Introduction
Among the factors that determine the state of reproductive health of the female population of Ukraine, the growth in the number of precancerous and oncological diseases of the reproductive organs, which occurs year by year, is of particular importance. Among the oncopathology of the reproductive system, the first place is occupied by cervical cancer (CC).
It is known that precancerous conditions lead to the onset of a carcinogenic process, so cervical dysplasia (CD), which occurs more often against the background of infection with the human papillomavirus (HPV), deserves special attention.
There is no doubt that HPV is of paramount importance in the genesis of neoplastic processes occurring in the cells of the cervix (CC) . In most countries of the world and in Ukraine, the fight against the increase in the incidence of CC is carried out through preventive and curative vaccination. However, at present, vaccination is available in our country only against HPV 16 and 18 types. It should also be remembered that if a woman has a virus in her body, any vaccination is no longer effective.
In recent decades, there has been a tense epidemiological situation due to the increase in infection with HPV among women of childbearing age (WCA).
According to WHO up to 500,000 new cases of HPV are detected every year in the world CC and about 240,000 women die every year from cervical cancer. World statistics show that almost 20,000,000 people in the United States are infected with HPV. Half (50%) of sexually active men and women become infected with HPV once in their lives. By the age of 50, at least 80% of women become infected with HPV. About 6,000,000 people are infected each year with HPV.
In the US, there are 2.8 million cases each year with an abnormal Pap test, more than 10,000 cases of CC caused by HPV and about 4000 deaths of women from CC .
In 93% of cases CC is caused by HPV, of which 70% of cases are types 16 and 18 .
In Ukraine, data on the number of women infected with HPVare not very informative.
A significant threat to the reproductive health of women is chronic inflammatory diseases of the genital organs (CVID), which, if not diagnosed and treated in time, affect the risk of other reproductive health disorders.
Dysplasia
Dysplasia is a process of violation of the transformation of the columnar epithelium into squamous. This process is a normal regenerative mechanism during which flattening of organelles, reduction of vacuoles and cell volume occurs. If, during such transformation, the virus enters the cell and uses it for replication, then the cell either dies or stops the process of its transformation. The most common method for diagnosing the cervix is the Pap test, or pap smear. The general standard for the result of a cytological study is the protocol approved at a conference in the city of Bethesda (USA) by a group of experts, which is recognized by the World Health Organization and the American Society of Cytopathology.
An important pathogenetic mechanism for the induction of the proliferative activity of cervical cells under the influence of HPV is the activation of the process of retinoblastoma protein phosphorylation by binding the latter to the E7 protein, activation of transcription factors (for example, E2F) and the beginning of the transition of the cell to the S-phase of the interphase of mitosis. In turn, the E6 protein is known for its ability to suppress the activity of pro-apoptotic proteins (such as p53) and also promotes pathological proliferation processes by suppressing apoptosis. The genes encoding the production of E6 and E7 proteins belong to the group of "early" genes of circular double-stranded DNA HPV.
The latest modern studies on the diagnosis of non-plastic processes of the cervix were aimed at determining the E7 protein in cervical mucus by enzyme immunoassay.
Studies have shown that 81% of dysplasias and 75% of CC cases had E7 protein. Determination of this protein can be an important diagnostic criterion for these diseases.
Changes in the cells of the cervix occur not only against the background of infection with viruses or other microbial factors, but also with the participation of changes in the redox processes of the cell.
In Ukraine, taking into account the high incidence of CD and CC, there is an urgent need to prevent the occurrence of cancer . Therefore, the definition of modern treatment options can be a prevention of the development of oncopathology.
Target
To identify new treatment options for cervical dysplasia in WCA.
Materials and research methods
We have comprehensively examined 50 WCA with CIDGO in which CD.
All examined women underwent:
- colposcopic examinations,
- cytological studies,
- the state of the vaginal microbiocenosis and the level of tumor necrosis factor alpha (TNF-α)
All studies were carried out before and after treatment, in accordance with the order of the Ministry of Health of Ukraine No. 236 of 04/02/2014
Colposcopy of the cervix was performed for all examined women using the OlympusOCS 500 device in dynamics before and after treatment.
The study of the microbiocenosis of the genital organs included the determination of the species and quantitative composition of the microflora. The analysis of the bacterial spectrum of the vagina and the recording of the results were carried out in accordance with the order of the Ministry of Health of Ukraine No. 234 of 10.05.2007.
Detection of HPV was carried out by the molecular biological method "Polymerase chain reaction", which belongs to amplification methods. The technique consists in the fact that with the help of DNA polymerase and RNA ligase enzymes, a larger number of identical DNA fragments HPV are obtained and identified by gel electrophoresis.
For immunological examination, serum obtained from the venous blood of some of the women studied was used. The concentration of cytokines (tumor necrosis factor) was determined using enzyme immunoassay.
Cytological smears from the cervical canal were taken with a special Cervex-Brush to obtain material from the transformation zone.
After sampling, the material was applied in a thin layer on glass, dried in air, fixed in Nikiforov's mixture for 10-20 minutes. and then painted according to Romanovsky - Giemsa and Papanicolaou. The study of preparations was carried out on an Olumpus CH-2 microscope in transmitted light mode.
Evaluation of dysplastic processes in the cervix was performed in accordance with the cytological classification of "Bethesda system" (2001).
In the complex therapy of CD and treatment of CIDGO in WCA we used API-NORM® NEO (vaginal suppositories), which is a natural anti-inflammatory agent to prevent neoplastic processes in gynecological diseases.< /p>
The preparation API-NORM® NEO includes a balanced composition based on bee products and plant components:
Basic Components- activated propolis extract
- St. John's wort
- Calendula extract
- celandine extract
- Vinca rosea extract
- Sea buckthorn oil
- polysorbate
- dimethyl sulfoxide
- polyethylene oxide
- ascorbic acid
- beeswax
This preparation differs from preparations of a similar orientation in its balanced combination of beekeeping products and plant components. The combination of these components has a complex effect, which leads to a decrease in clinical manifestations in acute and chronic inflammatory diseases of the pelvic organs and the urinary system. The plant components and bee products that make up this drug have a high level of efficacy and safety in terms of evidence-based medicine.
To achieve the goal of the study, our choice was on the drug API-NORM® NEO (vaginal suppositories) since this complex drug made from natural ingredients has been proven to have a complex effect , namely:
- anti-inflammatory
- immunomodulatory
- adaptogenic
- antispasmodic
- painkiller
- antioxidant
API-NORM® NEO enhances the phagocytic activity of the pelvis, activates a nonspecific immune response, inhibits malignant processes and prevents malignant transformation of cells, and also prevents unauthorized cell division, which stops the growth of tumors.
In complex therapy CD against the background of CIDGO drug API-NORM ® NEO (vaginal suppositories) was prescribed one suppository at night after hygiene procedures for 20 days. After 30 days, a second course was prescribed for 10 days with colposcopic and cytological control.
In case of effective treatment of CD against the background of CIDGO with a prophylactic purpose, the drug was used in a course of 5 days every month in within 3 months with colposcopic and cytological control.
For the treatment and prevention of inflammatory diseases of the genital organs in men - the sexual partners of women who underwent treatment for CD against the background of CIDGO the drug API-NORM® (rectal suppositories) was prescribed, which is a natural anti-inflammatory agent indicated for urological and proctological diseases.
Results and discussion
The survey involved 50 women aged 15 to 40.
Determination of the clinical features of the state of the cervix and changes in reproductive health, microbiocinosis, immunity indicators and characteristics of CIDGO was carried out depending on colposcopic changes in the cervix.
The results of clinical and colposcopic examination of women made it possible to establish the degree of abnormal changes in the cervix.
Thus, first degree abnormal colposcopic picture was found in 10 women (20%), and in the remaining women - 40 (80%) was second degree abnormal colposcopic picture.
| Ages of women (full years) | Women with CIDGO and CD , (n=50)< /th> | |||
|---|---|---|---|---|
| First degree of abnormal colposcopic picture | Second degree of abnormal colposcopic picture | |||
| abs.h | % | abs.h | % | |
| 15-19 years old | 1 | (1.0) | 3 | (6.0) |
| 20-25 years old | 4 | (4.0) | 8 | (16.0) |
| 26-30 years old | 7 | (7.0) | 19 | (38.0) |
| 31-35 years old | 6 | (6.0) | 8 | (16.0) |
| 36-40 years old | 2 | (2.0) | 2 | (4.0) |
| Total | 10 | (20.0) | 40 | (80.0) |
It can be seen from the data in the table that the first degree of abnormal colposcopic picture (delicate mosaic, delicate punctuation, thin acetic white epithelium; irregular, "geographical" border) is more common in women in the age range of 26-30 years. Along with this, the second degree of abnormal colposcopic picture (dense acetic-white epithelium, rough mosaic, rough punctuation, leukoplakia (keratosis, hyperkeratosis, erosion) is more common in the same age category, but it should be noted that such changes are quite common (16 0 %) occur in very young women in the 20-25 age group.
Women with CD have had various CIDGO
| Genital Pathology | Women with CIDGO and cervical dysplasia, (n=50) | |||
|---|---|---|---|---|
| First degree of abnormal colposcopic picture | Second degree of abnormal colposcopic picture | |||
| abs.h | % | abs.h | % | |
| Chronic vulvitis | 1 | (2.0) | 3 | (6.0) |
| Chronic vaginitis | 10 | (20.0) | 31 | (62.0) |
| Chronic cervicitis | 10 | (20.0) | 40 | (80.0) |
| Chronic inflammatory diseases of the uterus | 1 | (2.0) | 5 | (10.0) |
| Chronic salpingo-oophoritis | 7 | (14.0) | 33 | (66.0) |
The examined women showed various changes in their reproductive health.
| Indicators of changes in reproductive health | abs.h. | % |
|---|---|---|
| CIDGO | 50 | (100.0) |
| Irregular menstruation | 21 | (42.0) |
| Miscarriage | 9 | (18.0) |
| Perinatal mortality | - | - |
| artificial abortion | 17 | (34.0) |
| Spontaneous abortion | 7 | (14.0) |
| History of somatic pathology | 14 | (28.0) |
| Inflammatory diseases of the genital organs suffered in childhood and adolescence | 8 | (16.0) |
The data in the table shows that all examined women suffered from CIDGO. The high frequency of changes in reproductive health is the unfavorable background that can worsen the clinical course of cervical dysplasia.
The study of the state of microbiocinosis of the urogenital organs showed a high frequency of detection of pathogenic microflora at the level of the genital organs.
| Microbial Factors | abs.h. | % |
|---|---|---|
| Staphylococcus aureus | 23 | (46,0) |
| Staphylococcus aureus | 23 | (46,0) |
| Staphylococcus epidermidis | 10 | (20,0) |
| Diplococcus | 12 | (24,0) |
| Streptococcus | 17 | (34,0) |
| E. coli | 19 | (38,0) |
| Fusiform bacteria | 22 | (44,0) |
| Corynebacteria | 18 | (36,0) |
| Trichomonas | 2 | (4,0) |
| Chlamydia | 14 | (28,0) |
| Ureaplasma | 13 | (26,0) |
| Gardnerella | 15 | (30,0) |
| Yeast-like | <27/td> | (54,0) |
It should be noted that in the examined women with CIDGO and cervical dysplasia, pathogenic microorganisms were found in associations: the most frequent combinations were representatives of pathogenic coccal microflora in combination with chlamydia and yeast-like fungi. Infection with representatives of sexually transmitted infections (STIs).
The determination of PVI showed that the women examined were more likely to have highly oncogenic types HPV 16th and 33rd types, respectively 30 (60.0%) and 16 (32 .0% ). Other women had strains of HPV less oncogenic.
In order to determine the state of the pathogenetic indicator of immunity, we determined the content of the cytokine TNF-α in venous blood serum using enzyme immunoassay. The results of the study showed a significant increase in TNF-α, which amounted to 62.1 pg / ml.
Since TNF-α is a pro-inflammatory cytokine and is a factor in a non-specific immune response, it can be argued that in women with cervical dysplasia, against the background of CIDGO, caused by infection with a pathogenic STI and HPV negative changes in the cytokine status occur in microflora with the participation of STI.
The colposcopic picture was adequate in all patients. Type 1 transformation zone was determined in 84% of women, type 2 transformation zone was determined in 16% of women. Such signs of a normal colposcopic picture as nabotov and cysts were determined in 25% of women, open ducts of the glands were determined in 36% of the examined. In all examined women, the squamous epithelium was mature, signs of atrophy were NOT observed.
In more than half of the women, namely in 54%, the size of the altered epithelium was 2 cervical quadrants, and occupied an average of 45 ± 12% of the surface of the cervix.
The first degree of abnormal colposcopic picture was defined as a delicate mosaic in 26% of women, delicate punctuation in 18% of women, thin acetic white epithelium in 23% of women.
The second degree of abnormal colposcopic picture in the examined women was determined as a rough mosaic in 19% of women, rough punctuation in 18% of women, dense acetic white epithelium in 26% of women. Among the nonspecific signs of an abnormal colposcopic picture, the presence of cervical erosion in 67% of cases can be noted. The presence of unstained areas during the Schiller test was noted in all examined women.
Signs of invasive growth were not detected in the examined women.
Endometriosis of the cervix was found in 8% of the examined, signs of a previous treatment of the cervix in 20% of women, and polyps in 5% of the examined women, respectively.
The colposcopic picture of the vaginal walls in the examined women was not changed.
Pappanicolaou Pap smear samples were satisfactory, processed and examined in all women.
The studied samples did not contain intraepithelial lesions or oncopathology.
In 78% of the studied smears, inflammatory infiltration was present.
Among the cells of the transformation zone, swamosis cells of the superficial intermediate and parabasal layers were determined.
The cells in the smear were placed separately in 23% of the examined women, formed cell complexes in 25% of the women, and were placed in layers in 27% of the women.
Among glandular epithelial cells in the smear, there were mainly high prismatic secretory cells (45%) and metaplastic cells (31%), in 6% of cases small cubic reserve cells were determined.
Among the degenerative signs of epithelial cells, fatty or hydropic dystrophy of the cytoplasm (69% of cases), formation around nuclear "halos" (31% of cases) and an increase in the size of nuclei (25% of cases) were most often determined.
All examined women showed signs of viral damage to the epithelium.
Clinical manifestations PVI found in 30 (60%) women - in the form of a clinical form; in 17 (34%) women - subclinical form; 3 (6%) women have a latent form.
The same trend was observed regarding the age distribution of women affected by high-oncogenic and low-oncogenic types of HPV.
Complex treatment of cervical dysplasia was carried out on the basis of existing international protocols.
After the complex treatment, the signs of the inflammatory process at the level of the genital organs disappeared in all women with cervical dysplasia. Effective signs of complex treatment using the
The results of these studies showed that in women with cervical dysplasia, microbiocinosis and colposcopic picture normalized. Also, after treatment, a positive cytological picture of Pappanicolaou smears was observed.
SUMMARY
New approaches to the diagnosis of atypical colposcopic picture expand the possibilities of conservative treatment of benign diseases of the cervix.
Preparation
The effectiveness of the inclusion of
