NATIONAL INSTITUTE FOR HEALTH AND CLINICAL
EXCELLENCE
Diagnostics Assessment Programme
Adjunctive colposcopy technologies for examination of the
uterine cervix - DySIS, LuViva Advanced Cervical Scan, Niris
Imaging System and Zilico APX-100
Final scope
September, 2011
1. Introduction
The Medical Technologies Advisory Committee identified DySIS (DySIS
Medical) as potentially suitable for evaluation by the Diagnostics Assessment
Programme (DAP) on the basis of a briefing note. Scoping research carried
out by the DAP team identified three other technologies for potential inclusion
in the evaluation. These technologies include LuViva Advanced Cervical Scan
(Guided Therapeutics), Niris (Imalux Corporation) and Zilico APX 100 (Zilico
Ltd.) Attendees at the scoping workshop held on 25th July, 2011 supported the
inclusion of these technologies in the evaluation.
The scope outlines the approach for assessing the clinical and cost
effectiveness of these four technologies for use as colposcopy adjuncts. For
the purpose of this document, all four technologies are collectively referred to
as “adjunctive colposcopy technologies”.
2. Description of the technologies
This section describes the properties of the adjunctive colposcopy
technologies based on information provided to NICE by the manufacturers
and on information available in the public domain. NICE has not carried out an
independent evaluation of these descriptions.
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2.1.
Purpose of the medical technologies
The major role of colposcopy is in guiding diagnostic biopsy. If any abnormal
area is identified, a biopsy is taken and sent for histological analysis, or in
some cases treated immediately. Colposcopy defines the type and extent of
the abnormal area and allows the clinician to determine the grade of cervical
intraepithelial neoplasia (CIN).
The four technologies included in this evaluation are adjuncts to the standard
colposcope and have been designed for use during colposcopy examination
in the current care pathway. The four technologies, while using different
mechanisms, aim to aid in the selection of biopsy sites with improved
diagnostic accuracy.
2.2.
Product properties
DySIS (DySIS Medical): DySIS is an integrated digital image analysing
(optical) system combined with a colposcope that evaluates the blanching
effect of applying acetic acid to the epithelium (acetowhitening). It produces a
quantitative measurement of the rate, extent and duration of the
acetowhitening. The dynamic map produced can be overlaid on a colour
image of the tissue to assist the clinician to determine the presence and grade
of any neoplastic lesion.
DySIS has an optical head that provides uniform illumination with a focused
and collimated white light-emitting diode, and imaging with magnification
optics coupled to a 1,024 × 768, 8-bit/channel digital color charge-coupled
device (CCD) camera. The camera is interfaced with a computer and control
electronics unit and with a thin film transistor (TFT) monitor for image and
data display. To reduce surface reflections that might obscure the
acetowhitening effect, linear polarisers are placed in both the imaging and
illumination pathways, with their polarization axes perpendicular to each other.
The optical head has a typical working distance of 25 cm and does not come
in contact with the tissue. It captures images from a 23 mm × 20 mm area,
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including the transformation zone of the cervix. The optical head is mounted
on a mechanical arm to position and stabilize it, and locked onto an extension
shaft attached to the speculum, in order to position the acetic acid sprayer in a
position that optimises the spray pattern and also to ensure a stable field-ofview during image acquisition. For this reason, the speculum used with DySIS
is different from that used in conventional colposcopes.
LuViva Advanced Cervical Scan (Guided Therapeutics): This is a noninvasive device designed to be used either in primary care to augment current
cervical testing or as an additional test in women referred for investigation of
abnormal smear results or symptoms. The device uses optical spectroscopy
which shines light directly onto the surface of the cervix and analyses the
resulting fluorescence and reflection to identify areas where there may be
cellular changes.
The device consists of a base unit with a results display, and a single-use
guide. The guide is placed on the surface of the cervix which it automatically
scans using a light source and multimodal spectroscopy. By measuring the
nature of the resulting fluorescence and reflection, changes in the
biochemistry and structure of the cervical cells are detected and suspect
areas identified and displayed. Setting up the LuViva device takes 3-4
minutes. Scanning takes around 60 seconds and the results are displayed
immediately. It is claimed that the device may reduce the need to refer women
for further investigation, and may improve targeting and/or reduce
unnecessary cervical biopsies.
Niris Imaging System (Imalux Corporation): This is a non-invasive device
designed to be a valuable tool to aid in the detection and diagnosis of
diseases in their earliest stages, precise guidance of biopsy and surgery, and
in post-treatment surveillance in a multitude of clinical applications, one of
which is as an adjunct to colposcopy. It uses optical coherence tomography,
using harmless, near infrared light to produce real-time, high resolution, crosssectional imaging of tissue microstructure to aid in identifying a broad range of
diseases and abnormalities.
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A major strength of Niris is the ability to scan epithelial tissue. Niris provides
an optical biopsy by visualizing tissue microstructure to a depth of 1.6mm and
produces high spatial resolution cross-sectional images of tissue
microstructure.
The device consists of an image management console and docking station, a
laptop computer user interface, a 2.7mm front viewing, flexible, optical probe
and accessories. Recent enhancements include faster image acquisition and
measurement tools that give the healthcare professional the ability to analyze
and compare image data in real-time and at site of care. The average length
of use per treatment is 2 minutes.
Zilico APX 100 (Zilico Ltd): The APX 100 is a hand-held, point-of-care
device that uses electrical impedance spectroscopy to detect the presence of
cervical neoplasia. It is designed be used as an adjunct to colposcopy, aiding
the selection of biopsy sites and improving the diagnostic accuracy of current
procedures.
The APX 100 uses electrical impedance spectroscopy to measure the
impedance (resistivity) of cervical epithelium cells across a range of
frequencies and produce a spectrum showing the change of impedance with
frequency. The size of the impedance and the dependence of impedance on
frequency can both be related to the underlying cervical tissue structure.
Cervical neoplasia is associated with disorganization in the layer of flattened
epithelial cells on the surface of the cervix. The APX 100 uses this structural
change in the cervical epithelium to differentiate between cervical neoplasia
and healthy epithelium.
The device comprises a handset which takes impedance readings from the
cervical epithelium and a single-use disposable sleeve that covers the part of
the handset which comes into contact with the patient‟s cervix. A base station
charges the handset, collects the data and transfers it to a PC for storage.
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The test procedure involves taking a series of readings on the surface of the
cervix (8-15 readings depending on the size of the cervix), concentrating on
the transformation zone. This is said to take about 2 minutes and the data is
then analyzed in real-time. The analysis compares the patient spectra with
reference spectra derived from models of different cervical tissues and
calculates the probability that high-grade neoplasia is present at each reading
site. The results will show which readings, if any, indicate sites of high-grade
cervical intra-epithelial neoplasia (CIN) and the exact location for the biopsy
will be determined using the device in a second, single-point, operating mode.
In this mode the APX-100 will immediately indicate when it has been placed
onto high-grade CIN and the biopsy can be taken at this point or the patient
could be offered immediate treatment.
The primary application of the APX 100 is as an adjunct to colposcopy during
the colposcopic examination within the existing clinical pathway. It is said to
improve clinical management of patients by correctly identifying the presence
of high-grade neoplasia, reducing the number of false-negative and falsepositive results associated with current procedures. The results from the APX
100 are claimed to be objective and based on a detailed understanding of the
structure of the cervical epithelium and how it changes as neoplasia develops.
3. Description of the comparator
Conventional colposcopy is the comparator in the evaluation of adjunctive
colposcopy technologies. Colposcopy is an essential part of the NHS cervical
screening programme (NHSCSP). The purpose of carrying out a colposcopic
examination is to diagnose lesions in a cervix that is already suspected of
abnormality.
A colposcope is a low-power, stereoscopic, binocular field microscope with a
powerful light source used for magnified visual examination of the uterine
cervix to help in the diagnosis of cervical neoplasia. During the examination,
the features of the cervical epithelium are observed after the application of
normal saline, 3-5% acetic acid and Lugol‟s iodine in successive steps. As
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already mentioned, the application of acetic acid on abnormal epithelium
results in acetowhitening.
Acetowhitening is not unique to CIN and early cancer. It is also seen in other
situations such as immature squamous metaplasia, congenital transformation
zone, healing epithelium (associated with inflammation), leukoplakia and
condyloma.
According to NHSCSP guidelines (2010), the predictive value of a colposcopic
diagnosis of a high grade lesion (CIN 2 or worse) should be at least 65%. The
guideline also states that “colposcopists should be able to differentiate high
grade lesions (intraepithelial or otherwise) from low grade lesions in order to
avoid missing advanced disease and to reduce overtreatment for low grade
lesions”.
In colposcopy, there is considerable inter- and intra-observer variation in the
grading of CIN, particularly in low grade lesions. A meta-analysis on the
diagnosis of squamous CIN showed colposcopy to have a mean weighted
sensitivity of 96% and specificity of 48% when comparing normal with all
cervical abnormalities. Comparison of low-grade CIN with high-grade CIN and
cancer showed that the mean weighted sensitivity is 85% (range 30-99%) and
specificity is 69% (Mitchell et al, 1998). More recent studies have suggested
much poorer sensitivity of colposcopy (Jeronimo and Schiffman, 2006).
4. Target condition/indication
4.1.
Cervical cancer background
In 2007, there were 2828 new cases of cervical cancer diagnosed in the UK,
making it the 11th most common cancer in women and one that accounts for
2% of all cancers (Cancer Research UK, 2010).
The cervix is the lower part of the uterus (womb) and connects the uterus to
the vagina. The part of the cervix closest to the uterus is called the endocervix
and is lined by columnar cells. The part closest to the vagina is called the
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ectocervix and is lined by squamous epithelial cells. The point at which the
two types of cells meet is called the squamocolumnar junction. The location of
the squamocolumnar junction varies over a woman‟s lifetime and depends on
factors such as age, hormonal status, birth trauma, oral contraceptive use and
certain physiological conditions such as pregnancy. During puberty, the
influence of estrogen causes the cervix to swell and enlarge resulting in the
relocation of the squamocolumnar junction from the inner to the outer cervix.
Once this occurs, the columnar cells are exposed to the acidic environment in
the outer cervix leading to the destruction and replacement of columnar
epithelium by metaplastic squamous epithelium. This area, known as the
transformation zone, is where most cervical carcinogenesis occurs.
When squamous metaplasia occurs in the transformation zone, it is
irreversible. The newly formed metaplastic squamous epithelium may develop
further in two directions. In the majority of women, it may develop into a
mature squamous metaplastic epithelium, while in a very small minority of
women an atypical dysplastic epithelium may develop.
The squamous metaplastic cells can be infected by certain types of human
papilloma viruses (HPV) and transform into atypical cells with nuclear and
cytoplasmic abnormalities. There are over 100 subtypes of HPV, most of
which do not cause significant diseases in humans. Some subtypes of HPV
(notably 16 and 18) have been confirmed as agents causing cervical cancer
(and these are known as high-risk HPV ((HR-HPV). Women infected with HRHPV are at an increased risk of cervical intraepithelial neoplasia. The
uncontrolled proliferation and expansion of squamous metaplastic cells may
lead to the formation of an abnormal dysplastic epithelium which may regress
to normal, persist as dysplasia, or progress into invasive cancer after several
years (See Figure 1).
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Figure 1: Progression from normal cervix to invasive cancer (Kerkar and Kulkarni, 2006)
Normal cervix
HPV related changes
(80% regress)
20% progress
Low grade SIL
(60-80% regress)
15-20% progress within 2-3 years
High grade SIL
30-79% progress in 10 years
Invasive cervical cancer
4.2.
The NHS Cervical Screening Programme (NHSCSP)
The NHSCSP was set up in 1998 with the aim of reducing both the incidence
and mortality of invasive cervical cancer by screening all women at risk on a
regular basis. At present, all women between the ages of 25 and 64 are
eligible for a free cervical screen test every 3-5 years. The interval between
successive screening tests depends on the woman‟s age, as follows:
Age 25 years: first invitation
Age 25-49 years: every 3 years
Age 50-64 years: every 5 years
Age 65 years and over: those who have not been screened since age 50
or who have had recent abnormal tests
4.3.
Cytology in cervical cancer
Cervical screening is a test to check the health of the cervix and is not a test
for diagnosing cervical cancer. At this stage of the screening process, a
sample of cervical cells is sent to a laboratory to be studied under a
microscope. The results of the screening phase are based on cytology. There
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are 3 main terminology systems of reporting cytology results. Table 1 below,
shows a comparison of cytology classification systems.
Table 1: Comparison of Cytology classification systems
Bethesda System
Dyskaryosis System
Papanicolaou System
Normal limits
Infection
Reactive and reparative
changes
Atypical squamous cells
of undetermined
significance
Low grade squamous
intraepithelial lesion
(LSIL)
High grade squamous
intraepithelial lesion
(HSIL)
Squamous cell
carcinoma
Normal
Inflammatory atypia
I
II
Squamous atypia / HPV
atypia
IIR
Mild dyskaryosis
Moderate dyskaryosis
Severe dyskaryosis
Carcinoma in-situ
Squamous cell
carcinoma
III
IV
V
At the scoping workshop, it was agreed that the dyskaryosis terminology
should be used in reporting the results of this assessment where possible.
In addition to cytology, cells obtained from the cervix are also tested for HPV.
Referral to colposcopy depends on cytology results and the presence or
absence of HPV. According to recent guidelines (NHSCSP, 2011), women
with borderline and mild dyskaryosis on cytology who are also HPV positive
should be referred for colposcopy. Those who are HPV negative are returned
to routine recall (see table 2).
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Table 2: HPV triage management for borderline and mild dyskaryosis
HPV triage management
Cytology Result
HPV positive
HPV negative
Borderline
Refer to colposcopy
Routine recall
Mild Dyskaryosis
Refer to colposcopy
Routine recall
Other reasons for referral to a colposcopy clinic as given in previous NHSCSP
guidelines (2010) include:
3 consecutive inadequate samples.
1 test reported as moderate dyskaryosis
1 test reported as severe dyskaryosis.
1 test reported as possible invasion.
1 test reported as possible glandular neoplasia.
4.4.
Histology in cervical cancer
Excisional biopsy, taken during a colposcopy exam, combined with histology
is the gold standard in detecting high-grade CIN, but its reliability depends on
accurately taking the biopsy from the correctly identified site with the greatest
sum of abnormal characteristics. It has been shown that there is an imperfect
correlation between the visual changes of the cervical epithelium and the
severity of the preneoplastic and neoplastic changes. Histology results are
reported using one of the 3 terminology systems shown in table 3 below.
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Table 3: Terminology systems for histology results
Dysplasia Terminology
Original CIN
terminology
Modified CIN
terminology
Normal
Normal
Normal
Atypia
Koliocytic atypia, flat
condyloma, without
epithelial changes
Low-grade CIN
Mild dysplasia
CIN 1
Low-grade CIN
Moderate dysplasia
CIN 2
High-grade CIN
Severe dysplasia
CIN 3
High-grade CIN
Carcinoma in-situ
CIN 3
High-grade CIN
Invasive carcinoma
Invasive carcinoma
Invasive carcinoma
At the scoping workshop, it was agreed that the modified CIN terminology
should be used in reporting the results of this assessment where possible.
5. Scope of the evaluation
5.1.
Population
There are over 400,000 colposcopy appointments each year, 134,000 of
which are new referrals (Flanagan et al, 2011). This figure is based on the
previous care pathway. The introduction of HPV-triage to the pathway may
change the number of women referred for colposcopy.
Based on discussions at the scoping workshop and at the assessment subgroup meeting, the population for the assessment is women referred for
colposcopy due to any of the reasons listed in section 4.3. Separate analyses
will be performed according to incoming cytology findings. There are 2 groups
of cytology findings; low grade squamous intraepithelial lesions (borderline
and mild dyskaryosis) and high grade squamous intraepithelial lesions
(moderate and severe dyskaryosis). Other reasons for referral such as
suspicious cervix and post-coital bleeding are not included in the scope for
this evaluation.
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5.2.
Intervention
The interventions for this evaluation are the four adjunctive colposcopy
technologies. These are DySIS, LuViva Advanced Cervical Scan, Niris
Imaging System and Zilico APX-100.
5.3.
Comparator
In this assessment, conventional colposcopy will be the comparator to all four
adjunctive colposcopy technologies.
5.4.
Healthcare setting
The four technologies are all colposcopy adjuncts. As such, they could be
used in any setting where a colposcope is used. This would primarily be a
secondary care setting. However, in a few parts of England, colposcopy
examination is being trialled in primary care settings.
5.5.
Health outcomes
Intermediate measures from the diagnostic procedures include:
diagnostic test accuracy (sensitivity and specificity)
indeterminacy (test failure rate).
Direct outcomes from the test include side effects associated with colposcopy
such as bleeding post biopsy, pain/discomfort experienced during the
procedure and waiting times before results.
The indirect clinical outcomes associated with colposcopy as a result of being
classified as true negative, true positive, false negative or false positive may
include:
1. Number of biopsies undertaken
2. Morbidity and mortality from cancer
3. Morbidity and mortality from treatment and biopsies.
4. Patient throughput
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5. Patient compliance and number of patients who are
appropriately treated (as a result of improved see and treat
policy).
Data on these indirect outcomes are likely to be used along with clinical utility
scores to estimate QALYs as final health outcomes.
5.6.
Care pathway
The care pathway outlined below is from the NHSCSP‟s 2010 guidelines titled
„Colposcopy and Programme Management‟ and 2011 guidelines titled „HPV
triage and test of cure implementation‟ guide. .
Diagnosis
As mentioned above, referral for colposcopy is based on cytology results and
HPV infection. Diagnosis is made after colposcopy and can be based on
colposcopy results alone, or on colposcopy and histology results (if a biopsy is
taken during examination). Histological results can be normal, low-grade CIN,
high-grade CIN or invasive carcinoma (See table 3). .
If colposcopy shows acetowhitening (i.e is abnormal) a punch biopsy is taken
for histological analysis. If the whole transformation zone is not visible, the
woman can be placed under observation. Alternatively, a diagnostic excisional
procedure should be performed. This could be either a cold knife or loop
electrosurgical excision procedure (LEEP) conisation. Excisional biopsy
provides diagnostic information as well as therapeutic benefit.
Management/treatment
The appropriate management of women with CIN is based on colposcopy
results and is of critical importance to the success of the NHS cervical
screening programme. Four possible outcomes of a colposcopic exam and
histology are:
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I.
Normal: If the whole transformation zone is visible and is normal, the
woman is discharged and returned to routine cervical screening
intervals.
II.
Low-grade CIN: Women diagnosed with low-grade CIN should be
allowed to choose between immediate treatment and being placed
under observation (to be treated only if regression does not occur after
24 months). There is a high level of intra-observer and inter-observer
variability in the histological diagnosis of CIN 1 with an expert
pathology review committee downgrading 41 percent of CIN 1
diagnoses to normal and upgrading 13 percent to CIN 2 (Spitzer et al,
2006). When colposcopy is satisfactory observation without treatment
is recommended because most cases of CIN 1 will regress (Shafi et al,
1997 and Nasiell et al, 1986). If the woman chooses immediate
treatment, the cinician can perform either ablation or loop
electrosurgical excision procedure (LEEP).
III.
High-grade CIN: Women diagnosed with high-grade CIN should be
given immediate treatment. Approximately 43% of untreated CIN 2 and
32% of CIN 3 will regress spontaneously; 35% of CIN 2 and 56% of
CIN 3 will persist; and 22% of CIN 2 and 14% of CIN 3 will progress to
carcinoma-in-situ or invasive cancer (Mitchell et al, 1996). Treatment is
therefore essential in cases of high-grade CIN and involves the
removal of the whole transformation zone rather than the lesion alone.
Treatment can be either a cold knife or loop electrosurgical excision
procedure (LEEP) conisation. Figure 2 below shows the NHSCSP
(2011) protocol for managing abnormal cytology in women with the
introduction of HPV triage and HPV test for cure.
IV.
Invasive Carcinoma: Management of invasive carcinoma can be either
surgical (for example radical hysterectomy which involves the en-bloc
removal of the uterus, cervix and upper vagina) or non-surgical in the
form of radiotherapy, chemotherapy, or chemoradiotherapy.
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Figure 2: Protocol for managing women with borderline and mild dyskaryosis
Treatment Strategy
There is a variation in the management of women with moderate or severe
dyskaryosis who are referred for colposcopy. Some clinicians use a 2
appointment strategy where they take a punch biopsy in the first appointment
and treat in the second. Other clinicians prefer a see and treat approach
where the woman undergoes colposcopy exam and is treated in the same
appointment. One of the reasons behind taking a see and treat approach is
the fear of the woman failing to attend the second appointment. A sensitivity
analysis may be carried out during the assessment in order to determine at
what point of probability of non-return does see and treat become preferable
over the 2 appointment approach.
Follow-up
All women remain at risk following treatment and must be followed-up. The
NHSCSP 2011 guidelines recommend HR-HPV testing of women who have
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been treated for any grade of CIN in order to assess their risk of having
residual or recurrent disease. It applies to all women attending their first posttreatment follow up appointment or cytology test, irrespective of the grade of
treated CIN, and all women in annual follow up after treatment for CIN. The
guideline recommends for:
a) Treated women
All women entering the test of cure who have normal, borderline or mild
cytology and are HR-HPV will be invited for their next cytology test in 3
years regardless of their age. If at 3 years their cytology result is negative,
women aged over 50 years should revert to their normal recall pattern
(every 5 years). Women with moderate or worse cytology, whatever their
age, will be referred to colposcopy.
If a woman fails to attend colposcopy following treatment and returns to the
care of her GP before her first follow-up cytology, she should still be
included in the test of cure protocol.
A woman will be referred to colposcopy if test of cure shows borderline
changes or mild dyskaryosis or normal cytology and she is HR-HPV
positive. If colposcopy is satisfactory and negative she can be recalled in 3
years.
Women who reach 65 must be invited for screening until the protocol is
complete and otherwise comply with national guidance.
Women aged over 60 who have borderline changes or mild dyskaryosis
and test HR-HPV negative at triage can be ceased from the NHSCSP as
their next test-due date would be after 65.
Women aged over 60 who have mild, borderline or normal cytology and are
HR-HPV negative at test of cure will return for a further cytology test 3
years later, regardless of whether or not they will be aged over 65 when the
test is due. Only if this further cytology test is normal can they be ceased
from the programme.
b) Untreated women
Women with biopsy-proven untreated CIN1 will be managed by cytology at
12 months with or without colposcopy, depending on local practice. If
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cytology is borderline, repeat HPV triage. If it is not, follow up of 12 months
cytology alone should be in accordance with NHSCSP protocols.
Women who default from colposcopy should be referred once again when
they have their next cytology test, regardless of the test result. In these
circumstances no HPV test is required.
6. Modelling approach
Sufficient data is needed to allow economic modelling to proceed. The level of
data required will be set by the external assessment group (EAG).
6.1.
Modelling possibilities
Few areas of economic evaluation in diagnostics have the necessary
evidence required to determine cost-effectiveness forthcoming from a single
empirical study. Under such circumstances, decision analytic modelling
techniques are employed to combine data from different sources in order to
estimate long-term outcomes, and to attach cost and utility weights (Karnon et
al, 2004).
The aim and structure of the model will depend upon the NHSCSP guidelines
outlined in the final scope and the nature of the data obtained during the
systematic review of the assessment. .
6.2.
Existing Models
The University of Sheffield‟s School of Health and Related Research
(ScHARR) has developed a colposcopy capacity model and a colposcopy
clinical-effectiveness model in order to assess the impact of policy changes,
including the mild referral policy (referral to colposcopy after one mild
dyskaryosis result), upon the capacity and cost-effectiveness of colposcopy
clinics. Another model explored the health economic impact of liquid base
cytology (LBC) within the UK (Karnon et al, 2004).
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6.3.
Model structure
As no end-to-end studies were identified during the scoping phase, it is likely
that a linked evidence approach will need to be used in the modelling. The
intermediate measures and direct outcomes of the diagnostic strategies
employed will need to be related to changes in final health outcomes.
One question that may be addressed by the model is: “What would be the
likely impact of the new technology in terms of health outcomes, costs and
cost-effectiveness, when compared with conventional colposcopy practice?”
The model could be structured to have three or four elements. These could
be:
1. A diagnostic model
2. A state transition model to stimulate the natural history of the
disease
3. A model that reflects age-specific all-cause mortality.
Health outcomes, resource utilisation and costs can all be estimated. A health
service perspective of costs should be taken in the analysis and only direct
costs should be considered.
6.4.
Cost considerations
The costs of the adjunctive colposcopy technologies in this evaluation are
given in table 4 below. The costs have been provided to NICE by the
manufacturers.
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Table 4: Cost of adjunctive technologies and comparator
DySIS
LuViva
Niris
Indicative price of
£18,000 -
technology
£22,000
£11,500
$49,500.00
Zilico
Standard
APX100
colposcope
£2000
£6,000 -
US (+taxes
£12,000
+shipping)
Consumables
£3.50 per
Cervical
Probe (200
APX100
£2.00 per
examination
Guide
uses) $ 2,
single use,
examination
for a
£17.25 list
700 US.
disposable
for a
disposable
price, use
sleeve £20
disposable
cervical
one per
(one per
cervical
speculum
patient
patient)
speculum
N/A
10% of the
Sterile
disposable
sheath
(single use)
$ 30.00 US
each
Service/
£1600 per
Replace light
Not
maintenance cost
year for
source (bulb)
applicable
and frequency (if
maintenance
about once
typically
applicable)
contract after
every two
charged for a
warranty
years @
service
expires
£320
contract
5 years
5 years
Anticipated life
7-10 years
span of technology
Average length of
list price is
3 years for
5 years
the device
<15 minutes
use per treatment
Scan time is
4 minutes
2 minutes
< 15 minutes
about one
minute
Average frequency
<400,000.
Once per
Once per
5-10
400,000
of use
Reduction in
colposcopy
colposcopy
times/day
patients per
the number
referral
annum of
of patients
which 51%
recalled for
are recalls
colposcopy
examination
Further costs to be considered include:
a. Staff and training of staff
b. Medical costs arising from ongoing care following test results
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7. Equality issues
No potential equality issues have been identified in relation to this technology,
but there is evidence that cervical cancer may be more prevalent in certain
ethnic groups. Discussions at the scoping workshop highlighted the fact that
the rate of default in colposcopy, particularly in recall appointments, is higher
in deprived areas.
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Appendix A
Glossary
Acetowhitening
It is blanching of skin or mucous membranes after application of 3–5% acetic
acid solution. It is a sign of increased cellular protein and increased nuclear
density
Biopsy
An examination of the cellular characteristics of a tissue using a microscope
Chemoradiotherapy
The combination of simultaneous chemotherapy and radiation therapy.
Colposcopy
A procedure where the lining of the cervix (the neck of the womb) is closely
examined. A colposcopist uses a magnifying instrument called a colposcope
to check the cells that line the cervix for abnormalities.
Condyloma
It is a growth resembling a wart on the skin or a mucous membrane, usually of
the genitals or anus. Condyloma is also known as wart, genital wart,
venereal wart, and all are caused the human papilloma virus
Cytology
Cytology, more commonly known as cell biology, studies cell structure, cell
composition, and the interaction of cells with other cells and the larger
environment in which they exist. The term "cytology" can also refer to
cytopathology, which analyzes cell structure to diagnose disease.
Dyskaryosis
It is a condition in which some of the epithelial cells near the external orifice of
the uterus show abnormalities in their cellular nuclei
Dysplasia
Cervical dysplasia refers to abnormal changes in the cells on the surface of
the cervix that are seen underneath a microscope. Although these changes
are not cancer, they can lead to cancer of the cervix if not treated
Histology
It is the study of the microscopic anatomy of cells and tissues of plants and
animals
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Leukoplakia
It is a clinical term used to describe patches of keratosis (growth of keratin). It
is visible as adherent white patches on the mucous membranes of the oral
cavity, including the tongue, but also other areas of the gastro-intestinal tract,
urinary tract and the genitals
Neoplaisa
It is the process of abnormal and uncontrolled growth of cells.
Radical Hysterectomy
Radical hysterectomy refers to the excision of the uterus en bloc with the
parametrium (ie, round, broad, cardinal, and uterosacral ligaments) and the
upper one-third to one-half of the vagina, with the ovaries left intact.
Radiotherapy
It is the medical use of ionizing radiation, generally as part of cancer treatment
to control malignant cells.
Sensitivity
Sensitivity is a measure of how likely it is for a test to pick up the presence of
a disease in a person who has it. It is a measure of the probability of correctly
diagnosing a condition
Specificity
It is the probability that the test says a person does not have the disease
when in fact they are disease free. It is a measure of the probability of
correctly identifying a person who does not have the condition..
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Appendix B
Abbreviations
CIN
Cervical Intraepithelial Neoplasia
DAP
Diagnostic Assessment Programme
HPV
Human Papilloma Virus
NHS
National Health Service
NHSCSP
NHS Cervical Screening Programme
NICE
National Institute for Health and Clinical Excellence
SCJ
Squamocolumnar Junction
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Appendix C
Related NICE guidance
NICE Technology Appraisal Guidance 69. Guidance on the use of
liquid-based dytology for cervical screening. October 2003. Available:
http://www.nice.org.uk/nicemedia/live/11514/32743/32743.pdf
NICE Technology Appraisal Guidance 183. Topotecan for the
treatment of recurrent carcinoma of the cervix. Available:
http://guidance.nice.org.uk/TA183
NICE Interventional Procedures Guidance 160. High dose
brachytherapy for carcinoma. March 2006. Available
http://guidance.nice.org.uk/IPG160
NICE Interventional Procedures Guidance 338. Laparoscopic radical
hysterectomy for early stage cervical cancer. Available:
http://guidance.nice.org.uk/IPG338
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Appendix D
References
Cancer Research UK. (2010). Cervical cancer- UK incidence and
statistics. Available:
http://info.cancerresearchuk.org/cancerstats/types/cervix/incidence/.
Last accessed 23rd June 2011.
Flanagan, S. M., Wilson, S., Luesley, D., Damery, S. L., and
Greenfield, S. M. (2011). Adverse outcomes after colposcopy. BMC
Women’s Health. 11 (2).
Jeronimo, J and Schiffman, M. (2006). Colposcopy at a crossroads.
American Journal of Obstetrics and Gynaecology. 195 (2), 349-353.
Karnon, J., Peters, J., Platt, J., Chilcott, J., McGoogan, E. and Brewer,
N. (2004). Liquid-based cytology in cervical screening: an updated
rapid and economic analysis. Health Technology Assessment. 8 (20).
Kerkar, R. A. and Kulkarni, Y. V.. (2006). Screening for cervical cancer:
an overview. The Journal of Obstetrics and Gynaecology of India.
56(2), 115-122.
Mitchell, M.F., Schottenfeld, D., Tortolero-Luna, G., Cantor, S.B.,
Richards-Kortum, R. (1998). Colposcopy for the diagnosis of squamous
intraepithelial lesions: a meta-analysis. Obstetrics and Gynaecology. 91
(4), 626-631.
Mitchell, M.F., Tortolero-Luna, G., Wright, T., Sarkar, A., RichardsKortum, R., Hong, W.K. and Schottenfeld, D. (1996). Cervical human
papillomavirus infection and intraepithelial neoplasia: a review. Journal
of the National Cancer Institute. Monographs. 21 (1), 17-25.
Nasiell, K., Roger, V. and Nasiell M. (1986). Behavior of mild cervical
dysplasia during long-term follow-up. Obstetrics and Gynaecology. 67
(5), 665-669.
NHS Cervical Screening Programme (NHSCSP) (2010). Colposcopy
and programme management: Guidelines for the NHS Cervical
Screening Programme. 2nd ed. UK: NHSCSP. 10-17.
NHS Cervical Screening Programme (NHSCSP) (2011). HPV triage
and test of cure implementation guide.
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Shari, M.I., Lesley, D.M., Jordan, J.A., Dunn, J.A., Rolla son, T.P. and
Yates, M. (1997). Randomised trial of immediate versus deferred
treatment strategies for the management of minor cervical cytological
abnormalities. British Journal of Obstetrics and Gynaecology. 104 (5),
590-594.
Spitzer, M., Agar, B.S., Boltzmann, G.L. (2006). Management of
histological abnormalities of the cervix. American Family Physician. 73
(1), 105-112.
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Appendix E
Attendees of the assessment subgroup
meeting
The following people were in attendance at the assessment subgroup meeting
held on 1st September 2011:
External
Assessment Group
SCM
Name of representative
Job Title
Organisation
Alison Eastwood
Senior Research Fellow
Centre for Reviews and Dissemination,
The University of York
Eldon Spackman
Research Fellow
Centre for Health Economics, The
University of York
Mark Corbett
Research Fellow
Centre for Reviews and Dissemination,
The University of York
Mark Sculpher
Professor of Health Economics
Centre for Health Economics, The
University of York
Ros Wade
Research Fellow
Centre for Reviews and Dissemination,
The University of York
Simon Walker
Researcher
Centre for Health Economics, The
University of York
Robert Music
Director
Jo's Cervical Cancer Trust
Clinical Senior Lecturer in
Gynaecological Oncology
Imperial College London
Sadaf Ghaem-Maghami
Pierre Martin Hirsch
Consultant Gynaecologist
Lancashire Teaching Hospitals
Andrew Fish
Consultant Gynaecologist
Brighton and Sussex University
Hospitals NHS Trust
Phyllis Dunn
Clinical Lead Nurse
University Hospital of North
Staffordshire
SCM
SCM
SCM
SCM
NICE staff in attendance:
Name
Title
E-mail
Nick Crabb
Associate Director, Diagnostics Assessment
Programme
[email protected]
Hanan Bell
Technical Adviser, Diagnostics Assessment
Programme
[email protected]
Jackson Lynn
Project Manager, Diagnostics Assessment
Programme
[email protected]
Farouk Saeed
Technical Analyst, Diagnostics Assessment
Programme
[email protected]
Sarah Baggaley
Technical Analyst, Diagnostics Assessment
Programme
[email protected]
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