tissue specificity when a focal lesion is found have been
made, but not subjected to RCT. Recent reports suggest that there is
85
only moderate sensitivity for breast cancer and tissue
classification52,53. No studies have been performed using this
technology for screening.
C Thermography and Electrical Impedance Scanning must be
regarded as investigational techniques. Their use for breast screening
is not warranted.
Grade C, Level IV
10.5
Other situations
10.5.1 Women with prior breast cancer
Women with prior breast cancer have an increased risk of tumour
recurrence locally, metachronously in the opposite breast, or distant
metastatic disease. It is well-established that local chest wall
recurrence after mastectomy or ipsilateral breast recurrence after
excision and radiotherapy does not affect survival. It is unclear
whether a second contralateral cancer has any effect on survival.
It is common practice to recommend annual mammography of the
remnant breast on the ipsilateral side (if breast conservation has been
performed) and the contralateral breast, with US added if necessary.
However, there is no good evidence to support this practice. A recent
study of local recurrence rates after breast conserving surgery and
radiotherapy showed extremely low recurrence rates at 12 months,
even for women at high risk of local recurrence, and recommended
biannual surveillance screening for women who have had breast
conservation54. However, this is not yet widespread standard practice.
For the first few years after diagnosis, women are considered to be
under surveillance. The American Society of Clinical Oncology
recommends monthly BSE, at least 6-monthly CBE, and annual
mammography of the remnant and contralateral breast55. After 5 years
disease-free, women can be usually allocated to a routine screening
group. This practice is entirely empirical.
GPP Women with prior breast cancer should receive annual
screening mammography of the remnant and contralateral breasts. At
5 years disease-free post-surgery, they may return to the standard
screening interval for asymptomatic women of the same age.
GPP
86
10.5.2 Women with breast implants
There is no evidence that women with breast implants have increased
risk of breast cancer compared to age-matched women56. In fact,
epidemiological studies have suggested a reduced risk of breast cancer
in women with silicone implants57,58 though these findings do not
reach statistical significance, and no RCT has been conducted to
address this question. While screening mammography is more
challenging in these women as more views must be performed in
order to visualise the breast tissue adequately, there is also no
evidence that it increases the risk of implant rupture or subsequent
breast cancer if correctly performed. These women should be
screened on the same basis as normal risk, asymptomatic women.
A Women with breast implants are recommended to have routine
screening mammography once every 1-2 years, depending on their
age.
Grade A, Level Ia
10.5.3 Women with silicone breast injections
Women with freely injected silicone oil in the breast tissues are not
uncommon in Asia. The silicone oil acts to prevent accurate detection
of breast cancer using any available method. Radiographically, the oil
is extremely dense, thus, obscuring all mammographic detail.
Ultrasonically, the oil combines with breast tissue to produce dense
shadowing from virtually all the breast parenchyma, again obscuring
visualisation. Clinically, the oil results in reactive foreign body
granulomas which cause marked hardening and produce multiple
breast lumps, making clinical evaluation impossible. In addition,
silicone granulomas may cause false-positive enhancement on breast
MRI. This makes this test less useful. However, there have been case
reports of breast cancer in such women detected using MRI59.
GPP When encountered, women with free silicone or paraffin oil
injections in their breasts should be clinically examined and
counselled as to the futility of screening using any currently available
test. MRI may be useful in highly selected cases where there is a
strong suspicion of breast cancer.
GPP
87
10.6
Summary
There is strong evidence that mammographic screening once every 2
years is beneficial for women at normal risk of breast cancer over the
age of 50, and there is some evidence to support annual screening
mammography for women from 40-49. HRT adds only slightly to the
risk of developing breast cancer, and does not warrant more frequent
mammographic screening than for other women of similar age. Other
imaging technologies are not recommended for screening. BSE and
CBE do NOT affect survival but is recommended from age 30 as it
increases awareness of breast disease. Screening in very high risk
women, and the protocol used, remains empirical.
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19. Larsson LG, Nystrom L, Wall S, et al. The Swedish randomised
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Miller AB, Baines CJ, To T, et al. Canadian National Breast Screening
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Kaplan SS. Clinical utility of bilateral whole-breast US in the evaluation
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of breast cancer: new, multicentric, residual, and recurrent. Eur Radiol
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in screening women at high risk for breast cancer with MR imaging.
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Imbriaco M, Del Vecchio S, Riccardi A, et al. Scintimammography with
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93
94
11
Screening for cervical cancer
11.1
Introduction
Cervical cancer is the 4th most common cancer among Singapore
women1. The age-standardized incidence rate has been gradually
declining from 18 per 100,000 population per year (1968–1972) to
14.2 per 100,000 population per year (1993-1997). The agestandardized mortality rate for cervical cancer is 6.1 per 100,000
population per year (1993-1997).
11.2
Definition
The peak incidence of cervical intraepithelial neoplasia (CIN) 3 in
Singapore is between 35-39 years of age1. Only a very small number
of women aged 15-19 (1.25%) have significant CIN. Women between
20-25 years of age make up 7.7% of the total number with CIN 3.
The following groups are considered to be at higher risk for cervical
cancer:
2
• Human Immunodeficiency Virus positive women
3
• Cigarette smoking
4
• Immunosuppression
5
• Infection with oncogenic Human Papillomavirus
6
• History of sexually transmitted infections
7, 8
• Multiple sexual partners (either partner)
9
• Onset of sexual intercourse at an early age
The following groups are considered to be at low risk for cervical
cancer:
• Women who have had a hysterectomy in which the cervix was
removed unless the hysterectomy was performed because of
cervical cancer or its precursors10-14
15,16
• Women who have never had sexual intercourse
Therefore all women who had ever had sexual intercourse are advised
to have their first Pap smear by the age of 25 years.
95
11.3
Screening test and effectiveness
The Papanicolaou or Pap smear fulfils many of the WHO
recommendations for a screening test. Cervical cancer is firstly an
important public health problem. There is accepted treatment for
patients with preinvasive disease (CIN) of the cervix. The Pap smear
is a suitable test to pick up CIN of the cervix, and it is an acceptable
test to the public. The natural history of CIN and cervical cancer and
its development from the preinvasive to the invasive disease is welldocumented17. The Pap smear is a cheap and a cost-effective test.
B A well-run population-based cervical cancer screening programme
with good coverage reduces the incidence and mortality of cervical
cancer18,19.
Grade B, Level IIa
In a meta-analysis, the mean sensitivity of the Pap smear as a
screening test was 58% while the mean specificity was 69%20.
11.4
Age and gender for screening
B All women who have ever had sexual intercourse are advised to
have their first Pap smear by the age of 25 years1.
Grade B, Level III
B A woman can be discharged from screening at 65 years of age if the
smear taken at 65 years is negative and the previous smears were
negative21.
Grade B, Level III
However, women who have had sexual intercourse but have never had
a Pap smear should still undergo screening irrespective of age.
11.5
Frequency of screening
B Pap smear screening should be performed every 3 years22.
Grade B, Level IIa
96
11.6
Other relevant information
Women who have never had sexual intercourse need not have Pap
smear screening15,16. However if these women have any symptoms,
they should consult a doctor.
B There is evidence to show that HIV positive women should be
screened earlier and more frequently2, preferably annually.
Grade B, Level III
The adequacy of Pap smears depends on the presence of cells from
both the ectocervix and endocervix.
11.7
Summary
It is well established that cervical cancer incidence and mortality can
be reduced with regular Pap smear screening performed every 3 years.
References
1.
Chia KS, Seow A, Lee HP, et al. Cancer Incidence in Singapore 19931997. Singapore Cancer Registry Report No. 5, 2000.
2.
Abercrombie PD, Korn AP. Lower genital tract neoplasia in women with
HIV infection. Oncology 1998; 12:1735-9.
3.
Brinton LA, Schairer C, Haenszel W, et al. Cigarette smoking and
invasive cervical cancer. JAMA 1986; 255; 3265-9.
4.
Fraumeni JF, Hoover R. Immunosurveillance and cancer :
Epidemiological observations. In : Epidemiology and Cancer Registries
in the Pacific Basin, Natural Cancer Institute Monograph 1977; No. 47,
pp 121-6.
5.
Campion MJ. Human papillomavirus and anogenital neoplasia. In :
Munoz N, Bosch FX, Jensen OM (eds). Human papillomavirus and
cervical cancer. IARC Scientific Publications 1989; No. 94, International
Agency for Research on Cancer ; Lyon, pp 41-65.
97
6.
Levin ML, Kress LC, Goldstein H. Syphilis and cancer. New York State
J Med 1942; 41:1737.
7.
Brinton LA, Hamman RF, Huggins GR, et al. Sexual and reproductive
risk factors for invasive squamous cell cervical cancer. J Natl Cancer Inst
1987; 79:23.
8.
Buckley JD, Doll R, Harris RWC, et al. Case-control study of husbands
of women with dysplasia or carcinoma of the cervix uteri. Lancet 1981;
ii:1010.
9.
La Vecchia C, Franceschi S, Decarli A, et al. Sexual factors, venereal
diseases and the risk of intraepithelial and invasive cervical neoplasia.
Cancer 1986; 58:935.
10. Fetters MD, Fischer G, Reed BD. Effectiveness of vaginal Papanicolaou
smear screening after total hysterectomy for benign disease. JAMA 1996;
275:940-7.
11. Miller JM, Chambers DC, Miller JM. The need for Pap tests after
hysterectomy for benign disease. Results of a study of black patients.
Postgrad Med 1987; 82:200-2, 205.
12. Piscitelli JT, Bastian LA, Wilkes A, et al. Cytologic screening after
hysterectomy for benign disease. Am J Obstet Gynecol 1995; 173:42430.
13. Roman LD, Morris M, Eifel PJ, et al. Reasons for inappropriate simple
hysterectomy in the presence of invasive cancer of the cervix. Obstet
Gynecol 1992; 79:485-9.
14. Chen RJ, Chang DY, Yen ML, et al. Independent clinical factors which
correlate with failures in diagnosing early cervical cancer. Gynecol Oncol
1995; 58:356-61.
15. Kjaer SK, Chackerian B, Van Den Brule AJ, et al. High-risk human
papillomavirus is sexually transmitted : Evidence from a follow-up study
of virgins starting sexual activity (intercourse). Cancer Epidemiol
Biomarkers Prev 2001; 10:101-6.
16. Broso PR. The age for beginning and the frequency for performing the
Pap test. Minerva Ginecol 1994; 46:565-9.
98
17. McIndoe WA, McLean MR, Jones RW, et al. The invasive potential of
carcinoma in situ of the cervix. Obstet Gynecol 1984; 64:451-8.
18. Anderson GH, Boyes DA, Benedet JL, et al. Organisation and results of
the cervical cytology screening programme in British Columbia, 1995-85.
BMJ 1988;296:975-8.
19. Laara E, Day NE, Hakama M. Trends in mortality from cervical cancer in
the Nordic countries : association with organized screening programmes.
Lancet 1987; 1:1247-9.
20. Fahey MT, Irwig L, Macaskill P. Meta-analysis of Pap test accuracy. Am
J Epidemiol 1995; 141:680-9.
21. Eddy DM. Screening for cervical cancer. Ann Intern Med 1990; 113:21426.
22. IARC Working Group on evaluation of cervical cancer screening
programmes. Screening for squamous cervical cancer: duration of low
risk after negative results of cervical cytology and its implication for
screening policies. Br Med J (Clin Res Ed) 1986; 293:659-64.
99
100
12
Screening for uterine cancer
12.1
Introduction
Uterine cancer is the 8th most common cancer among Singapore
women1. In Singapore the disease has shown an increase over time,
from an age-standardized incidence rate of 4.8 per 100,000 population
in 1968-1972, to 8.2 per 100,000 population in 1993-97.
12.2
Definition2
Average Risk
Women with no identified risk factors
Increased
Risk
History of unopposed estrogen therapy
Late menopause
Tamoxifen therapy
Nulliparity
Infertility or failure to ovulate
Obesity
Diabetes
Hypertension
High Risk
12.3
Women with or at risk of hereditary nonpolyposis colorectal cancer (HNPCC)
Screening tests and effectiveness
B There is insufficient evidence to establish whether a decrease in
mortality from endometrial cancer occurs with screening by
endometrial sampling or transvaginal ultrasound3, 4.
Grade B, Level IIb
C Although the diagnosis of endometrial cancer occasionally
originates with an abnormal Pap test of cytological material from the
uterine cervix, this method has been evaluated and found to be
insensitive for endometrial screening5.
Grade C, Level IV
101
B There is no indication that screening is warranted for women who
are at average or increased risk for endometrial cancer4,5.
Grade B, Level IIb
C Hereditary Non-Polyposis Colorectal Cancer is a syndrome in
which there is an inherited tendency to develop colorectal cancer.
Women with or at risk for hereditary non-polyposis colorectal cancer
(HNPCC-Appendix 1)6 are considered high risk and should be offered
annual screening for endometrial cancer with endometrial biopsy by
age 35.
Grade C, Level IV
Women in this high-risk group should be informed about the risks and
symptoms of endometrial cancer, and should be informed about
potential benefits, risks, and limitations of testing for early
endometrial cancer2, preferably by tertiary centres.
12.4
Other relevant information
Although screening is inappropriate for the general population, a
strategy of early evaluation of postmenopausal bleeding with
judicious use of hysteroscopy and endometrial biopsy is important for
the early detection of endometrial cancer7.
12.5
Summary
There is currently insufficient evidence to screen for uterine cancers
other than in women with or at high risk for hereditary non-polyposis
colorectal cancer.
102
Appendix 1. International Collaborative Group Clinical
Criteria for Diagnosing HNPCC (Amsterdam II)6
1) There should be at least 3 relatives with an HNPCC-associated cancer
(cancer of colorectum [CRC], endometrium, small bowel, ureter or renal
pelvis).
2) One relative should be a first degree relative of the other two.
3) At least two successive generations should be affected.
4) At least one case should have been diagnosed before age 50 years.
5) Familial adenomatous polyposis should be excluded in the CRC case(s) if
any.
References
1.
Chia KS, Seow A, Lee HP, et al. Cancer Incidence in Singapore 19931997. Singapore Cancer Registry Report No. 5, 2000.
2.
American Cancer Society guidelines on testing for early endometrial
cancer detection - update 2001. In: American Cancer Society guidelines
for the early detection of cancer. Cancer J Clin 2001; 51:54-9.
3.
Pritchard KI. Screening for endometrial cancer: is it effective? Ann Int
Med 1989; 110: 177-9.
4.
Eddy D. ACS Report on the cancer-related health checkup. CA: Cancer J
Clin 1980; 30:193-240.
5.
Burke JR, Lehman HF, Wolf FS. Inadequacy of papanicolaou smears in
the detection of endometrial carcinoma. N Eng J Med 1974; 291:191-2.
6.
Vasen HF, Watson P, Mecklin JP, et al. New clinical criteria for
hereditary nonpolyposis colorectal cancer (HNPCC) syndrome proposed
by the International Collaborative group on HNPCC. Gastro-enterology
1999; 116:1453–6.
7.
Menon U, Jacobs IJ. Tumor markers and screening. In : Berek JS, Hacker
NF (eds). Practical Gynecologic Oncology. Philadelphia : Lippincott
Williams & Wilkins, 2000: 51.
103
104
13
Screening for ovarian cancer
13.1
Introduction
Ovarian cancer is the 6th most common cancer among Singapore
women1. The age-standardized incidence rate is 11.4 per 100,000
population per year (1993-1997). The age-standardized mortality rate
of ovarian cancer is 4.3 per 100,000 population per year (1993-1997).
13.2
13.3
Definition
Average Risk
Asymptomatic pre- and post-menopausal women2
High Risk
Those with 2 or more first degree relatives with
ovarian cancer and those with strong evidence of a
hereditary predisposition for ovarian cancer2,3
(including women with or at high risk for
hereditary breast-ovarian cancer and hereditary
non-polyposis colorectal cancer)
Screening tests and effectiveness
Average Risk
Routine pelvic examination, ultrasound, transvaginal sonography
(TVS), serum tumour antigens or combination have poor positive
predictive value for early detection of ovarian carcinoma. The
effectiveness of screening is unknown2, 4-10.
B Routine population screening for ovarian cancer by ultrasound, the
measurement of tumour markers, or pelvic examination is not
recommended.
Grade B, Level IIa
High Risk
There is evidence of higher positive predictive value for detection,
because of higher prevalence in this group but the effectiveness of
screening is unknown2.
105
These women should be referred to tertiary centres11 for annual
multimodal screening with pelvic exam, TVS and Ca 125*3.
However, there is no data demonstrating that screening this group of
high risk women reduces their mortality from ovarian cancer3.
GPP There is insufficient evidence to recommend for or against the
screening of asymptomatic women at increased risk of developing
ovarian cancer. Experts suggest referral of these women to tertiary
centres for multimodal screening.
GPP
*The tumour-associated antigen, Ca 125, is a high molecular weight glycoprotein noted
to be elevated in many ovarian cancers.
13.4
Summary
There is insufficient evidence to establish that routine screening for
ovarian cancer with Ca 125, transvaginal ultrasound or pelvic
examination in women at average risk is beneficial. Women at high
risk for ovarian cancer should be referred to a tertiary centre.
References
1.
Chia KS, Seow A, Lee HP, et al. Cancer Incidence in Singapore 19931997. Singapore Cancer Registry Report No. 5, 2000.
2.
Gladstone CQ. Screening for ovarian cancer. Canadian Task Force on
Preventive Health Care. Systematic reviews & recommendations. 1994;
870-81.
3.
National Institutes of Health. Ovarian cancer: screening, treatment, and
follow-up.
National Institutes of Health Consensus Conference
Statement, 1994.
4.
Van Nagell JR Jr, DePriest PD, Reedy MB, et al. The efficacy of
transvaginal sonographic screening in asymptomatic women at risk for
ovarian cancer. Gynecol Oncol 2000; 77:350-6.
106
5.
Grover S, Quinn MA, Weideman P Koh H, et al. Screening for ovarian
cancer using serum Ca125 and vaginal examination: report on 2550
females. Int J Gynecol Cancer 1995; 5:291-5.
6.
Einhorn N, Bast R, Knapp R, et al. Long-term follow-up of the
Stockholm Screening Study on ovarian cancer. Gynecologic Oncology
2000; 79:466-70.
7.
DePriest PD, Gallion HH, Pavlik EJ, et al. Transvaginal sonography as a
screening method for the detection of early ovarian cancer. Gynecol
Oncol 1997; 65:408-14.
8.
Van NJ, Jr, Gallion HH, Pavlik EJ, et al. Ovarian cancer screening.
Cancer 1995; 76:2086-91.
9.
Menon U, Jacobs I. Ovarian cancer screening in the general population.
Ultrasound Obstet Gynecol 2000; 15:350-3.
10. Woolf SH. Report of the US Preventative Services Task Force. Guide to
Clinical Preventive Services, Second Edition. Screening for ovarian
cancer.
11. American College of Physicians. Screening for ovarian cancer. Ann Int
Med 1994; 121:141-2.
107
108
14
Screening for tuberculosis
14.1
Introduction
There has been a world-wide resurgence of Tuberculosis (TB) in the
last decade. The World Health Organisation declared TB a global
emergency in 1993 based on estimates that every year, there would be
about 8 million new TB cases and 2-3 million TB deaths world wide1.
About one third of the world’s population (2 billion) are infected by
the TB bacillus, and several tens of millions of these have been
infected by the multi-drug resistant TB germ.
Despite Singapore’s economic progress and improvements in living
standards and health care, its TB incidence has remained high (49-56
per 100,000) in the decade from 1987 through 1997, being 5-10 times
that of developed countries in the West2.
It is likely that the rates have not declined because there is still
significant ongoing transmission of TB in the community due to
delays in diagnosis and treatment. Moreover, it is also likely that
many patients are not adhering to and completing treatment, hence
remaining infectious or being at high risk for disease relapse. The
rates of HIV and TB drug resistance are low at present and the
standard short course TB regimens are still effective2. The key priority
of Singapore’s national control programme is therefore to reduce the
infectious pool in the community by early diagnosis, and the prompt
and complete treatment of all infectious cases. Appropriate contact
screening plays an important, though secondary, role in the national
programme3.
14.2
The Pathogenesis of TB
TB is spread primarily by tiny airborne particles (droplet nuclei)
containing the tubercle bacillus or Mycobacterium tuberculosis
expelled by a person who has infectious TB. If another person inhales
these droplet nuclei, transmission may occur. Persons who are thus
infected (but who do not have TB disease) are asymptomatic and are
considered to have Latent TB Infection (LTBI). They may be
identified by a positive tuberculin skin test. However, the test only
becomes positive 4 to 12 weeks after infection. Because they do not
have TB disease, persons with LTBI are not infectious to others.
109
About 10% of recently infected persons will develop TB disease at
some time in their lives, but the risk is highest in the first year or so
following the acquisition of infection. Persons who are
immunosuppressed, especially those with HIV infection are also more
likely to develop active TB disease following infection.
Even though TB is spread by the airborne route, it is far less infectious
than the viral airborne illnesses such as chicken pox and measles.
Whereas viral illnesses may be contracted during very short exposures
(less than a few hours), TB transmission generally requires prolonged
exposures (weeks of sharing air with an untreated infectious index
case). Thus, as a rule, TB contact investigations are not performed on
casual contacts of a TB case.
Screening for LTBI may be performed in high risk groups. These
include close contacts of an infectious TB case (Index case), persons
with HIV infection, persons with certain medical conditions (diabetes
mellitus, head and neck cancers, haematologic malignancies, chronic
malabsorption,
end-stage
renal
disease,
and
prolonged
immunosuppressive therapy) and persons who use illicit intravenous
drugs. In Singapore, priority has been accorded to the screening for
LTBI in close contacts of an Index case.
14.3
Screening for LTBI with the Tuberculin Skin Test
(TST) for preventive treatment of infected contacts
TST screening for LTBI is recommended only for identifying
candidates for treatment of latent TB infection (generally with
isoniazid, INH). Therefore, it is recommended only in persons at high
risk of breakdown to TB disease. Indiscriminate screening or
erroneous selection of subjects could lead to the needless
administration of INH and the unnecessary exposure of these subjects
to the risk of hepatitis which in some cases can be fatal4.
The administration and reading of the TST is very operator
dependent5. Intra-observer and inter-observer variability is increased
with untrained personnel, and personnel who do not perform the test
on a regular basis. Both false positive and false negative readings can
result from technical as well as biological factors. In the TB Control
Unit, the Mantoux test is performed using the 1 TU RT-23 tuberculin
110
from the Serum Statens Institute, Denmark according to a WHO
recommendation6.
Therefore contact investigations should be carefully performed by
trained and experienced personnel, and always begin with an
identified Index case. (In the absence of data around the Index case, it
would therefore be impossible to perform meaningful contact
investigations, as can be seen by the discussion below.) In assessing
the probability of transmission, the investigator considers the
infectiousness of the Index case, the susceptibility of the contact, the
environment in which the exposure occurred, and the duration of
exposure during the infectious episode. The key is to determine the
infectiousness of the Index case and this is assessed by the site of TB
disease (pulmonary, laryngeal), the presence of cavities on the chest
radiograph, the bacteriological status (whether sputum smear or
culture positive), and the presence and duration of cough7. Exposures
of long duration (weeks rather than days) are given higher priority for
testing. Closed environments, especially if poorly ventilated, are more
likely to result in transmission. Also, recently infected contacts are
much more likely to develop active TB disease than subjects infected
in the remote past. To determine these factors, the TB Control Unit
staff conduct the contact investigations which involve interviewing
the Index case, interviewing the contacts, and not infrequently,
performing a site visit (the workplace, home, prison or nursing home).
The TST reaction is then interpreted in the light of the data obtained
from the investigations.
Contact investigations should not be equated with merely performing
a TST and taking an arbitrary cut-off level as “positive”. Such results
may occur in persons with Mycobacteria Other Than Tuberculosis
(MOTT) infection, remote TB infection (without risk factors), or even
previous BCG vaccination, none of whom should be given INH
chemoprophylaxis as they would be needlessly exposed to the risk of
drug-induced hepatitis. In Singapore, there is almost universal BCG
vaccination at birth, and BCG re-vaccination of schoolchildren has
been practised until recently8. Also, MOTT is prevalent in Singapore.
These factors would confound the interpretation of the TST in our
population.
As shown in Table 4, when contact investigations have appropriately
identified a high risk group, a positive TST may have a positive
predictive value of 86% i.e. 9 of 10 contacts would be correctly
111
prescribed preventive treatment. However, when indiscriminate TSTs
are done in low risk groups, a positive TST may have a positive
predictive value of only 50% or lower i.e. 5 of 10 persons thus
identified may be needlessly exposed to the hepatotoxic effects of
INH.
Table 4: Example for the Dependence of the Predictive
Value of a Positive Test on the Prevalence
Example 1:
90% Sensitivity
90% Specificity
40% Prevalence
Test
pos
neg
tot
present
360
40
400
Condition
absent
60
540
600
Example 2:
90% Sensitivity
90% Specificity
10% Prevalence
total
420
580
1000
Predictive value of a positive test:
360 / 420 = 86%
Test
pos
neg
tot
present
90
10
100
Condition
absent
90
810
900
total
180
820
1000
Predictive value of a positive test:
90 / 180 = 50%
Two situations with the same operating characteristics sensitivity and
specificity) of the test, but a different prevalence of the condition in the
population.
In the first example, the prevalence is 40% in the population, thus 400
of these 1,000 people have the condition. Using the sensitivity shows
that 90% of these 400, thus 360 people are correctly and 40 incorrectly
identified as having the condition. Using specificity information shows
that 90% of 600, thus 540 are correctly and 60 incorrectly identified as
not having the condition. The predictive value of a positive test result in
this situation is 86%. In other words, a positive test truly identifies
about 9 out of 10 cases and in the 10th the test is wrong.
In the second example, the prevalence is much lower. Using the same
test with the same operating characteristics, a positive test is correct in
only half of the cases: the test is virtually useless in this situation.
Ref: www.tbrieder.org – Updated: 26-Jan-01.
112
14.3.1 Health Care Workers (HCW)
Contact investigation with TST screening is only done when there is
an identified infectious Index case. The only exception to this rule is
the screening of HCWs.
Because HCWs are constantly exposed to untreated or even
undiagnosed cases of infectious TB, it is often impossible to assign an
episode of exposure. Therefore, HCWs form a special group of
contacts who should be screened periodically (annually) with the TST
if the initial TST is negative9. If the TST converts from negative to
positive during annual screening, preventive treatment should be
given.
14.3.2 A In summary, screening for latent TB infection with the
Tuberculin Skin Test (TST) is recommended only for identifying
candidates for treatment of latent TB infection (generally with INH).
Therefore, it is recommended only in persons at high risk of
breakdown to TB disease4.
Grade A, Level 1b
Indiscriminate screening or erroneous selection of subjects could lead
to the needless administration of INH and the unnecessary exposure of
these subject to the risk of drug-induced hepatitis which in some cases
may be fatal.
14.4
Screening for active TB disease with the chest X-ray
Because TB affects the lungs in >80% cases, it would be reasonable to
assume that the chest X-ray (CXR) could be used as a tool to detect
early pre-symptomatic TB disease. However, the yield is so low that
mass X-ray screening is not recommended by TB experts10-12. Data
from Singapore showed that of 10,598 screening CXRs done from
October 1997 to November 1998, only 4 bacteriologically confirmed
cases were detected, a yield of only 0.04%. The Ministry of Health
stopped performing mass CXR screening on Oct 2001. It is much
more cost effective to perform CXRs on patients who present with
prolonged cough (>3 weeks).
There are certain special circumstances when screening CXR may be
beneficial:
113
1.
Before admission into long term residential facilities in
congregate settings, e.g. nursing homes, correctional facilities, it
may be beneficial to perform a screening CXR to pick up active
PTB because (a) entrants into such facilities may belong to
groups at high risk of PTB; (b) an undetected and untreated case
of PTB can infect many other persons because of the closeness of
contacts in such congregate settings. (Note that even in such
congregate settings annual CXR screening is not recommended.)
2.
High risk TB infected persons who have been identified by
contact investigations for the treatment of LTBI must have CXRs
done4. Here, the CXR is performed to exclude active TB disease
before commencement of INH preventive treatment. This is to
ensure that INH monotherapy is not inadvertently given to
patients with TB disease, in which case the monotherapy would
not only be ineffective but also dangerous as it would engender
the development of drug-resistance.
B Therefore, as a rule, mass CXR screening for TB is not
recommended13.
Grade B, Level III
14.5
Summary
1.
Screening in TB
Screening is possible for Latent TB Infection (LTBI) and Active
TB Disease.
2.
Definition
Latent TB Infection (LTBI):
A TST screening for latent TB infection is recommended only
for identifying candidates for treatment of latent TB infection
(generally with INH). Therefore, it is recommended only in
persons at high risk of breakdown to TB disease.
Grade A, Level Ib
Indiscriminate screening or erroneous selection of subjects could
lead to the needless administration of INH and the unnecessary
exposure of these subject to the risk of drug-induced hepatitis
which in some cases maybe fatal.
114
Active TB Disease:
B As a rule, mass CXR screening for active TB is not
recommended.
Grade B, Level III
3.
Screening test and effectiveness
Latent TB Infection (LTBI):
The TST only provides a better positive predictive value when
high risk groups are screened. In Singapore, TST screening for
LTBI is performed in carefully identified close contacts of
infectious Index cases.
Active TB Disease:
CXR screening in asymptomatic subjects is not recommended as
the yield is extremely low13.
4.
Age and gender for screening
Latent TB Infection (LTBI):
There is no age or gender restriction, once a high risk group is
identified4.
Active TB Disease:
Mass CXR screening should not be performed regardless of age
or gender.
5.
Frequency of screening
Latent TB Infection (LTBI):
Contact screening investigations are performed only once around
an infectious Index case7. Repeat investigations are not indicated
except in tuberculin–negative health care workers who are
continually exposed to infectious TB cases.
Active TB Disease:
Annual CXR screening is not recommended13.
References
1.
Raviglione MC, Snider DE Jr, Kochi A. Global epidemiology of
tuberculosis. Mortality and Morbidity of a worldwide epidemic.
JAMA 1995; 273:220-6.
115
2.
Singapore: Department of Clinical Epidemiology, Communicable
Disease Centre, Tan Tock Seng Hospital and Ministry of Health,
Communicable Disease Surveillance Report 1997.
3.
Chee CBE, Wang YT. Political Will - The Singapore Tuberculosis
Elimination Programme. In Tuberculosis: A Comprehensive
International Approach. Reichman LB and Hershfield ES, editors.
New York: Marcel Dekker; 2000; 727-44.
4.
American Thoracic Society. Targetted Tuberculin Testing and
Treatment of latent tuberculous infection. Am. J. Respir Crit Care
Med 2000; 161:S221-47.
5.
Menzies RI. Tuberculin Skin Testing. In Reichman LB, Hershfield
ES, eds. Tuberculosis. A Comprehensive International Approach. 2nd
edition. Marcel Dekker. 2000; 279-322.
6.
World Health Organisation. The WHO standard tuberculin test.
WHO/TB/Techn.
Guide/3:1-19.
Geneva:World
Health
Organisation;1963.
7.
Etkind SC, Veen J. Contact Follow-up in High-and low- prevalence
countries. In Reichman LB, Hershfield ES, eds. Tuberculosis. A
Comprehensive International Approach. 2nd edition. Marcel Dekker
2000: 377-99.
8.
Chee CBE, Soh CH, Boudville IC, Chor SS, Wang YT. Interpretation
of the Tuberculin skin test in Mycobacterium bovis BCG vaccinated
Singaporean schoolchildren. Am J Respir Crit Care Med 2001;
164:958-61.
9.
Blumberg HM. Tuberculosis infection control. In Reichman LB,
Hershfield ES, eds. Tuberculosis. A Comprehensive International
Approach. 2ndedition. Marcel Dekker. 2000; 609-43.
10.
ReichmanLB. Tuberculosis screening and chest X-ray films. Chest
1975; 68S:448-51.
11.
Toman K. Mass Radiography in tuberculosis control. WHO Chron
1976; 30:51-7.
116
12.
Swallow J, Sbarbaro JA. Analysis of tuberculosis casefinding in
Denver, Colorado, 1965-70. Health Services Rep 1972; 87:375-84.
13.
Reider H. Case finding in high- and low- prevalences countries. In
Reichman LB, Hershfield ES, eds. Tuberculosis. A Comprehensive
International Approach. 2nd edition. Marcel Dekker 2000: 323-39.
117
118
15
Screening for hepatitis B
15.1
Introduction
Hepatitis B Virus (HBV) infection is a common disorder in
Singapore. In Singapore, about 6% of the population have chronic
hepatitis B infection1. Chronic hepatitis B results from infection
during the perinatal period and in early childhood. Most infections in
the above age groups are sub-clinical and remain asymptomatic. They
are detected in adulthood incidentally during blood donation, health
screening or screening prior to vaccination.
HBV infection and its complications are major worldwide health
problems. There are approximately 300 million people with chronic
HBV infection in the world and more than half live in the Asia Pacific
region. Twenty-five percent of those infected are at risk of serious
illness and eventual death from cirrhosis and/or primary
hepatocellular carcinoma (PHC)2.
In Singapore, hepatocellular carcinoma is one of the top 10 cancers
affecting males in Singapore and Hepatitis B infection is the main
etiological factor.
15.2
Definition
15.2.1 Chronic hepatitis B infection
It is now accepted that the term Hepatitis B "carrier" be dropped as the
term connotes a benign state.
A person is considered to develop chronic hepatitis B infection if he
fails to clear Hepatitis B surface antigen (HBsAg) within 6 months
following an acute infection. In most patients, the clinical course of
the chronic disease is mild and indolent until the late stages.
However, the pattern of chronic HBV infection and its clinical
outcome can be markedly variable. While some patients remain
asymptomatic, others develop progressive liver disease leading to
cirrhosis and primary hepatocellular carcinomas.
119
The natural progression of neonatally and childhood acquired chronic
HBV infection may be divided into three phases:-
15.3
(1)
A high viral replicative (immune-tolerant) phase is usually
seen in patients younger than 20 years old. This phase is
characterised by high titres of HBsAg, HBeAg, and serum HBVDNA but relatively mild or even unrecognized clinical illnesses
with normal aminotransferase levels (ALT/AST). Minimal or no
liver damage is found on liver biopsies3.
(2)
A low viral replicative (immune-elimination/clearance or 'e'
sero-conversion) phase occurs in subjects between the ages of
20 and 40 years. A clinical picture indistinguishable from that of
acute hepatitis may be seen during this phase. Liver biopsy
usually shows the presence of chronic hepatitis and/or active
cirrhosis4.
(3)
A non-replicative (latent infection) phase is usually seen in
patients aged about 40 years of age. HBsAg persists during this
phase. There is now no serological or histological evidence of
active HBV replication. Serum ALT/AST levels may become
normal although histologic progression to cirrhosis and PHC may
occur. About 1-2% of patients will lose their HBsAg and develop
anti-HBs each year. About 40% of subjects with chronic HBV
infection will develop cirrhosis at a rate of about 2% per year4.
Screening for hepatitis B infection
15.3.1 Accuracy of Screening Tests
The principal screening test for detecting current (acute or chronic)
HBV infection is the identification of HBsAg. Tests for HBsAg are
98% sensitive and specific for detecting chronic hepatitis B carrier5.
Spontaneous clearance of HBsAg occurs each year in 1% of persons
with chronic HBV infection.
15.3.2 Who to screen
A All pregnant women should be tested for HBsAg during the early
antenatal visit. The test may be repeated in the third trimester if acute
hepatitis is suspected, an exposure to hepatitis has occurred or the
120
woman practices a high-risk behaviour such as intravenous drug
abuse6,7.
Grade A, Level Ib
A Serological screening for HBsAg and anti-HBs should be
performed pre-vaccination for all except newborns6,7.
Grade A, Level Ib
A Persons who remain at risk of HBV infection such as health care
workers and dialysis patients should be screened using HBsAg and
anti-HBs and vaccinated against hepatitis B if the test is negative.
Such individuals should then be tested for response to the
vaccination8.
Grade A, Level Ib
B Screening high risk individuals like those with a family history of
hepatitis B infection, liver cancer or those at high behavioural risk
should be performed. They should be tested at baseline and whenever
exposure is suspected.
Grade B, Level IIa
C Routine screening for HBV infection in the general population is
not recommended but recommendations for screening may be made
based on cost-effectiveness analyses. Such analyses suggest that
screening can be cost-effective in groups with an HBV marker
prevalence >20%9.
Grade C, Level IV
15.4
Summary
In practice, screening for chronic hepatitis B infection is
recommended as part of the antenatal screening for all women. It is
also recommended for individuals engaged in high-risk activities for
acquiring hepatitis B infection. Screening for HBsAg and anti-HBs
should be performed pre-vaccination for all except newborns.
Screening for hepatitis B infection in our general population is not
recommended as the prevalence of hepatitis B infection in Singapore
is only 5-6%.
121
References
1.
Goh KT, Ding JL, Monteiro EH, et al. Hepatitis B infection in
households of acute cases. Journal of Epidemiology & Community
Health. 1985; 39:123-8.
2.
Wu G, Zhou Y, Zhao W, et al. Study on the natural history of chronic
hepatitis B.Chung Hua Kan Tsang Ping Tsa Chih. 2002; 10:46-8.
3.
Lok ASF, Lai CL. A longitudinal follow-up of asymptomatic hepatitis B
surface antigen positive Chinese children. Hepatol 1998; 5:1130-3.
4.
Chan HL, Ghany M, Lok ASF. Hepatitis B. In Schiff’s Disease of the
Liver, 8th edition. Ed. Schiff ER, Sorrell MF, Maddrey WC. LippincottRaven publishers. Philadelphia 1999.
5.
McCreedy JA, Morens D, Fields HA, et al. Evaluation of enzyme
immunoassay (EIA) as a screening method for hepatitis B markers in an
open population. Epidemiol Infect 1991; 107:673-84.
6.
American Academy of Pediatrics and American College of Obstetricians
and Gynecologists. Guidelines for perinatal care. 3rd ed, Washington DC:
American College of Obstetricians and Gynecologists. 1992.
7.
American Academy of Pediatrics. Hepatitis B. In: Peter G. ed. 1994 Red
Book: Report of the Committee on Infectious Diseases. 23rd ed. Eik
Grove Village. IL: American Academy of Pediatrics. 1994:224-38.
8.
Lok ASF, McMahon BJ. Chronic Hepatitis B. Hepatology 2001;
34:1225-41.
9.
American College of Physicians Task Force on Adult Immunization and
Infectious Diseases Society of America. Guide for adult immunization.
3rd ed. Philadelphia: American College of Physicians. 1994.
122
16
Screening for renal diseases
16.1
Introduction
At the end of May 1997, there were 1968 patients on hemodialysis
and another 340 on peritoneal dialysis in Singapore1. By December
2000, the prevalent dialysis population increased to 2830 patients with
2321 on hemodialysis and 509 on peritoneal dialysis2. The number of
new patients with end stage renal disease (ESRD) in Singapore is
about 650 patients a year and diabetes mellitus is the commonest
cause accounting for 47% of cases, followed by chronic
glomerulonephritis, which accounts for 29% and hypertensive
nephrosclerosis accounting for 9%3. The incidence and prevalence of
end stage renal disease are expected to increase unless urgent
measures are taken to rectify this. In fact, it has been reported by the
United States Renal Data System that Singapore has the third highest
ESRD incidence rate in the world4.
It is reasonable to believe that patients with end stage renal failure
represent only a small fraction of all individuals with chronic renal
disease. This is further compounded by the fact that chronic renal
insufficiency is asymptomatic and mild renal disease may often go
undiagnosed and untreated. In the United States, it has been shown
that about 10% of men and a smaller proportion of women have mild
renal insufficiency5,6. However, the exact number of people affected
in Singapore is unknown as there has been no national survey in this
regard. This is unfortunate in view of the growing number of effective
interventions available to retard the progression of renal disease and
ameliorate many of its co-morbid conditions.
16.2
Prevalence and significance of proteinuria
The Australian Diabetes, Obesity and Lifestyle (AusDiab) Study7
found proteinuria in 2.5% of the study population. A more recent US
study estimated that 1.5% of people aged 6 years and over have
proteinuria8. Locally, a cohort from the Central Man Power Base
(CMPB) screening programme was studied in the 1970’s.
Approximately 2% of young adult males who register for compulsory
national service at the age of 16 years were found to have urinary
abnormalities9. The majority of these subjects have a mild form of
123
glomerulonephritis. However, 6% did progress to end stage renal
disease over a period of 6 years10.
Proteinuria has been reported to be a potent predictor of ESRD and is
associated with a 15-fold increased risk of developing end stage renal
disease within 10 years11. Patients with greater than 1 gram
proteinuria were more likely to have progression of the disease, and
aggressive reduction of the blood pressure is beneficial12. There are
instances where proteinuria is transient and due to the upright position
(postural proteinuria). This is frequently benign. There are a number
of other events such as exercise, fever, sleep apnea, or congestive
heart failure that can transiently increase urinary protein excretion.
These factors must be considered in the evaluation of the patient.
Recent screening data using urine dipstick in Singapore have shown
that proteinuria (≥ 1+ or 30 mg/dl) was detected in 1% of the screened
young adult working population13.
16.3
Who do we need to screen
Screening for renal disease in the general population is not presently
recommended by the US Preventive Services Task Force14 and it is
believed that the types of evidence required for such a
recommendation are not available15. The Canadian Task Force on
Periodic Health Examination in its 1994 report16 also did not
recommend dipstick proteinuria screening of asymptomatic adults to
prevent progressive renal disease. The rationale then was that
effective, nontoxic therapy to arrest or slow disease progression was
not available for most renal disorders.
However, there is now good evidence that ACE inhibitors have renalprotecting properties independent of their antihypertensive effect.
ACE inhibitors reduce urinary protein excretion in both diabetic and
non-diabetic patients17,18. In addition, the results of a meta-analysis
demonstrated a 30% reduction in the relative risk of developing end
stage renal disease in patients treated with ACE inhibitors compared
with conventional antihypertensives19. More recently, the Irbesartan in
Diabetic Nephropathy Trial (IDNT)20 and Reduction of Endpoints in
NIDDM with Angiotensin II Antagonist Losartan Study (RENAAL)21
were prospective randomized controlled trials that demonstrated the
renal protective effects of angiotensin receptor blockers in patients
with Type II diabetes and nephropathy.
124
C A healthy asymptomatic individual may undergo opportunistic
screening with urine dipstick examination22.
Grade C, Level IV
The US Multiple Risk Factor Intervention Trial23 had also showed that
older age, smoking, hypertension and diabetes were significant risk
factors for end stage renal disease. Familial aggregation of renal
disease, in excess of that predicted by clustering of diabetes and
hypertension, had also been reported in a population-based casecontrol study24.
C Specific individuals at increased risk (e.g. age over 50 years,
hypertension, smoking, diabetes and family history of renal disease)
of chronic renal disease should undergo annual dipstick testing for
proteinuria25.
Grade C, Level IV
16.4
Screening tests and effectiveness
Dipstick testing for proteinuria is widely available and easily
performed by asking the person to collect a clean-catch, midstream,
and random urine specimen. It is cheap and costs about $0.50 per test.
An abnormal urine result was defined as the presence of ≥ 1+ protein
(equivalent to ≥ 30 mg/dl) as poor discrimination between negative
and trace-positive dipstick readings had been previously reported26.
The test has about 85% sensitivity and specificity25. About 15% of
people without proteinuria have a falsely positive result and those who
have a positive dipstick result should have their protein excretion rate
quantified. Measurement of the 24-hour urinary protein excretion rate
has long been the gold standard but is inconvenient, cumbersome and
expensive for the patient. Collecting a clean, mid-stream, “spot” urine
for measurement of protein or albumin-to-creatinine ratio is an
alternative method to quantitate proteinuria. Single voided urine
protein creatinine ratio provides a relatively accurate estimation of 24hour urine protein excretion27,28. However this must be done under
standardized conditions (first voided, morning clean mid-stream
sample) as there are variations in 24-hour protein excretion.
C Individuals with a positive dipstick proteinuria should have a spot
urinary protein-creatinine ratio test to quantitate their proteinuria27,28.
Grade C, Level IV
125
Most dipsticks also test the urine for blood, glucose, leukocytes or
nitrites. The presence of hematuria, especially among smokers and in
the older persons, should prompt the exclusion of a urinary tract
malignancy. The interpretation and further diagnostic steps required to
evaluate the presence of hematuria and/or proteinuria on urinalysis
have been discussed in a previous set of Clinical Practice Guidelines
on Glomerulonephritis29. The frequency of isolated dipstick
haematuria (≥1+) has been reported to be 9% of young adults13.
Serum creatinine can be used as a crude marker for glomerular
filtration rate and is easily available. Dietary intake, total muscle mass
and certain medication may interfere with renal creatinine excretion.
This may, therefore, make it difficult to detect patients in earlier
stages of chronic renal disease30. In a study of patients with chronic
renal disease, it was noted that at least 50% reduction in glomerular
filtration rate was needed before a rise in serum creatinine above the
normal levels (defined as > 123 µmol/l)31 occurred.
The prevalence of elevated creatinine (>132 µmol/l in man and >123
µmol/l in woman) has been estimated at around 8-9% for both males
and females5. However, a much larger study, the Third National
Health and Nutritional Examination Survey (NHANES III), reported
that in the total US population, 9.7% of males and 1.8% of females
have a creatinine level of ≥ 132 µmol/l (about 10.9 million people)6.
The presence of hypertension has been associated with elevated serum
creatinine32. High diastolic blood pressure has been identified as a
significant predictor of ESRD in a screened population33. Screening
for hypertension (≥ 140/90 mmHg) and control of blood pressure may
retard the progression of renal disease12.
C Individuals at increased risk of developing chronic renal disease
should undergo testing of serum creatinine in order to estimate the
glomerular filtration rate34.
Grade C, Level IV
16.5
Summary
Previously, universal screening was not recommended because of the
lack of treatments to improve outcomes and the prevalence of chronic
renal disease was much lower. There is now good evidence to suggest
126
that the prevalence of earlier stages of chronic renal disease is higher
than previously known and earlier detection would allow institution of
treatment to prevent or delay the progression of renal disease.
References
1.
Woo KT, Lee GSL. First Report of the Singapore Renal Registry 1997,
Singapore, Continental Press, 1998.
2.
Woo KT. Final End of Term Report from National Committee on Renal
Care, Singapore, 2001.
3.
Woo KT. Chairman, National Committee on Renal Care, personal
communication.
4.
United States Renal Data System: International comparisons of ESRD
therapy. In: USRDS 1999 Annual Data Report, Bethesda, MD, National
Institutes of Health, National Institute of Diabetes and Digestive and
Kidney Diseases 1999; 173-84.
5.
Culleton BF, Larson MG, Evan JC, et al. Prevalence and correlates of
elevated serum creatinine levels: The Framingham Heart Study. Arch
Intern Med 1999;159:1785-90.
6.
Jones CA, McxQuillan GM, Kusek JW, et al. Serum creatinine levels in
the US population: Third National Health and Nutrition Examination
Survey. Am J Kidney Disease; 32: 992-9.
7.
Diabesity and associated disorders in Australia – 2000: the accelerating
epidermic. Final report of the Australian Diabetes, Obesity and Lifestyle
Study. Melbourne: International Diabetes Institute, 2001.
8.
Jones CA, Francis ME, Eberhardt MS, et al. Microalbuminuria in the US
population: third National Health and Nutrition Examination Survey. Am
J Kidney Disease 2002; 39: 445-59.
9.
Pwee HS et al. Clinical aspects of asymptomatic hematuria and
proteinuria. Ann Acad Med Singapore 1975; 4:7-10.
127
10. Pwee HS et al. Clinical course of asymptomatic hematuria and
proteinuria – a six year study. In: Proceedings of 3rd Colloquium in
Nephrology, Toyko, 1979; 20-7.
11. Iseki K, Iseki C, Ikemiya Y, et al. Risk of developing end-stage renal
disease in a cohort of mass screening. Kidney Int 1996; 49:800-5.
12. Peterson JC, Adler S, Burkart JM, et al. Blood pressure control,
proteinuria, and the progression of renal disease. The Modification of
Diet in Renal Disease Study. Ann Intern Med 1995; 123:754-62.
13. Ramirez SPB, McClellan W, Port FK, et al. Risk factors for proteinuria in
a large, multiracial, SouthEast Asian population. J Am Soc Nephrol 2002;
13:1907-17.
14. US Preventive Services Task Force: Guide to Clinical Preventive
Services, 2nd Edition, Rockville, MD, US Preventive Services Task Force,
1996.
15. Harris RP, Helfand M, Woolf SH,et al., for the Methods Work Group,
Third US Preventive Services Task Force: Current methods of the US
Preventive Services Task Force: A review process. Am J Prev Med 2001;
20 (Sppl 3):21-35.
16. Nagai R, Wang EEL, Feldman W. Dipstick proteinuria screening of
asymptomatic adults to prevent progressive renal disease. In: Canadian
Task Force on the Periodic Health Examination. Canadian Guide to
Clinical Preventive Health Care. Ottawa: Health Canada, 1994; 436-45.
17. Lewis EJ, Hunsicker LG, Bain RP, et al., for the Collaborative Study
Group. The effect of angiotensin-converting enzyme inhibition on
diabetic nephropathy. N Engl J Med 1993; 329:1456-62.
18. The GISEN Group. Randomized placebo-controlled trial of effect of
ramipril on decline in glomerular filtration rate and risk of terminal renal
failure in proteinuric, non-diabetic nephropathy. Lancet 1997; 349:185763.
19. Giatras I, Lau J, Levey AS for the Angiotensin-Converting-Enzyme
Inhibition and Progressive Renal Disease Study Group. Effect of
angiotensin-converting enzyme inhibitors on the progression of
128
nondiabetic renal disease: a meta-analysis of randomized trials. Ann
Intern Med 1997; 127:337-45.
20. Lewis EJ, Hunsicker LG, Clarke WR, et al for the Collaborative Study
Group. Renoprotective effect of the angiotensin-receptor antagonist
irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J
Med 2001; 345:851-60.
21. Brenner BM, Cooper ME, de Zeeuw D, et al for the RENAAL Study
Investigators. Effects of losartan on renal and cardiovascular outcomes in
patients with type 2 diabetes and nephropathy. N Engl J Med 2001;
345:861-79.
22. Keane WF, Eknoyan G for the Committee. Proteinuria, albuminuria, risk,
assessment, detection, elimination (PARADE): A Position Paper of the
National Kidney Foundation. Am J Kidney Dis 1999; 33:1004-10.
23. Klag MJ, Whelton PK, Randall BL, et al. End–stage renal disease in
African-American and white men: 16-year MRFIT findings. JAMA 1997;
277:1293-8.
24. Lei HH, Perneger TV, Klag MJ, et al. Familial aggregation of renal
disease in a population-based case-control study. J Am Soc Nephrol
1998; 9:1270-6.
25. Cass A. Kidney disease: are you at risk? Med J Aus 2002; 176: 515-6.
26. Harrison NA, Rainford DJ, White GA, Cullen SA, Strike PW:
Proteinuria: What value is the dipstick? Br J Urol 1989; 63: 202-8.
27. Ginsberg JM, Chang BS, Matarese RA, et al. Use of single voided urine
samples to estimate quantitative proteinuria. N Engl J Med 1983;
309:1543-6.
28. Schwab SJ, Christensen RL, Dougherty K, et al. Quantitation of
proteinuria by use of protein-to-creatinine ratios in single urine samples.
Arch Intern; 147:943-4.
29. Clinical Practice Guidelines: Glomerulonephritis. MOH Clinical Practice
Guidelines 6/2001. Singapore, 2001.
129
30. Perrone RD, Madias NE, Levey AS. Serum creatinine as an index of
renal function: new insights into old concepts. Clin Chem 1992; 38:
1933-1953.
31. Shemesh O, Golbetz H, Kriss JP, et al. Limintations of creatinine as a
filtration marker in glomerulopathic patients. Kidney Int. 1985; 28:830-8.
32. Coresh J, Wei GL, McQuillan G, et al. Prevalence of high blood pressure
and elevated serum creatinine level in United States: Findings from the
Third National Health and Nutrition Examination Survey (1988-1994).
Arch Intern Med 2001; 161:1207-16.
33. Iseki K, Ikemiya Y, Fukiyama K. Blood pressure and risk of end-stage
renal disease in a screened cohort. Kidney Int 1996; 55:S69-71.
34. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease:
Evaluation, classification and stratification. Am J Kidney Dis 2002; 39:
S72-5.
130
17
Screening for osteoporosis
This guideline on osteoporosis screening complements the Ministry of
Health Clinical Practice Guidelines 2/2002 on Osteoporosis.
17.1
Introduction
Fractures are the most serious complication of osteoporosis, and
constitute an evolving public health problem in terms of disability,
mortality and cost in Singapore as in the rest of Asia where the
population is ageing rapidly1. The incidence of all osteoporotic
fractures, such as forearm2, vertebral2,3 and hip fracture, increases with
age2-4. The incidence of fragility fractures is higher in women than in
men, for any given age2,3.
The age-adjusted hip fracture incidence rates in men and women in
Singapore above the age of 50 years have risen 1½-fold and 5-fold
respectively since the 1960s4, and are among the highest in Asia. Hip
fractures in Singapore have been associated with a mortality of 20% at
two years5. Of the survivors, 20% became semi- or fully dependent,
42% became less or non-ambulant, and only 8% were cared for by
chronic health care facilities suggesting that the main social and
economic burden was borne by the families of those affected.
Vertebral fractures are also associated with significant complications
including back pain, height loss, kyphosis and limitation of activity6,
and increased mortality3.
17.2
Definition
Bone mineral density (BMD) is currently central to the diagnosis of
osteoporosis in the absence of a fracture7. An individual experiencing
a fragility fracture (fracture due to minimal trauma, such as after fall
from standing height or less) also has osteoporosis, regardless of bone
density. Operationally, osteoporosis is defined as a value for BMD
that is 2.5 standard deviations or more below the mean value in young
adults (T-score ≤ –2.5 SD)8.
The problem of osteoporosis can be approached in several ways.
Firstly, a population-based strategy addresses lifestyle issues such as
good nutrition, exercise, and avoidance of smoking and alcohol abuse
in an attempt to improve the overall health of the population, although
there is little evidence about the effect of changing these behaviours
131
on fracture risk. Secondly, a high-risk strategy, targets interventions at
individuals at high risk for osteoporosis either by screening (where
those who meet set criteria are evaluated) or case-finding (where those
who have risk factors are evaluated).
C Although the definition of osteoporosis is based on BMD, it is not
advisable to screen BMD in the whole population since BMD
measurements are costly, and the cost-benefit or cost-effectiveness of
such a strategy has not been demonstrated7,9. There is no cheap, easily
available screening test for the detection of osteoporosis. Hence, the
emphasis should be on proper selection of individuals for diagnostic
BMD testing, preferably guided by the presence of risk factors for
osteoporosis in a case-finding approach7,9.
Grade C, Level IV
17.3
a.
Screening tests and effectiveness
Bone Mineral Density
In recent years, several techniques have been available for the
measurement of BMD10. Prospective studies have shown that the risk
of fracture increases progressively with decreasing BMD, the gradient
of risk varying according to the measurement site and technique
used11.
i.
Dual-energy x-ray absorptiometry (DXA) of hip and spine
DXA measurements at the unfractured or non-dominant hip fulfill the
role of a ‘gold standard’ for diagnosing osteoporosis, having the best
overall predictive value for hip fractures and other osteoporotic
fractures, and having been validated against fracture risk in many
prospective studies9,12. The lumbar spine (anteroposterior projection)
is the preferred site for monitoring therapeutic response since in most
trials, the largest changes in BMD with treatment have occurred at this
site13.
ii. Single energy X-ray absorptiometry (SXA) and DXA of
forearm or heel (peripheral)
iii. Quantitative ultrasound (QUS) of the heel or tibia
iv. Quantitative computed tomography (QCT) of the spine
132
The advantages of the peripheral systems and QUS are small size,
portability, low or absent radiation exposure, ease of operation,
shorter scan times and lower cost. QUS correlates fairly well with
DXA and predicts fracture risk independently of DXA14. The use of
QCT as a screening tool has not been well investigated8, and it has a
relatively higher radiation dose10.
Current status of different BMD techniques:
Current BMD measurement techniques have different degrees of
precision errors (1-4%) and accuracy errors (2-15%), and this is a
limitation in the use of these techniques12. Concordance of BMD
measurements between different sites and techniques has been poor12.
Heterogeneity exists between skeletal sites, in that low BMD at one
site does not necessarily confirm low BMD at another15. T-scores at
different sites and with different techniques yield different
information on fracture risk, and are not interchangeable16.
The role of central DXA (hip and spine) in diagnosis and therapeutic
monitoring is well-established, and should remain the method of
choice for measuring BMD. There is emerging data that peripheral
bone densitometry measurements using DXA, SXA and QUS (Tscores ≤ –2.5 SD) may be useful for the diagnosis of osteoporosis17.
However, peripheral techniques have not been used as entry criterion
in osteoporosis intervention trials, and it is uncertain if therapies are
beneficial in women using these techniques to diagnose osteoporosis7.
Their role in monitoring response to therapy appears limited18,19.
b. Biochemical Markers of Bone Turnover
There is currently no role for bone turnover markers in the diagnosis
of osteoporosis. Biochemical indices of bone turnover have the
potential of aiding in fracture risk assessment and predicting rates of
bone loss, and have been used in monitoring the response to
treatment9, 20.
17.4
a.
Age and gender for screening
C All individuals with prior fragility fractures during adulthood
should be considered for BMD measurement and osteoporosis
treatment.
Grade C, Level IV
133
b. Postmenopausal women
C Several clinical evaluation tools have been developed to assist in
the case-finding strategy for detecting osteoporosis21-25, all of which
perform similarly. BMD should be measured in individuals at highest
risk for osteoporosis identified using such tools.
Grade C, Level IV
The US National Osteoporosis Foundation (NOF) guidelines, which
use an age criterion, has recommended BMD testing in all women
over the age of 65 years21, and in postmenopausal women under 65
years of age with risk factors for hip fracture independent of bone
density, including history of previous fracture as an adult, family
history of fracture, body weight <57 kg or current cigarette smoking.
It is not yet clear if these criteria are applicable to Asians.
C The Osteoporosis Self-assessment Tool for Asians (OSTA), which
is based on age and weight, categorises postmenopausal Asian women
into high, moderate and low risk of having osteoporosis on subsequent
BMD measurement22, and may be used as a basis for case-finding
(Tables 5, 6 and 7).
Grade C, Level IV
TABLE 5: Osteoporosis Self-Assessment Tool for Asians
(OSTA)
Age
(yr)
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85-89
40-44
45-49
50-54
Weight (kg)
55-59
60-64
65-69
70-74
75-79
Low Risk
Moderate Risk
High Risk
Copyright 2001, MSD, Whitehouse Station, NJ, USA. All rights reserved. Reproduced with
permission.
134
TABLE 6: Approximate calculation method to categorize
osteoporosis risk from OSTA, and recommended action based on
OSTA risk category
Osteoporosis
Risk
Estimated %
with
osteoporosis22
High
44 – 61
Approximate
Calculation :
Age (yr) minus
Weight (kg)
> 20
Moderate
10 - 15
0 – 20
Low
1-3
<0
*
Recommended Action
Recommend BMD
measurement.
Evaluate for risk factors*
(Table 7), and measure BMD
if these are present.
Osteoporosis prevalence is
low. Can defer BMD unless
has past fragility fracture or
has condition known to be
associated with osteoporosis.
The number of risk factors for osteoporosis which should be present in an individual to
improve the likelihood of detecting osteoporosis in this category remains unclear.
TABLE 7: Risk factors for low bone mass for which BMD
measurement might be considered
Non-modifiable
•
Personal history of previous fracture as an adult
•
History of fracture in a first degree relative (especially maternal)
•
Low body weight & older age
Potentially Modifiable
•
Current cigarette smoking
•
Alcohol abuse (stronger data in men)
•
Early natural or surgical menopause before age 45 years, or prolonged
premenopausal amenorrhea lasting > 1 year
•
Drugs e.g. corticosteroids (equivalent to prednisolone > 7.5 mg/day for
more than 6 months), excess thyroxine, anticonvulsants
•
Ongoing disease conditions e.g. hypogonadism, hyperthyroidism,
hyperparathyroidism, Cushing’s syndrome, chronic obstructive airways
disease, liver disease, malabsorption, chronic renal failure, rheumatoid
arthritis, organ transplantation and anorexia nervosa
•
Prolonged immobilization, poor health or frailty
•
Lifelong low calcium intake (< 500 mg/day among Asians)
•
Lack of regular physical activity
135
Other indications for measuring bone density7,9
C The following are other indications for measuring bone density:
1.
2.
3.
Radiological evidence of osteopenia or vertebral deformity
Women who are considering therapy for osteoporosis, if BMD
testing would facilitate the decision to initiate therapy
Monitoring of treatment
Grade C, Level IV
c.
Premenopausal women
C Screening for osteoporosis in premenopausal women is not
recommended7,9. There are very few recognised interventions for
premenopausal women with osteoporosis. Nevertheless, BMD
measurement may be considered in those with significant risk factors
for fracture.
Grade C, Level IV
d. Men
C There is as yet no recommendation for screening of osteoporosis
in men. There is an unresolved controversy with regard to deriving
the T-scores using 2.5 SD or more below the mean for young
women12, or for young men26 as the diagnostic threshold for
osteoporosis in men. The relationship between risk factors and
osteoporosis and fractures in men is less well-studied. Established
interventions for men with osteoporosis are few. Measuring BMD in
those with significant risk factors for osteoporosis is a reasonable
strategy.
Grade C, Level IV
e.
Patients on long-term corticosteroid therapy
In the context of corticosteroid-induced osteoporosis, a higher
incidence of fractures has been observed, with fractures appearing to
occur at higher BMDs27. Clinical risk factors for steroid-associated
fractures include low bone density, cumulative steroid dose, age, low
body weight, smoking, diseases associated with low bone density such
as rheumatoid arthritis, sex hormone deficiency in both sexes, a
family history of osteoporosis28, and probably a prior history of
fracture and immobilization.
C It would be reasonable to consider patients scheduled for, or
already on, long-term (>6 months), higher-dose (>7.5 mg/day)
136
corticosteroid therapy with clinical risk factors for steroid-associated
fractures, for BMD measurement at baseline and after an interval of 6
months to a year to detect bone loss29. It has been suggested that a Tscore of -1.5 SD or below at the femoral neck and/or spine be used as
the intervention threshold for corticosteroid-induced osteoporosis30.
Grade C, Level IV
17.5
Frequency of screening
Women with osteoporosis, who are being monitored for progression
or who are being treated, should have a follow-up bone density
measurement, usually at an interval of at least one year. The
anteroposterior lumbar spine measurement would usually show the
more obvious changes with treatment, but in the elderly where
spurious elevations of spine BMD may occur, e.g. from lumbar facet
joint osteoarthritis or aortic calcification, the hip measurement may be
more reliable for monitoring treatment response.
C In women with osteopenia (BMD between 1 and 2.5 S.D. below
the mean peak bone mass of young adults) a reasonable interval for a
follow-up BMD might be 1 to 2 years, while in those with normal
BMD (more than -1 S.D. below the mean peak bone mass of young
adults) a more reasonable interval may be 2 to 5 years9.
Grade C, Level IV
17.6
Other relevant information
There are several limitations with BMD measurements. There have
been few controlled trials on whether women who receive bone
density screening have better outcomes in terms of fewer fractures
than women who are not screened. Although BMD remains the best
method of detecting and diagnosing osteoporosis, a significant
number of women with osteoporosis do not fracture, and conversely,
a significant number of women with fragility fractures do not have
low bone density.
Nevertheless, there is emerging data that BMD measurement has
some advantages. It has been found that treatment of individuals after
fragility fractures remains inadequate31,32. However, BMD
measurements appear to have resulted in modifications of
137
lifestyle33,34, and improved treatment initiation rates35,36. The effects
of these on overall fracture rates remains to be determined.
17.7
Summary
C All individuals with prior fragility fractures during adulthood
should be considered for BMD measurement and osteoporosis
treatment.
Grade C, Level IV
C Population screening using BMD is not recommended for
postmenopausal women. A case-finding strategy is preferred,
measuring BMD in individuals at highest risk for osteoporosis
identified using clinical evaluation tools such as OSTA or NOF
guidelines, and clinical risk factor evaluation.
Grade C, Level IV
C Women with osteoporosis, who are being monitored for
progression or who are being treated, should have a follow-up bone
density measurement, usually at an interval of at least one year. In
women with osteopenia, a reasonable interval might be 1 to 2 years,
while in those with normal BMD, a more reasonable interval may be 2
to 5 years.
Grade C, Level IV
C Screening is not recommended for premenopausal women and
men. BMD measurement should be considered in those at high risk
for fracture.
Grade C, Level IV
C BMD measurement should be considered in patients with high risk
for steroid-associated fractures, who are initiating or already on longterm higher-dose corticosteroid therapy.
Grade C, Level IV
138
References
1.
Gullberg B, Johnell O, Kanis JA. World-wide projections for hip
fracture. Osteoporos Int 1997; 7:407-13.
2.
Riggs BL, Melton LJ III. Involutional osteoporosis. N Engl J Med 1986;
314:1676-86.
3.
Center J, Nguyen T, Schneider D, et al. Mortality after all major types of
osteoporotic fracture in men and women: an observational study. Lancet
1999; 353:878-82.
4.
Koh LKH, Saw SM, Lee JJM, et al. Hip fracture incidence rates in
Singapore 1991-1998. Osteoporos Int 2001; 12:311-8.
5.
Mitra AK, Low CK, Chao AK, et al. Social aspects in patients following
proximal femoral fractures. Ann Acad Med Singapore 1994; 23:876-8.
6.
Ross P. Clinical consequences of vertebral fractures. Am J Med 1997;
103:30S-42S; discussion 42S-3S.
7.
NIH Consensus Development Panel on Osteoporosis prevention,
diagnosis, and therapy. JAMA 2001; 285:785-95.
8.
Assessment of fracture risk and its application to screening for
postmenopausal osteoporosis. Report of a WHO Study Group. World
Health Organ Tech Rep Ser 1994; 843:1-129.
9.
National Osteoporosis Foundation. Osteoporosis: review of the evidence
for prevention, diagnosis and treatment and cost-effectiveness analysis.
Osteoporos Int 1998; 8:S1-80.
10. Genant HK, Engelke K, Fuerst T, et al. Noninvasive assessment of bone
mineral and structure: state of the art. J Bone Miner Res 1996; 11:70730.
11. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of
bone mineral density predict occurrence of osteoporotic fractures. BMJ
1996; 312:1254-9.
139
12. Kanis J, Gluer C. An update on the diagnosis and assessment of
osteoporosis with densitometry. Committee of Scientific Advisors,
International Osteoporosis Foundation. Osteoporos Int 2000; 11:192202.
13. Hochberg MC, Greenspan S, Wasnich RD, et al. Changes in bone
density and turnover explain the reductions in incidence of nonvertebral
fractures that occur during treatment with antiresorptive agents. J Clin
Endocrinol Metab 2002; 87:1586-92.
14. Bauer D, Gluer C, Cauley J, et al. Broadband ultrasound attenuation
predicts fractures strongly and independently of densitometry in older
women. A prospective study. Study of Osteoporotic Fractures Research
Group. Arch Intern Med 1997; 157:629-34.
15. Davis J, Ross P, Wasnich R. Evidence for both generalized and regional
low bone mass among elderly women. J Bone Miner Res 1994; 9:305-9.
16. Faulkner KG, Von Stetten E, Miller P. Discordance in patient
classification using T-scores. J Clin Densitom 1999; 2:343-50.
17. Siris E, Miller P, Barrett-Connor E, et al. Identification and fracture
outcomes of undiagnosed low bone mineral density in postmenopausal
women: results from the National Osteoporosis Risk Assessment. JAMA
2001; 286:2815-22.
18. Drake WM, Brown JP, Banville C, et al. Use of phalangeal bone mineral
density and multi-site speed of sound conduction to monitor therapy with
alendronate in postmenopausal women. Osteoporos Int 2002; 13:249-56.
19. Gonnelli S, Cepollaro C, Montagnani A, et al. Heel ultrasonography in
monitoring alendronate therapy: a four-year longitudinal study.
Osteoporos Int 2002; 13:415-21.
20. Delmas P, Eastell R, Garnero P, et al. The use of biochemical markers of
bone turnover in osteoporosis. Committee of Scientific Advisors of the
International Osteoporosis Foundation. Osteoporos Int 2000; 11:S2-17.
21. Physician's guide to prevention and treatment of osteoporosis.
Washington D.C.: National Osteoporosis Foundation, 1998.
140
22. Koh LKH, Ben Sedrine WB, Torralba TP, et al. A simple tool to identify
Asian women at increased risk of osteoporosis. Osteoporos Int 2001;
12:699-705.
35. Weinstein L, Ullery B. Identification of at-risk women for osteoporosis
screening. Am J Obstet Gynecol 2000; 183:547-9.
24. Lydick E, Cook K, Turpin J, et al. Development and validation of a
simple questionnaire to facilitate identification of women likely to have
low bone density. Am J Manag Care 1998; 4:37-48.
25. Cadarette S, Jaglal S, Kreiger N, et al. Development and validation of
the Osteoporosis Risk Assessment Instrument to facilitate selection of
women for bone densitometry. CMAJ 2000; 162:1289-94.
26. Orwoll E. Assessing bone density in men. J Bone Miner Res 2000;
15:1867-70.
27. Eastell R, Reid D, Compston J, et al. A UK Consensus Group on
management of glucocorticoid-induced osteoporosis: an update. J Intern
Med 1998; 244:271-92.
28. Michel B, Bloch D, Wolfe F, et al. Fractures in rheumatoid arthritis: an
evaluation of associated risk factors. J Rheumatol 1993;20:1666-9.
29. Recommendations for the prevention and treatment of glucocorticoidinduced osteoporosis: 2001 update. American College of Rheumatology
Ad Hoc Committee on Glucocoritcoid-Induced Osteoporosis. Arthritis
Rheum 2001; 44:1496-503.
30. Compston J, Audran M, Avouac B, et al. Recommendations for the
registration of agents used in the prevention and treatment of
glucocorticoid-induced osteoporosis. Calcif Tissue Int 1996;59:323-7.
31. Cuddihy MT, Gabriel SE, Crowson CS, et al. Osteoporosis intervention
following distal forearm fractures: a missed opportunity? Arch Intern
Med 2002; 162:421-6.
32. Bellantonio S, Fortinsky R, Prestwood K. How well are communityliving women treated for osteoporosis after hip fracture? J Am Geriatr
Soc 2001; 49:1197-204.
141
33. Rolnick SJ, Kopher R, Jackson J, et al. What is the impact of
osteoporosis education and bone mineral density testing for
postmenopausal women in a managed care setting? Menopause 2001;
8:141-8.
34. Marci CD, Anderson WB, Viechnicki MB, et al. Bone mineral
densitometry substantially influences health-related behaviors of
postmenopausal women. Calcif Tissue Int 2000; 66:113-8.
35. Fitt NS, Mitchell SL, Cranney A, et al. Influence of bone densitometry
results on the treatment of osteoporosis. CMAJ 2001; 164:777-81.
36. Pressman A, Forsyth B, Ettinger B, et al. Initiation of osteoporosis
treatment after bone mineral density testing. Osteoporos Int 2001;
12:337-42.
142
18
Screening for visual acuity for the elderly
18.1
Introduction
Vision problems are common and potentially serious amongst older
people, and lead to an increased risk of falls and accidents.
The most common causes of visual impairment amongst the elderly
include cataract, uncorrected refractive errors, presbyopia, age-related
macular degeneration, diabetic retinopathy and glaucoma1.
18.2
Age and gender for screening
In the elderly, screening and the correction of correctable visual
problems lead to a restoration of vision and subjective improvements
in a variety of vision-related functions, as well as improvements in
objective measures of physical and intellectual function.
Vision problems are more likely in persons over 65 years, and they are
more likely to lead to serious consequences such as accidental
injuries.
Routine screening with visual acuity testing in people over 65 years
leads to improvements in measured visual acuity.
There is little chance that the screening method will lead to any harm2.
18.3
Screening test and effectiveness
B The population to be screened includes any person age 65 years and
above, and the screening test involves using a Snellen chart to test
each eye2.
Grade B, Level III
Asking screening questions about visual function has yielded mixed
results when compared to the use of a Snellen acuity chart. The
question “Do you have difficulty seeing distant objects?” had a
sensitivity of 28% in detecting visual acuity worse than 6/12 3.
Poor vision can be easily detected by the use of a Snellen chart.
Ophthalmoscopy can be used to detect ocular media opacities like
143
cataracts. However, there is little data on the sensitivity and specificity
of these examinations in both healthcare and community settings.
B Any person screened and found to have vision worse than 6/12 can
be referred for assessment and treatment2.
Grade B, Level III
18.4
Frequency of screening
C The optimal frequency for screening is not known and is left to the
discretion of the screener2.
Grade C, Level IV
18.5
Other relevant information
C Besides visual acuity testing using the Snellen chart, there is
insufficient evidence to recommend for or against routine screening
with ophthalmoscopy by the primary care physician in an
asymptomatic elderly patient2.
Grade C, Level IV
18.6
Summary
Routine vision screening using Snellen chart acuity testing is
recommended for those 65 years and above. The test is fairly
objective and more useful than asking about visual function.
References
1.
American Academy of Ophthalmology: Comprehensive adult eye
evaluation, preferred practice pattern. San Francisco: American Academy
of Ophthalmology 1996.
2.
USPSTF “Guide to Clinical Preventive Services” Recommendations Screening for visual impairment. 2nd edition; 1996.
3.
Stone DH, Shannon DJ. Screening for impaired visual acuity in middle
age in general practice. BMJ 1978; 2:859-61.
144
19
Screening for sexually transmitted infection
19.1
Introduction
The control and prevention of sexually transmitted infections (STI)
remains a major global public health problem. STI can result in
unnecessary human suffering and financial cost. Some STI can be
cured, but for others, there is no effective treatment. All STI, however,
can be prevented and therefore health education, prevention and
screening programmes play an important role in STI control.
There has been a change in the trends of STI in Singapore over the
last two decades1. Important advances in medicine, particularly the
development of antibiotics, have resulted in effective treatment for
several bacterial STI. Increasing public awareness and health
education programmes have been introduced to prevent STI
transmission. In addition, the HIV pandemic has influenced social and
sexual behaviour to a certain extent. On the other hand, increasing
affluence and globalisation of the economy result in increased travel
and high-risk behaviour.
19.2
Screening for chlamydia trachomatis infection
Chlamydia trachomatis is a major cause of urethritis in men and
cervicitis and pelvic inflammatory disease (PID) in women. It can lead
to sequelae of ectopic pregnancy and infertility. In Singapore, a case
control longitudinal study of 100 subfertile women in a tertiary
teaching hospital revealed an 8% prevalence of genital Chlamydia
trachomatis infection, with the highest incidence in women aged
below 25 years old2. The authors suggested routine screening for
chlamydial infection for subfertile couples, especially if patients are in
the younger age group. In the DSC Clinic, 46% of chlamydial
infections in females were detected in those under 25 years of age.
19.2.1 Screening women
Women and adolescents through age 20 years are at highest risk for
chlamydial infection. However, most reported data indicate that
infection is prevalent among women aged 20-25 years. Age is the
most important risk factor, and continues to be the best predictor of
145
chlamydial infection in young women, with most studies evaluating
cut-offs at age younger than 25 years3.
The US Preventive Services Task Force (USPSTF) strongly
recommends that clinicians routinely screen all sexually active women
aged 25 years and younger and other asymptomatic women at
increased risk for infection, for chlamydia3.
The Centers for Disease Control and Prevention (CDC) also uses age
as the primary determinant for screening. It recommends at least
annual screening for sexually active women aged 20-24 years who
meet either of the following criteria: inconsistent use of a barrier
contraceptive or more than one sexual partner during the last 3
months4.
The UK National guidelines identify age less than 25 years, a new
sexual partner or more than one sexual partner in the recent past, lack
of barrier contraception, the use of the oral contraceptive pill and
women undergoing termination of pregnancy as risk factors for
chlamydial infection5.
The Expert Advisory Group for the Chief Medical Officer in the UK
recommends that clinicians should consider opportunistic screening of
any woman undergoing instrumentation of the uterus because even in
low prevalence groups there may be a resultant risk of ascending
infection6. It also recommends that screening for chlamydial infection
be undertaken in the following clinical scenarios: women presenting
with pelvic inflammatory disease (PID), mucopurulent cervicitis,
vaginal discharge and lower abdominal pain; men presenting with
urethral discharge, epididymitis, non-specific urethritis and reactive
arthritis, and in infants and parents of infants with ophthalmia
neonatorum or neonatal pneumonitis. It is suggested that patients
attending STD clinics, as well as their partners, should be targeted for
screening as they represent high-risk groups.
The strongest evidence supporting screening is a well-designed
randomized trial in Seattle which demonstrated that screening women
at risk (prevalence of infection 7%) reduced the incidence of PID from
28 per 1000 woman-years to 13 per 1000 woman-years7. In addition,
two ecological analyses in Sweden reported reductions in ectopic
pregnancy and PID with the advent of community-based screening for
chlamydial infection8, 9 .
146
A Sexually active women with the following risk factors may be at
higher risk of chlamydial infection and should be considered for
screening: those aged 25 years and younger, who have a new sexual
partner, who have partners with symptoms of an STI or who have had
two or more partners in the past 12 months and lack the use of barrier
contraception.
Grade A, Level Ib
A Women undergoing termination of pregnancy with risk factors (as
above) should be screened.
Grade A, Level Ib
C Women undergoing instrumentation of the uterus should be
considered for screening on an individual case basis because even in
low prevalence groups, there may be a resultant risk of ascending
infection.
Grade C, Level IV
The optimal interval for screening is uncertain. For women with a
previous negative screening test, the interval for re-screening should
take into account changes in sexual partners. Re-screening at 6 to 12
months may be appropriate for previously infected women because of
high rates of reinfection.
19.2.2 Screening pregnant women
There is evidence from 3 separate studies at the University of
Washington, each involving a different study design, that links
antenatal chlamydial infection with prematurity, defined by preterm
delivery, and/or low birth weight10-12.
B Pregnant women aged 25 years and younger and other pregnant
women at higher risk for infection (i.e. women who have had two or
more sexual partners in the past 12 months, or partners with
symptoms of an STI) should be considered for screening.
Grade B, Level IIb
The optimal timing of screening in pregnancy is uncertain. Screening
early in pregnancy provides greater opportunity to improve pregnancy
outcomes, but screening in the third trimester may be more effective
at preventing transmission of chlamydial infection to the newborn.
147
There is little evidence regarding the effectiveness of screening
asymptomatic pregnant women who are not in high-risk groups.
19.2.3 Screening men
There is no data on established guidelines for screening men, and no
data regarding aged-based recommendations on screening in men.
C Asymptomatic men with high-risk behaviour such as frequent
partner change, lack of use of barrier protection or sex with prostitutes
can be considered for screening. These patients should be referred to
specialist centres for counselling, and investigation13.
Grade C, level IV
GPP In men, a Gram-stained urethral smear taken 4 hours from the
last void of urine showing presence of 5 or more leukocytes per highpower field indicates urethritis. This may be due to Chlamydia
trachomatis or other organisms, as well as other factors that may not
be sexually transmitted. These patients should be assessed by
specialist centres for counselling and advice.
GPP
19.2.4 Screening methods
A number of tests are available to identify chlamydial infection that
uses endocervical or urethral swab specimens and urine specimens.
Until recently, culture has been accepted as the most specific test but
it requires specialized handling and laboratory services.
A Screening can be performed using cultures or enzyme
immunoassays (EIA) on endocervical swabs in women and urethral
swabs in men3,4,7.
Grade A, Level Ia
At present the chlamydia culture test is not done by any laboratory in
Singapore. Antigen detection tests such as enzyme immunoassay
(EIA) can be used. It is inexpensive but has a sensitivity of between
70-80% only, although specificity remains high (96-100%).
A Nucleic acid amplification tests (NAAT) using polymerase chain
reaction (PCR) or ligase chain reaction (LCR) can also be used in
148
screening on endocervical or urethral swabs, and have the advantage
of being used on non-invasive specimens such as urine.
Grade A, Level Ia
The sensitivities and specificities of NAAT are all high, ranging from
82-100%14. NAATs perform equally well on endocervical, urethral
swabs and urine samples15. However, as obtaining an invasive sample
is likely to deter asymptomatic individuals, urine testing offers
considerable advantages. These tests are much more costly though.
LCR and PCR testing requires dedicated equipment, air conditioned
rooms and experienced staff to run effectively and it is unlikely to be
cost effective for all laboratories to offer such a testing service15.
Local agreement on testing methods and how to organize testing is
required to ensure effective use of resources. Although urine testing
offers considerable advantages for asymptomatic populations, it may
not be the most appropriate or cost effective procedure for all
situations. In situations where visualization of the cervix is required as
part of the medical examination, obtaining an endocervical swab
would probably be more appropriate.
The actual prevalence of chlamydial infections among the local
population has not been studied. Appropriate screening strategies need
to take into account the characteristics of the patient population to
further identify risk groups. More local epidemiological studies should
be performed. It is important to ensure high validity for any test used
in low prevalence populations as incorrect results may have serious
consequences for the individuals concerned. Therefore antigen
detection as well as NAAT methods can be used for screening,
depending on resources available and populations tested.
C Serological tests based on genus-specific complement fixation test
are not useful in the diagnosis of chlamydial genital infections, with
the possible exception of lymphogranuloma venereum16.
Grade C, Level IV
GPP The optimal frequency of screening is a matter of clinical
discretion. Screening for chlamydia infection should be performed
about 1 week after high-risk exposure or change of sex partner.
GPP
149
19.3
Screening for syphilis
Syphilis is caused by infection with the bacterium Treponema
pallidum, which can be transmitted congenitally or by sexual contact.
In 2001, there were 159 cases of infectious syphilis, 798 cases of noninfectious syphilis, and 4 cases of congenital syphilis notified in
Singapore. Infectious syphilis comprises primary and secondary
syphilis and early latent syphilis, which is defined as a period of 1
year from acquisition of infection. The incidence of infectious and
non-infectious syphilis has shown a steady decline over the past 2
decades. This is also reflected in the decline in number of cases of
congenital syphilis, with 20 cases detected in 1978, to 4 cases last
year. Congenital syphilis can result in fetal or perinatal death, as well
as an increased risk of medical complications in surviving newborns17.
19.3.1 Screening men and women
Early detection of syphilis in asymptomatic persons permits the
initiation of antibiotic therapy to eradicate the infection, thereby
preventing both clinical disease and transmission to sexual contacts.
The American College of Physicians recommends serologic screening
for syphilis in high-risk adults (prostitutes, persons who engage in sex
with multiple partners in areas in which syphilis is prevalent, contacts
of persons with active syphilis)18.
C All men and women at increased risk for infection, including sex
workers, persons who exchange sex for money or drugs, persons with
other STIs (including HIV) and genital ulceration, and sexual contacts
of persons with active syphilis should be screened.
Grade C, Level IV
19.3.2 Screening pregnant women
Early detection and penicillin treatment during pregnancy has the
added benefit of reducing the risk to the fetus of acquiring congenital
syphilis19.
The American College of Obstetricians and Gynecologists and the
American Academy of Pediatrics recommend routine prenatal
150
screening for syphilis at the first prenatal visit, after exposure to an
infected partner and in the third trimester for patients at high risk20.
The USPSTF strongly recommends routine serologic testing for
syphilis for all pregnant women and for persons at increased risk for
infection21.
The CDC recommends obtaining serology for syphilis from all
women at the first antenatal visit22. Routine screening for all pregnant
women is justified in view of the severe neonatal morbidity and
mortality associated with congenital syphilis, as well as its potential
preventability. There is evidence from several studies which
demonstrate that prenatal screening for syphilis is cost-effective, even
when the prevalence of the disease among pregnant women is as low
as 0.005%23,24.
B Pregnant women should be screened at their first antenatal visit.
Grade B, Level III
C Pregnant women at higher risk of infection (i.e. women who have
partners with symptoms of an STI, or continue to engage in sexual
activity with multiple partners, or a partner who has sex with multiple
partners) should have screening repeated in the third trimester.
Grade C, Level IV
19.3.3 Screening methods
The testing strategy varies depending on several factors, including
whether the aim is to detect all stages of syphilis or only infectious
syphilis.
In the USA, France and Belgium, non-treponemal tests are used for
screening. This does not detect most adequately treated cases, thus
simplifying patient assessment. There are however a few
disadvantages. It may yield false negative reactions in early infections
(prozone phenomenon) and with concomitant HIV infection, and it
lacks sensitivity in late stage infections.
In Germany and Holland, the TPHA test is used for screening. This
provides a good screen for all stages beyond the early primary stage.
151
The UK has adopted the VDRL/TPHA combination for screening as
this detects more primary infections. However, this combination is
labour intensive, requires subjective interpretation and cannot be
easily automated.
More recently, specific EIA tests have been used as a screening test.
The advantages of this technique are objective results, the ability to
link to computer systems (thus reducing human errors) and automated
processing25. These tests have not been fully evaluated in Singapore.
In Singapore nontreponemal tests (VDRL, RPR) are used for
screening. The sensitivity of these tests varies with the levels of
antibodies present during the stages of disease18.
19.3.4 Interpretation of test results
In early primary syphilis, when antibody levels may be too low to
detect, results may be nonreactive, and the sensitivity of
nontreponemal tests is 62-76%.26 Antibody levels rise as disease
progresses; titres usually peak during secondary syphilis, when the
sensitivity of nontreponemal tests approaches 100%.
In late syphilis, titres decline; in untreated late syphilis, test sensitivity
averages 70%26. Nontreponemal tests titres decline or revert to normal
after successful treatment.
Positive screening tests must be confirmed by a specific test such as
Treponema pallidum hemeagglutination or particle agglutination
(TPHA and TPPA) or fluorescent treponemal antibody absorption
(FTA-ABS).
C Screening for syphilis is performed using nontreponemal tests such
as RPR or VDRL. Positive results should be confirmed with a specific
test such as TPPA or TPHA. Both nontreponemal and treponemal
tests can be combined for use in screening, although this would be
more costly and labour-intensive.
Grade C, Level IV
GPP The optimal frequency of screening is a matter of clinical
discretion. Screening for syphilis should be performed 1 month after
exposure, and repeated again after 3 months.
GPP
152
C Follow up serologic tests should be obtained to document declines
in titres after treatment. They should be performed using the same test
initially used to document infection (e.g. VDRL or RPR) to ensure
compatibility27.
Grade C, Level IV
At DSC, the intervals for follow-up serology testing are at 3, 6, 12, 18
and 24 months after diagnosis27.
19.4
Screening for gonorrhoea
Gonorrhoea is caused by Neisseria gonorrhoeae. Gonococcal
infections produce urethritis, epididymitis, and proctitis in men, but
few long-term complications. It causes pelvic inflammatory disease in
women, and pregnant women with gonorrhoea are at increased risk of
obstetric complications (e.g. stillbirth, low birthweight).
Pharyngeal gonorrhoea usually occurs in association with anogenital
infection, and can result in transmission through oral sex28. Early
detection and treatment of gonococcal infection in asymptomatic
persons offer the potential benefits of complete cure, prevents future
complications of infection, reduces transmission to uninfected
partners, and identifies sexual contacts who are likely to be infected.
Due to ethical considerations that preclude placebo-controlled trials of
treatment, the benefits of early detection are based largely on indirect
evidence.
19.4.1 Screening women and men
The USPSTF recommends routine screening for N. gonorrhoeae in
asymptomatic women in high-risk groups29. High-risk groups include
commercial sex workers, persons with a history of repeated episodes
of gonorrhoea, and young women (under age 25 years) with two or
more sexual partners in the last year. Actual risk, however, will
depend on the local epidemiology of the disease.
The Canadian Task Force on the Periodic Health Examination advises
against routine screening for gonorrhoea in the general population but
recommends screening of high-risk patients 30.
153
The American College of Obstetricians and Gynecologists (ACOG)
recommends obtaining endocervical culture in pregnant women on
their first antenatal visit only if they are in one of the high-risk
categories for gonorrhoea31.
C Women at high risk of infection – including sex workers, women
with a history of repeated episodes of gonorrhoea, and women with
two or more sex partners in the previous year should be screened.
Grade C, Level IV
GPP Homosexual men with frequent partner change or other highrisk behaviour (i.e. those who have sex with partners with symptoms
of an STI, those who do not use barrier protection including
unprotected receptive and insertive oral and anal intercourse) should
be considered for screening.
GPP
19.4.2 Screening methods
The most sensitive and specific test for detecting gonococcal infection
in asymptomatic persons is direct culture from sites of exposure
(urethra, endocervix, throat, and rectum). Under quality-controlled
conditions, the sensitivity of culture is high for both male and female
anogenital gonorrhoea and for pharyngeal gonococcal infections.
In women and men, a single endocervical or urethral swab culture is
estimated to have a sensitivity of 80-95%32,33. Microscopic
examination of Gram-stained urethral or cervical specimens can detect
infection with N. gonorrhoeae.
The sensitivity of Gram-stained urethral specimens is higher in
symptomatic men (90-95%) than in asymptomatic men34. The
sensitivity of Gram-stained cervical specimens is lower (60-70%).
Culture of endocervical specimens in women and urethral specimens
in men is therefore the preferred method for screening.
C The ideal screening test is isolation of Neisseria gonorrhoeae by
culture from the appropriate sites.
Grade C, Level IV
154
GPP Sites to be sampled will be determined by the history of sexual
contact – urethra, cervix, rectum or pharynx.
GPP
GPP The optimal frequency of screening is a matter of clinical
discretion. Screening for gonorrhoea should be performed about 1
week after exposure.
GPP
19.5
Screening for genital Herpes Simplex Virus Infection
Both Herpes Simplex Virus (HSV) types 1 and 2 can cause genital
herpes, but HSV-2 causes the majority of primary and recurrent
genital herpes infections35.
There is insufficient evidence to recommend routine screening for
genital HSV in asymptomatic persons, using culture, serology, or
other tests.
The USPSTF does not recommend routine screening for HSV
infection in asymptomatic persons, including asymptomatic pregnant
women36.
GPP Routine screening for genital herpes simplex virus (HSV)
infection by viral culture, serology or other means is not
recommended for asymptomatic men or women, including
asymptomatic pregnant women.
GPP
History and physical examination are not adequate screening tests for
either active or latent genital HSV infection. If a test were to be used,
viral culture still remains the “gold standard”. However, the sensitivity
of the test is dependent on the time at which it is performed. Viral
cultures have a sensitivity of 93% for vesicles, to 72% for ulcers and
27% for crusted lesions37.
The present serological tests available locally are not specific enough
to reliably distinguish HSV-1 and 2 in some circumstances, and are
not recommended.
155
The newer type-specific serological tests are based on HSV-specific
glycoprotein G2 for the diagnosis of infection with HSV-2 and
glycoprotein G1 for the diagnosis of infection with HSV-1.
Currently, the FDA-approved, gG-based type-specific assays include
POCkit™ HSV-2 (manufactured by Diagnology) and HerpeSelect™-1
ELISA IgG or HerpeSelect™-2 ELISA IgG (manufactured by Focus
Technology, Inc)38. Because almost all HSV-2 infections are sexually
acquired, type-specific HSV-2 antibody indicates anogenital infection,
but the presence of HSV-1 antibody does not distinguish anogenital
from orolabial infection.
The CDC in Atlanta recommends that although serologic assays for
HSV-2 should be made available to persons who request them,
screening for HSV-1 and HSV-2 infection in the general population is
not recommended.
19.6
Screening for Human Immunodeficiency Virus
Infection
C Clinicians should assess risk factors for human immunodeficiency
virus (HIV) infection in all persons by carefully obtaining a sexual
history and inquiring about injecting drug use.
Grade C, Level IV
19.6.1 Risk groups
C Counselling and testing for HIV should be offered to all persons at
increased risk of infection. These include those with STI, men who
have sex with men39, past or present injecting drug users39, persons
who exchange sex for drugs or money and their sex partners40,
persons whose past or present sex partners were HIV-infected, and
persons who have had a blood transfusion or an organ transplant that
had not previously been screened41.
Grade C, Level IV
19.6.2 Screening pregnant women
Although there is insufficient evidence to show that routine antenatal
screening for HIV in low prevalence areas is beneficial, a policy of
offering screening to pregnant women may still be considered because
156
timely institution of anti-retroviral therapy can prevent mother-tochild HIV transmission42.
GPP Pregnant women should be offered the test in the first trimester.
GPP
19.6.3 Screening methods
C Screening for HIV is performed using ELISA. A positive result
requires 2 reactive ELISA tests and confirmation with the Western
Blot (WB) assay, performed by experienced laboratories that receive
regular external proficiency testing13.
Grade C, Level IV
19.6.4 Frequency of screening
Persons with nonreactive test results should be given post-test
counselling. The frequency of testing of seronegative individuals is a
matter of clinical discretion.
C Persons who continue to exhibit high-risk behaviour should have
screening tests on a regular basis. The frequency at which these
individuals are screened is a matter of clinical discretion. Screening
for HIV should be performed 6-monthly in a person who continues to
exhibit high-risk behaviour.
Grade C, Level IV
C Persons with recent high-risk behaviour should be screened at 1
month, 3 months and 6 months after the last high-risk exposure to rule
out a possible initial false negative initial result42.
Grade C, Level IV
19.7
Screening for Genital Human Papillomavirus (HPV)
infection
Genital HPV infection is a viral infection that is common among
sexually active adults. Infection is almost always sexually transmitted.
However, the incubation period is variable and it is often difficult to
determine the source of infection13.
157
C Women with a history of STI may be at increased risk for cervical
cancer, which is linked to certain HPV types. However, the HPV
types that frequently cause anogenital warts do not cause cancer13.
The Pap smear is a screening test for cervical carcinoma and not a
screening test for STIs, and women who have external genital warts
do not need to have Pap smears more frequently than women who do
not have warts.
Grade C, Level IV
In patients without visible warts, subclinical infection may exist. In
this situation, manifestations of HPV infection occur in the absence of
external genital warts. Subclinical infection may sometimes be
detected with the use of acetic acid application, but this is not a
specific test for HPV infection, and the sensitivity and specificity of
this procedure for screening have not been defined13.
The CDC in Atlanta does not recommend the use of this procedure or
any other means to detect subclinical infection. It also recommends
that women with anogenital warts do not require Pap smears more
frequently than women without warts13.
C Clinical examination with the unaided eye is the oldest diagnostic
technique in detection of genital warts. However, “subclinical” genital
HPV infection, a condition used to refer to manifestations of infection
in the absence of genital warts, may still exist. No screening tests for
subclinical infection are available, and there are no recommendations
for routine screening.
Grade C, Level IV
References
1.
Ang P, Chan RK. Sexually transmitted diseases in Singapore – trends
in the last two decades. Ann Acad Med 1997; 26:827-33.
2.
Yeong CT, Lim TLW, Lin R, et al. Routine screening for Chlamydia
trachomatis in subfertile women – is it time to start? Singapore Med J
2000; 41:111-3.
158
3.
US Preventive Services Task Force. Screening for Chlamydial
infection. Recommendations and rationale. Am J Prev Med 2001;
20:90-4.
4.
Centers for Disease Control and Prevention. Recommendations for
prevention and management of Chlamydia trachomatis infections.
MMWR 1993; 42:1-39.
5.
Clinical Effectiveness Group (Association of Genitourinary Medicine
and the Medical Society for the Study of Venereal Diseases). National
guideline for the management of Chlamydia trachomatis genital tract
infection. Sex Transm Inf 1999; 75:S4-S8.
6.
CMO’s Expert Advisory group Chlamydia trachomatis. London;
Department of Health 1998.
7.
Scholes D, Stergachis A, Heidrich FE, et al. Prevention of pelvic
inflammatory disease by screening for cervical chlamydial infection.
N Engl J Med 1996; 334:1362-6.
8.
Kamwendo F, Forslin L, Bodin L, et al. Decreasing incidences of
gonorrhoea and chlamydia associated acute pelvic inflammatory
disease. A 25-year study from an urban area of central Sweden. Sex
Transm Dis 1996; 23:384-91.
9.
Egger M, Low N, Smith GD, et al. Screening for chlamydial
infections and the risk of ectopic pregnancy in a county in Sweden:
ecologic analysis. BMJ 1998; 316:1776-80.
10.
Martin DH et al. Prematurity and perinatal mortality in pregnancies
complicated by maternal Chlamydia trachomatis infections. JAMA
1982; 247:1585-8.
11.
Sweet RL, et al. Chlamydia trachomatis infection and pregnancy
outcome. Am J Obstet Gynecol 1987; 156:824-33.
12.
Martius J, et al. Relationship of vaginal Lactobacillus species, cervical
Chlamydia trachomatis, and bacterial vaginosis to preterm birth.
Obstet Gynecol 1989; 129:1247-57.
13.
Centers for Disease Control. Sexually Transmitted Diseases
Treatment Guidelines 2002. MMWR 2002; 51:88-97.
159
14.
Nelson HD, Helfand M. Screening for Chlamydial infection. Am J
Prev Med 2001; 20:95-107.
15.
Quinn TC. DNA amplification assays: a new standard for diagnosis of
chlamydia trachomatis infections. Ann Acad Med Singapore 1995;
24:627-33.
16.
Puolakkainen M, Koussa M, Saikku P. Clinical conditions associated
with positive complement fixation serology for Chlamydiae.
Epidemiol Infect 1987; 98:101-8.
17.
Marx R, Aral SG, Rolfs RT, et al. Guidelines for the prevention and
control of congenital syphilis. MMWR 1988; 37:1-13.
18.
Hart G. Syphilis test in diagnostic and therapeutic decision making. In
Sox HC Jr, ed. Common diagnostic tests: use and interpretation. 2nd
ed. Philadelphia: Lea & Febiger, 1986.
19.
Marx R, Aral SG, Rolfs RT, et al. Congenital syphilis, United States,
1983-1985. MMWR 1986; 35:625-8.
20.
American Academy of Pediatrics and American College of
Obstetricians and Gynecologists. Guidelines for perinatal care. 3rd ed.
Washington, DC, 1992; 133-5.
21.
USPSTF “Clinical Preventive Services”
Screening for syphilis. 2nd ed., 1996.
22.
Centers for Disease Control and Prevention. Sexually transmitted
disease guidelines. MMWR 1998; 47:40.
23.
Stray-Pedersen B. Economic evaluation of maternal screening to
prevent congenital syphilis. Sex Transm Dis 1983; 10:167-72.
24.
Williams K. Screening for syphilis in pregnancy: an assessment of the
costs and benefits. Commun Med 1985; 7: 37-42.
25.
Eaglestone SI, Turner AJL. Serological diagnosis of syphilis. Comm
Dis Public Health 2000; 3:158-62.
26.
Hart G. Syphilis tests in diagnostic and therapeutic decision making.
Ann Intern Med 1986; 104: 368-76.
160
Recommendations
–
27.
Ed: R Chan. Sexually transmitted diseases management guidelines
1999. National Skin Centre, Singapore.
28.
Hutt DM, Judson FN. Epidemiology and treatment of oropharyngeal
gonorrhoea. Ann Intern Med 1986; 104:655-8.
29.
USPSTF “Clinical Preventive Services”
Screening for gonorrhoea. 2nd ed., 1996.
30.
Canadian Task Force on the Periodic Health Examination. Canadian
guide to clinical preventive health care. Ottawa: Canada
Communication Group. 1994; 168-175.
31.
American College of Obstetricians and Gynecologists. Gonorrhoea
and chlamydial infections. ACOG Technical Bulletin no. 190.
Washington, DC: American College of Obstetricians and
Gynecologists, 1994.
32.
Goh BT, Varia KB, Ayliffe PF, et al. Diagnosis of gonorrhoea by
gram-stained smears and cultures in men and women: role of the
urethral smear. Sex Transm Dis 1985; 12: 135-9.
33.
Romanowski B, Harris JRW, Wood H, et al. Improved diagnosis of
gonorrhoea in women. Sex Transm Dis 1986; 13:93-6.
34.
Centers for Disease Control. Guide for the diagnosis of gonorrhoea
using culture and Gram-stained smear. Atlanta: Centers for Disease
Control, 1991.
35.
Corey L, Adams HG, Brown ZA, et al. Genital herpes simplex virus
infections: clinical manifestations, course, and complications. Ann
Intern Med 1983; 98:973-83.
36.
USPSTF “Clinical Preventive Services” Recommendations
Screening for Genital Herpes Simplex. 2nd ed., 1996.
37.
Corey L, Holmes KK. Genital herpes simplex virus infections: current
concepts in diagnosis, therapy, and prevention. Ann Intern Med 1983;
98:973-83.
38.
Center for Disease Control. Sexually Transmitted Diseases Treatment
Guidelines 2002. MMWR 2002; 51:19-20.
161
Recommendations
–
–
39.
Centers for Disease Control and Prevention. Update: Public health
surveillance for HIV infection – United States, 1989 and 1990.
MMWR 1990; 39:853,859-61.
40.
Centers for Disease Control and Prevention. HIV/AIDS surveillance
report 1995; 7:1-34.
41.
Centers for Disease Control and Prevention. Treatment guidelines
2002. MMWR 2002; 51:88-97.
42.
USPSTF “Clinical Preventive Services” Recommendations –
Screening for Human Immunodeficiency Virus infection. 2nd ed.,
1996.
162
20
Clinical audit
There are no clinical audit indicators recommended for general
screening per se. This is because the denominator, in reference to the
population that consults in the general clinic setting, cannot be
determined.
This is in contrast to national screening programmes where potential
clinical audit indicators can be monitored and measured.
163
164
Self-assessment (MCQs)
After reading the Clinical Practice Guidelines, you can claim one CME point
under Category III (Self-Study) of the SMC Online CME System. Before you
login to claim the CME point, we encourage you to evaluate whether you have
mastered the key points in the Guidelines by completing this set of MCQs. This
is an extension of the learning process and is not intended to “judge” your
knowledge and is not compulsory. The answers can be found at the end of the
section.
Instruction : Choose the best answer
1.
The cholesterol screening guidelines recommend screening in the
following individuals regardless of age:
A. all diabetics
(True/False)
(True/False)
B. all subjects with BMI greater than 30 kg/m2
C. subjects with impaired glucose tolerance but not impaired fasting
glycaemia
(True/False)
D. subjects with intermittent claudication
(True/False)
E. all subjects with pre-existing coronary heart disease
(True/False)
2. Subjects must be considered for cholesterol screening if:
A. undergoing multiphasic health examination at 45 years of age
(True/False)
B. ex-smoker aged 30 years
(True/False)
C. family history of diabetes mellitus
(True/False)
D. family history of hypertension
(True/False)
E. family history of lipid problems
(True/False)
3. Hypertension is defined as resting blood pressure
A.
B.
C.
D.
E.
4.
≥
≥
≥
≥
≥
130/85mmHg
140/85mmHg
140/90mmHg
140/95mmHg
160/100mmHg
Screening of hypertension is carried out in the following situations, except
A. at least two yearly for all adults aged 21 years and above who have
normal blood pressure
169
B. routinely during the antenatal care for pregnant mothers
C. routinely for children above the age of 7 years old
D. yearly for those who are at risk such as those with diabetes mellitus,
or borderline high blood pressure
E. any patient aged 21 years and above who comes to consult the doctor
in the clinic
5.
Concerning screening for type 2 diabetes mellitus:
A. community screening in healthy individuals is recommended
B. best performed on an opportunistic basis in at risk individuals
C. should be conducted in all women during pregnancy
D. a repeat screen in individuals previously found to have impaired
glucose tolerance (IGT), should be conducted at 3 yearly intervals
E. subject with no risk factors should be screened starting at age 20 years
6.
The recommended screening test for diabetes mellitus is measurement of:
A. random capillary blood glucose
B. fasting plasma glucose
C. glycosylated haemoglobin (HbA1c)
D. urine microalbumin
7.
Which of the following diagnostic modalities have been shown to be costeffective in screening heavy smokers for early lung cancer?
A. physical examination
B. sputum cytology
C. chest x-ray
D. plasma carcinoembryonic antigen assay
E. low-dose spiral computed tomography
F. none of the above
8.
A 55-year-old shipyard worker with an 80 pack-year smoking history
consults you for a symptomatic exacerbation of bronchitis over the last
three weeks. Hemoptysis is denied, and physical examination and chest Xray are unremarkable. You prescribe a course of antibiotics, and also
advise him:
A. to stop smoking
B. to have an immediate ESR and sputum cytology performed
C. to return for a follow-up chest X-ray in six months’ time, just in case
he is in the ‘window period’ prior to early radiologic screen detection
D. if he is very worried about early lung cancer, he should proceed to
bronchoscopy at this time, and follow up with further bronchoscopies
each year for the next five years
170
E. if money is no object, he should now have a low-dose spiral CT to
exclude surgically curable lung cancer
9.
Hepatocellular carcinoma (HCC) surveillance
A. is proven strongly to result in better survival in patients with
hepatitis B
B. is accurate based on alfa-fetoprotein level alone
C. uses CT scan or MRI as a rountine screen
D. is not proven to show survival advantage but provides assurance to the
individual patient
10. One of the roles of HCC screening in Hepatitis B patient is:
A. early detection of small cancer which may benefit from surgical
resection
B. to track the disease progression
C. offer palliative care
D. so that the whole family can be alerted and sent for screening for HCC
11. The following may be considered at high risk of developing colorectal
cancer except
A. patient with a past history of colonic polyps
B. sister whose brother developed colon cancer at the age of 40 years
C. son whose father developed rectal cancer at the age of 80 years
D. patient with longstanding ulcerative colitis
12. A man at the age of 50 years wishes to be screened for colon cancer,
option would include:
A. CT scan of the abdomen
B. Serum CEA
C. Faecal Occult Blood Testing
D. Serum AFP
13. Screening for high risk group for prostate cancer should start at age:
A. 30 years
B. 40 years
C. 50 years
D. 60 years
E. 70 years
14. For a premenopausal 35 year old woman who has no symptoms or family
history of breast or ovarian cancer, the most suitable method of breast
screening is:
171
A.
B.
C.
D.
E.
mammography
mammography with ultrasound
ultrasound alone
regular self-examination
clinical examination
15. For a 55-year old asymptomatic woman on conventional hormone
replacement therapy, breast screening is best performed using:
A. mammography only at yearly intervals
B. mammography only at two yearly intervals
C. mammography with ultrasound at one year intervals
D. mammography with ultrasound at two year intervals
E. regular clinical examination
16. Population based cancer screening is appropriate for the following
gynaecological cancers:
A. Ovarian Cancer
B. Cervical Cancer
C. Uterine Cancer
D. All of the above
17. In a woman who has been having regular Pap smear tests, screening can be
discontinued at age:
A. 55 years
B. 60 years
C. 65 years
D. 70 years
18. The following factors place a woman at an increased risk for endometrial
cancer except:
A. early menopause
B. tamoxifen therapy
C. nulliparity
D. obesity
19. The following statements concerning screening for uterine cancer are true
except:
A. there is insufficient evidence to establish a decrease in mortality from
uterine cancer with screening by transvaginal ultrasound
B. pap smear tests are very useful for uterine cancer screening
C. women with hereditary non-polyposis colorectal cancer are considered
to be at high risk for uterine cancer
172
D. early evaluation of postmenopausal bleeding is important for early
detection of uterine cancer
20. The following tests have high positive predictive value for early detection
of ovarian carcinoma in women at average risk:
A. routine pelvic examination
B. transvaginal sonography
C. serum tumour antigens
D. combinations of the above
E. none of the above
21. The following are true for women at high risk of ovarian carcinoma
except:
A. they may have 2 or more first degree relatives with ovarian cancer
B. they should be referred to tertiary centres for multimodal screening
C. annual screening will reduce their mortality from ovarian cancer
D. there is evidence of higher positive predictive value in screening
22. In the context of Screening for Latent TB Infection (LTBI) with the
Tuberculin Skin Test (TST), the following statements are True or False :
A. the TST is recommended only for identifying candidates who are at
high risk of breakdown into TB disease, and who will therefore
benefit from preventive treatment.
(True/False)
B. reliable TST readings are easily obtained because intra-observer and
inter-observer errors are negligible.
(True/False)
C. the TST is so specific that the positive predictive value remains high
even when the tested population is at a low risk of TB infection.
(True/False)
D. a reactive TST in a suspected contact should be interpreted as positive
and indicating preventive treatment, even when no data about the
Index case, the environment in which the contact occurred, and the
duration of exposure, are available.
(True/False)
E. because preventive treatment with isoniazid (INH) carries a small but
definite risk of hepatitis, it should be prescribed only in carefully
assessed and selected subjects.
(True/False)
23. You will advise hepatitis B screening to one of the following patients in
your clinic,
A. a 45 year old man attending your clinic for upper respiratory tract
infection
B. a 32 year old man attending your clinic for urethritis
173
C. a 75 year old lady who loves to eat cockles
D. a 12 year old girl who is sure that she was vaccinated at birth but is
keen to know her present hepatitis B status
24. Which of the following statements is incorrect?
A. dipstick testing for proteinuria is 85% specific
B. dipstick testing for proteinuria is 95% sensitive
C. positive dipstick testing for proteinuria should have protein excretion
rate documented
D. To avoid 24-hour protein collection, a spot urine for ProteinCreatinine ratio can be used to quantitate the proteinuria
E. dipstick for protein of >1+ is equivalent to 30mg/dl of proteinuria
25. With regard to screening for osteoporosis,
A. dual energy x-ray absorptiometry (DXA) of the hip is a cheap,
effective method of widespread screening for osteoporosis
(True/False)
B. forearm DXA or calcaneal or multi-site quantitative ultrasound (QUS)
are cheap, effective methods of widespread screening for osteoporosis
(True/False)
C. dual energy x-ray absorptiometry (DXA) of the hip is the technique of
choice to diagnose osteoporosis in selected individuals identified to be
at high risk of having osteoporosis
(True/False)
D. low BMD measured at the calcaneus confirms that low BMD will be
found at the hip or spine
(True/False)
E. a reasonable interval for follow-up BMD testing in postmenopausal
women is 6 monthly
(True/False)
F. the utilization of BMD measurement in clinical practice has led to
enhanced success in maintaining lifestyle modifications, and in
improved rates of initiating therapies for osteoporosis
(True/False)
26. The following are more likely to have osteoporosis:
A. a woman aged 50 years compared to one aged 70 years (True/False)
B. a woman weighing 70 kg compared to one weighing 40 kg
(True/False)
C. a smoker compared to a non smoker
(True/False)
D. an individual with a family history of fracture
(True/False)
E. a social drinker
(True/False)
F. individuals on long-term corticosteroid therapy
(True/False)
174
27. An effective way of assessing visual function in the elderly in a primary
healthcare setting is:
A. asking a person about his visual problem
B. checking the visual acuity of the eyes
C. a torchlight examination
D. an ophthalmoscope examination
28. Measuring distance visual acuity involves:
A. testing both eyes simultaneously
B. testing each eye one at a time
C. testing distance should be 6 feet using a standard Snellen chart
D. using a newspaper for testing
29. Regarding serological testing for syphilis:
A. a negative VDRL rules out diagnosis of syphilis
(True/False)
B. serological tests for syphilis is strongly recommended for all pregnant
women at the first antenatal visit
(True/False)
C. recent viral infections can cause a false positive VDRL result
(True/False)
D. patients who remain positive for VDRL and TPHA results after
treatment for syphilis represent cases of therapeutic failure
(True/False)
30. Regarding screening for sexually transmitted infections:
A. screening for chlamydia trachomatis infection in women is only
indicated if they are symptomatic
(True/False)
B. serological tests are useful in screening for gonorrhoea (True/False)
C. screening for HIV is done using the Western Blot (WB) assay
(True/False)
D. Nucleic acid amplification tests such as PCR or LCR can be used
accurately on urine specimens in men to detect Chlamydia trachomatis
infection
(True/False)
175
Answers
1A.
1B.
1C.
1D.
1E.
2A.
2B.
2C.
2D.
2E.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
True
False
False
True
True
True
False
False
False
True
C
C
B
B
F
A
D
A
C
C
C
D
B
B
C
A
B
E
C
22A.
22B.
22C.
22D.
22E.
23.
24.
25A.
25B.
25C.
25D.
25E.
25F.
26A.
26B.
26C.
26D.
26E.
26F.
27.
28.
29A.
29B.
29C.
29D.
30A.
30B.
30C.
30D.
176
True
False
False
False
True
B
B
False
False
True
False
False
True
False
False
True
True
False
True
B
B
False
True
True
False
False
False
False
True
Workgroup members
The members of the workgroup, who were appointed in their personal
professional capacity, are:
Chairman:
Prof Chee Yam Cheng
Chairman, Medical Board
Tan Tock Seng Hospital
Members:
Dr Ang Chong Lye
Director
Singapore National Eye Centre
Prof Aw Tar Choon
Senior Consultant, Department of Laboratory Medicine
National University Hospital
Dr Chee Tek Siong
Consultant Cardiologist
Chee Heart Specialists Pte Ltd
East Shore Medical Centre
Dr Christopher Cheng
Head, Urology Department
Singapore General Hospital
Assoc Prof Cheong Pak Yean
President, College of Family Physicians Singapore
College of Medicine Building
Assoc Prof Chia Kee Seng
Department of Community,
Occupational And Family Medicine
National University of Singapore
Assoc Prof Richard Epstein
Director, Division of Academic Affairs
National Cancer Centre
177
Prof Fock Kwong Ming
Chief, Department of Medicine
Chairman, Medical Board
Changi General Hospital
Prof Goh Chee Leok
Medical Director
National Skin Centre
Assoc Prof Ho Tew Hong
Chief of Gynaecology
KK Women’s And Children’s Hospital
Dr Leonard Koh
Senior Consultant, Department of Endocrinology
Singapore General Hospital
Assoc Prof Adrian Leong
Chief, Surgery Department
National University Hospital
Dr Tan Chee Eng
Head, Department of Endocrinology
Singapore General Hospital
Assoc Prof Thai Ah Chuan
Consultant, Department of Medicine
National University Hospital
Assoc Prof Wang Shih Chang
Chief, Diagnostic Imaging
National University Hospital
Assoc Prof Sonny Wang Yee Tang
Director, Tuberculosis Control Department
Tan Tock Seng Hospital
Dr Wong Kok Seng
Senior Consultant and Head
Department of Renal Medicine
Singapore General Hospital
Secretariat:
Health Promotion Board
178
Acknowledgements
The Committee would like to thank the following co-authors who have assisted
in drafting the guidelines.
Screening for renal diseases:
Dr Chan Choong Meng
Consultant, Department of Renal Medicine
Singapore General Hospital
Prof Woo Keng Thye
Senior Consultant, Department of Renal Medicine
Chairman, Division of Research and Medicine
Singapore General Hospital
Screening for cervical/ovarian/uterine cancers:
Dr Jeffrey Low Jen Hui
Consultant, Gynaecological Oncology Unit
KK Women’s and Children’s Hospital
Dr Pritam Singh
Consultant, Gynaecology Associates Women’s Medical Centre
Mount Elizabeth Medical Centre
Dr Tay Eng Hseon
Consultant and Head, Gynaecological Oncology Unit
KK Women’s and Children’s Hospital
Dr Adelina Wong
Associate Consultant, Gynaecological Oncology Unit
KK Women’s and Children’s Hospital
Screening for obesity:
Dr Jeannette Lee
Department of Community,
Occupational and Family Medicine
National University of Singapore
179
Screening for blood cholesterol:
Dr Tai E Shyong
Consultant, Department of Endocrinology
Singapore General Hospital
Screening for sexually transmitted infection:
Dr Roy Chan
Senior Consultant, National Skin Centre
Head, Department of STD Control
Dr Tan Hiok Hee
Consultant, National Skin Centre
Deputy Head, Department of STD Control
Screening for hepatitis B and liver cancer:
Dr Teo Eng Kiong
Consultant, Department of Medicine
Changi General Hospital
Screening for prostate canceer:
Dr Sim Hong Gee
Registrar, Department of Urology
Singapore General Hospital
180
List of Endorsing Agencies
List of agencies/committees endorsing chapters in the
guidelines on screening and members providing feedback (in
alphabetical order):
Academy of Medicine:
(Blood cholesterol)
Dr Sum Chee Fang
(Diabetes mellitus)
Dr Sum Chee Fang
Dr Sunil Sethi
(Obesity)
Dr Sum Chee Fang
(Lung cancer)
Dr Khoo Kei Siong
(Hepatocellular carcinoma)
Dr Khoo Kei Siong
Dr Lucien Ooi
Dr Sunil Sethi
(Colorectal cancer)
Dr Eu Kong Weng
Dr Goh Poh Sun
Dr Khoo Kei Siong
Dr Sunil Sethi
(Prostate cancer)
Dr Khoo Kei Siong
Dr Michael Wong
Dr Tan Puay Hoon
(Breast cancer)
Dr Ann S A Tan
Dr Chang Tou Choong
Dr Chua Yang
Dr Jeffrey J H Low
Dr Khoo Kei Siong
Dr Lai Fon Min
Dr Samuel Ng
Dr Suresh Nair
Dr Tan Puay Hoon
Dr Thoo Fei Ling
181
(Cervical cancer)
Dr Ann S A Tan
Dr Chang Tou Choong
Dr Chua Yang
Dr Jeffrey J H Low
Dr Khoo Kei Siong
Dr Lai Fon Min
Dr Suresh Nair
(Uterine cancer)
Dr Ann S A Tan
Dr Chang Tou Choong
Dr Chua Yang
Dr Jeffrey J H Low
Dr Khoo Kei Siong
Dr Lai Fon Min
Dr Suresh Nair
(Ovarian Cancer)
Dr Ann S A Tan
Dr Chang Tou Choong
Dr Chua Yang
Dr Jeffrey J H Low
Dr Khoo Kei Siong
Dr Lai Fon Min
Dr Suresh Nair
(Tuberculosis)
Dr Alan Ng W K
Dr Tan Ai Ling
(Hepatitis B)
Dr Ooi Choon Jin
Dr Tan Ai Ling
(Osteoporosis)
Dr Julian Thumboo
(Visual acuity for the elderly)
Dr Ong Sze Guan
Dr Suresh Sahadevan
(Sexually transmitted infections)
Dr Ann S A Tan
Dr Chang Tou Choong
Dr Chua Yang
Dr Jeffrey J H Low
Dr Lai Fon Min
Dr Tan Ai Ling
Dr Suresh Nair
182
College of Family Physicians, Singapore:
(All chapters)
A/Prof Cheong Pak Yean
A/Prof Goh Lee Gan
Dr Lee Kheng Hock
Dermatological Society of Singapore:
(Sexually transmitted infections)
Dr Cheong Wai Kwong
Dr Tan Hiok Hee
Diabetic Society of Singapore:
(Blood cholesterol, Diabetes mellitus,
Obesity, Renal disease)
Dr Lim Su Chi
Dr Sum Chee Fang
Dr Tan Hwee Huan
Dr Tavintharan
Dr Yeo Kim Teck
Endocrine and Metabolic Society of Singapore: Dr Daphne Khoo
(Blood cholesterol, Diabetes mellitus,
Obesity, Osteoporosis)
National Cancer Center of Singapore Pte Ltd:
(Colorectal cancer)
Prof Soo Kee Chee
National Committee on Cancer Care:
(Colorectal cancer)
A/Prof Adrian Leong
A/Prof Francis Seow Choen
National Committee on Renal Care:
(Renal disease)
Dr A. Vathsala
Dr Akira Wu
A/Prof Evan Lee
Dr Grace Lee
Dr Li Man Kay
Dr Lina Choong Hui Lin
Dr Wong Kok Seng
Prof Woo Keng Thye
Prof Yap Hui Kim
Co-opted
Dr Gordon Ku
Dr Pary Sivaraman
Dr Stephen Chew
Dr Tan Han Khim
183
Obstetrical & Gynaecological Society
of Singapore:
(Cervical, Uterine and Ovarian cancers)
Dr Chia Yin Nin
Dr Tay Eng Hseon
Osteoporosis Society (Singapore):
(Osteoporosis)
Dr Lau Tang Ching
Dr Leonard Koh
Dr Leong Keng Hong
Ms Louisa Zhang
Dr Noor Hafizah
Dr Saw Seang Mei
Prof Shamal Das De
Dr Tan Seang Beng
Singapore Cancer Society:
(Colorectal cancer)
Prof Low Cheng Hock
A/Prof Michael Hoe
Singapore Cardiac Society:
(Blood cholesterol, Hypertension)
Prof Chia Boon Lock
Dr Low Lip Ping
Singapore Diabetes Guidelines:
(Blood cholesterol)
A/Prof Thai Ah Chuan
Singapore Lipid Guidelines Workgroup:
(Blood cholesterol)
Prof Chia Boon Lock
Dr Tan Chee Eng
Singapore Hypertension Society:
(Hypertension)
Dr Low Lip Ping
Singapore National Heart Association:
(Blood cholesterol, Obesity)
Dr Low Lip Ping
Singapore Radiological Society:
(Breast cancer)
Dr Andrew Tan Gee Seng
Dr Anthony Goh Soon Huat
Dr Gervais Wan Saicheong
Dr Harvey Teo Eu Leong
Dr Hoe Wei Ming John
A/Prof Wang Shih Chang
184
Singapore Society of Ophthalmology:
(Visual acuity for the elderly)
Dr Aliza Jap
Dr Daniel Sim Han Jen
Dr Francis Oen Tuck Soon
Dr Geh Min
Dr Hoh Sek Tien
Dr Lim Boon Ang
Dr Rahat Husain
Dr Steve Seah Kah Leng
Singapore Thoracic Society:
(Lung cancer, Tuberculosis)
Dr Alan Ng
Dr Constance Lo
Dr John Abisheganaden
Dr Kong Po Marn
Dr Lee Pyng
Prof Lim Tow Keang
Dr Loo Chian Min
Dr Yap Wee See
Singapore Urological Association:
(Prostate cancer)
Dr Chin Chong Min
Dr Christopher Cheng
Dr Damian Png
Dr David Consigliere
Dr I Swaminathan
Dr James Tan
Dr Lewis Liew
Dr Ng Foo Cheong
Dr Pearllyn Quek
Dr Sam Peh
Dr Weber Lau Kam On
The Protem Committee of the Association
of Colorectal Surgeons (Singapore):
(Colorectal cancer)
The Society for Colposcopy and Cervical
Pathology of Singapore:
(Cervical, Uterine and Ovarian cancers)
185
Dr Goh Hak Su
Dr Adelina Wong
Dr Jeffrey Low Jen Hui
Dr Pritam Singh
Dr Tay Eng Hseon
Agencies vetting chapters in the guidelines on screening:
Gastroenterological Society of
Singapore (Liver Group):
(Hepatocellular carcinoma & Hepatitis B)
Dr Dede Sutedja
Dr Lui Hock Foong
Prof Ng Han Seong
Dr Ong Tze Zen
Dr Roland Chong Siong Eng
Dr Tan Chee Kiat
Dr Teo Eng Kiong
Dr Yap Chin Kong
The Cancer Institute and A/Prof Benjamin Ong and Dr JJ Murkherjee
(Lung cancer, Hepatocellular carcinoma,
Colorectal cancer, Prostate cancer, Breast cancer)
186
CLINICAL PRACTICE GUIDELINES
Health Screening
(Summary Booklet)
Ministry
of Health
NMRC
National Medical
Research Council
Mar 2003
MOH Clinical Practice Guidelines 6/2003
Levels of evidence and grades of recommendation
Levels of evidence
Level
Type of Evidence
Ia
Evidence obtained from meta-analysis of randomised controlled
trials.
Ib
Evidence obtained from at least one randomised controlled trial.
IIa
Evidence obtained from at least one well-designed controlled study
without randomisation
IIb
Evidence obtained from at least one other type of well-designed
quasi-experimental study.
III
Evidence obtained from well-designed non-experimental descriptive
studies, such as comparative studies, correlation studies and case
studies.
IV
Evidence obtained from expert committee reports or opinions and/or
clinical experiences of respected authorities.
Grades of recommendation
Grade
Recommendation
A
(evidence levels Ia,
Ib)
Requires at least one randomised controlled trial as part
of the body of literature of overall good quality and
consistency addressing the specific recommendation.
B
(evidence levels IIa,
IIb, III)
Requires availability of well conducted clinical studies
but no randomised clinical trials on the topic of
recommendation.
C
(evidence level IV)
Requires evidence obtained from expert committee
reports or opinions and/or clinical experiences of
respected authorities. Indicates absence of directly
applicable clinical studies of good quality.
GPP
(good practice
points)
Recommended best practice based on the clinical
experience of the guideline development group.
Executive summary of recommendations
Details of recommendations can be found in the main text at the pages indicated.
Screening for blood cholesterol
C In screening for cholesterol, the optimal test is a full lipid profile
including LDL-cholesterol, fasting triglyceride and HDL cholesterol.
(pg 25)
Grade C, Level IV
GPP If the results are optimal based on the current recommendations for
Singapore, we recommend repeat screening at 3 yearly intervals. (pg 24)
GPP
B Screening should be carried out in all individuals above the age of 40
years on an opportunistic basis. (pg 24)
Grade B, Level IIb
A All patients with pre-existing coronary heart disease, stroke or
peripheral vascular disease should be screened irrespective of age. (pg 24)
Grade A, Level Ia
A All patients with diabetes mellitus should be screened irrespective of
age. (pg 24)
Grade A, Level Ib
B All individuals with impaired fasting glycaemia or impaired glucose
tolerance should be screened at any age. (pg 24)
Grade B, Level III
B All individuals with a family history and/or clinical evidence of familial
hyperlipidaemia should be screened after the age of 2 years. (pg 24)
Grade B, Level IIa
GPP Earlier screening from age 30 should be considered for individuals
with other risk factors for CHD e.g. smoking, hypertension, family history
of premature CHD. (pg 24)
GPP
1
B Earlier screening from age 30 years should be considered for those of
Indian ethnicity. (pg 24)
Grade B, Level III
Screening for hypertension
C Blood pressure should be measured at least once every 2 years for
adults aged 21 years and above with diastolic pressure below 85 mmHg
and a systolic pressure below 130 mmHg (i.e. normal BP). (pg 30)
Grade C, Level IV
A Measurements are recommended annually for persons with a diastolic
blood pressure of 85-89 mmHg or systolic blood pressure of 130-139
mmHg (i.e. high normal BP). Persons with higher blood pressures or
major coronary risk factor such as diabetes mellitus require more frequent
measurement. (pg 30)
Grade A, Level Ib
C Any person aged 21 years and above should have their blood pressure
measured during any visit to a physician ("case finding"). (pg 31)
Grade C, Level IV
A Sphygmomanometry is the recommended method for blood pressure
measurement, and it should be performed in accordance with the
recommended technique. (pg 31)
Grade A, Level Ia
A Pregnant women should have their blood pressure checked routinely as
part of the prenatal care. (pg 32)
Grade A, Level Ia
A Routine counselling to promote physical activity and a healthy diet for
the primary prevention of hypertension is recommended for all adults.
(pg 31)
Grade A, Level Ia
Screening for diabetes mellitus
C Screening of asymptomatic individuals at high risk for type 2 diabetes
mellitus should be carried out on an opportunistic basis. (pg 35)
Grade C, Level IV
2
C Screening should begin at age 40 years, and be considered at an earlier
age (e.g. 30 years) if risk factors for diabetes are present. (pg 35)
Grade C, Level IV
B Fasting plasma glucose (FPG) is the recommended test for screening in
the clinical setting because it is easy to perform and convenient.
Individuals with a FPG ≥ 7.0 mmol/L should have a repeat testing on a
different day to confirm the diagnosis of diabetes. Individuals with FPG of
6.1-6.9 mmol/l on screening should undergo a 75g oral glucose tolerance
test (OGTT) to determine precisely the degree of glucose intolerance.
(pg 38)
Grade B, Level III
B OGTT is also a suitable test for screening. (pg 38)
Grade B, Level III
C Individuals found to have normal glucose tolerance on screening and
who do not have risk factors for developing diabetes should have repeat
screening at 3 yearly intervals. For those with diabetes risk factors, repeat
screening may be performed more frequently e.g. at annual interval.
(pg 39)
Grade C, Level IV
B Those detected to have impaired fasting glycemia (IFG) or impaired
glucose tolerance (IGT) should have repeated screening on an annual
interval in view of the high rate of conversion to diabetes. (pg 39)
Grade B, Level III
Screening for obesity
B Body mass index (BMI) and waist circumference can be used to classify
obesity and assess risk. (pg 41)
Grade B, Level III
C All individuals ≥18 years of age should be screened. (pg 42)
Grade C, Level IV
GPP Screening should be done once a year for all individuals ≥ 18 years.
(pg 42)
GPP
3
Screening for lung cancer
A Neither chest X-ray nor sputum cytology is recommended for
screening. (pg 46)
Grade A, Level Ib
C The screening efficacy of low-dose spiral CT is unknown at present.
(pg 46)
Grade C, Level IV
Screening for hepatocellular carcinoma (HCC)
GPP There is no evidence to support population-based surveillance for
HCC. However, HCC surveillance should be offered to patients with
chronic hepatitis B infection, hepatitis C liver cirrhosis and liver cirrhosis
from other etiologies. HCC surveillance should be performed periodically
with alpha-fetoprotein 3 to 6 monthly and ultrasound of the liver at 6 to 12
monthly interval. There is no definite recommended age to start
surveillance. However, it is noted that the local statistics showed that HCC
detection starts to increase from the age of 30 years. (pg 52)
GPP
C Current accepted tests used for HCC surveillance include ultrasound of
the hepato-biliary system and alpha feto-protein level. (pg 49)
Grade C, Level IV
Screening for colorectal cancer
A Asymptomatic individuals above the age of 50 years should undergo
screening for colorectal cancer. This would include asymptomatic
individuals with a family history limited to non-first degree relatives. The
screening options would be faecal occult blood testing annually. (pg 62)
Grade A, Level Ia
B Alternatively, other methods that could be employed in this group
include flexible sigmoidoscopy every 5 years; (pg 62)
Grade B, Level IIa
4
B or colonoscopy every 10 years. (pg 62)
Grade B, Level IIb
(Those with a positive faecal occult blood test would undergo colonoscopy
or when technically not possible, a barium enema.)
B In individuals with a history of colorectal cancer in a first degree
relative aged 45 years or younger or with a family history of two or more
affected first degree relatives, colonoscopy is recommended every 3 years
performed 10 years prior to the youngest case in the family. (pg 62)
Grade B, Level IIa
B In individuals who have a history of colorectal cancer in a first degree
relative over the age of 45 years, colonoscopy is recommended every 10
years. The age of commencing colonoscopy is 10 years prior to the
youngest case in the family or age 50 years whichever is earlier. (pg 62)
Grade B, Level IIb
A In individuals with a personal past history of colorectal polyps,
colonoscopy is recommended one year after polypectomy in the presence
of high risk features (polyp > 1cm, multiple, villous architecture) or three
years after polypectomy in the absence of high risk features (solitary,
tubular architecture). (pg 62)
Grade A, Level Ib
B In individuals with a personal past history of colorectal cancer,
colonoscopy is recommended one year after resection provided that total
imaging of the bowel was achieved prior to surgery. (pg 62)
Grade B, Level IIa
B In individuals with a family history of familial adenomatous polyposis,
flexible sigmoidoscopy is recommended annually from the onset of
puberty. (pg 62)
Grade B, Level IIb
Genetic counselling should be considered.
5
B In individuals with a family history of Hereditary Non-polyposis
Colorectal Cancer, colonoscopy is recommended every two years 10 years
prior to the diagnosis of colorectal cancer in the youngest family member.
(pg 62)
Grade B, Level IIb
Genetic counselling should be considered.
B In individuals with left-sided ulcerative colitis, colonoscopy is
recommended every 1-2 years from the 15th year after diagnosis. For
individuals with pan-colitis, colonoscopy is recommended every 1-2 years
from the 8th year after diagnosis. (pg 62)
Grade B, Level IIb
C Plasma CEA (carcinoembryonic antigen) levels are not recommended
for use in the screening of asymptomatic, average risk individuals. (pg 61)
Grade C, Level IV
Screening for prostate cancer
A Population screening for prostate cancer should not be recommended at
present among Asians. (pg 68)
Grade A, Level Ia
GPP High-risk men, such as men above 50 years of age with a history of
a first degree relative with prostate cancer at a young age (<60 years),
should be offered screening. (pg 68)
GPP
B Combined use of prostate specific antigen (PSA) and digital rectal
examination (DRE) has a higher detection rate for prostate cancer than
either test alone. (pg 68)
Grade B, Level IIb
B Transrectal ultrasound (TRUS)-guided biopsy for raised PSA and/or
abnormal DRE is recommended. (pg 69)
Grade B, Level IIb
6
Screening for breast cancer
A All normal risk, asymptomatic women 50-64 years of age should be
screened with mammography only, every 2 years. Ultrasound and breast
examination are not routinely required. (pg 80)
Grade A, Level Ia
A In Western nations, the evidence supports mammographic screening
every 2 years for all normal risk women 65-75 years of age. However, for
Singaporean women the much lower incidence of breast cancer in this age
group suggests that screening mammography may be less beneficial. If
individual screening is performed, it should be at two-yearly intervals.
Ultrasound and breast examination are not routinely required. (pg 80)
Grade A, Level Ia
A Women with breast implants are recommended to have routine
screening mammography once every 1-2 years, depending on their age.
(pg 87)
Grade A, Level Ia
A Normal risk, asymptomatic women under 40 years should not undergo
breast screening with any imaging modality. (pg 81)
Grade A, Level Ib
A Clinical breast examination has been proven to confer no mortality
benefit in a screening population. (pg 83)
Grade A, Level Ib
B Breast ultrasound and MRI can both detect cancers that are occult on
mammography. However, they should not be used for routine breast
screening outside of clinical trials. (pg 84)
Grade B, Level IIa
B Nuclear scintimammography shows promise as an adjunct technique for
detection of breast cancer in limited circumstances, usually in conjunction
with mammography. Its use for breast screening is unwarranted. (pg 85)
Grade B, Level III
7
C Women at normal risk aged 40-49 years should be encouraged to have
annual screening mammography. Ultrasound and breast examination are
not routinely required. (pg 81)
Grade C, Level IV
C Women on conventional hormone replacement therapy have a very
slightly increased risk of breast cancer. They should have regular
screening mammography. Those aged 40-49 years should be screened
annually, and those aged 50-65 years biannually, for up to 5 years after
cessation of HRT. (pg 81)
Grade C, Level IV
C Women who are at very high risk of breast cancer by virtue of being a
BRCA gene carrier, or a very strong first-degree family history of breast
cancer, should perform monthly breast self examination, 6-monthly
clinical breast examination and ultrasound, and annual mammography.
Screening should start as early as 5 years before the age of onset of breast
cancer in the youngest family member. Breast magnetic resonance
imaging should be considered, but only if cost is not problematic and the
expertise and equipment for MRI-guided breast needle biopsy and
localisation are available. (pg 82)
Grade C, Level IV
C Thermography and Electrical Impedance Scanning must be regarded as
investigational techniques. Their use for breast screening is not warranted.
(pg 86)
Grade C, Level IV
GPP Women with prior breast cancer should receive annual screening
mammography of the remnant and contralateral breasts. At 5 years
disease-free post-surgery, they may return to the standard screening
interval for asymptomatic women of the same age. (pg 86)
GPP
GPP Despite evidence that it has no survival benefits, BSE is generally
recommended as it is felt to improve women’s awareness of their own
breasts and breast cancer. As the incidence of breast cancer is extremely
low before the age of 30 years, BSE is only recommended from the age of
30 years for normal risk women. (pg 84)
GPP
8
GPP When encountered, women with free silicone or paraffin oil
injections in their breasts should be clinically examined and counselled as
to the futility of screening using any currently available test. MRI may be
useful in highly selected cases where there is a strong suspicion of breast
cancer. (pg 87)
GPP
Screening for cervical cancer
B Well-run population-based cervical cancer screening programme with
good coverage reduces the incidence and mortality of cervical cancer.
(pg 96)
Grade B, Level IIa
B All women who have ever had sexual intercourse should have a Pap
smear by the age of 25 years. (pg 96)
Grade B, Level III
B Pap smear screening should be performed every 3 years. (pg 96)
Grade B, Level IIa
B Screening can be discontinued at age 65 years if the smear taken at age
65 years was negative and the previous smears were negative. (pg 96)
Grade B, Level III
B HIV positive women should be screened earlier and more frequently,
preferably annually. (pg 97)
Grade B, Level III
Screening for uterine cancer
B There is no indication that screening is warranted for women who are at
average or increased risk* for endometrial cancer. (pg 102)
Grade B, Level IIb
*Women may be regarded as being average risk, increased risk or high risk for
endometrial cancer.
C Hereditary Non-Polyposis Colorectal Cancer is a syndrome in which
there is an inherited tendency to develop colorectal cancer. Women with or
9
at risk for hereditary non-polyposis colorectal cancer (HNPCC) are
considered high risk and should be offered annual screening for
endometrial cancer with endometrial biopsy by age 35 years. (pg 102)
Grade C, Level IV
Screening for ovarian cancer
B Routine population screening for ovarian cancer by ultrasound, the
measurement of tumour markers, or pelvic examination is not
recommended. (pg 105)
Grade B, Level IIa
GPP There is insufficient evidence to recommend for or against the
screening of asymptomatic women at increased risk of developing ovarian
cancer. Experts suggest referral of these women to tertiary centres for
multimodal screening. (pg 106)
GPP
Screening for tuberculosis
A Tuberculin Skin Test (TST) screening for latent TB infection is
recommended only for identifying candidates for treatment of latent TB
infection (generally with isoniazid, INH). Therefore, it is recommended
only in persons at high risk of breakdown to TB disease. (pg 113)
Grade A, Level Ib
(Indiscriminate screening or erroneous selection of subjects could lead to
the needless administration of INH and the unnecessary exposure of these
subjects to the risk of drug-induced hepatitis which in some cases may be
fatal.)
B As a rule, mass chest X-ray screening for TB is not recommended.
(pg 114)
Grade B, Level III
Screening for hepatitis B
A All pregnant women should be tested for HBsAg during the early
antenatal visit. The test may be repeated in the third trimester if acute
10
hepatitis is suspected, an exposure to hepatitis has occurred or the woman
practices a high-risk behaviour such as intravenous drug abuse. (pg 120)
Grade A, Level Ib
A Serological screening for HBsAg and anti-HBs should be performed
pre-vaccination for all except newborn. (pg 121)
Grade A, Level Ib
A Persons who remain at risk of HBV infection such as health care
workers and dialysis patients should be screened using HBsAg and antiHBs and vaccinated against hepatitis B if the test is negative. Such
individuals should then be tested for response to the vaccination. (pg 121)
Grade A, Level Ib
B Screening high risk individuals like those with a family history of
hepatitis B infection, liver cancer or those at high behavioural risk should
be performed. They should be tested at baseline and whenever exposure is
suspected. (pg 121)
Grade B, Level IIa
C Routine screening for HBV infection in the general population is not
recommended but recommendations for screening may be made based on
cost-effectiveness analyses. Such analyses suggest that screening can be
cost-effective in groups with an HBV marker prevalence >20%. (pg 121)
Grade C, Level IV
Screening for renal diseases
C A healthy asymptomatic individual may undergo opportunistic
screening with urine dipstick examination. (pg 125)
Grade C, Level IV
C Specific individuals at increased risk (e.g. age over 50 years,
hypertension, smoking, diabetes and family history of renal disease) of
chronic renal disease should undergo annual dipstick testing for
proteinuria. (pg 125)
Grade C, Level IV
11
C Individuals at increased risk of developing chronic renal disease should
undergo testing of serum creatinine in order to estimate the level of
glomerular filtration rate. (pg 126)
Grade C, Level IV
C Individuals with a positive dipstick proteinuria should have a spot
urinary protein-creatinine ratio test to quantitate their proteinuria. (pg 125)
Grade C, Level IV
Screening for osteoporosis
C All individuals with prior fragility fractures during adulthood should be
considered for BMD measurement and osteoporosis treatment. (pg 133)
Grade C, Level IV
C Population screening using BMD is not recommended for
postmenopausal women. A case-finding strategy is preferred, measuring
BMD in individuals at highest risk for osteoporosis identified using
clinical evaluation tools such as OSTA or NOF guidelines, and clinical
risk factor evaluation. (pg 138)
Grade C, Level IV
C Women with osteoporosis, who are being monitored for progression or
who are being treated, should have a follow-up bone density measurement,
usually at an interval of at least one year. In women with osteopenia, a
reasonable interval might be 1 to 2 years, while in those with normal
BMD, a more reasonable interval may be 2 to 5 years. (pg 138)
Grade C, Level IV
C Screening is not recommended for premenopausal women and men.
BMD measurement should be considered in those at high risk for fracture.
(pg 138)
Grade C, Level IV
C BMD measurement should be considered in patients with high risk for
steroid-associated fractures, who are initiating or already on long-term
higher-dose corticosteroid therapy. (pg 138)
Grade C, Level IV
12
Screening for visual acuity for the elderly
B The population to be screened includes any person 65 years and above,
and the screening test involves using a Snellen chart to test each eye.
(pg 143)
Grade B, Level III
B Any person screened and found to have vision worse than 6/12 can be
referred for assessment and treatment. (pg 144)
Grade B, Level III
C The optimal frequency for screening is not known and is left to the
discretion of the screener. (pg 144)
Grade C, Level IV
C Besides visual acuity testing using the Snellen chart, there is
insufficient evidence to recommend for or against routine screening with
ophthalmoscopy by the primary care physician in asymptomatic elderly
patient. (pg 144)
Grade C, Level IV
Screening for other sexually transmitted infections
Chlamydia trachomatis infection
A Sexually active women with the following risk factors may be at higher
risk of chlamydial infection and should be considered for screening: those
aged 25 years and younger, who have a new sexual partner, who have
partners with symptoms of an STI or who have had two or more partners
in the past 12 months and lack the use of barrier contraception. (pg 147)
Grade A, Level Ib
A Women undergoing termination of pregnancy with risk factors (as
above) should be screened. (pg 147)
Grade A, Level Ib
B Pregnant women aged 25 years and younger and other pregnant women
at higher risk for infection (i.e. women who have had two or more sexual
partners in the past 12 months, or partners with symptoms of an STI)
should be considered for screening. (pg 147)
Grade B, Level IIb
13
C Women undergoing instrumentation of the uterus should be considered
for screening on an individual case basis because even in low prevalence
groups, there may be a resultant risk of ascending infection. (pg 147)
Grade C, Level IV
C Asymptomatic men with high-risk behaviour such as frequent partner
change, lack of use of barrier protection or sex with prostitutes can be
considered for screening. These patients should be referred to specialist
centres for counselling, and investigation. (pg 148)
Grade C, Level IV
A Screening can be performed using cultures or enzyme immunoassays
(EIA) on endocervical swabs in women and urethral swabs in men.
(pg 148)
Grade A, Level Ia
A Nucleic acid amplification tests (NAAT) using polymerase chain
reaction (PCR) or ligase chain reaction (LCR) can also be used in
screening on endocervical or urethral swabs, and have the advantage of
being used on non-invasive specimens such as urine. (pg 148)
Grade A, Level Ia
C Serological tests based on genus-specific complement fixation test are
not useful in the diagnosis of chlamydial genital infections, with the
possible exception of lymphogranuloma venereum. (pg 149)
Grade C, Level IV
GPP In men, a Gram-stained urethral smear taken 4 hours from the last
void of urine showing presence of 5 or more leukocytes per high-power
field indicates urethritis. This may be due to Chlamydia trachomatis or
other organisms, as well as other factors that may not be sexually
transmitted. These patients should be assessed by specialist centres for
counselling and advice. (pg 148)
GPP
GPP The optimal frequency of screening is a matter of clinical
discretion. Screening for chlamydia infection should be performed about 1
week after high-risk exposure or change of sex partner. (pg 149)
GPP
14
Syphilis
C All women and men at increased risk for infection, including sex
workers, persons who exchange sex for money or drugs, persons with
other STIs (including HIV) and genital ulceration, and sexual contacts of
persons with active syphilis should be screened. (pg 150)
Grade C, Level IV
B Pregnant women should be screened at their first antenatal visit.
(pg 151)
Grade B, Level III
C Pregnant women at higher risk of infection (i.e. women who have
partners with symptoms of an STI, or continue to engage in sexual activity
with multiple partners, or a partner who has sex with multiple partners)
should have screening repeated in the third trimester. (pg 151)
Grade C, Level IV
C Screening for syphilis is performed using nontreponemal tests such as
RPR or VDRL. Positive results should be confirmed with a specific test
such as TPPA or TPHA. Both nontreponemal and treponemal tests can be
combined for use in screening, although this would be more costly and
labour-intensive. (pg 152)
Grade C, Level IV
C Follow up serologic tests should be obtained to document declines in
titres after treatment. They should be performed using the same test
initially used to document infection (e.g. VDRL or RPR) to ensure
compatibility. (pg 153)
Grade C, Level IV
GPP The optimal frequency of screening is a matter of clinical
discretion. Screening for syphilis should be performed 1 month after
exposure, and repeated again after 3 months. (pg 152)
GPP
15
Gonorrhoea
C Women at high risk of infection – including sex workers, women with a
history of repeated episodes of gonorrhoea, and women with two or more
sex partners in the previous year should be screened. (pg 154)
Grade C, Level IV
GPP Homosexual men with frequent partner change or other high-risk
behaviour (i.e. those who have sex with partners with symptoms of an STI,
those who do not use barrier protection including unprotected receptive
and insertive oral and anal intercourse) should be considered for screening.
(pg 154)
GPP
C The ideal screening test is isolation of Neisseria gonorrhoeae by culture
from the appropriate sites. (pg 154)
Grade C, Level IV
GPP Sites to be sampled will be determined by the history of sexual
contact – urethra, cervix, rectum or pharynx. (pg 155)
GPP
GPP The optimal frequency of screening is a matter of clinical
discretion. Screening for gonorrhoea should be performed about 1 week
after exposure. (pg 155)
GPP
Genital Herpes Simplex
GPP Routine screening for genital herpes simplex virus (HSV) infection
by viral culture, serology or other means is not recommended for
asymptomatic men or women, including asymptomatic pregnant women.
(pg 155)
GPP
HIV
C Clinicians should assess risk factors for HIV infection in all persons by
obtaining a careful sexual history and inquiring about drug use. (pg 156)
Grade C, Level IV
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C Counselling and testing for HIV should be offered to all persons at
increased risk of infection. These include those seeking treatment for STI;
men who have sex with men; past or present injecting drug users; persons
who exchange sex for drugs or money and their sex partners; persons
whose past or present sex partners were HIV-infected, and persons who
have had a blood transfusion or an organ transplant that had not previously
been screened. (pg 156)
Grade C, Level IV
GPP Pregnant women should be offered the test in the first trimester.
(pg 157)
GPP
C Screening for HIV is performed using ELISA. A positive result requires
2 reactive ELISA tests and confirmation with the Western Blot (WB)
assay, performed by experienced laboratories that receive regular external
proficiency testing. (pg 157)
Grade C, Level IV
C Persons who continue to exhibit high-risk behaviour should have
screening tests on a regular basis. The frequency at which these
individuals are screened is a matter of clinical discretion. Screening for
HIV should be performed 6-monthly in a person who continues to exhibit
high-risk behaviour. (pg 157)
Grade C, Level IV
C Persons with recent high-risk behaviour should be screened at 1 month,
3 months and 6 months after the last high-risk exposure to rule out a
possible initial false negative result. (pg 157)
Grade C, Level IV
Genital Human Papillomavirus (HPV) infection
C Women with a history of STI may be at increased risk for cervical
cancer, which is linked to certain HPV types. However, the HPV types that
frequently cause anogenital warts do not cause cancer. The Pap smear is a
screening test for cervical carcinoma and not a screening test for STIs, and
women who have external genital warts do not need to have Pap smears
more frequently than women who do not have warts. (pg 158)
Grade C, Level IV
17
C Clinical examination with the unaided eye is the oldest diagnostic
technique in detection of genital warts. However, subclinical genital HPV
infection, a term used to refer to manifestations of infection in the absence
of genital warts, may still exist. No screening tests for subclinical infection
are available, and there are no recommendations for routine screening.
(pg 158)
Grade C, Level IV
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