Cervical Cancer

Pre-cancerous diseases of the cervix or dysplasia are diseases characterized by atypia of cells of the mucous membrane of the cervix and the cervical canal.

Pre-cancerous conditions are not cancer, but under certain circumstances and lack of therapy, they have a great chance to transform into cervical cancer.

[1], [2], [3], [4], [5],

Risk factors

HPV is the most important risk factor for developing precancerous conditions of the cervix.

Other, equally important factors:

• Multiple sexual partners.
• Smoking.
• Weakened immunity.
• Long-term oral contraceptive use.

[6], [7],

Pathogenesis

In the pathogenesis of this process lies a violation of the maturation and differentiation of cells of the part of the layer of stratified squamous epithelium, covering the cervix.

The formation of dysplasia can be carried out in two directions:

1. in the process of squamous metaplasia of reserve cells and
2. against the background of a violation of physiological transformations in the stratified squamous epithelium, occurring under the influence of the hypothalamic-pituitary-ovarian system.

In the mild form of dysplasia, proliferation of the cells of the deepest layers of the squamous epithelium — the basal and parabasal; the cells of the upper part of the reservoir are mature and differentiated and retain the normal structure and polarity of the location.

The mild form of dysplasia is characterized by involvement of the lower half of the epithelial layer into the pathological process; cell atypia with mild and moderate forms of dysplasia is not observed.

The combination of severe dysplasia or pre-invasive cancer into the CIN III category is determined by a similar clinical manifestation of these processes and therapeutic approaches. A feature of this form of dysplasia is the preservation of the maturation and differentiation of cells only in the surface layer of the squamous epithelium, as well as the pronounced atypia of its cells (an increase and hyperchromia of the nuclei).

Macroscopically dysplasia can be in the form of ectopia, ectropion, leukoplakia.

[8], [9], [10],

Symptoms of the precancerous cervical disease

In most women, background and precancerous diseases of the cervix are erased. Women consider themselves practically healthy and have no complaints.

The clinical manifestations of a more pronounced process suspicious of malignant transformation include the appearance of watery whitening, contact bleeding, scanty bleeding before and after menstruation.

[11], [12], [13]

Stages

According to the International classification, there are three degrees of precancerous conditions of the cervix - cervical intraepithelial neoplasia (CIN).

• CIN I - mild dysplasia;
• CIN II - moderate dysplasia;
• CIN III - severe dysplasia and preinvasive cancer.

[14], [15], [16]

Diagnostics of the precancerous cervical disease

Comprehensive examination of patients with background and precancerous cervical processes includes bacterioscopic and bacteriological examinations of vaginal discharge, cervical canal and urethra, colposcopy, cytological and histological examinations of the cervix.

[17], [18], [19], [20],

Colposcopy

Extended colposcopy is a mandatory method of comprehensive examination of patients, since many pathological processes of the cervix, including the initial forms of cancer, are asymptomatic. When colposcopy evaluate:

• Colour;
• the state of the vascular pattern;
• surface and level of stratified squamous epithelium;
• the transition zone of the epithelium (cervical canal and cervix);
• the nature and shape of the glands;
• reaction to the sample with a solution of acetic acid;
• reaction to the sample of Schiller.

Acetic acid test (3% solution) aims to:

• remove mucus from the surface of the cervix;
• cause short-term swelling of the epithelium and, accordingly, change the color shade of the mucous membrane;
• cause spasm of unchanged vessels.

Against the background of a pale edematous mucous membrane, the boundaries of flat and cylindrical epithelium, the level of cylindrical epithelium, as well as various pathological transformations of multi-layered flat epithelium are more clearly identified. Moreover, against the background of edema of the mucous membrane, unchanged vessels spasm, while atypical vessels, on the contrary, become more pronounced and distinct.

Schiller's sample - iodine molecules, interacting with glycogen (the substrate of the mature stratified squamous epithelium), stains the unaltered mucosa in a dark color (iodine-positive zones). The immature, keratinized squamous epithelium, the cylindrical and atypical epithelium that do not contain or have a small amount of glycogen, do not stain absolutely or acquire a weak shade (iodine-negative zones)

[21], [22], [23]

Colpomicroscopy

The method is an in vivo histological examination of the cervix. Colpomicroscopy has an advantage over colposcopy, since the results of this method are comparable to histological examination. Compared with cytological examination, colpomicroscopy is different in that it allows one to study the morphological structure of not individual cells or their complexes, but the structure of the tissue without disturbing the integrity of the cells. However, due to the relative complexity of the technique, colpomicroscopy is not widely used in everyday practice.

[24], [25], [26]

Cytological examination

Normally, in cytological preparations of smears from different parts of the cervix, unchanged cells of the stratified squamous epithelium, as well as prismatic cells lining the cervical canal, are determined. When background processes in smears are found in a significant number of cells of the cylindrical epithelium. The mild form of dysplasia is characterized by the predominance of cells in the intermediate layer of squamous epithelium with signs of dyskaryosis in the form of nuclear hypertrophy and a slight disturbance of the nuclear-cytoplasmic ratio; with a moderate degree of dysplasia, cells of the parabasal layer with signs of nuclear atypia prevail. A severe form of dysplasia is characterized by the appearance of increased numbers of basal and parabasal cells in smears with pronounced signs of dyskaryosis, impaired nuclear-cytoplasmic ratio, an increase in the number of mitoses.

The accuracy of cytological diagnosis of dysplastic changes does not exceed 30%, background processes - 50%. Therefore, the diagnosis of pathological conditions of the cervix is carried out only in accordance with the results of histological examination of biopsy material.

[27], [28], [29], [30], [31], [32], [33], [34]

Biopsy

Biopsy is the most accurate method for diagnosing cervical disease. Biopsy is recommended in all cases of non-healing erosions. Cervical tissue during biopsy is taken from a negative iodine site.

[35], [36], [37], [38]

Treatment of the precancerous cervical disease

In the treatment of background processes of the cervix, there are two methods - medication and non-drug.

Drug method

The method is based on a general or local effect of drugs on the pathologically changed surface epithelium of the cervix and uterus. Drug therapy is carried out in the form of local applications of drugs (Solkovagin, vagotyl). The preparations are a mixture of organic and inorganic acids, which have a selective coagulating effect on the cylindrical epithelium. During treatment, they are applied to the pathological focus without damaging healthy tissue. The treatment is painless, does not cause adverse reactions. Cicatricial changes of the cervix after drug treatment is not formed, correctly applied drug provides complete destruction of the pathological focus due to sufficient penetration depth.

[39], [40], [41], [42], [43], [44], [45],

Non-drug method

Non-drug treatment of background processes of the cervix includes:

• laser exposure (high and low intensity);
• cryodestruction;
• surgical intervention.

[46], [47], [48], [49], [50],

Low intensity laser therapy (infrared or helium-neon radiation)

The mechanism of biological action of low-intensity laser radiation is based on the interaction of the electric field created by a laser beam with the electromagnetic fields of the body’s cells and tissues. The radiation of an infrared laser stimulates the activity of the most important bioenergetic enzymes - dehydrogenase and cytochrome oxidase, catalase, as well as other enzymes of cellular metabolism. The low-intensity laser accelerates the regenerative processes of epithelial tissues, stimulates blood circulation and blood formation, and also has an anti-inflammatory, analgesic and bactericidal effect. The technique of low-intensity laser therapy is to irradiate the affected area of the cervix for 3-5 minutes (10-15 procedures).

Drug and / or low-intensity laser therapy is carried out for no more than 3 weeks; in the absence of a positive effect, the use of destructive methods of treatment is shown. High-intensity laser exposure. For the treatment of diseases of the cervix uterine carbon dioxide (CO ₂ ) radiation is used. The mechanism of action of a CO ₂ laser is based on a sufficiently strong absorption of coherent radiation by biological tissues, as a result of which rapid heating and destruction of biotissue occurs in the zone of action of the laser beam. At the same time, in the initial stage of laser radiation, decomposition of the biological tissue with evaporation of the liquid and carbonization of the solid phases is observed; Further, as the temperature rises, the carbonized skeleton of the biological tissue burns out.

CO ₂ laser vaporization of the epithelial cover of the cervix is painless, does not cause bruising and stenosis of the cervical canal, tissue necrosis is minimal, and recovery time is shorter than with other methods of physical destruction.

[51], [52], [53]

Cryodestruction

Low-temperature effect has a wide spectrum of biological effect - from cryopreservation to tissue cryodestruction.

Cryocoagulation is carried out by contact, liquid gases — nitrogen and nitrous oxide, freon, carbon dioxide — and physical factors that potentiate the cryoeffect — electromagnetic radiation, ultrasound, exposure to radioactive isotopes — are used as a cooling agent. The duration of cryoapplication is determined by the nature and prevalence of the pathological process and averages 3-4 minutes.

The advantages of cryodestruction include the formation of a limited area of necrosis with minor damage to the surrounding tissue, the absence of hardening of the connective tissue, painlessness of the procedure; The disadvantages are long periods of flat epithelium regeneration, prolonged exudation of tissues, incomplete freezing both in depth and on the surface, which does not ensure the death of all pathologically altered cells and, thus, increases the likelihood of recurrence of cervical diseases, the frequency of which after cryotherapy reaches 42%.

Surgical treatment is subject to post-traumatic background diseases of the cervix - breaks, ectropion, cicatricial deformity, cervical vaginal fistula. For these purposes, various types of reconstructive plastic surgery are used (wedge-shaped and cone-shaped amputation, cervical plastic surgery, suturing of cervico-vaginal fistulas).

In congenital, or physiological, ectopia, only dynamic observation is carried out.

[54], [55], [56],