A dramatic increase in cervical diseases associated with human papillomaviruses (HPV) in women of reproductive age has been observed over the past decades. An accurate differential diagnosis of the severity of cervical intraepithelial neoplasia and the choice of the optimal treatment requires the search for effective biomarkers with high diagnostic and prognostic value. The objective of this study was to introduce a method for rapid shotgun lipidomics to differentiate stages of HPV-associated cervix epithelium transformation. Tissue samples from 110 HPV-positive women with cervicitis (n = 30), low-grade squamous intraepithelial lesions (LSIL) (n = 30), high-grade squamous intraepithelial lesions (HSIL) (n = 30), and cervical cancers (n = 20) were obtained. The cervical epithelial tissue lipidome at different stages of cervix neoplastic transformation was studied by a shotgun label-free approach. It is based on electrospray ionization mass spectrometry (ESI-MS) data of a tissue extract. Lipidomic data were processed by the orthogonal projections to latent structures discriminant analysis (OPLS-DA) to build statistical models, differentiating stages of cervix transformation. Significant differences in the lipid profile between the lesion and surrounding tissues were revealed in chronic cervicitis, LSIL, HSIL, and cervical cancer. The lipids specific for HPV-induced cervical transformation mainly belong to glycerophospholipids: phosphatidylcholines, and phosphatidylethanolamines. The developed diagnostic OPLS-DA models were based on 23 marker lipids. More than 90% of these marker lipids positively correlated with the degree of cervix transformation. The algorithm was developed for the management of patients with HPV-associated diseases of the cervix, based on the panel of 23 lipids as a result. ESI-MS analysis of a lipid extract by direct injection through a loop, takes about 25 min (including preparation of the lipid extract), which is significantly less than the time required for the HPV test (several hours for hybrid capture and about an hour for PCR). This makes lipid mass spectrometric analysis a promising method for express diagnostics of HPV-associated neoplastic diseases of the cervix.

Cervical cancer is one of the most common cancers in women with pronounced stages of precancerous lesions. Accurate differential diagnosis of such lesions is one of the primary challenges of medical specialists, which is vital to improving patient survival. The aim of this study was to develop and test an algorithm for the differential diagnosis of cervical lesions based on lipid levels in scrapings from the cervical epithelium and cervicovaginal canal. The lipid composition of the samples was analyzed by high-performance chromato-mass spectrometry. Lipid markers were selected using the Mann–Whitney test with a cutoff value of 0.05 and by projections to latent structures discriminant analysis, where a projection threshold of one was chosen. The final selection of variables for binomial logistic regressions was carried out using the Akaike information criterion. As a result, a final neoplasia classification method, based on 20 logistic regression sub-models, has an accuracy of 79% for discrimination NILM/cervicitis/LSIL/HSIL/cancer. The model has a sensitivity of 83% and a specificity of 88% for discrimination of several lesions (HSIL and cancer). This allows us to discuss the prospective viability of further validation of the developed non-invasive method of differential diagnosis.

The burden of persistent papillomavirus infection on public healthcare is not limited to cervical cancer (CC). At present, cervical cancer continues to be one of the most common types of cancer worldwide, although HPV also causes anogenital warts. As there is no HPV treatment available, nowadays researchers focus on the search for new therapeutic platforms, new agents for HPV-associated diseases relapse prevention after surgical treatment. Significant anticancer effects of resveratrol have been demonstrated in a variety of cancers, including breast cancer, skin cancer, lung cancer, pancreatic cancer, and stomach cancer. In CC cells, resveratrol stimulates apoptosis of cancer cells, increases expression of HPV E6 and E7, and the expression of p53 tumor suppressor protein. Protective effects on CC cells migration and invasion is achieved by inhibiting NF-κB transcription and AP-1 mediated MMP9 expression. Resveratrol demonstrates a whole range of anti-inflammatory effects, ranging from the suppression of the pro-inflammatory cytokines IL-1α, IL-1β, IL-6, IL-17 expression and inflammatory mediator prostaglandin E2, to the suppression of the formation of ROS and NO. I3K has a proven antitumor efficacy based on the molecular mechanisms of pathological cell proliferation and tumor transformation in hormone- dependent tissues, including cervical epithelial cells. Resveratrol and I3K have a wide range of studied positive therapeutic effects that can significantly reduce the likelihood of development and progression of HPV-associated lesions.

Among gynaecological diseases in women of reproductive age the leading place is occupied by inflammatory diseases of the lower part of the genital tract (70%), a significant proportion of which are inflammatory processes of the vagina and cervix uteri. In ⅔ of women, cervicitis is most often asymptomatic, so they do not seek medical treatment, and 65–77.6% have a transition to a chronic form. Thus, chronic cervicitis is diagnosed in almost one in three women who seek assistance from a gynaecologist due to leukorrhea, and there is no tendency for a decrease in frequency. The article presents an actual view on the problem of inflammatory diseases of the lower genital tract. The analysis of some researches devoted to the influence of local immunity and the state of vaginal microflora on the development of chronic inflammatory diseases is carried out. The results of proteomic researches of cervicovaginal fluid in early diagnostics of inflammatory diseases of the lower genital tract and the possibility of using cytokine biomarkers in clinical practice with the aim of prediction of pathological state and choice of further treatment tactics of the patient are presented. Efficiency of use of the combined medication on the basis of chlorhexidine and dexpantenol possessing pronounced antimicrobial, regenerating and metabolic action and applied in therapy of acute and chronic vaginitis; bacterial vaginosis; endo-, exocervicitis that is topical in therapy of inflammatory diseases of the lower genital tract is considered.

Новые национальные медицинские критерии приемлемости методов контрацепции (2022): вклад в охрану репродуктивного здоровья женщин

This review is aimed to analyse research data on the lower genital tract microbiome and factors effecting its composition, as well as the relationship with HPV-associated cervical diseases. Modern studies show that certain types of lactobacilli can play a protective role by reducing the likelihood of human papillomavirus (HPV) infection and contributing to its elimination. At the same time, dysbiotic changes, including decreased levels of lactobacilli and increased levels of opportunistic pathogens, are associated with the development of bacterial vaginosis and other abnormal vaginal biocenosis. These conditions can contribute to the persistence of HPV, increasing the risk of cervical intraepithelial neoplasia and cervical cancer. Most studies show significant differences in the vaginal microbiome composition in women with cervical intraepithelial neoplasia and malignant cervix neoplasms as compared to healthy patients. Anaerobic bacteria such as Gardnerella vaginalis, Mobiluncus spp., Peptoniphilus spp., Parvimonas micra, Prevotella spp. that can inhibit the growth of lactobacilli and disrupt the normal balance of microflora play an important role in this process. In addition, decreased levels of Lactobacillus crispatus are associated with a higher probability of HPV persistence and dysplasia progression. Studying mechanisms of interaction between vaginal microbiota and HPV is critically important to understand the mechanisms of pathogenesis of precancerous and malignant processes of the cervix. Further study of these aspects will allow the development of new prevention and treatment strategies to modulate vaginal microflora and reduce the risk of disease progression.