Introduced early in the last century (1925) by Hinselman
Visualisation of the lower genital tract before and after
applying an acetic acid solution under magnification
with an appropriate light source
Introduction Introduction
Colposcopy as a Colposcopy as a screening toolscreening tool
Combination of cytology & colposcopy in primary screening to
reduce the impact of false negative results of cytology
Cervical cytology :Cervical cytology : reported by Georgios Papanicolaou (1943)
Proven its efficacy during the last 50 years by reducing both
incidence & mortality from cervical cancer
False negative rate ☞ vary from 10% to 80% with an estimate of 20–25% being generally
acceptable
Known prevalence of CIN in the general population(1–2%)
False negative rate of cytology ☞ 20% In a total population of 10,000 women screened, 100 → pre-invasive lesion
80 → detected with cytology 20 → missed
9920 women ☞ referred & undergo colposcopic exam
in order to detect the 20 missed ones
Colposcopy in primary screening ☞ Expensive Time-consuming Requires extensive training Unnecessary psychological morbidity in women Long-term pregnancy-related morbidity
Colposcopy as a Colposcopy as a screening toolscreening tool
Obvious Disadvanta
ges
Diagnostic accuracy of Diagnostic accuracy of colposcopycolposcopy ① <Colposcopic findings>② Unsatisfactory colposcopy (upper limit of transformation
zone or squamous columnar junction not
visible) ① Subtle (e.g. simple HPV infection) Normal (e.g. immature or metaplasia changes)
Histological Dx ☞ punch bx or excision of transformation zone
Diagnostic deficiencies of colposcopy : Colposcopic impression vs histological Dx
In a series of 2100 women, Colposcopic & histological agreement only 37%
∴ Colposcopy → an excellent secondary test for cervical disease
in women with abnormal cytology
The HPV DNA testing, as a The HPV DNA testing, as a triage tool for colposcopic triage tool for colposcopic referralreferral
10% of screened population ☞ borderline or minor cytological
abnormalities (such as ASCUS, AGUS, LgSIL) on cervical smear
5–47% of lesions presenting c low grade cytological phenotype
☞ Reveal in histology an occult high grade CIN
Management options : ① Immediate referral to colposcopy for every woman c minor findings in cytology ② Selection of those likely to have underlying high-grade
ds
Currently available triage methods Repeat cytology
HPV DNA test
Recent meta-analysis by Arbyn et al. (2004)Recent meta-analysis by Arbyn et al. (2004)Accuracy of HPV DNA test & repeat cytology as
triage methods for equivocal cytological findings (ASCUS/AGUS) & for an histological outcome of CIN II+ or CIN III+
HPV DNA test, in Hybrid Capture-2 (HC-2) I. Increased sensitivity (95%) vs repeat cytology
(82%)II. Specificity : Low without statistically significant
difference HC-2 (67%) vs Repeat Cytology (58%)
The Conclusion : HPV DNA test → improved accuracy (higher sensitivity, similar specificity) Compared to repeat Pap smear
The HPV DNA testing, as a The HPV DNA testing, as a triage tool for colposcopic triage tool for colposcopic referralreferral
HPV DNA testing in the triage of cases with low-
grade cytology (i.e. HPV infection and CIN1) Sensitivity of HC-2 ☞ high (97%) Specificity ☞ low (29%)
Significantly lower specificity than repeat Pap smear (40%)
Not more performable to women c LSIL than repeat cytology
More research identify accurate LSIL triage methods such as HPV typing & molecular progression markers (HPV specific viral load, mRNA E6/7, cell cycle
proteins, etc.)
The HPV DNA testing, as a The HPV DNA testing, as a triage tool for colposcopic triage tool for colposcopic referralreferral
Management of low grade squamous intraepithelial lesion I. Immediate referral to colposcopyII. Repetition of Pap smear in six months
Accuracy parameters of cytology & HPV DNA test as triage tools
☞ geographically vary
HPV infection and subtypes’ rate may vary between countries
These phenomena might influence cost-benefit calculations
as the costs of these tools vary quite significantly in countries
The HPV DNA testing, as a The HPV DNA testing, as a triage tool for colposcopic triage tool for colposcopic referralreferral
Colposcopy during Colposcopy during pregnancypregnancy
During pregnancy, the need for colposcopy
① Women that conceive after the punch biopsies but prior to the definite treatment of the lesion② Those with a lesion detected after an
opportunistic smear during usually the first antenatal visits ③ After abnormal cytology → subsequently to be
pregnant
Conservative management and surveillance even when the index smear indicates high-
grade SIL with repeat cytology & colposcopy every 2–
3 months
Extension of the squamous columnar junction to the ectocervix
→
Treatment for preinvasive lesions during pregnancy
Increased risk of severe intraoperative haemorrhage Possibility of incomplete excision & disease
persistence↑
Biopsy Where there is cytologic or colposcopic impression of stromal invasion
Conventional knife wedge Bx → Small loop wire excision which contain stroma in order to safely confirm or exclud invasion
Colposcopy during Colposcopy during pregnancypregnancy
Satisfactory colposcopy
CIN – how to treatCIN – how to treat
The majority of women who are diagnosed with CIN ☞ Young & yet to start or complete their family
Need for conservative treatment Not compromise therapeutic efficacy Preserve Cx anatomy & future cervical function
Hysterectomy Radical procedure rarely used today Limited to older women with coexisting uterine
pathology or women who have completed their families
CIN – how to treatCIN – how to treat Prior to hysterectomy, invasive ds needs to be excluded by histological evaluation of the transformation zone
Cold knife conzationCold knife conzation Conservative Tx aimed at preserving cervical
anatomy Rarely used today by out-patient conservative
procedures Requires general anaesthesia & hospitalisation Fertility & pregnancy-related morbidity is associated
Restricted in selected cases (particularly in older women)
I. Suspicion of microinvasionII. Severe glandular lesions III. Residual/recurrent ds after more conservative Tx
The more recent conservative methods of Tx
Destructive (electrocoagulation, cryotherapy, laser ablation)
Excisional (laser conization & electrosurgical excision -LLETZ/
LEEP/NETZ)
Destructive techniques
Rather easier to perform Destroy the transformation zone epithelium Cone specimen is not provided Marginal status can not be evaluated Precise grade of the treated lesion – not
guarantied More intensive or longer f/u
CIN – how to treatCIN – how to treat
Excisional techniques ☞ Comprehensive histological evaluation of
excised tissue with precise evaluation of excision margins
LLETZ :: Most popular, by combining all the
advantages of the excisional techniques
Relatively shorter duration Low cost Good compliance Simplicity Easier learning curve
CIN – how to treatCIN – how to treat
In incomplete excision, histologically residual disease ☞ 30–40%
More likely to exist when the endocervical margins are involved
Clear excisional margins ☞ 3–5% risk of residual ds
Extension of the CIN to the endocervical glands & increased age
Augment the possibilities of an incomplete Tx
Detection, via colposcopy, of HPV satellite lesions outside the transformation zone →→ Independent factor towards treatment failure
CIN – how to treatCIN – how to treat
Excisional methods as part of “see and treat” policy ☞ Both evaluation & treatment are performed in
the first visit
Risk of over-treatment Implemented if unnecessary treatment(+) in
less than 10%
“Select and treat” policy involves biopsy Prior to treatment which confirms or excludes
the presence & the exact grade of the lesion
Minimise the over-treatment rates↓ Demand a repeat visit for the appropriate Tx
CIN – how to treatCIN – how to treat
Randomized controlled trial comparing LLETZ followed or not by cautery of remaining cervical
crater
Avoiding generalized haemostatic cauterization following
LLETZ, particularly around the newly created os, Better follow-up satisfactory colposcopy rates Significantly lower cervical stenosis rates
Bleeding ↓↓after loop electrosurgical excision ☞ significantly less bleeding when treatment was
performed during the follicular rather than the luteal phase
--- J. Nuovo, J. Melnikow, A.R. Willan and B.K. Chan, Treatment outcomes for squamous intraepithelial lesions, Int J Gynaecol Obstet 68 (2000), pp. 25–33.
CIN – how to treatCIN – how to treat
Despite the theoretical advantages of excisional techniques,
the evidence base clearly suggests that all the conservative
methods of treatment present more or less similar efficacy
in terms of eradicating intra-epithelial lesions
Systematic review on the risk of invasive cervical cancer
following conservative therapy
4–5-fold greater risk in this group compared to the general population that
remains stable throughout next eight postoperative years
CIN – how to treatCIN – how to treat
Long-term effects on future fertility & Long-term effects on future fertility & pregnancy outcome following pregnancy outcome following conservative treatment for CINconservative treatment for CIN
Recent meta-analysis by Kyrgiou et al.(2006)
Cold knife conization risk of preterm delivery low birth weight caesarean section rate
LLETZ : risk of preterm delivery, low birth weight
& premature rupture of the membranes ↑↑
Laser conization : similar pregnancy-related morbidity
Laser ablation : none of the parameters to be affected
Figure 3. (A) Cumulative forest plot presenting the risk for obstetric outcomes & different methods of treatment. (T): favours treatment, (C): favours control. Black: statistically significant. Grey: trends (but failed to reach level of signifi-cance). White: non-significant. (B) Relative risks and 95% confidence intervals For each outcome and method used.
The limited data on fertility outcome presented in this review
did not reveal any adverse effects
Prospectively designed studies dealing with long-term effects
on fertility do not exist & would be very difficult to undertake
All the original studies were retrospective c all the limitations
that this implies and the data on confounding factors that
predispose to prematurity might have been incomprehensive
Long-term effects on future fertility & Long-term effects on future fertility & pregnancy outcome following pregnancy outcome following conservative treatment for CINconservative treatment for CIN
Future prospectively designed research might give more
insight onto whether possible different patterns of cervical
behaviour during subsequent pregnancy Related to the proportion of either the cervical
volume or the endocervical canal excised
Meta-analysis supports observation management of low grade
lesions, who have an extremely low risk of progression
For young nulliparous women ☞ Reintroduction of laser ablation in selected cases
Long-term effects on future fertility & Long-term effects on future fertility & pregnancy outcome following pregnancy outcome following conservative treatment for CINconservative treatment for CIN
Follow up after treatmentFollow up after treatment Both cytology & colposcopy are used in different
schemes, combinations, intervals and duration
In the majority of cases the residual lesion → picked-up during
the first few years following Tx, by performing cytology
CIN I ☞ follow-up protocol is cytology at 6, 12 and 24 months
if every examination is negative then return to national screening programme
HgSIL ☞ more intensively monitored with cytology at 6 and 12 months afterwards
If cytology turns positive, colposcopy necessity
Follow up after treatmentFollow up after treatment Involved or uncertain margins following excisional
treatment ☞ Combination of cytology and colposcopy
Reported of higher sensitivity than cytology alone Specificity is reduced, but to a less extend than
performing colposcopy in all cases (clear and involved margins)
An immediate second excision in case of involved endocervix
margins(+) in cases of women older than 50 years of age or
in cases of glandular intraepithelial neoplasia
In case of an ablative treatment → a longer and closer follow-up surveillance is essential involving probably colposcopy
An increased risk for invasive cervical disease lasting nearly
20 years following CIN treatment
Reported that HPV DNA test is more sensitive, compared to
colposcopy or cytology in detecting CIN treatment failures
Both HPV DNA test & cytology aiming to minimize possibility
of false negative findings
Estimation of HPV viral load → Relation to the higher or lower possibility of Tx
failure
Follow up after treatmentFollow up after treatment
Application and combination of cytology, colposcopy
& more recently developed follow-up markers incorporated within the existing
guidelines & alter the follow-up algorithms
Follow up after treatmentFollow up after treatment
Colposcopy should not be used as a screening method for the detection of CIN
HPV DNA test (HC-2) has a role in the triage of women c ASCUS, but not in those cases presenting c low grade abnormalities in the index smear
Excisional conservative methods of treatment of CIN present long term obstetric morbidity
Follow up policy could introduce HPV DNA test for the earlier recognition of treatment failures
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