1. The up-to-date evidence on colposcopy practice
Cancer Treatment Review (2006)32,
The up-to-date evidence on colposcopy practice
and treatment of cervical intraepithelial neoplasia
: The cochrane colposcopy & cervical cytopathology
collaborative group (C5 group) approach
OBGY R4 Eun Suk Lee

2. Introduction 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

3. Colposcopy as a screening tool
Combination of cytology & colposcopy in primary screening to
reduce the impact of false negative results of 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

4. Colposcopy as a screening tool
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
Obvious Disadvantages

5. Diagnostic accuracy of colposcopy
<Colposcopic findings>
Unsatisfactory colposcopy (upper limit of transformation zone or
squamous columnar junction not visible)
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

6. The HPV DNA testing, as a triage tool for colposcopic referral
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 :
Immediate referral to colposcopy
for every woman c minor findings in cytology
Selection of those likely to have underlying high-grade ds
Currently available triage methods Repeat cytology
HPV DNA test

7. The HPV DNA testing, as a triage tool for colposcopic referral
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)
Increased sensitivity (95%) vs repeat cytology (82%)
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

8. The HPV DNA testing, as a triage tool for colposcopic referral
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.)

9. The HPV DNA testing, as a triage tool for colposcopic referral
Management of low grade squamous intraepithelial lesion
Immediate referral to colposcopy
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

10. Colposcopy during pregnancy
During pregnancy, the need for colposcopy
Women that conceive after the punch biopsies
but prior to the definite treatment of the lesion
Those with a lesion detected after an opportunistic
smear during usually the first antenatal visits
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

11. Satisfactory colposcopy
Colposcopy during pregnancy
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
Satisfactory colposcopy

12. CIN – how to treat Hysterectomy
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

13. CIN – how to treat Cold knife conzation
Prior to hysterectomy, invasive ds needs to be excluded
by histological evaluation of the transformation zone
Cold 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)
Suspicion of microinvasion
Severe glandular lesions
Residual/recurrent ds after more conservative Tx

14. CIN – how to treat Destructive techniques
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

15. CIN – 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

16. CIN – 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

17. CIN – 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

18. CIN – 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.

19. CIN – 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

21. Long-term effects on future fertility & pregnancy outcome following conservative 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

22. 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.

23. Long-term effects on future fertility & pregnancy outcome following conservative treatment for CIN
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

24. Long-term effects on future fertility & pregnancy outcome following conservative 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

25. Follow 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

26. Follow 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

27. Follow up after treatment
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

28. Follow 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

29. 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