TREATMENT METHODS FOR CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN 3)

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TREATMENT METHODS FOR CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN 3)

It is worth remembering that neither cytology nor colposcopy are able to provide a definitive diagnosis of neoplastic changes in the cervix. The evidence of CIN from a Pap smear or colposcopic examination of   aceto white areas is at best presumptive.
A definitive diagnosis of CIN can only be provided by tissue biopsy and the demonstration of histological changes of CIN in the cervix (eu).

For this reason one or more colposcopically directed punch biopsies should always be taken when an area of aceto white is detected in the cervix. The biopsies should be taken from the most abnormal looking areas of the cervix using a specially designed biopsy forceps with the aim of excluding invasion (eu).

Once a histological diagnosis has been obtained, appropriate treatment can be applied. Ablative techniques such as radical electrocoagulation diathermy, cryocautery, laser vaporisation, and cold coagulation are currently used for the treatment of CIN (eu).

It should be remembered that colposcopic biopsies are generally small and not easy to target so that the most severe pathological changes lesion in the cervix may occasionally be missed on punch biopsy. Large loop excision of the transformation zone (LLETZ) provides a satisfactory solution to this problem   as it combines diagnostic biopsy with treatment. The whole lesion is excised by a single sweep of the diathermy loop and all the tissue removed can be processed for histological examination (eu).

Cone biopsy (cold knife or laser) are often reserved for those cases where the lesion appears to be intraepithelial in nature but extend outside the range of colposcopic appraisal or where the   cytology suggests a   more serious condition than that seen at colposcopy. Cone biopsy is also recommended if the cytology suggests glandular neoplasia as colposcopy can be uninformative in   cases of Aden carcinoma in situ or early invasive cervical adenocarcinoma (eu).

Management of women with high-grade abnormal smears

Treatment strategies

Traditionally after colposcopy, punch biopsies were taken from the cervix and the patient was sent home to return another time for treatment. This may result in a loss of up to 25% of patients not returning for a second clinic attendance. Therefore, in recent years, it has become common practice to offer excision treatment at the first visit directly following the colposcopy (5).

The two main conservative methods of treatment are ablative or excisional techniques. The cure rates for both techniques are in excess of 90%. The need for conservative treatment is apparent considering the morbidity of the more radical procedures, their effect on reproductive function and the high incidence of pre-cancerous lesions amongst younger age groups (8).

The decision for conservative management relies on accurate colposcopic assessment, visualization of the lesion in its entirety and the exclusion of invasive disease by directed biopsy/biopsies. When considering the choice of actual technique, an important consideration is the depth of the tissue destruction required (8).

The Bethesda classification has clarified diagnostic and treatment strategies in the area of CIN. In general, treatment is offered for high-grade squamous intraepithelial lesions (HSIL) (CIN2/3 in European histological terms), and conservative management is indicated for low-grade squamous intraepithelial lesions (LSIL) (CIN1/HPV) (1).

The efficacy and safety of LLETZ for HSIL, and the adoption of conservative management for LSIL render the need for any new medical therapies tenuous (1).

Low-grade dysplasia

Most LSILs, particularly in women younger than 30 years, will regress spontaneously and do not need treatment. If follow-up is possible, women with LSILs should undergo cytologic and colposcopic evaluations every 6 months until regression or progression is diagnosed. If follow-up is not feasible, it is recommended that LSILs be treated once confirmed histologically. In other words, “look and LLETZ/LEEP” (large loop excision of the transformation zone/loop electrosurgical excision procedure) should not be performed in women with low-grade lesions because of the high likelihood of excessive or unnecessary treatment (3).

High-grade dysplasia

The treatment of HSILs may be ablative or excisional.

When planning treatment, several factors need to be taken into account. These include the patient's age, parity and further desire for fertility, menstrual status, general health, immune status, and availability for follow-up and return visits (5).

Ablative treatment is only appropriate when the lesion is seen in its entirety on colposcopic evaluation (adequate colposcopic evaluation), and a biopsy of the most abnormal area confirms the presence of a preinvasive lesion. In addition, there should be no evidence of any glandular abnormality or microinvasive disease. Ablative techniques include cryotherapy, cold coagulation, electrocautery, and carbon dioxide laser vaporization (3).

The two main conservative methods of treatment are ablative and excisional techniques. The cure rates for both techniques are over 90%. The need for conservative treatment is apparent, considering the morbidity of the more radical procedures, their effect on reproductive function and the high incidence of precancerous lesions in younger patients (2). The decision to undertake conservative management relies on an accurate colposcopic assessment, visualisation of the lesion in its entirety, and the exclusion of invasive disease by directed biopsy/biopsies (2).

When considering the choice of technique, an important consideration is the depth of the tissue destruction required (2).

Excision vs ablative management

For decades, local ablative techniques have been used to treat cervical premalignant lesions. These have now largely been replaced by low-morbidity excisonal techniques, the most frequent of which are laser cone biopsy or LLETZ (also referred to as LEEP; in this chapter, the term ‘LLETZ’ will be used throughout). The excisional techniques offer the advantage of obtaining a large specimen for pathological assessment to define the disease as well as the completeness of treatment. Both techniques can be performed under local or general anaesthesia and both yield good haemostasis. Matters of cost, movability of equipment and time taken to perform the techniques will frequently decide which apparatus will be purchased. This led to worldwide popularity of LLETZ (5).

Non-excisional techniques

Previously, laser vaporization and cryotherapy techniques were commonly used to treat cervical preneoplasia. The shared disadvantage of non-excisional techniques is the unavailability of large resection specimens for histopathological analysis. These techniques proved to be effective to treat cervical preneoplasia but have mainly been replaced by LLETZ (5).

Ablative treatments

Ablative techniques include cryotherapy, cold coagulation, electrocautery, and carbon dioxide laser vaporization (3).

In ablative treatment the lesion has to be seen in its entirety and it can be destroyed by heat using diathermy, freezing using cryotherapy, or vaporization using a carbon dioxide laser (3).

Cryocautery destroys tissue by freezing using probes of various shapes and sizes, and is probably best reserved for small, low-grade lesions. Lesion size is important in determining the success or failure of all of these treatments, but it is especially important in cryocautery. The duration of the freeze is 2 minutes from the appearance of the ice ball. A freeze/thaw/freeze technique is usually advocated. With larger lesions, multiple applications may be necessary. The depth of destruction is approximately 4 mm and this may be inadequate for some CIN lesions. Depth of destruction cannot be accurately gauged, and incomplete eradication of disease may lead to regenerating epithelium covering the residual disease. Despite these reservations, the technique is worthy of consideration as cryoprobes are cheap and widely available and can be used in an outpatient setting without analgesia and with minimal discomfort to the patient. Healing is rapid and the endocervical canal is not compromised; thus, fertility is not impaired (2).

Cryocautery destroys tissue by freezing using probes of various shapes and sizes, and is probably best reserved for small low-grade lesions. Whilst lesion size is important in determining success or failure of any of the treatment modalities used, it is especially important when using cryocautery. The duration of the freeze is 2 min from the appearance of the ice ball. A freeze/thaw/freeze technique is usually advocated. With larger lesions, multiple applications may be necessary. The depth of destruction is approximately 4 mm and this may be inadequate for some of the CIN lesions. Depth of destruction cannot be gauged accurately and incomplete eradication of disease may lead to regenerating epithelium covering the residual disease. Despite these reservations, the technique is worthy of consideration as cryoprobes are cheap and widely available, and can be used in an outpatient setting without analgesia with minimal discomfort to the patient. Healing is rapid and the endocervical canal is not compromised, so fertility is not impaired (8).

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To assess the effectiveness of cryotherapy treatment delivered by general practitioners in primary care settings, as part of a screen-and-treat approach for cervical cancer prevention. Women aged between 25 and 49 years residing in San Martin, Peru, who were positive on visual inspection screening were treated, if eligible, with cryotherapy following biopsy. Cryotherapy treatment was performed for 1398 women; of these, 531 (38%) had a histology result of cervical intraepithelial neoplasia (CIN). Cryotherapy effectively cured CIN in 418 (88%) women, including 49 (70%) women with a baseline diagnosis of CIN 3. Cryotherapy is an effective treatment for cervical precancerous lesions; ...

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