Публикации 2026

#

Fertility Preservation Strategies in Cervical Cancer Patients: A Narrative Review

<h1>ABSTRACT</h1> <h2>Introduction:</h2> <p>Infertility is a global medical problem. In recent years, there has been an increase in the prevalence of infertility. One of the factors contributing to the increase in infertility cases is cancers of reproductive age and the consequences of their treatment. Cervical cancer is one of the most common malignant diseases among women and the leading cause of cancer-related death in Kazakhstan.</p> <h2>The Purpose of the Study:</h2> <p>The purpose of this literature review is to summarize current data on approaches to preserving the reproductive function of women after treatment for cervical cancer.</p> <h2>Methods:</h2> <p>A search of available literature was conducted in international scientific databases on the topic of female infertility associated with cervical cancer. The search included Scopus, MEDLINE, PubMed, Embase, and Google Scholar databases from 2000 to September 2024.</p> <h2>Results:</h2> <p>Classical treatments for cervical cancer include radical hysterectomy with or without radiation therapy and pelvic chemoradiation therapy. Unfortunately, these treatment options can lead to infertility. Given the increasing incidence of early-stage cervical cancer in women of reproductive age, new treatment approaches are being introduced to preserve women&rsquo;s reproductive function.</p> <h2>Conclusions:</h2> <p>The development of an integrated approach to the effective diagnosis and treatment of cervical precancerous lesions and early stages of cervical cancer is of particular importance for the timely treatment and preservation of the reproductive function of women of reproductive age.</p>

  • Author : 7. Terzic, M., Bapayeva, G. B., Ukybassova, T. M., Aimagambetova, G. N., Kamzayeva, N. K., Kim, Y. O., Primbetov, B. U., Imankulova, B. Z., Kongrtay, K. K., & Kadroldinova, N. O.

  • Publication year: 2026

#

Cervicovaginal Mycobiome Restructuring by HPV and Bacterial Community State Types in a Kazakhstani Shotgun Metagenomic Cohort: Lactobacillus iners as a Candida-Permissive Niche Associated with α-9 HPV

<h2>Abstract</h2> <p>Cervicovaginal dysbiosis is an established co-factor of high-risk human papillomavirus (HPV) persistence and cervical neoplastic development, yet most studies address the bacterial compartment in isolation, leaving fungal communities and bacterial&ndash;fungal cross-kingdom interactions underexplored, particularly in Central Asian populations. We performed shotgun metagenomic sequencing (mNGS) of cervicovaginal samples from 311 Kazakhstani women undergoing routine cervical screening. HPV status was determined using combined PCR and mNGS methods, and cervical screening was completed using liquid-based cytology (NILM, ASC-US, LSIL, ASC-H). Bacterial, viral, and fungal taxa were profiled from a single shotgun dataset with Kraken2 pipeline. Bacterial community state types (CSTs) were determined based on dominant bacterial species, functional gene content was annotated against KEGG using eggNOG, and covariate-adjusted associations were estimated using MaAsLin3. Mycobiome &beta;-diversity differed significantly by HPV status (p&nbsp;= 0.003). In particular,&nbsp;Candida&nbsp;positivity was significantly associated with HPV presence and with high-risk &alpha;-9 HPV in cytologically normal (NILM) samples (OR = 3.6, [1.6&ndash;9.6],&nbsp;p&nbsp;&le; 0.001). Covariate-adjusted analysis was consistent with this positive association (q &lt; 0.05). Concurrently, among CSTs,&nbsp;Lactobacillus iners-dominated CST III and dysbiotic&nbsp;Gardnerella vaginalis-dominated CST IV showed a 3-fold higher&nbsp;Candida albicans&nbsp;prevalence (p&nbsp;&lt; 0.01). Further analysis demonstrated that, functionally, both of these CSTs had depleted capacity for lactate metabolism (ko00620,&nbsp;p&nbsp;&lt; 0.0001) and, in particular, for the genetic capacity for pyruvate-dependent H<sub>2</sub>O<sub>2</sub>&nbsp;generation (half that of the&nbsp;L. crispatus-dominated CST I). These findings support&nbsp;L. iners&nbsp;as a metabolically permissive rather than protective&nbsp;Lactobacillus&nbsp;and suggest cross-kingdom functional signatures as candidate biomarkers for HPV acquisition and persistence in Central Asia, a region previously absent from the cervicovaginal microbiome literature.</p> <p>Keywords:&nbsp;</p> <p><a href="https://www.mdpi.com/search?q=cervicovaginal+microbiome">cervicovaginal microbiome</a>;&nbsp;<a href="https://www.mdpi.com/search?q=cervicovaginal+mycobiome">cervicovaginal mycobiome</a>;&nbsp;<a href="https://www.mdpi.com/search?q=human+papillomavirus+%28HPV%29">human papillomavirus (HPV)</a>;&nbsp;<a href="https://www.mdpi.com/search?q=Lactobacillus+iners">Lactobacillus iners</a>;&nbsp;<a href="https://www.mdpi.com/search?q=Candida">Candida</a>;&nbsp;<a href="https://www.mdpi.com/search?q=shotgun+metagenomics">shotgun metagenomics</a>;&nbsp;<a href="https://www.mdpi.com/search?q=bacterial%E2%80%93fungal+cross-kingdom+interactions">bacterial&ndash;fungal cross-kingdom interactions</a>;&nbsp;<a href="https://www.mdpi.com/search?q=Central+Asia">Central Asia</a></p>

  • Author : 10. Kozhakhmetov, S., Kushugulova, A., Vinogradova, E., Rakhmankulova, A., Terzic, M., Bapayeva, G., Aimagambetova, G., Kamzayeva, N., Kim, Y., Primbetov, B., Imankulova, B., Kongrtay, K., Kadroldinov

  • Publication year: 2026

#

Tiered Functional Screening Identifies an Autochthonous Vaginal Lactiplantibacillus plantarum Strain with Probiotic Potential

<h2>Abstract</h2> <p>Persistent high-risk human papillomavirus (HPV) infection drives cervical cancer, a leading cause of cancer-related mortality among women in low- and middle-income countries; its clinical course is shaped by the cervicovaginal microbiome, in which&nbsp;Lactobacillus-dominated communities are associated with enhanced viral clearance. Despite this, vaginal probiotic interventions often demonstrate limited colonization efficiency, and autochthonous strain libraries from Central Asia remain absent. We applied a tiered functional screening workflow to a collection of 235 vaginal lactic acid bacterial isolates recovered from 400 women undergoing routine gynecological examination in Astana, Kazakhstan. The workflow sequentially filtered isolates on (i) antimicrobial activity against seven urogenital indicator pathogens using the deferred antagonism assay, (ii) surface adhesion by the Brilis erythrocyte assay, and (iii) biofilm-forming capacity by crystal violet retention and laser-capture-microdissection (LCM) microscopy. Species-level identification of the selected candidate was performed by whole-genome shotgun sequencing followed by Kraken2 taxonomic classification. From 235 isolates, three rounds of phenotypic filtering identified four broad-spectrum antimicrobial candidates (127-3, 127-4, 107-2, 107-4) with non-overlapping inhibitory profiles against seven urogenital indicator strains. Adhesion phenotyping segregated candidates into low- and moderate-adhesion groups, with none reaching the high-adhesion threshold. Among all four candidates, only strain 127-4 produced a reproducible biofilm-associated signal (crystal violet retention OD490 = 0.09 &plusmn; 0.07 at 24 h; 0.08 &plusmn; 0.03 at 48 h), consistent with early surface attachment under static conditions. Whole-genome shotgun sequencing assigned 97.81% of classified reads to&nbsp;Lactiplantibacillus plantarum, supporting preliminary identification of the selected isolate as&nbsp;L. plantarum&nbsp;strain 127-4. Composite ranking confirmed 127-4 as the only isolate combining broad antimicrobial activity (5/7 indicators), moderate adhesion (specific adhesion index, SPA = 2.95), and a detectable biofilm-associated phenotype. We report the first systematic functional screening of autochthonous cervicovaginal lactic acid bacteria from a Central Asian population and identify&nbsp;L. plantarum&nbsp;127-4 as a probiotic candidate with an integrated trait profile rarely identified through single-criterion screening approaches. Beyond candidate identification, this work establishes a transferable workflow for assembling functionally annotated vaginal&nbsp;Lactobacillus&nbsp;collections from underrepresented populations, providing a foundation for future population-specific probiotic interventions targeting cervicovaginal health.</p> <p>Keywords:&nbsp;</p> <p><a href="https://www.mdpi.com/search?q=cervicovaginal+microbiome">cervicovaginal microbiome</a>;&nbsp;<a href="https://www.mdpi.com/search?q=Lactiplantibacillus+plantarum">Lactiplantibacillus plantarum</a>;&nbsp;<a href="https://www.mdpi.com/search?q=autochthonous+probiotic">autochthonous probiotic</a>;&nbsp;<a href="https://www.mdpi.com/search?q=biofilm+formation">biofilm formation</a>;&nbsp;<a href="https://www.mdpi.com/search?q=vaginal+lactobacilli">vaginal lactobacilli</a>;&nbsp;<a href="https://www.mdpi.com/search?q=HPV">HPV</a>;&nbsp;<a href="https://www.mdpi.com/search?q=Central+Asia">Central Asia</a>;&nbsp;<a href="https://www.mdpi.com/search?q=strain-level+functional+screening">strain-level functional screening</a></p>

  • Author : 9. Nazarova, V., Kamzayeva, N., Kozhakhmetov, S., Kushugulova, A., Terzic, M., Bapayeva, G., Primbetov, B., Imankulova, B., Aimagambetova, G., Kim, Y., Kongrtay, K., Kadroldinova, N., Galym, M., Makha

  • Publication year: 2026

#

Multi-kingdom cervical microbiome structure in health and dysbiosis: a cross-sectional study from Kazakhstan

<h2>Abstract</h2> <p><strong>Introduction:&nbsp;</strong></p> <p>The cervicovaginal microbiome is a key determinant of reproductive health. Its multi-kingdom structure and ecological interactions remain insufficiently characterized across diverse populations. This study aimed to define the composition and cross-kingdom dynamics of the cervical microbiome in women without HPV infection and with normal cytology in a Kazakhstani population.</p> <p><strong>Methods:&nbsp;</strong></p> <p>In this cross-sectional study, cervical samples from 92 reproductive-age women were analyzed using whole-genome metagenomic sequencing to characterize bacterial, viral, fungal, and archaeal communities, together with predicted functional pathways. Microbial communities were stratified into community state types based on dominant bacterial species.</p> <p><strong>Results:&nbsp;</strong></p> <p>Bacterial composition differed markedly across community states, with&nbsp;<em>Lactobacillus</em>-dominated profiles associated with low diversity and anaerobe-rich communities associated with higher diversity. In contrast, viral, fungal, and archaeal diversity remained relatively stable, although descriptive compositional shifts indicated variation in bacteriophages, methanogenic archaea, and opportunistic fungi in non-<em>Lactobacillus</em>&nbsp;communities. Functional analyses indicated CST-associated pathway differences, suggesting greater metabolic flexibility in dysbiotic states, and exploratory network analysis revealed CST-associated restructuring of bacterial and cross-kingdom co-variation patterns. Notably, more than half of participants exhibited non-<em>Lactobacillus</em>-dominated communities despite the absence of infection or cytological abnormalities, indicating population-specific microbiome configurations.</p> <p><strong>Discussion:&nbsp;</strong></p> <p>Study demonstrates that the cervical microbiome is accompanied by exploratory cross-kingdom compositional variation and ecological states traditionally considered dysbiotic may represent stable, population-specific configurations, highlighting the need for context-dependent definitions of microbial health.</p>

  • Author : 8. Rakhmankulova, A., Kozhakhmetov, S., Kovenskiy, A., Mukhanbetzhanov, N., Katkenov, N., Jarmukhanov, Z., Terzic, M., Bapayeva, G., Ukybassova, T., Aimagambetova, G., Kim, Y., Primbetov, B., Imankulo

  • Publication year: 2026

#

Systems analysis of the HPV–microbiome–biofilm triad

<h2>Abstract</h2> <p><strong>Background:&nbsp;</strong></p> <p>Human papillomavirus (HPV) remains the leading cause of cervical cancer worldwide, however, its pathogenesis cannot be sufficiently explained by viral factors alone. Accumulating evidence highlights the critical role of cervicovaginal microbiome composition and biofilm formation in shaping viral persistence, epithelial barrier disruption and carcinogenic progression.</p> <p><strong>Methods:&nbsp;</strong></p> <p>This systems-based integrative synthesis analyzed peer-reviewed literature published between January 2000 and July 2025, retrieved from PubMed and Google Scholar with additional records identified through backward citation screening. The collected data were synthesized to construct a conceptual model of the HPV&ndash;microbiome&ndash;biofilm triad and to evaluate its clinical and biological implications.</p> <p><strong>Results:&nbsp;</strong></p> <p>The analysis indicates that depletion of Lactobacillus-dominated communities and expansion of anaerobic taxa, particularly Gardnerella vaginalis, are associated with biofilm development, chronic inflammation and immune modulation. These interrelated processes form self-reinforcing feedback loops that promote HPV persistence and reduce therapeutic efficacy. Microbiome dysbiosis and biofilm formation were further linked to impaired epithelial integrity, altered cytokine signaling pathways and clinically relevant phenotypes including immune escape, metabolic shifts and treatment non-responsiveness.</p> <p><strong>Discussion:&nbsp;</strong></p> <p>This systems perspective challenges reductionist pathogen-centered models and emphasizes the importance of integrating microbiome profiling and biofilm dynamics into cervical cancer risk stratification and therapeutic strategies. The coupled interactions between microbial communities, host immunity and viral persistence underscore the cervicovaginal ecosystem as an active regulator of disease progression rather than a passive bystander. Incorporating ecosystem-based parameters into clinical decision-making may enhance prognostic assessment and improve treatment outcomes, particularly in low- and middle-income countries where high HPV prevalence coincides with increased microbiome vulnerability.</p> <p><strong>Systematic Review Registration:&nbsp;</strong></p> <p><a href="https://www.crd.york.ac.uk/PROSPERO/" target="_blank">https://www.crd.york.ac.uk/PROSPERO/</a>, identifier CRD420251208178.</p>

  • Author : 6. Nazarova, V., Kamzayeva, N., Ukybassova, T., Kozhakhmetov, S., & Kushugulova, A.

  • Publication year: 2026