Cervical Neoplasia Research Articles

HIV prevalence among cervical (pre)cancer diagnoses in Suriname: a retrospective population study.

To determine the prevalence of HIV in women with (pre)cancerous cervical lesions in Suriname and their retention in care. A retrospective population study including all women diagnosed with (pre)invasive cervical intraepithelial neoplasia (CIN I to III or cervical cancer) in the only pathology department, during 2010-2020. The HIV test coverage and the HIV positivity ratio were determined through matching pathology data with the national HIV test database. The relation between retention in HIV care up to 2022 and different covariates was determined through Kaplan-Meier survival analysis and log-rank tests. There were 2 901 (1 395 CIN I, 396 CIN II, 444 CIN III, and 666 cervical cancer) diagnoses of (pre)invasive cervical neoplasia. An overall HIV test coverage of 57.5% and a positivity ratio of 5.8% were found, with no difference among the (pre)cancer stages. The undiagnosed prevalence (women not previously known HIV-positive at cervical diagnosis) was 1.6% and 2.9% among precancer and cancer diagnoses, respectively. The median time in care of women with cervical cancer was 8 months for those not on antiretroviral therapy (ART) and 4 years for those starting ART. Among women with precancer stages this was 5 and 10 years, respectively (p < 0.05). HIV testing, followed by treatment initiation when found HIV-positive, should be prioritized in women diagnosed with cervical neoplasia. This will enhance the individual clinical outcomes and facilitate the control of the HIV epidemic in Suriname.

HPV-Independent Cervical Adenocarcinoma Discovered by Cytology-Based Screening: A case report of gastric type adenocarcinoma of the uterine cervix from cytopathology to histopathology

Abstract Introduction/Objective In recent years, the relative prevalence of adenocarcinoma has increased, comprising 20–25% of all cervical carcinomas in developed countries. Approximately 15% of cervical adenocarcinomas are unrelated to human papilloma virus (HPV) infection. With the shift toward HPV primary testing, an increased understanding of HPV-independent cervical adenocarcinomas becomes more important. Methods/Case Report This case report demonstrates a rare case of gastric-type adenocarcinoma (GAS) of the cervix discovered during a routine well-woman exam. Patient-reported episodes of vaginal spotting were noted prior to screening. HPV testing by PCR on the initial pap smear was negative. Cytology findings raised concerns about endocervical glandular cell abnormalities. Subsequent cervical biopsy revealed GAS, a finding supported by positive CK7, MUC5AC, CDX2, and aberrant (mutant) p53 expression by immunohistochemistry. HPV independence was further confirmed by negative results on mRNA ISH for high-risk HPV and HPV16/18. Results (if a Case Study enter NA) NA Conclusion Here we discuss the impact of cytology-based screening on HPV-independent cervical cancers, with focus on adenocarcinoma. While the move to primary HPV screening has been shown to be effective at identifying HPV-related neoplasms, it ineffectively addresses HPV-independent malignancies. In this particular population, cytology-based screening remains indispensable. The described case demonstrated subtle cytologic features consistent with endocervical glandular abnormality, ultimately correlating with subsequent histologic findings of HPV-independent GAS. Negative HPV results combined with subtle cytomorphologic changes displayed by some adenocarcinomas on PAP smear could present a significant diagnostic pitfall. Additionally, p16+ expression attributable to aberrant p53 pathways (rather than HPV) may further contribute to potential diagnostic errors. While further research into best practices for early detection of HPV-independent cervical neoplasias should be conducted, this team suggests both clinical survey and referral for cytologic screening following reports of abnormal vaginal bleeding and/or watery discharge and screener education focused on cervical GAS.

TLR4 Downregulation Identifies High-Risk HPV Infection and Integration in H-SIL and Squamous Cell Carcinomas of the Uterine Cervix.

Growing scientific evidence suggests a link between the expression of toll-like receptor 4 (TLR4) and cervical cancer carcinogenesis. Specifically, a close relation between TLR4 expression and FIGO stage, lymph node metastases, and tumor size has been reported in cervical cancer. In the present study, we aimed to evaluate the relationship between TLR4 expression levels and human papillomavirus (HPV) infection and/or high-risk (hr) HPV integration status in patients with a histological diagnosis of high-grade squamous intraepithelial lesion (H-SIL), and squamous cell carcinoma (SCC) of the uterine cervix. Sixty biopsies of cervical neoplasia, comprising H-SIL (n = 20) and SCC (n = 40), were evaluated for TLR4 expression by immunohistochemistry. All samples were positive for high-risk HPV as confirmed by in situ hybridization (ISH) and broad-spectrum PCR followed by Sanger sequencing analysis. The intensity of TLR4 staining was higher in tissues negative for intraepithelial lesion or malignancy (NILM) than in H-SIL, and further reduced in SCC. Moreover, statistically significant differences have been observed in the percentage of TLR4 expression between NILM and H-SIL and between H-SIL and SCC, with higher percentages of expression in H-SIL than in SCC. Our results showed a significant downregulation of TLR4 in HPV-related H-SIL and SCC, compared to NILM. These data support the hypothesis that TLR4 expression is suppressed in HPV-driven oncogenesis.

Population-based risk factors and urogenital comorbidities associated with genital herpes: A nationwide study of 4 million women

ObjectivesTo explore the population-based risk factors for genital herpes in women and examine whether genital herpes occurs at higher rates in women diagnosed with cervical neoplasia and common urogenital infections. MethodsAn open cohort study consisting of 4,097,075 women ≥15 years of age in Sweden (2002-2018). The outcome was genital herpes diagnosis. The predictor variables were sociodemographic factors (age, educational level, family income, region of residence, and country of origin) and urogenital comorbidities (cervical carcinoma neoplasia, cystitis, vaginosis, and vulvovaginitis) and parity. National registers and primary health care data were used. Cox regression models were used to estimate hazard ratios with 95% confidence intervals. Interactions tests were conducted. ResultsA total of 15,727 women received a genital herpes diagnosis in inpatient and outpatient specialist care settings during the study period. Sociodemographic factors and parity were associated with genital herpes. than women without these comorbidities. ConclusionsGenital herpes occurs with higher rates in women of high family income, young age, Swedish origin, co-occurrence of urogenital comorbidities, and nulliparity. The findings can be used by clinicians when encountering women with these risk factors.

Age distribution of patients with multiple High-Risk Human Papilloma Virus (HR-HPV) genotypes and HPV vaccine recommendations by age

Introduction: The aim of this study to identify the age distribution of patients with multiple high risk Human Papilloma Virus (HR-HPV) genotypes and to evaluate HPV vaccination programs through age distribution. Methods: Patients between the ages of 20-70, who had cervical screening (cervical smear) and HPV genotype tests between January 2017 and December 2021 in Gynecology and Obstetrics Department in Tınaztepe University Hospital, were included in this study. HR-HPV genotype tests and age information which were performed evaluated retrospectively. Results: The study consisted of 66 patients analysis with multiple HR-HPV genotypes. The median age of the patients with multiple HR- HPV was found to be 32.6 years old. The most frequent combination of multiple HR-HPV was found two sub-types of HR-HPV (66.7%), median age was found as 36.6 years old. In this study the frequency for three sub-types of HR-HPV was found 24.2% and median age for this group was found to be 34.7 years old. We found frequency in patients with four or more sub-types of HR-HPV as 9.1%, and the median age for this group as 33.1 years old was found. Conclusion: The most common cause of cervical cancer is HPV infection. Multiple HR-HPV infection progression may promote high risk cervical lesions and neoplasia. HPV genotype testing results considering combination of subtypes may direct individual treatment, follow-up protocols for patients. HPV vaccination research may comprise multiple HR-HPV subtypes relations and age distribution for optimal immunization.

Exploring oxysterols and protein carbonylation in cervicovaginal secretions as biomarkers for cervical cancer development

Cervical cancer, a major global health issue and the fourth most common cancer among women, is strongly linked to Human Papillomavirus (HPV) infection. Emerging evidence indicates that oxidative stress plays a critical role in the carcinogenesis of cervical tissue. This study investigates the relationship between oxidative stress markers—specifically oxysterols, lipid oxidation, and protein carbonylation—and the progression of cervical neoplasia.Oxysterols, which are elevated in various inflammatory diseases and cancers, were measured in cervicovaginal fluid samples using LC-MS/MS. The targeted oxysterols included 27-hydroxycholesterol (27-OHC), 7β-hydroxycholesterol (7β-OHC), 7-ketocholesterol (7-KC), and 7α,27-dihydroxycholesterol (7α,27-diOHC). Among these, 7α,27-dihydroxycholesterol was significantly increased in correlation with the severity of neoplastic stages. In parallel, protein carbonylation, an indicator of cellular oxidative stress, was assessed. Results revealed higher levels of protein carbonylation in neoplastic samples compared to non-neoplastic controls. These modifications were further analysed through redox proteomics to identify the specific proteins affected.The study demonstrates that elevated lipid oxidation and protein carbonylation in cervicovaginal secretions are linked to the development and progression of cervical cancer. Identifying these biomarkers may improve screening strategies, enabling the identification of individuals at increased risk for cervical neoplasia and guiding timely interventions.

The significance of extensive HPV genotyping for cervical high-grade neoplasia among women with atypical glandular cells.

To examine the associated risk of cervical intraepithelial neoplasm grade 3+ (CIN3+) lesions in patients with AGC and extensive human papillomavirus (HPV) genotyping. Cases with atypical glandular cell (AGC) interpretation on a Papanicolaou (Pap) test were identified along with associated extensive HPV genotyping and histologic follow-up results. Within this cohort of 469,694 Pap tests, 0.4% were diagnosed as AGCs. In total, 1267 cases had concurrent high-risk HPV (hrHPV) genotyping, and 40.3% were hrHPV positive. The percentage of AGC cases with cervical CIN3+ on histologic follow-up was 52.2% when hrHPV was positive, whereas it was 4.9% with a negative hrHPV result. The top 5 hrHPV genotypes associated with cervical CIN3+ in this cohort were HPV16, HPV18, HPV58, HPV52, and HPV33. Indeed, 92.8% of the hrHPV-associated CIN3+ lesions identified in this cohort were positive for at least one of these HPV genotypes. The sensitivity of detecting cervical CIN3+ lesions was 85.6% with the top 5 hrHPV genotypes (HPV16/18/58/52/33) and only increased to 89.0% when the additional 12 genotypes were included. In patients with an AGC Pap, the risk of having a cervical CIN3+ lesion is greatly increased by positivity for hrHPV types 16, 18, 58, 52, and/or 33. Incorporating comprehensive HPV genotyping into AGC cytology allows for refined risk stratification and more tailored management strategies.

Clinical significance of atypical glandular cells on cytology: 10 years' experience of a colposcopic referral center.

'Atypical glandular cells' (AGC) is an uncommon cytological result of cervical Pap smears which includes a wide of histopathological diagnoses, from benign to premalignant and malignant cervical disorders, endometrial cancer and, occasionally, other genital malignancies. This study aims to provide a comprehensive overview of AGC, assessing risk factors and clinical and histological features in affected patients. A retrospective analysis was conducted on a cohort of 239 women diagnosed with AGC between 2012 and 2022 at the 'Regional Referral Center for Prevention, Diagnosis and Treatment of HPV-related Genital Disorders', Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Following AGC detection, patients underwent colposcopy with endocervical sampling and endometrial assessment via pelvic ultrasound. Selective cases also received endometrial biopsies. Among a total of 190 women who underwent both colposcopy and endometrial assessment, 116 (61%) had negative clinical and histopathological findings. The remainder displayed various abnormalities: 36 women (18.9%) were found to have endometrial or cervical polyps, 23 (12.1%) were diagnosed with preinvasive cervical neoplasia, and 21 (10.9%) with invasive cervical or endometrial disease. Menopause, multiparity, and older age were all significantly associated with endometrial cancer, but none of the abovementioned variables were significantly associated with cervical neoplasia. Our data confirm that AGC may reveal the presence of a wide range of histopathological conditions. Patients diagnosed with AGC should undergo a careful evaluation including both colposcopy with endocervical sampling and an endometrial assessment.

Evaluation of Cervix by Colposcopic Directed Histopathology: A Single Center Study

Background: The most common malignancy among women worldwide is cervical cancer. With the right screening, it is a disease that can be prevented and cured. Colposcopy is a useful method for identifying and treating precancerous cervical lesions after primary screening. The most reliable method for identifying precancerous lesions is histopathology. Objectives: Purpose of This study aims to evaluate the cervix by colposcopic directed histopathology in a tertiary care hospital. Methods: This Cross-sectional study was conducted among 67 patients from North east medical college and Hospital, Sylhet. The study was done for the period of “January 2022 to June 2023 “. Patients having the following complaints: positive visual inspection of the cervix (VIA + ve) with 3-5% acetic acid, post-coital bleeding, postmenopausal bleeding, and intermenstrual bleeding were recruited for the study. Written informed consent was obtained from the participants. Results: Out of the total cases, 23 (34.33%) had squamous cell carcinoma, 14 (20.89%) had LSIL, 11 (16.42%) had adenocarcinoma, 9 (13.43%) had HSIL, and 7 (10.45%) had cervical intraepithelial neoplasia. Adenosquamous was 4.48% in 3 instances. Conclusion: The colposcopic guided histological investigation found squamous cell carcinoma to be the most common cervical neoplasia in this study. Afterwards, a large proportion of cases are attributed to LSIL, adenocarcinoma, HSIL, CIN, and adenosquamous carcinoma.

Sodium valproate affects the expression of p16INK4a and p21WAFI/Cip1 cyclin‑dependent kinase inhibitors in HeLa cells.

p16INK4a and p21WAF1/Cip1 are cyclin-dependent kinase inhibitors involved in cell cycle control, which can function as oncogenes or tumor suppressors, depending on the context of various extracellular and intracellular signals, and cell type. In human papillomavirus-induced cervical cancer, p16 INK4a shows oncogenic activity and functions as a diagnostic marker of cervical neoplasia, whereas p21 WAF1/Cip1 acts as a tumor suppressor and its downregulation is associated with the progression of malignant transformation. Several histone deacetylase (HDAC) inhibitors promote the positive and negative regulation of a number of genes, including p16 INK4a and p21 WAF1/Cip1; however, the effects of sodium valproate (VPA) on these genes and on the proteins they encode remain uncertain in HeLa cervical cancer cells. In the present study, these effects were investigated in HeLa cells treated with 0.5 or 2 mM VPA for 24 h, using reverse transcription-quantitative PCR, confocal microscopy and western blotting. The results revealed a decrease in the mRNA expression levels of p16 INK4a and a tendency for p16INK4a protein abundance to decrease in the presence of 2 mM VPA. By contrast, an increase in the protein expression levels of p21WAF1/Cip1 was detected in the presence of 0.5 and 2 mM VPA. Furthermore, VPA was confirmed to inhibit HDAC activity and induce global hyperacetylation of histone H3. Notably, VPA was shown to suppress p16 INK4a, a biomarker gene of cervical carcinoma, and to increase the abundance of the tumor suppressor protein p21WAF1/Cip1, thus contributing to the basic knowledge regarding the antitumorigenic potential of VPA. Exploration of epigenetic changes associated with the promoters of p16 INK4a and p21 WAF1/Cip1, such as histone H3 methylation, may provide further information and improve the understanding of these findings.

A Systematic Review of Human Papillomavirus Vaccination Challenges and Strategies to Enhance Uptake.

Human papillomavirus (HPV) vaccination has revolutionized cervical cancer prevention. Clinical trials confirm that the quadrivalent (HPV types 6, 11, 16, 18) and bivalent (HPV types 16, 18) vaccines effectively prevent HPV infections and cervical neoplasia. The latest HPV vaccine protects against nine virus types responsible for 90% of cervical cancer cases globally. Despite their undoubted effectiveness in reducing morbidity and mortality associated with HPV infections, challenges in vaccine coverage and uptake persist. The current study aimed to identify the primary challenges associated with HPV vaccination, propose effective strategies to improve vaccination uptake, and compile relevant evidence into a comprehensive overview to inform policy and practice. A systematic review protocol, following PRISMA-P and PRISMA guidelines, was established. Articles were sourced from the Web of Science using keywords from a comprehensive review of HPV vaccination challenges and strategies. Studies published between 1 January 2020, and 1 May 2024, including RCTs and observational, qualitative, and cross-sectional studies, were included, while reviews, protocols, and commentaries were excluded. Titles, abstracts, and full texts were screened per PRISMA guidelines. The review identified five key strategies to improve HPV vaccination uptake: parental and school engagement, use of technology and multimedia tools, healthcare providers' role, multicomponent interventions, and targeted interventions for immigrant groups. This review emphasized the need for a multifaceted approach to improving vaccination rates, offering a robust foundation for policy and stakeholder initiatives.

LINE-1 ORF1p is a Promising Biomarker in Cervical Intraepithelial Neoplasia Degree Assessment.

Cervical intraepithelial neoplasia (CIN) represents a spectrum of preinvasive squamous lesions within the cervical epithelium, whose identification is a diagnostic challenge due to subtle histomorphological differences among its categories. This study explores ORF1p, a nucleic acid-binding protein derived from long interspersed nuclear element-1 (LINE-1), as a potential biomarker for enhancing CIN diagnosis. A comprehensive analysis of 143 cervical specimens, encompassing CIN I (n=20), CIN II (n=46), CIN III (n=14), invasive cancer (n=32), and nondysplastic cases (normal cervical epithelia (n=24) and atrophy (n=7) were conducted. ORF1p, Ki67, and p16 expressions were evaluated using immunohistochemistry. ORF1p immunopositivity was detected in the vast majority [110/112 (98.2%)] of dysplastic and neoplastic (CIN and invasive cancer) specimens, whereas 19/24 (79.2%) of normal cervical specimens lacked ORF1p expression. The observed pattern of ORF1p expression showed a progressively increasing extent and intensity with advancing CIN grades. CIN I exhibited mild ORF1p expression in the lower one or two-thirds of the cervical epithelium [14/16 (87.5%)], whereas CIN II demonstrated moderate to strong ORF1p expression spanning the lower two-thirds [29/46 (63.0%)]. Pronounced transepithelial ORF1p immunopositivity characterized CIN III cases [13/14 (92.8%)] and cervical cancer [30/32 (93.8%)]. These findings propose ORF1p as a valuable indicator even for detecting CIN I, effectively discerning them from normal cervical tissue (p < 0.0001). Our findings underscore the potential of ORF1p as an early diagnostic marker for cervical neoplasia.

Impact of human papillomavirus types on uterine cervical neoplasia.

Human papillomavirus (HPV) is a major cause of cervical cancer. As the natural history of HPV-associated cervical lesions is HPV genotype-dependent, it is important to understand the characteristics of these genotypes and to manage them accordingly. Among high-risk HPVs, HPV16 and 18 are particularly aggressive, together accounting for 70% of HPV genotypes detected in cervical cancer. Other than HPV16 and 18, HPV31, 33, 35, 45, 52, and 58 are also at a high risk of progression to cervical intraepithelial neoplasia (CIN)3 or higher. Recent studies have shown that the natural history of HPV16, 18, 52, and 58, which are frequently detected in Japan, depends on the HPV genotype. For example, HPV16 tends to progress in a stepwise fashion from CIN1 to CIN3, while HPV52 and 58 are more likely to persist in the CIN1 to CIN2 state. Among the high-risk HPVs, HPV18 has some peculiar characteristics different from those of other high-risk HPV types; the detection rate in precancerous lesions is much lower than those of other high-risk HPVs, and it is frequently detected in highly malignant adenocarcinoma and small cell carcinoma. Recent findings demonstrate that HPV18 may be characterized by latent infection and carcinogenesis in stem cell-like cells. In this context, this review outlines the natural history of HPV-infected cervical lesions and the characteristics of each HPV genotype.

Performance of an ancillary test for cervical cancer that measures miRNAs and cytokines in serum and cervical mucus.

Currently, human papillomavirus tests and cytology are used to screen for cervical cancer. However, more accurate ancillary screening tests are needed. MicroRNAs (miRNAs) and cytokines are promising biomarkers that are aberrantly expressed in cervical cancer. Therefore, the potential of developing new screening markers based on the levels of miRNAs and cytokines in serum and local mucus samples from the same patients with cervical neoplasia was investigated. miRNA screening was performed by microarray and measurement using real-time reverse-transcriptase PCR. Cytokine were measured using multiplex bead assay, and changes in expressions were analyzed based on disease severity. As lesions progressed, miR-20b-5p, -155-5p, -144-3p, -451a, and -126-3p expression levels were increased in mucus, and miR-16-5p, -223-3p, and -451a expression levels were decreased in serum. Regarding cytokines, IL-6, IL-8, monocyte chemoattractant protein-1, Eotaxin, interferon-γ, and RANTES were increased, whereas granulocyte-colony-stimulating factor (G-CSF) was significantly decreased in mucus. miRNAs and cytokines in serum did not have high diagnostic accuracy. However, a combination of miR-20b-5p, -451a, -126-3p, Eotaxin, as well as G-CSF in mucus samples, had high diagnostic accuracy with an area under the receiver operating characteristic curve of 0.989 (0.979-0.999). Our results suggest that using mucus for this ancillary test is more beneficial than serum.

Exposure to polycyclic aromatic hydrocarbons promotes the progression of low-grade cervical intraepithelial neoplasia: A population-based cohort study in China.

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

Vitamins in Gynecologic Malignancies.

The combination of vitamin A and D derivatives with classical chemotherapeutic treatments results in more satisfactory outcomes. The use of drug combinations, such as 9cUAB130 with carboplatin and cisplatin with TAC-101, shows enhanced cytotoxic effects and reductions in ovarian tumor volume compared to single-drug treatments. Combining cisplatin with calcitriol and progesterone increases VDR expression, potentially enhancing the effectiveness of anticancer therapy in ovarian cancer. The effectiveness of vitamin derivatives in anticancer treatment may vary depending on the characteristics of the tumor and the cell line from which it originated. An increase in thiamine intake of one unit is associated with an 18% decrease in HPV infection. Higher intake of vitamin C by 50 mg/day is linked to a lower risk of cervical neoplasia. Beta-carotene, vitamin C, and vitamin E are associated with risk reductions of 12%, 15%, and 9% in endometrial cancer, respectively. A balanced daily intake of vitamins is important, as both deficiency and excess can influence cancer development. It has been observed that there is a U-shaped relationship between group B vitamins and metabolic markers and clinical outcomes.

The Female Genital Tract Microbiome: a review

The human microbiome, a complex ecosystem consisting of microorganisms and their genetic material, profoundly impacts physiological processes crucial for human health. Among various niches within the human body, the female genital tract harbours a diverse microbial community, known as the vaginal microbiota, which plays a pivotal role in maintaining vaginal health and preventing infections. This review explores the intricate relationship between the vaginal microbiota and gynaecological conditions, including bacterial vaginosis, human papillomavirus (HPV) infection, cervical neoplasia, endometrial cancer, ovarian cancer, preterm birth, and infertility. Changes in the composition of the vaginal microbiota, known as dysbiosis, have been associated with a higher risk of these conditions. Notably, dysbiosis characterized by a reduction in protective Lactobacillus species and an increase in anaerobic organisms is associated with bacterial vaginosis, HPV infection persistence, and neoplastic development. Furthermore, alterations in the vaginal microbiota during pregnancy have implications for gestational outcomes, with a low frequency of lactobacilli predisposing women to preterm birth. Moreover, abnormal vaginal flora has been implicated in female infertility, affecting embryo implantation, tubal factors and pregnancy outcomes. Although there has been progressing in understanding the role of the vaginal microbiome in gynaecological health, additional research, particularly randomized controlled trials, is necessary to clarify the underlying mechanisms and devise targeted therapies.

Role of Geminin as a Tool for Augmenting Accurate Diagnosis of Cervical Neoplasia.

To determine the role of geminin as a tool for differentiating various types of cervical intraepithelial neoplasia (CIN) and cervical carcinoma (CC). Seventy women newly diagnosed with CIN or CC undergoing cervical biopsy were included; their clinical profile, human papilloma virus (HPV) positivity, and colposcopy findings were noted, and biopsy tissue was analyzed for geminin content. On geminin immunohistochemistry, 100% of women with CIN3 and 96.29% of women with CC had geminin two plus or more. When analyzed as ordinal variables, there was a significant correlation (spearman's rho 0.35, p 0.01) between geminin and biopsy results (CIN1, CIN2, CIN3, and CC). Screening tests for cervical cancer, like conventional pap smears, liquid-based pap smears, and triaging with HPV, have limitations. It is important to be able to differentiate between high-grade lesions, invasive cancer, and low-grade lesions. The detection of geminin in these cells may aid in the confirmation of the diagnosis and ensure adequate treatment. Cervical intraepithelial lesions and carcinoma cervix demonstrated a correlation between increased geminin expression in CIN1 vs. CC and CIN2 vs. CC. Geminin may be a potential surrogate marker for higher-grade cervical lesions, and further research is needed to corroborate evidence in this direction.

Identifying Biomarkers for Cervical Neoplasia: A Label-free Proteomic Analysis of Cervicovaginal Fluid

Identifying Biomarkers for Cervical Neoplasia: A Label-free Proteomic Analysis of Cervicovaginal Fluid

The role of long non-coding RNAs and circular RNAs in cervical cancer: modulating miRNA function.

Cervical cancer (CC) is a primary global health concern, ranking as the fourth leading cause of cancer-related death in women. Despite advancements in prognosis, long-term outcomes remained poor. Beyond HPV, cofactors like dietary deficiencies, immunosuppression, hormonal contraceptives, co-infections, and genetic variations are involved in CC progression. The pathogenesis of various diseases, including cancer, has brought to light the critical regulatory roles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). The aberrant expression of these miRNAs, lncRNAs, and circRNAs plays a pivotal role in the initiation and progression of CC. This review provides a comprehensive summary of the recent literature regarding the involvement of lncRNAs and circRNAs in modulating miRNA functions in cervical neoplasia and metastasis. Studies have shown that lncRNAs and circRNAs hold great potential as therapeutic agents and innovative biomarkers in CC. However, more clinical research is needed to advance our understanding of the therapeutic benefits of circRNAs and lncRNAs in CC.