Angelina A. Odyvanova

Хронический неспецифический цервицит (ХНЦ) остается одной из частых воспалительных патологий шейки матки у женщин репродуктивного возраста. У части пациенток формируется персистирующее течение с рецидивами и устойчивым воспалительным фенотипом, что связывают с анаэробно-ассоциированным дисбиозом и особенностями иммунного/стресс-реактивности. В статье дается оценка прогностического значения микробиологических и молекулярно-генетических факторов в отношении риска персистирующего течения ХНЦ на основании 12-месячного проспективного наблюдения. В исследование были включены 140 женщин 18–49 лет: 70 пациенток с ХНЦ и 70 условно здоровых женщин. Выраженный анаэробно-ассоциированный дисбиоз и носительство вариантов CRHR2 ассоциированы с повышенным риском персистенции ХНЦ. Интеграция qPCR-профиля микробиоты и генотипирования CRHR2 в прогностическую модель позволяет выделять группы риска и обосновывать персонифицированный подход к терапии.

Background. Chronic non-specific cervicitis (CNC) remains one of the most common inflammatory diseases of the cervix; however, its clinical and morphological criteria and diagnostic significance remain poorly defined, especially with negative test results for human papillomavirus (HPV) and common sexually transmitted infections (STIs). Aim. To characterize the clinical, morphological, and microbiological features of CNC in women of reproductive age, with the strict exclusion of HPV-associated and specific infectious diseases of the cervix. Materials and methods. A retrospective analysis of data from 152 women aged 18–49 was conducted: 131 patients with histologically confirmed CNCs and 21 healthy women. Clinical and history data, extended colposcopy, liquid-based cytology, diagnosis of HPV and STIs using polymerase chain reaction, the state of vaginal biocenosis according to the “Femoflor-16” panel, and the histological data of biopsy specimens were evaluated. Statistical analysis included the Mann–Whitney U test, the Fisher test, and calculation of the odds ratio with a 95% confidence interval. Results. CNC was associated with an earlier age of onset of sexual activity (p = 0.03), a high incidence of chronic salpingo-oophoritis (45.8%), and dysbiosis episodes (41.2%). Histologically, CNC was characterized by almost universal lymphoplasmacytic infiltration (97.7%) and variable reactive epithelial changes. In patients with CNC, anaerobic-associated dysbiosis with Lactobacillus spp. deficiency was much more common. Colposcopic and cytological changes often mimicked low-grade squamous intraepithelial lesions, leading to diagnostic challenges. Conclusion. CNC is an independent, microbiota-dependent inflammatory cervix phenotype that complicates the interpretation of screening tests. Morphological verification and assessment of the microbiocenosis are key components of diagnosing and differentiating CNCs from intraepithelial lesions.

The issue of cervicitis and vulvovaginitis is relevant worldwide due to the increasing incidence in women of reproductive age. To date, the significant role of chronic cervicitis in the development of cancer and other diseases of the reproductive system, including cervical cancer, has been proven. In recent years, a number of large studies have been conducted, covering a significant part of the clinical issues, pathogenesis, and epidemiology of cervicitis. However, there is a clear need for further studies of both the etiological factors and the pathogenetic mechanisms of inflammatory cervical disease to support the treatment choice.

Currently, cervicitis of nonspecific etiology is one of the urgent problems of modern gynecology due to the extremely high frequency of their occurrence, a tendency to a chronic relapsing course, a negative impact on reproductive health, and the risk of developing a number of complications. The role of violations of vaginal microbiocenosis and local immune status in the development of CNC has been convincingly shown. The replacement of lactobacilli with predominantly anaerobic microorganisms (Ureaplasma, Mycoplasma, Gardnerella vaginalis, Prevotella, Peptostreptococcus spp. and Bacteroides spp.), characteristic of bacterial vaginosis, is extremely often detected in patients with CNC. Of particular importance from the point of view of clarifying the pathophysiological mechanisms of development and the development of new diagnostic and prognostic markers, as well as the personalization of CNC therapy, is the study of the cytokine status. Cervicitis and other inflammatory diseases of the lower genital tract are characterized by an increase in the expression of pro-inflammatory cytokines with simultaneous inhibition of the formation of anti-inflammatory cytokines. Significant multidirectional changes in the balance of pro- and anti-inflammatory cytokines were revealed in active and chronic sluggish cervicitis. It should be noted that, despite the variety of proposed approaches to CNC therapy, this problem is still far from being solved to date. One of the promising directions is the personalization of CNC therapy based on molecular genetic markers (polymorphisms of cytokine genes, Toll-like receptors, genes of the detoxification system). The use of such a personalized approach can significantly increase the effectiveness of CNC treatment and reduce the risk of disease recurrence.