BENIGN AND PREMALIGNANT CONDITIONS OF THE CERVIX:
Cervical anatomy and histopathology:
Transformation zone
The ectocervix is covered by squamous epithelium, a stratified epithelium very similar to skin, but lacking keratin. The canal of the cervix, is lined by columnar epithelium, only one cell thick, and the point where these two epithelia meet is called the squamocolumnar junction (SCJ)
the uterine cervix increases in size in response to oestrogens; and because the cervix is anchored at the vaginal fornices the end result of any enlargement is eversion of the cervixand exposure the columnar epithelium of the endocervical canal (the columnar epith is arranged into folds forming crypts and ridges). This occurs dramatically in the neonate under the influence of maternal oestrogens, at puberty under the influence of rising oestrogen levels, during the use of the combined oral contraceptive pill and during the first pregnancy and this is called ectopy (display of columnar epithelium)previously known as ‘erosion’.
In approximately 4% of women there will be extension of the squamocolumnar junction into the anterior and posterior fornices.
Macroscopically the columnar epithelium is red in color because of single cell layer allowing the blood vessels in the underlying stroma to be seen through it.
cervical metaplasia
Exposure of this columnar epithelium to low pH as found within the vagina promotes a series of physiological changes, known as squamous metaplasia, the metaplasia occurs at the transformationzone. The squamous epithelium is rich withglycogen.
Nabothian follicle:
Metaplasia usually occurs initially in the ridges of the mucous membrane folds and may well bridge over the crypts leaving a squamous cover with columnar epithelium remaining within the crypts, if a crypt cannot expel the mucus produced from the columnar epithelium a retention cyst or Nabothian follicle will occur. They are entirely benign and are not associated with infection, i.e they are not a sign of cervicitis.
ENDOCERVICAL POLYPS
The recognition of endocervical polyps at the time of taking a cervical smear is common and usually increases with age up to the menopause. Occasionally these polyps will be symptomatic producing heavy vaginal discharge or bleeding upon coital contact.
Histology of these polyps will show that they consist of columnar epithelium sometimes with metaplastic squamous epithelium across the tip. Malignant change is most unusual. However, if these polyps are removed by polypectomy, tissue should be sent for histology.
Because 15% of uterine tumours will be polypoidal and occasionally will extrude through the external cervical os.
premalignant cervical conditions (dysplasia)
dysplasia:
The process of metaplasia can be disrupted by external influences and can lead to disordered squamous epithelium called dysplastic epithelium.
Aetiology:
1- HPV is implicated in this process, although HPV infection alone does not appear to be sufficient to cause dysplasia.
2- Smoking and
3- immune suppression appear to be additional factors which may act as co-agents.
Dysplastic epithelium lacks the normal maturation of cells as they move from the basal layer to the superficial layer.
The nuclei tend to be larger, more variable in size and shape and more actively dividing than inhealthy squamous epithelium.
Dysplasias (cervical intraepithelial neoplasia) (CIN):
They are graded as mild, moderate or severe, depending on the degree of cytological atypia and also the thickness of the epithelium involved.
1- CIN I affects only the deepest third of the epithelium from the basal layer upwards, with maturation seen more superficial to that.
2- CIN II affects two-thirds of the thickness of the epithelium,
3- CIN III shows no maturation throughout the full thickness, it is severe dysplasia/ or called carcinoma in situ.
A simpler classification is the BETHESDA classification uses the term squamous intraepithelial lesion (SIL) to involve all grades of CIN (cervical intraepithelial neoplasia). SIL is further subdivided into two categories – low grade which
includes cellular changes associated with human papilloma virus (HPV) infection and CIN 1, and high-grade SIL which includes CIN 2 and 3.
Natural history of CIN (Progressive potential of CIN):
The progressive potential of high-grade lesions or CIN 3 has been calculated to be 18% at 10 years and 36% at 20 years.
Women with continuing abnormal cytology after initial management of carcinoma in situ of the cervix were almost 25 times more likely to develop invasive carcinoma than women who have normal follow-up cytology.
Previously it was believed that CIN III develop from CIN I and II, and only CIN III lesions would progress to invasive cancer. but now it is believed that CIN III lesions probably arise as such from the start.
Cervical screening programmes:
in underdeveloped countries 75% of the cases of cervical cancer present with an advanced stage, while in the developed countries 75% of the cases present early and cure can be expected. This is partly due to education of women in developed countries they present early because of symptoms and as part of screening programmes for cervical cancer.
cervical cancer is a preventable condition and considerable effort goes into detecting and treating the pre-invasive disease, which have a direct effect on incidence and mortality.
The cervical screening programme in the UK was established in 1988 and has made significant lowering in the incidence of cervical carcinoma by 42% between 1988 and 1997 inEngland. And it saves approximately 4,500 lives per year.
the screening program should cover the at-risk population women between the ages of 25 and 64 to offer cervical cytology screening every 3–5 years.
*indications for screening (risk factors for cervical carcinoma):
1- early marriage.
2- multiple sexual partners.
3- liberal sex.
4- young age at 1st pregnancy.
5- high parity.
6- lower socioeconomic status.
7- smoking.
Screening intervals for cervical pathology:
Age group (years) Frequency of screening
25 First invitation
25–49 Three yearly
50–64 Five yearly
65+ Only screen those who have not been screened sinceage50 or
those whohave had recent abnormal tests.
Cytology (pap smear):
Exfoliative cervical cytology is a technique developed by Papanicolaou to collect the cells that had been shed from the skin of the cervix, spread them on a glass slide and stain them using a specially developed technique.
Originally cells were washed from the vagina and collected in the posterior fornix, a more efficient technique of exfoliative cytology involves scraping the cervix to collect cells directly by Eyre's spatula (wooden spatula).
Findings in pap smear: either normal squamous epithelial cells or cells with little maturation and have large nuclei, a large degree of cytological atypia and increased nuclear: cytoplasmic ratio.
Smears may show borderline nuclear changes or mild, moderate or severe dyskaryosis.
If smear show abnormal glandular cells or borderline nuclear changes in glandular cells, such woman should be referred to colposcopy urgently because of the high risk of invasive cancer of the cervix or endometrium.
The sensitivity of cervical cytology is about 50 percent, but because CIN takes about 10 years on average to become invasive, missed lesions are detected on second and third subsequent samples.
The specificity of cervical cytology is about 92 per cent.
Management of abnormal cervical smears
Ideally all women with abnormal cervical cytology should have colposcopic assessment.
The aim of colposcopy is:
1) to exclude an invasive process.
2) to identify the extent of the abnormality and its likely grade which may allow a more conservative approach to management.
For adequate colposcopy, the Whole of the transformation zone(TZ) needs to be visualized. If the TZ is not fully visualized, then colposcopy is termed unsatisfactory. This inability to visualize the squamocolumnar junction (SCJ) may bean indication for excisional biopsy of the cervical transformation zone.
Colposcopy
The basic principles of colposcopy: A system of low power magnification, (binocular operating microscope with magnification of between 5 and 20 times). It has been used to examine the cervix in detail to identify CIN and pre-clinical invasive cancer
The cervix is first examined for abnormal vessel patterns known to be associated with premalignant and malignant lesions of the cervix.
To assist in the identification of abnormal vessels, the cervix may be washed with normal saline and may be viewed through a green filter which highlights the blood vessels as black lines.
. Application of 3-5 per cent acetic acid to the cervix highlights CIN areas as white, compared with the pink colour of normal epithelium.
Abnormal findings are:
1-Acetowhite epithelium
2-abnormal subepithelial capillary pattern
*mosaicism
*punctation.
*Abnormal branching vessel are suggestive of micro invasive carcinoma.
Schiller's test identifies normal squamous epithelium, normal mature squamous epithelium contains abundant glycogen that stains dark brown with iodine and the test involves the application of Lugol's iodine solution to the ectocervix. The normal squamous epithelium will stain dark brown, whereas columnar epithelium, abnormal squamous epithelium and immature normal squamous epithelium will not.
Usually a colposcopic-directed biopsy will be taken from the most abnormal areas of the epithelium to confirm the diagnosis.
Colposcopy is considered complete if healthy columnar epithelium is identified within the endocervical canal. If the transformation zone extends up the canal out of view, colposcopy is unsatisfactory because there may be more abnormal lesions in the canal out of sight.
If the woman is pregnant at the time of colposcopic assessment, a conservative approach is usually employed and treatment undertaken after delivery. If cancer is suspected,then a large biopsy, usually a wedge biopsy, is taken under general anesthesia as there is a risk for significant hemorrhage.
abnormal vascular pattern by colposcope
Punctuation seen by colposcope
TREATMENT OF CIN
two main methods of treatment are:
1- ablative techniques
2- excisional techniques
both techniques have a Cure rates in excess of 90%.
Recently there has been a tendency towards using excisional methods. This allows better histopathological interpretation of the excised specimen.
The depth of destruction of any local treatment modality is important. A depth of crypt involvement with CIN suggest that 3.8 mm would eradicate premalignant disease in 99.7% of cases. However, some gland crypts are involved by CIN up to 5 mm in depth were found, so ablation to a depth of 5–8 mm has been recommended. If depth of destruction is inadequate, then this deep-seated component may be a source of residual or recurrent disease.
Diagrammatic representation of large loop excision of the transformation zone(LLETZ).
Ablative techniques
Cryocautery
It destroys tissue by freezing using probes of various shapes and sizes and is used for small lesions.
lesion size is important in determining success or failure of any treatment modalityand it is especially important with cryocautery. With larger lesions, multiple applications is required. The depth of destruction is approximately 4 mm and this may be inadequate for some of the CIN lesions.
electrodiathermy
1- electrodiathermy destroys tissue more effectively (up to 1 cm depth ) than cryocautery,
2- but it require general, regional or local anesthesia.
3- can be a needle or ball electrodes or by using a wire loop used in an excisional mode.
Cold coagulation:
Heat is applied to tissue using a Teflon-coated thermosound. Using overlapping applications of the thermosound for 20 s at 100◦C, the Whole of the transformation zone may be treated. The procedure does not usually require analgesia. Measurement of the depth of destruction is difficult. Depth of destruction depend on the time and temperature applied..
Laser:
A micromanipulator attached to the colposcope is used to manipulate the laser and treatmentis conducted under direct vision.
1- the technique is precise,
2- it allows good control of the depth of destruction,
3- good haemostasis
4- excellent healing as there is minimal thermal damage to the adjacent tissue.
Excisional methods
Transformation zone excision by laser and diathermy loop have been used.
1- Laser excision is technically requires a high-power density beam with a small spot size that can function as a knife
2- Diathermy loop excision using low power voltageapparatus is now widely practiced. The technique is termed as large loop excision of transformation zone (LLETZ) or as loop electrosurgical excisionprocedure (LEEP).
Success rates following local excisional techniques is similar to those with laser ablation and cold coagulation.
There is no adverse effect on fertility and the outcome of subsequent pregnancies.
(LLETZ)
3- Cone biopsy
4- hysterectomy still retain a place in the management of CIN. Hysterectomy is done if CIN is present in a woman with other gynaecological conditions such as fibroids, menorrhagia or prolapse.
The size and shape of the cone biopsy is decided according to the colposcopic findings. The internal os and as much of the endocervical canal are left intact as is possible within the confines of disease eradication. This limits haemorrhagic morbidity and fertility will be little compromised.
Those women should be followed up by pap smear. A persistent cytological abnormality after cone biopsy is an indicator of residual disease; such women need further treatment.
TREATMENT FAILURES
The primary objective of treating women with CIN is to prevent invasive cervical cancer. If invasive disease develops or if there is residual CIN, the initial treatment is termed a failure.
Women who have undergone treatment of CIN remain at higher risk for invasive cervical disease. Therefore women who have been treated for CIN need long-term follow-up.
Colposcopic assessment is technically more difficult in those that have undergone previous treatment. Islands of CIN and invasive disease can be buried under an apparently normal surface epithelium.
Non-treatment and serial colposcopy*
The progressive potential of low-grade lesions is unknown and cannot be predicted from cytological, colposcopic or histological criteria. Many of these low-grade lesions will regress, but others will persist or progress, in a transient population, early intervention may be the preferred option as women are unlikely to adhere to asurveillance programme.
Flow diagram for management of abnormal cervical cytology