Association of IL-1ß gene polymorphisms rs1143627, rs1799916, and rs16944 with altered risk of triple-negative breast cancer.

PURPOSE: Breast cancer (BC) is the most recognized malignancy in females globally and is heterogeneous in its clinical manifestation, among which the triple-negative (TNBC) subtype is the most aggressive. This study examines the associations between IL-1ß polymorphisms and BC and TNBC susceptibility. METHODS: Genotyping ofIL-1ßrs1143627, rs1799916, and rs16944 polymorphisms was done in 488 women with BC (130 TNBC, 358 non-TNBC) and 476 cancer-free control women using real-time PCR genotyping. RESULTS: The minor allele and genotype frequencies of rs1799916, rs1143627, and rs16944 significantly differed among BC cases and controls and remained after correcting key covariates. On the other hand, minor allele and genotype frequencies of only rs16944 significantly differed between TNBC and non-TNBC cases. Spearman correlation analyses demonstrated that all three variants correlated positively with menopausal status and Her2 status but negatively with menarche, breastfeeding, and cancer type. In addition, rs1143627 and rs16944 correlated positively with HR and ER, while rs1799916 correlated positively with Ki67 status. The three variants correlated negatively with menarche, breastfeeding, and cancer type in non-TNBC cases but positively with histological grading in non-TNBC and Her2 in TNBC cases. A positive correlation was noted between rs1143627 and rs1799916 and age (<40 years) and between rs1799916 and rs16944 with menopausal status. We confirmed that GCG haplotype imparted BC susceptibility, while TCA and TTG haplotypes were protective of BC. Among TNBC cases, only GCG and TCA haplotypes remained protective of TNBC after adjustment. CONCLUSIONS: Our study highlights the association between IL-1ßgenetic polymorphisms and BC and TNBC susceptibility, suggesting these variants' diagnostic/prognostic capacity in BC patients.

Estimates of the incidence, prevalence, and factors associated with common sexually transmitted infections among Lebanese women.

BACKGROUND: We analyzed the prevalence of active infection with common curable sexually transmitted infections (STIs) including N. gonorrhea, C. trachomatis, T. vaginalis, and T. pallidum, as well as active infection with HPV, herpes simplex virus types I (HSV-1) and II (HSV-2), M. hominis, M. genitalium, C. albicans, and Ureaplasma in 351 Lebanese women. METHODS: A cross-sectional study, involving 351 sexually active women, 40 years or younger, who were recruited from outpatient Obstetrics and Gynecology clinic attendees between September 2016 and November 2017. RESULTS: The prevalence of active infection was low at 0.3% for N. gonorrhea, 0.6% for HSV-2, 2.8% for C. trachomatis, and 2.9% for any curable STIs. Prevalence of active HPV infection was high assessed at 15.7% for high-risk and 12.2% for low-risk genotypes. Furthermore, the prevalence was 2.0% for M. genitalium, 6.8% for ureaplasma, 13.7% for Candida albicans, and 20.5% for M. hominis. No active infections with T. vaginalis, T. pallidum, or HSV-1 were observed. Significant age differences were noted in the prevalence of high-risk and low-risk HPV genotypes, but no such differences were noted in the prevalence of other infections. No appreciable variations were identified in the prevalence of key STIs based on smoking, marital status, or the number of sexual partners. CONCLUSIONS: The study documented active infection with substantial prevalence for multiple STIs among women attending outpatient gynecology and obstetrics clinics in Lebanon. These findings underscore the importance of strengthening STI surveillance, linkage to care, and prevention interventions in reducing STI incidence among women.

Menopausal Status Impact on the Quality of Life in Kazakhstani Healthcare Workers: A Cross-sectional Study.

BACKGROUND: Menopausal quality of life (MenQoL) is a common concern that primary healthcare workers often encounter. Menopause has a significant impact on women's health, but studies examining its effect on the MenQoL of menopausal healthcare employees have produced conflicting results. OBJECTIVE: The aim of this study was to compare the quality of life related to menopausal status (pre-, peri-, or postmenopausal) in healthcare workers from various clinical settings in Kazakhstan. DESIGN: This was a cross-sectional study. PARTICIPANTS: In total, 222 menopausal healthcare workers (physicians, nurses/midwives, administrative staff, and cleaners) were enrolled from hospitals affiliated with the University Medical Center (UMC) in Kazakhstan. MAIN MEASURES: The outcome variable was assessed using the Menopausal Quality of Life Questionnaire (MENQOL), which evaluates MenQoL across four domains of menopausal symptoms: physical, psychological, vasomotor, and sexual. KEY RESULTS: The most frequently reported menopausal symptoms were physical ones, such as feeling tired or worn out (70.7%), followed by feeling a lack of energy (65.3%) and dry skin (64.1%). The postmenopause group had the highest mean MenQoL score in the vasomotor domain (mean 3.46 ± 1.84). There was a borderline statistical significance when comparing postmenopause and perimenopause groups in the physical domain. The pairwise comparison of mean sexual scores revealed that postmenopause women had the highest average score (3.3 ± 2.36) compared to both premenopause (mean 2.3 ± 1.82) and perimenopause (mean 2.22 ± 1.58) groups (p < 0.05). CONCLUSIONS: Menopausal status has influence on the MenQoL of healthcare workers. The study findings could have important implications for policymakers as they provide insight into the factors influencing the quality of life of menopausal healthcare employees. Creating a more menopause-friendly work environment may not only enhance the well-being of healthcare personnel but also improve their overall job satisfaction and performance.

Predictive Role of Progesterone Levels for IVF Outcome in Different Phases of Controlled Ovarian Stimulation for Patients With and Without Endometriosis: Expert View.

The study aimed to review the role of basal, trigger, and aspiration day progesterone levels (PLs) as predictors of in vitro fertilization (IVF) success for patients with and without endometriosis. A non-systematic review was conducted by searching papers published in English during the period of 1990-2023 in MEDLINE and PubMed, Embase, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), and Web of Science. The most widely used IVF predictor success was the trigger day progesterone serum level. Many studies utilize the threshold level of 1.5-2.0 ng/ml. However, the predictive power of only progesterone level failed to show high sensitivity and specificity. Contrary, progesterone level on the trigger day combined with the number of mature retrieved oocytes had the highest predictive power. High baseline progesterone level was associated with poor IVF outcomes. Research on progesterone and IVF success in patients with endometriosis is limited but indicates that endometriosis patients seem to benefit from higher progesterone concentrations (≥ 37.1 ng/ml) in IVF cycles. Currently, there is limited data for a definitive insight into the mportance of progesterone in the estimation of IVF success. Nonetheless, this summarized evidence could serve as up-to-date guidance for the role of progesterone in the prediction of IVF outcomes, both in patients with and without endometriosis.

Prevalence of high-risk human papillomavirus infection and genotype distribution among Kazakhstani women with abnormal cervical cytology.

AIM: This study aimed to identify the prevalence and distribution of high-risk human papillomavirus (HR-HPV) types among Kazakhstani women with abnormal cervical cytology. METHODS: A cross-sectional study was performed from May 2019 to June 2020. Cervical samples were collected from women in the different regions of Kazakhstan. RESULTS: A total of 316 patients' samples were analysed for HR-HPV using real-time multiplex PCR. Cervical cytology abnormalities were reported according to the Bethesda classification. HPV detection by cytology showed a statistically significant association with HPV status and the number of HPV infection types (p < .05). Among women with abnormal cervical cytology, 62.4% were positive for HPV infection of those 79.4% had low-grade squamous intraepithelial lesions (LSIL), and 20.6% had high-grade squamous intraepithelial lesions (HSIL). Among patients with LSIL, 77.4% had HPV16 and 58.8% were infected with HPV18. Among patients with HSIL, 41.2% had HPV18 and 22.6% - HPV16. CONCLUSIONS: There is a high prevalence of HR-HPV types among Kazakhstani women with abnormal cervical cytology. The most identified types were HPV16, 18, 31, 33 and 52. There is an emergency need to implement an HPV vaccination program to prevent cervical lesion development.

Comparison of diagnostic accuracy and acceptability of self-sampling devices for human Papillomavirus detection: A systematic review.

Objective: Cervical cancer screening coverage remains low in many countries worldwide. Self-sampling approach for cervical cancer screening has a good potential to improve the screening coverage. This study aims to compare different types of HPV self-sampling devices for cervical cancer screening to identify the most accurate and acceptable device(s). Methods: A systematic review was performed on data extracted from all studies specific to HPV self-sampling devices by searching relevant articles in PubMed, Google Scholar, Scopus, Web of Science, ScienceDirect, Cochrane Library, and EBSCO published from 2013 to October 2023. The study was registered in PROSPERO (CRD42022375682). Results: Overall, 70 papers met the eligibility criteria for this systematic review and were included in the analysis: 22 studies reported self-sampling devices diagnostic accuracy, 32 studies reported self-sampling devices acceptability and 16 studies reported both (accuracy and acceptability). The most popular self-sampling devices were Evalyn Brush, FLOQ Swab, Cervex-Brush, and Delphi Screener. Out of overall 38 studies analyzing self-sampling devices' diagnostic accuracy, 94.7% of studies reported that self-collected specimens provided sensitivity and specificity comparable with clinician-collected samples; acceptability of Evalyn Brush, FLOQ Swab, Delphi Screener, and Colli-Pee, varied between 84.2% and 100%. Conclusion: The self-sampling approach has a good potential to increase cervical cancer screening coverage. Evalyn Brush, Cervex-Brush, FLOQ Swab, and Delphi Screener self-sampling devices for HPV detection were the most commonly utilized and found to be the most accurate, and patient-acceptable. HPV detection accuracy using these self-sampling devices had no significant difference compared to the sampling performed by healthcare providers.

Epidemiology of spontaneous pregnancy loss in Kazakhstan: A national population-based cohort analysis during 2014-2019 using the national electronic healthcare system.

INTRODUCTION: Spontaneous pregnancy loss (SPL) is a common health problem that affects 1:10 of childbearing women, and is linked with physical and psychological complications. As the number of nationwide studies on the incidence of SPL is few, especially from middle-income countries, in this study we investigated the epidemiology, complications and outcomes of SPL before 22 weeks of gestation by analyzing large-scale healthcare data from the Unified Nationwide Electronic Healthcare System (UNEHS) in Kazakhstan. MATERIAL AND METHODS: A population-based study among women who experienced SPL in any healthcare setting of the Republic of Kazakhstan during the period of 2014-2019. The International Classification of Diseases (ICD) 10th edition and ICD 9th edition's procedural codes were utilized to retrieve data using relevant diagnostic and procedural codes. RESULTS: In total, 207 317 records of women who have experienced an SPL before 22 weeks of gestation were analyzed from all Kazakhstani regions. The estimated prevalence of SPL was 8.7%, with a 20% decline over a 6-year period. The SPL cases ratio comprises on average 6.2 per 1000 reproductive-age women. Incomplete miscarriage (ICD-10 code "O03.4") was the most common type (37.8%), followed by blighted ovum (ICD-10 code "O02.0"; 34.1%) and missed abortion (ICD-10 code "O02.1"; 13.5%). The most common management methods were dilation and curettage of the uterus (ICD-9 code "69.0"; 84.7%) and aspiration curettage of the uterus (ICD-9 code "65.0"; 15%), whereas medical management was rarely performed (2.6%). CONCLUSION: The information available in UNEHS adequately identifies types of miscarriages and treatment methods. Although the prevalence of SPL before 22 weeks of gestation is decreasing, management of miscarriages requires closer attention.

Unveiling the Role of the Work Environment in the Quality of Life of Menopausal Physicians and Nurses.

BACKGROUND: There is a lack of scientific evidence regarding the specific challenges faced by menopausal medical professionals in different work settings. This study aims to investigate the relationship between work environment and the menopausal quality of life (QoL) in physicians and nurses. METHODS: This survey was conducted using the Menopausal Quality of Life Questionnaire (MENQOL) with a sample of 35 menopausal physicians and 95 nurses employed in health facilities in Astana and Kyzylorda cities, Kazakhstan. RESULTS: Physicians reported a higher frequency of menopausal symptoms compared to nurses. The difference was statistically significant (p < 0.05) for symptoms such as decreased productivity (60.00% vs. 38.20%), flatulence or gas pains (71.43% vs. 48.39%), weight gain (79.41% vs. 61.80%), changes in skin appearance (79.59% vs. 50.00%), and changes in sexual desire (58.82% vs. 33.70%). Physicians with managerial duties had a significantly higher occurrence of vasomotor symptoms compared to non-managerial physicians (mean 3.35 ± 2.14 vs. 1.69 ± 0.89) and also had a higher mean psychological score (mean 3.26 ± 1.28 vs. 2.29 ± 1.19). CONCLUSIONS: These findings reflect differences between the menopause effects related to work environment for doctors and nurses, and shed light on the specific challenges faced by them during menopause. In addition, it is important to consider socio-demographic and workplace-related factors in investigating their impact on the QoL.

The effects of sildenafil citrate on intrauterine growth restriction: a systematic review and meta-analysis.

BACKGROUND: An increase in vascular resistance of uterine vessels is associated with intrauterine growth restriction (IUGR). Sildenafil citrate, a phosphodiesterase-5 inhibitor that stabilizes cyclic guanosine monophosphate (cGMP) and increases nitric oxide levels, improves placental perfusion by dilation of spiral arteries and is beneficial in managing IUGR. This study aims to determine the effectiveness of sildenafil citrate in improving perinatal outcomes in IUGR pregnancies. METHODS: Meta-analysis was performed on data extracted from all studies specific to sildenafil citrate in IUGR management, searching relevant articles on PubMed, Medline, Google Scholar, Embase, and Cochrane databases. Publications identified by the manual search, based on references in reviews, were also included. Dichotomous results were presented as risk ratio (95% confidence interval), while continuous results were expressed as mean difference (MD); samples represented by the random effects model. RESULTS: Nine trials were included where the sildenafil citrate effect was compared with a placebo or no intervention. A significant increase in birth weight [SMD (95% CI), 0.69 (0.31, 1.07)] was seen in IUGR pregnancies managed with sildenafil. However, gestational age (SMD (95% CI), 0.44 (-0.05, 0.94], fetal death rate [RR (95% CI), 0.56 (0.17, 1.79)] in IUGR pregnancies was not changed by sildenafil. Neonatal death [RR (95% CI), 0.93 (0.47, 1.86)] and neonatal intensive care unit (NICU) admissions [RR (95% CI), 0.76 (0.50, 1.17)] were not significantly different between sildenafil and control groups. CONCLUSION: Sildenafil citrate increases birth weight and prolonged pregnancies but did not affect stillbirth rate, neonatal death, and NICU admission. TRIAL REGISTRATION: The study was registered in PROSPERO on September 18, 2021 (CRD42021271992).

Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box.

Recurrent pregnancy loss is a complex health challenge with no universally accepted definition. Inconsistency in definitions involves not only the number of spontaneous abortions (two or three) that are accepted for recurrent pregnancy loss but the types of pregnancy and gestational age at miscarriage. Due to the heterogeneity of definitions and criteria applied by international guidelines for recurrent pregnancy loss, the true incidence of recurrent miscarriage, which is reported to range from 1% to 5%, is difficult to estimate. Moreover, the exact etiology of recurrent pregnancy loss remains questionable; thus, it is considered a polyetiological and multifactorial condition with many modifiable and non-modifiable factors involved. Even after thoroughly evaluating recurrent pregnancy loss etiology and risk factors, up to 75% of cases remain unexplained. This review aimed to summarize and critically analyze accumulated knowledge on the etiology, risk factors, relevant diagnostic options, and management approach to recurrent pregnancy loss. The relevance of various factors and their proposed roles in recurrent pregnancy loss pathogenesis remains a matter of discussion. The diagnostic approach and the management largely depend on the etiology and risk factors taken into consideration by a healthcare professional as a cause of recurrent miscarriage for a particular woman or couple. Underestimation of social and health consequences of recurrent pregnancy loss leads to compromised reproductive health and psychological well-being of women after miscarriage. Studies on etiology and risk factors for recurrent pregnancy loss, especially idiopathic, should be continued. The existing international guidelines require updates to assist clinical practice.

Knowledge and attitudes of mothers toward HPV vaccination: A cross-sectional study in Kazakhstan.

BACKGROUND: Although recommended for all member states of World Health Organization, there is no national human papillomavirus vaccination program in Kazakhstan. Furthermore, there are no studies in Kazakhstan that evaluate the mothers' perception of human papillomavirus vaccines. OBJECTIVES: This study aims to assess the knowledge and attitudes toward human papillomavirus vaccination among mothers in Kazakhstan and the factors associated with their attitudes. DESIGN: A cross-sectional study was performed during the period of December 2021-February 2022. The STROBE guideline for cross-sectional studies was applied. METHODS: Paper-based structured questionnaires were filled out by 191 mothers, 141 of whom had daughters. The attitude score was assessed as per the Likert-type scale. The Chi-square and Fisher's exact tests, with a significance value of < 0.05 were used to analyze the relationships between the characteristics of mothers and their attitude scores. RESULTS: The following factors were significantly associated with mothers' attitudes toward human papillomavirus vaccination: a place of residence, family income, number of children, and refusal of vaccination for themselves (p < 0.005). Of all participants, only 45% of all mothers, 41% of mothers with a female, and 46% of mothers with male children had positive attitudes toward human papillomavirus vaccination. The child's gender was not a significant determinant. Overall, the level of knowledge about human papillomavirus vaccination was found to be low. The median total score is 0 out of 12 for women who have negative and neutral attitudes toward human papillomavirus vaccines. Among women who have positive attitudes toward HPV vaccines, the median score is around 3 points. CONCLUSION: Before the implementation of the human papillomavirus vaccination program into the Kazakhstani national vaccination calendar, comprehensive and adequate information and education campaigns are required on the national level for parents and the population in general.

Reproductive and Obstetric Outcomes after Fertility-Sparing Treatments for Cervical Cancer: Current Approach and Future Directions.

Cervical cancer is one of the leading causes of cancer-related death in women of reproductive age. The established fertility-sparing approaches for the management of early-stage cervical cancer for women who plan pregnancy are associated with a decline in fecundity and an increased risk of pregnancy complications. This article aims to offer an overview of fertility-sparing approaches and the management of potential subfertility and pregnancy complications after these treatments. An extensive search for the available data about infertility and cervical cancer, fertility-sparing techniques in patients with cervical cancer, fertility treatment, obstetrical complications, and pregnancy outcomes in cervical cancer patients was completed. Fertility-preserving procedures such as loop electrosurgical excision procedure (LEEP), cold-knife conization, and trachelectomy in women diagnosed with cervical cancer can be considered as safe and effective treatments that preserve reproductive potential. Current fertility-preserving procedures, based on the balance of the oncological characteristics of patients as well as their desire for reproduction, allow one to obtain acceptable reproductive and obstetric outcomes in women treated for cervical cancer. Nevertheless, careful monitoring of pregnancies obtained after fertility-preserving procedures is recommended, since this cohort of patients should be considered at higher risk compared with a healthy population.

Reproductive and Obstetric Outcomes after UAE, HIFU, and TFA of Uterine Fibroids: Systematic Review and Meta-Analysis.

Novel treatment options for uterine fibroids, such as uterine artery embolization (UAE), ultrasound-guided and magnetic resonance-guided high-intensity focused ultrasound (USgHIFU and MRgHIFU), and transcervical radiofrequency ablation (TFA) methods, are widely used in clinical practice. This systematic review and meta-analysis (CRD42022297312) aims to assess and compare reproductive and obstetric outcomes in women who underwent these minimally invasive approaches for uterine fibroids. The search was performed in PubMed, Google Scholar, ScienceDirect, Cochrane Library, Scopus, Web of Science and Embase. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) and Cochrane guidelines. The articles were selected to meet the following eligibility criteria: (1) research article, (2) human subject research, and (3) the study of pregnancy outcomes after the treatment of uterine fibroids by either one of three methods-UAE, HIFU, and TFA. The analysis of 25 eligible original articles shows a similar rate of live births for UAE, USgHIFU, MRgHIFU, and TFA (70.8%, 73.5%, 70%, and 75%, respectively). The number of pregnancies varied considerably among these studies, as well as the mean age of pregnant women. However, the results of pregnancy outcomes for TFA are insufficient to draw firm conclusions, since only 24 women became pregnant in these studies, resulting in three live births. The miscarriage rate was highest in the UAE group (19.2%). USgHIFU was associated with a higher rate of placental abnormalities compared to UAE (2.8% vs. 1.6%). The pooled estimate of pregnancies was 17.31% to 44.52% after UAE, 18.69% to 78.53% after HIFU, and 2.09% to 7.63% after TFA. The available evidence confirmed that these minimally invasive uterine-sparing treatment options for uterine fibroids are a good approach for patients wishing to preserve their fertility, with comparable reproductive and obstetric outcomes among the different techniques.

Biological Role of Folic Acid in Pregnancy and Possible Therapeutic Application for the Prevention of Preeclampsia.

The rationale and importance of folic acid supplementation during pregnancy for fetal congenital defect prevention are accepted worldwide. Moreover, a sufficient plasma concentration of folates can reduce the incidence of spontaneous abortions, and support the normal expansion of placental blood vessels, ensuring physiological placental blood flow, thus promoting appropriate fetal growth and development. Furthermore, there is emerging evidence that long-term supplementation with folic acid can effectively prevent preeclampsia. Preeclampsia is unique to the human species in complications during pregnancy, which contributes to maternal and perinatal mortality worldwide. In the pathogenesis of preeclampsia abnormal placental invasion, the excess of antiangiogenic factors and maternal-placental syndrome play a key role. Increased blood levels of homocysteine during pregnancy are associated with the risk of preeclampsia. Moreover, hyperhomocysteinemia has been proposed to be an independent risk factor for preeclampsia. Folate supplementation helps to decrease elevated levels of homocysteine; thus, the role of folic acid supplementation in pregnancy is even more important. Multiple reports suggest that folate administration decreases the level of serum homocysteine and, therefore, reduce the risk and severity of preeclampsia. However, the association between folic acid supplementation and the decreased risk of preeclampsia has been investigated with controversial conclusions. Currently, the optimal dose of folic acid that is effective for preeclampsia prevention remains uncertain. In this review, we aim to summarize the accumulated knowledge on the role of folic acid in the pathogenesis of preeclampsia, and the possible impact of folate supplementation on the decreased risk of preeclampsia.

Depression, Anxiety, and Stress in Kazakhstani Women with Recurrent Pregnancy Loss: A Case-Control Study.

Background: Recurrent pregnancy loss (RPL) is associated with increased incidence and severity of depression, anxiety, and stress, and screening for these comorbidities following miscarriages is beneficial for women with RPL who are planning future pregnancies. This study aims to investigate depression, anxiety, and stress among Kazakhstani women with RPL. Methods: This was a case−control study involving 70 women with confirmed RPL and 78 ethnically matched control women. Depression, anxiety, and stress were evaluated using the Depression Anxiety Stress Scales (DASS)-21 instrument. Linear regression and correlation analysis were used in assessing the association of RPL with symptoms of depression, and/or anxiety, and/or stress, after adjusting for key covariates. Results: Women with RPL were found to have significantly higher mean scores for depression (p < 0.001), anxiety (p < 0.001), and stress (p < 0.001) symptoms. Mild−moderate stress and mild−moderate and severe−extreme depression and anxiety symptoms were more frequent in the RPL group than in the control group. Regression analysis demonstrated that RPL was the only significant variable associated with anxiety, depression, and stress symptoms. Conclusion: The results of this study suggest that women with RPL are more likely to experience heightened symptoms of depression, anxiety, and stress. Proper psychological counseling is recommended for women with RPL, as well as their spouses.

Genetic diversity of human papillomavirus (HPV) as specified by the detection method, gender, and year of sampling: a retrospective cross-sectional study.

PURPOSE: This study assesses HPV prevalence and genotype distribution in Lebanon, and identifies differentials in HPV infection, infection with multiple genotypes, and with high-risk genotypes, by sex, age, and year of data collection. METHODS: Study participants comprised 1042 female and 160 male participants between 2006 and 2018. HPV genotyping was done by PCR and hybridization (2006-2013) or real-time PCR (2013 onwards). Diversity of HPV genotypes across gender, age groups, and years of data collection was tested by applying Shannon Diversity Index. RESULTS: The overall HPV prevalence was 44.8% among study participants, and threefold higher in women than men. Single HPV infection was seen in two-third of HPV-positive participants. Women were less likely to be infected with multiple HPV strains, but more likely to be infected with high-risk or mixed-risk HPV genotypes. HPV-16 (11.0%, 9.8%) and HPV-53 (8.5%, 4.9%) were the most prevalent high-risk HPV genotypes in women and men, respectively, while HPV-18 prevalence was 4.9% in men and 3.1% in women, while HPV-59 prevalence was 6.6% in men and 2.1% in women. Samples collected post-2011 from women showed twice higher odds of HPV infection than those collected earlier and were threefold more likely to be infected with multiple HPV strains, and twice more likely to be infected with high-risk genotypes compared to those tested earlier. Women scored higher on Shannon index indicating high diversity in HPV types and frequency, with trend of increased diversity over time. While the odds of HPV infection remained associated with sex and temporal trend in multivariable analysis, odds of having high-risk genotypes was mainly associated with infection with multiple HPV strains. CONCLUSION: Our study showed high diversity in HPV genotypes and an increasing trend of infection with multiple and high-risk genotypes in recent years. Findings underscore the need for effective screening/surveillance and HPV vaccination programs.

Prevalence of Precancerous Cervical Lesions among Nonvaccinated Kazakhstani Women: The National Tertiary Care Hospital Screening Data (2018).

OBJECTIVE: At the present time, cervical cancer remains the fourth most prevalent cancer among women worldwide. Most cervical cancer cases are attributed to high-risk human papillomavirus (HPV) infection. Because the natural history of cervical cancer takes decades, the disease could be prevented if premalignant conditions are identified and appropriately managed. The aim of this study is to identify the prevalence of precancerous lesions among non-vaccinated women attending the national tertiary care hospital in Kazakhstan. METHODS: This was a retrospective study of the cervical cancer screening database (2018) from the national tertiary care hospital in Kazakhstan. Records of 6682 patients, who had cervical cytology tests by Papanicolaou (Pap test), were analyzed. Out of the revised cases, 249 patients had abnormal cervical cytology reports. The Pap test was performed using liquid-based cytology (LBC). The data were analyzed using the statistical software STATA 16. A p-value of less than 0.05 was considered statistically significant. RESULTS: In this retrospective analysis of 6682 patients' records, we found 3.73% (249 patients) out of all Pap tests performed in 2018 were abnormal. The prevalence of high-grade squamous intraepithelial lesion (HSIL) was high at 19.28%, and the proportion of atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells (ASCs-H) was 18.47%, while low-grade squamous intraepithelial lesion (LSIL) were identified in 62.25% of the cases. Almost 25% of the women included in the study had concurrent lower and upper genital tract infections. CONCLUSION: Although the overall rate of abnormal Pap test results was not high, the study shows the elevated prevalence of HSIL. It calls the attention of local policymakers and gynecology specialists and requires immediate actions to improve the prophylactic measures to decrease morbidity and mortality from cervical cancer in Kazakhstan.

Unique ESR1 and ESR2 estrogen receptor gene variants associated with altered risk of triple-negative breast cancer: A case-control study.

BACKGROUND: We previously reported on the association between ESR1 and ESR2 gene variants and heightened risk of breast cancer (BC). Here we investigated the association of common ESR1 and ESR2 gene variants with triple negative BC (TNBC). METHODS: This retrospective case-control study involved 488 BC patients (130 TNBC, 358 non-TNBC patients). ESR1 (rs2234693, rs9340799, rs3020314, rs3798577) and ESR2 (rs928554, rs944459, rs4986938, rs1256049, rs1256030, rs1271572) genotyping was done by real-time PCR. RESULTS: While minor allele frequencies (MAF) of ESR1 variants were comparable between TNBC and non-TNBC subjects, significantly higher ESR2 rs1256049 MAF was seen in TNBC patients. Significantly higher frequency of ESR1 rs3798577 T/C and C/C genotypes were noted in TNBC cases, and significant differences were seen in ESR2 rs928554, rs1256049, and rs1271572 genotype distribution. Increased TNBC risk was associated with ESR1 rs3798577 T/C and C/C genotypes according to codominant and dominant models, while positive association of ESR2 rs928554 with TNBC was seen according to codominant and recessive models, and positive association of ESR2 rs1256049 with TNBC was seen according to codominant and dominant models. Positive interactions were noted between ESR2 rs1271572-ESR1 rs3020314, ESR2 rs1271572-ESR1 rs9340799, and ESR2 rs1271572-ESR1 rs2234693, ESR2 rs4986938-ESR1 rs2234693, and ESR2 rs928554-ESR1 rs9340799. Haplotype analysis confirmed the positive association of ESR1 CATT with TNBC, while ACGGCTC and ACGGTT ESR2 haplotypes were positively associated with TNBC. CONCLUSION: Results of this study confirmed the association of unique ESR1 and ESR2 genetic variants with altered risk of TNBC. This suggests possible diagnostic and prognostic role of these variants with TNBC independent of their association with BC.

Does Vaccination Protect against Human Papillomavirus-Related Cancers? Preliminary Findings from the United States National Health and Nutrition Examination Survey (2011-2018).

Most oropharyngeal and anogenital cancers are caused by human papillomavirus (HPV). Although HPV vaccines showed high efficacy against oropharyngeal and anogenital HPV infections, and cancer precursors in randomized clinical trials, there are limited data on the effectiveness of HPV vaccination against HPV-related cancers. We aimed to evaluate the association of HPV vaccination with HPV-related cancers among a nationally representative sample of United States adults, aged 20-59 years. In a cross-sectional study combining four cycles from the National Health and Nutrition Examination Survey, from 2011 through 2018, we used a survey-weighted logistic regression model, propensity score matching and multiple imputations by chained equations to explore the association of HPV vaccination with HPV-related cancers. Among 9891 participants, we did not find an association of HPV vaccination with HPV-related cancers (adjusted OR = 0.58, 95% CI 0.19; 1.75). Despite no statistically significant association between HPV vaccination and HPV-related cancers, our study findings suggest that HPV-vaccinated adults might have lower odds of developing HPV-related cancers than those who were not vaccinated. Given the importance of determining the impact of vaccination on HPV-related cancers, there is a need to conduct future research by linking cancer registry data with vaccination records, to obtain more robust results.

Prophylactic Human Papillomavirus Vaccination: From the Origin to the Current State.

Immunization is the most successful method in preventing and controlling infectious diseases, which has helped saving millions of lives worldwide. The discovery of the human papillomavirus (HPV) infection being associated with a variety of benign conditions and cancers has driven the development of prophylactic HPV vaccines. Currently, four HPV vaccines are available on the pharmaceutical market: Cervarix, Gardasil, Gardasil-9, and the recently developed Cecolin. Multiple studies have proven the HPV vaccines' safety and efficacy in preventing HPV-related diseases. Since 2006, when the first HPV vaccine was approved, more than 100 World Health Organization member countries reported the implementation of HPV immunization. However, HPV vaccination dread, concerns about its safety, and associated adverse outcomes have a significant impact on the HPV vaccine implementation campaigns all over the world. Many developed countries have successfully implemented HPV immunization and achieved tremendous progress in preventing HPV-related conditions. However, there are still many countries worldwide which have not created, or have not yet implemented, HPV vaccination campaigns, or have failed due to deficient realization plans associated with establishing successful HPV vaccination programs. Lack of proper HPV information campaigns, negative media reflection, and numerous myths and fake information have led to HPV vaccine rejection in many states. Thus, context-specific health educational interventions on HPV vaccination safety, effectiveness, and benefits are important to increase the vaccines' acceptance for efficacious prevention of HPV-associated conditions.