Search Results (109)

The lymphocystis disease virus (LCDV) is a widespread disease in Mediterranean aquaculture and could lead to losses in fry as well as prevent the sale of adult gilthead seabream (Sparus aurata), affecting both hatchery and on-growing stages. Although LCDV infections are often considered self-limiting, they can lead to severe outcomes due to skin microbiome alterations that promote secondary infections, while also reducing growth and marketability, causing substantial economic losses. Basic biosecurity measures are not successful, and there is no available commercial vaccine. This study evaluated diets supplemented with Origanum vulgare and Cinnamomum zeylanicum essential oils (1% and 2%) in gilthead seabream experimentally infected with LCDV. Preventive feeding (90 days before infection) and therapeutic feeding (initiated at infection) were compared across 11 experimental groups, including infected, recovered, and control groups. Results showed that essential oils were more effective prophylactically than therapeutically, highlighting their protective role when incorporated into diets. Cinnamon-supplemented groups consistently exhibited lower prevalence and mortality than oregano groups. High DNA damage values linked to reduced mortality, particularly in the CIN90.1 group, demonstrated that viral dissemination was most restricted. In conclusion, essential oils modulated LCD progression by influencing viral interactions with DNA damage repair mechanisms, supporting their potential for disease control in intensive aquaculture. Full article

Background: There is limited available data about the natural history and clinical characteristics of patients affected by high-grade vaginal intraepithelial neoplasia (or vaginal intraepithelial neoplasia 2/3 or vaginal high-grade squamous intraepithelial lesion, HSIL). The aim of the study was to review clinical characteristics and treatment outcomes of a large cohort of patients with vaginal HSIL. Methods: A retrospective analysis was performed for patients with histologically confirmed VaIN 2/3 treated at two Italian referral centers from 2003 to 2022. Demographics, referring cytology, associated cervical and vulvar HSIL treatment modalities, follow-up visits, and vaccination status were recorded. The primary outcome was risk of recurrence; the secondary outcome was risk of progression to invasive carcinoma after treatment. Results: 323 women were included in the analysis: 69.7% (225) had VaIN2, and 30.3% (98) had VaIN3. Mean age at diagnosis was 55.43 years (range 24–93 years). 20.4% had a previous hysterectomy, mainly for cervical intraepithelial neoplasia (CIN)/invasive squamous carcinoma (64.6%). In total, 55.2% underwent ablative therapy, and 44.8% underwent excisional treatment. Over a mean follow-up of 62.43 months, 22.0% of patients recurred as vaginal HSIL. At univariate analysis older age, VaIN grade 3, previous hysterectomy, associated cervical lesions, associated vulvar HSIL, and excisional treatment were significantly associated with increased risk of recurrence. At multivariate analysis, only hysterectomy and excisional treatment maintained significance. Five patients progressed to invasive vaginal carcinoma, with a median time to invasion of 87.1 months. Conclusions: The risk of recurrence of vaginal HSIL is higher in patients treated with excisional methods and/or those who have undergone hysterectomy for both benign and preinvasive lesions. Long-term follow-up is essential to monitor clinical outcomes and prevent disease progression. Full article

Infection with oncogenic human papillomavirus (HPV) remains a leading cause of cervical cancer and other HPV-related diseases. This situation persists despite the availability of effective prophylactic vaccines. While global vaccination programs have significantly reduced the incidence of HPV in adolescents and young adults, many women presenting with HPV infection or squamous intraepithelial lesions (SIL) were not covered by primary prevention. This review was performed with the aim of evaluating the impact of administering the 9-valent HPV vaccine in adult women who are HPV-positive or have histologically confirmed cervical precancerous lesions. Following the PRISMA 2020 guidelines, a search was performed in the MEDLINE, Scopus, and Cochrane Library databases. A total of 653 studies were retrieved, of which 7 studies, including 19,414 women, met the inclusion criteria. According to the literature, vaccination was linked to significant reductions in persistent HPV infection, progression of SIL, and recurrence of high-grade lesions after surgical removal. Complete HPV remission was achieved in up to 72.4% of vaccinated women, compared to 45.7% among unvaccinated controls. Vaccination after conization lowered the recurrence risk of CIN2+ lesions by 87%, with benefits seen regardless of timing. The most significant effect was observed when vaccine administration was performed before the surgical procedure. Furthermore, HPV vaccination notably enhanced viral clearance and decreased the likelihood of repeated surgical interventions. Despite differences in study design and follow-up definitions, the overall evidence supports additional vaccination in HPV-positive adult women as an effective measure to reduce recurrence and promote viral remission. These findings emphasize the need for clear guidelines and wider access to HPV vaccination for adult populations. Full article

Objectives: To evaluate the diagnostic and prognostic value of histophenotyping of the extracellular matrix of the cervical stroma at cervical intraepithelial neoplasia (CIN). Methods: Retrospective analysis of 160 biopsies and surgical preparations of the cervix in women of reproductive age included cases of CIN 1–3 and the group with confirmed persistence or lesion progression (CIN P) at repeated biopsy. The control group (n = 40) consisted of morphologically intact cervical tissue. Histophenotypes were evaluated by staining with hematoxylin, eosin, and Masson trichrome, and classified as follows: normal (dense parallel bundles of type I collagen), intermediate (disorganized and fragmented type I collagen fibers), and myxoid (amorphous weakly fibrillar matrix). The clinical, viral, and inflammatory characteristics between histophenotypes were statistically compared. Results: The distribution of histophenotypes of the extracellular matrix of the cervix varied significantly depending on the CIN degree (p < 0.001). In the control group, the normal pattern was detected in 97.5% of cases; its frequency decreased from CIN 1 (27.5%) to CIN 2 (12.5%) and was absent at CIN 3. The frequency of the myxoid pattern increased significantly in severe and persistent forms: 55% at CIN 3 and 62.5% at CIN P. Human papillomavirus 16/18 was most frequently detected in groups with intermediate (69.1%) and myxoid (27.2%) patterns. Inflammatory changes were more often accompanied by disorganized extracellular matrix; however, intermediate and myxoid types also occurred in the absence of inflammation. Conclusions: The myxoid histophenotype of the extracellular matrix is significantly associated with the high degree of dysplasia and CIN persistence. It can reflect the morphological equivalent of tumor-associated stroma remodeling. Histophenotyping of the extracellular matrix of the cervix appears to be a promising method of risk stratification and may complement existing diagnostic algorithms for CIN. Full article

Background/Objectives: Persistent human papillomavirus (HPV) infection is the leading cause of cervical intraepithelial neoplasia (CIN), a known precursor to cervical squamous carcinoma. While progesterone receptor membrane component 1 (PGRMC1) has been implicated in various cancers, its specific role in cervical carcinogenesis has remained uncertain. This study aimed to elucidate the function of PGRMC1 in the progression of CIN. Methods: Bioinformatics techniques were employed to assess the expression levels of PGRMC1 in cervical cancer tissues and to investigate its correlation with patient prognosis. To explore the functional role of PGRMC1, we manipulated its expression in the cervical cancer cell line HeLa using siRNA. Subsequently, we evaluated cell migration via the scratch assay, and invasion through the Transwell assay. We employed mass spectrometry to identify proteins interacting with PGRMC1 and confirmed these interactions using co-immunoprecipitation (co-IP). Further co-IP experiments were conducted to pinpoint the specific binding sites of these protein interactions, and immunofluorescence staining was utilized to observe the spatial distribution of interacting proteins within the cells. The phosphorylation status of VIM was further confirmed by WB. At the clinical level, we collected cervical biopsy specimens from HPV-positive patients and verified the expression patterns of PGRMC1 and VIM using immunohistochemical staining in cervical squamous cell carcinoma (CSCC) tissues. Results: We discovered a correlation between progressively increasing PGRMC1 expression and the severity of CIN as well as a poor prognosis. Knockdown of PGRMC1 resulted in the inhibition of migration and invasion capabilities in cervical cancer cells. Furthermore, PGRMC1 was found to physically interact and colocalize with Vimentin (VIM). Notably, PGRMC1 knockdown specifically increased phosphorylation at the Ser-39 residue of VIM. Conclusions: Our findings suggest that PGRMC1 facilitates CIN progression by binding to VIM and suppressing Ser-39 phosphorylation, thereby promoting the migration and invasion of cervical carcinoma cells. This study enhances our understanding of PGRMC1’s role in CIN progression and lays an experimental foundation for targeted therapeutic approaches to cervical squamous carcinoma. Full article

Background: Cervical intraepithelial neoplasia grade 2 (CIN2) represents a controversial lesion in cervical cancer prevention. Traditionally included in the aggregate CIN2+ endpoint for reasons of diagnostic stability and statistical power, isolated CIN2 has unique biological characteristics: greater interobserver variability, a high probability of spontaneous regression and a lower risk of progression compared to CIN3. Objectives: To critically describe the epidemiology, natural history and management strategies of CIN2, integrating data from clinical and population-based studies and comparing the recommendations of the main international guidelines. Methods: A narrative review was conducted using a search of PubMed and Scopus (1990–January 2025). Prospective and retrospective studies on isolated CIN2, screening and vaccination trials with CIN2+ endpoints, biomarker research, and consensus documents (ASCCP, ESGO, GISCi, Ministry of Health, WHO) were included. Results: Clinical studies have shown a high probability of CIN2 regression (50–70% within two years, >70% in those <25 years), compared to a 10–15% risk of progression, especially in the presence of persistent HPV16. Screening trials and vaccine evaluations with CIN2+ endpoints have documented the efficacy of the HPV test and a dramatic reduction in lesions in vaccinated cohorts, which was also confirmed for isolated CIN2. The most recent guidelines have progressively adopted a risk-based approach, which allows for active surveillance in young women or those seeking to conceive, while the WHO maintains a screen-and-treat model in resource-limited countries. Conclusions: CIN2 is not a lesion to be treated automatically, but rather a paradigmatic model for personalized management. Integrating epidemiological and clinical data, supported by biomarkers, allows for reducing overtreatment without compromising oncological safety. Full article

Background/Objectives: Most cervical intraepithelial neoplasias (CINs) regress over time. Diagnostic screenings are limited and cannot identify the disease trend, which leads to the risk of overtreatment. Reliable methods are needed to preselect patients who will probably progress. The diagnostic GynTect^® assay offers sensitive and specific CIN identification from cervical scrapes, measuring the methylation of six marker genes. We studied the main marker (ZNF671) methylation on formalin-fixed paraffin-embedded (FFPE) material to determine if the kit provides prognostic information too. Methods: We tested 289 FFPE samples from 139 patients with varying CIN grades and disease trends, including regressive, persistent, progressive, and recurrent disease. Additionally, we correlated age and human papillomavirus (HPV) status with the results. Results: Although there are differences between FFPE material and cervical scrapes, we achieved a similar increase in ZNF671 methylation with increasing neoplasia grade (dysplasia-free: 0%, CIN 1: 8.20%, CIN 2: 26.73%, CIN 3: 32.43%, carcinoma: 100%). In addition, ZNF671 is more likely to detect recurring (27.12% of positives) and progressive (59.32% of positives) neoplasia. Patients with regressive (1.69% of positives) or persistent (11.86% of positives) trends less frequently show ZNF671 methylation. Interestingly, patients with HPV 16 infection (52.54% of positives) and >30 years (89.83% of positives) are more likely to appear ZNF671 methylation-positive. However, patients < 30 years with persistent neoplasia (42.86% of positives) also show methylation more frequently. Conclusions: The methylation of ZNF671 is measurable in cervical FFPE material and has prognostic value. Since ZNF671-methylated samples are most likely to be progressing, we recommend the closer monitoring of patients with GynTect^®-positive test results. Full article

While nutrition is often considered a protective factor against cancer, there is a scarcity of strong, conclusive evidence supporting its direct impact on cervical cancer (CC) prevention. This study aims to review the existing literature on the relationship between women’s nutrition and infection by the human papillomavirus (HPV) and the development of CC. It explores the key nutrients, foods, and dietary patterns that may influence the onset and progression of this disease, including research carried out in sub-Saharan Africa, other low-income countries, and worldwide. The review process revealed that, despite the large initial pool of articles, the majority were excluded because they were not focused on nutrition and CC. However, the articles that met the inclusion criteria suggested an association between diet and lower susceptibility to persistent HPV infections, which could progress into cervical lesions or cancer. Notably, lower folate intake was associated with up to a nine-fold higher risk of CIN3+ lesions (OR 8.9, 95% CI 3.4–24.9), while increased consumption of certain vitamins and antioxidant-rich foods consistently correlated with lower HPV persistence and progression. These results could indicate that consuming antioxidant compounds, certain vitamins, dietary patterns, and functional foods may offer protective benefits against developing this disease and its progression. By emphasizing nutrition as a modifiable factor, this review seeks to raise awareness and propose a holistic approach to CC prevention—integrating public health, dietary considerations, and equity-driven strategies. Full article

Background/Objectives: In Romania, where cervical cancer incidence remains among the highest in the European Union, a risk-based management strategy could support more precise allocation of limited resources. The aim of this study was to test the prognostic utility of immediate pre-treatment and post-treatment risk predictions, derived from the American Society of Colposcopy and Cervical Pathology (ASCCP) risk-based management guidelines for the prediction of progression, regression or persistence of high-grade cervical dysplasia. Methods: In this prospective cohort study, we included 223 patients aged over 30 years who underwent self-referred or targeted screening with or without histologically confirmed cervical intraepithelial neoplasia (CIN) of any grade. We employed Fine and Gray’s subdistribution hazard model that evaluated the cumulative incidence function for each specific outcome, treating other outcomes as competing events. These outcomes were further stratified depending on the type of high-grade dysplasia. Results: The immediate post-treatment risk was significantly associated with subsequent progression of cervical dysplasia. For a cut-off of 60%, the immediate post-treatment risk was able to significantly predict the progression of both CIN2+ and CIN3+. On the other hand, the immediate pre-treatment risk > 60% was significantly associated with progression of CIN3+, but not of CIN2+. Also, the immediate pre-treatment risk was significantly associated with regression, but this observation did not persist at the >60% threshold. Both pre- and post-treatment risk > 60% were strongly associated with persistence across histologic subgroups. Conclusions: The ASCCP-derived immediate risk estimates, especially post-treatment risk > 60%, proved effective in predicting progression and persistence of high-grade cervical dysplasia. Full article

Background: Cervical cancer remains a major global health burden, particularly in regions with limited early detection. The Loop Electrosurgical Excision Procedure (LEEP) is commonly used to diagnose and treat cervical intraepithelial neoplasia (CIN). The lymphocyte-to-monocyte ratio (LMR) is a potential biomarker for cancer risk stratification. It reflects immune function and tumor-related inflammation. Lower LMR values suggest reduced antitumor immunity and increased tumor-promoting inflammation, which are linked to cancer development and progression. This study examines relationships between preoperative LMR and histopathological outcomes after LEEP. Methods: This retrospective study included 374 patients undergoing the LEEP for cervical dysplasia. Preoperative LMR values were compared across four histopathological categories: negative, low-grade, high-grade lesions, and invasive carcinoma. The Kruskal–Wallis test assessed group differences, with Mann–Whitney U tests for pairwise comparisons. ROC curve analysis (n = 369) evaluated LMR’s diagnostic performance, and logistic regression evaluated its independent predictive value. Results: LMR significantly differed across cytological (p = 0.04) and histological groups (p = 0.036). Post hoc analysis revealed significantly lower LMR in invasive carcinoma versus low-grade lesions in cytology and for both low- and high-grade lesions in histology. ROC analysis yielded an AUC of 0.680. An LMR cutoff <4.49 showed 82.6% sensitivity and 50.0% specificity. Stricter cutoff (<3.89) increased specificity (66.8%) but decreased sensitivity (60.9%). Both had high negative predictive values (97.7% and 96.2%) but low positive predictive values (9.9% and 10.9%). Conclusions: LMR may serve as a complementary biomarker to predict higher-grade cervical lesions and help rule out invasive disease, aiding patient triage in resource-limited settings. Full article

Background and Objectives: Human papillomavirus (HPV) is the most prevalent sexually transmitted infection worldwide and, beyond its oncogenic potential, may impair reproductive health in both sexes. This review examines HPV’s effects on male and female fertility, obstetric outcomes, vertical transmission, and fertility-sparing management in oncology. Materials and Methods: A systematic search of PubMed, Embase, and Scopus was conducted using terms related to HPV and reproduction. Additional search terms included those related to therapeutic vaccines, antivirals, and genotype prevalence. English-language human studies reporting clinical reproductive outcomes were included. Thirty-seven studies met the inclusion criteria. Two reviewers independently screened and assessed study quality using a simplified GRADE framework. Results: In men, seminal HPV infection correlates with reduced progressive motility (SMD ≈ −0.85), abnormal morphology, and increased DNA fragmentation. In women, high-risk HPV doubles the odds of infertility (OR ≈ 2.3) and is associated with endometrial involvement. High first-trimester viral load predicts vertical transmission (aOR 6.4), which is also increased by vaginal delivery (RR 1.8) and is linked to PROM (OR 1.8) and preterm birth (OR 1.8). Modeling suggests that nine-valent vaccination plus 5-year HPV-based screening could reduce CIN2+ by up to 80% and excisional treatments by >75%. Fertility-sparing surgery in early cervical cancer yields a <4% recurrence and up to 68% live birth rates. Conclusions: This review uniquely synthesizes reproductive and oncologic impacts of HPV and emphasizes risk stratification, multidisciplinary prevention, and fertility preservation. Integration of HPV DNA quantification, personalized care, and vaccine-based strategies offers a path toward optimized outcomes in both sexes. Full article

Lactobacillus species play a fundamental role in maintaining a healthy vaginal microbiota and have been increasingly recognized for their protective effects against high-risk human papillomavirus (HR-HPV) infection and the progression of cervical intraepithelial neoplasia (CIN). These beneficial bacteria contribute to host defense through multiple mechanisms, including the production of lactic acid that sustains a low vaginal pH, enhancement of epithelial barrier integrity via E-cadherin regulation, and modulation of immune signaling pathways such as interferon responses and NF-κB activity. Lactobacillus strains exert anti-inflammatory effects by downregulating pro-inflammatory cytokines and interfering with oncogenic pathways including Wnt/β-catenin and the expression of HPV E6 and E7 proteins. Additionally, they may regulate tumor-suppressor microRNAs and modulate dendritic cell and macrophage activity, supporting antiviral immunity. Recent studies have explored their potential influence on CIN regression and HR-HPV clearance, particularly the strains Lactobacillus crispatus and L. gasseri, which are associated with favorable microbial community states. This review explores the potential mechanisms through which Lactobacillus species contribute to HR-HPV clearance and the regression of cervical dysplasia, integrating evidence from molecular studies, in vivo models, and clinical trials. The emerging role of probiotic interventions as adjunctive strategies in HPV management is also discussed, highlighting their possible synergy with conventional treatments and prophylactic vaccination. Full article

Background/Objectives: This study evaluated the real-world effectiveness of prophylactic Human Papillomavirus (HPV) vaccination in Korean women aged over 26 years, focusing on its impact on persistent HPV infection and disease progression. Methods: This multicenter prospective study analyzed data from the Korea HPV Cohort (2010–2021). After applying exclusion criteria, the final analytical cohort included 1,231 women aged ≥ 27 years with cytologic findings of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions and HPV infection. Propensity score matching was used to compare vaccinated (n = 340) and unvaccinated (n = 891) participants. After matching, 273 vaccinated and 273 unvaccinated individuals were included in the final analysis. The primary outcomes were persistent HPV infection and progression to biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Logistic and Cox regression models were employed, with additional age-stratified analyses. Results: Among women aged 27–39 years, vaccination was significantly associated with a 54% reduction in the odds of persistent HPV infection (odds ratio = 0.46; 95% CI: 0.22–0.96; p = 0.040). In the full cohort, vaccinated participants had a 62% lower risk of progression to CIN2+ compared with unvaccinated participants (hazard ratio = 0.38; 95% CI: 0.18–0.81; p = 0.011). Body mass index had a notable impact on HPV persistence in HPV 16/18 genotype groups. Conclusions: HPV vaccination effectively reduced persistent infection and progression to CIN2+ in Korean women, particularly those vaccinated before age 40. These findings support the age-extended HPV vaccination policies in South Korea. Full article

Persistent high-risk human papillomavirus (HR-HPV) infection is closely associated with the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. In recent years, the potential impact of viral co-infections on this process has also been investigated. This study investigated the presence of HR-HPV, HSV-1/2, and HHV-8 DNA in formalin-fixed paraffin-embedded (FFPE) cervical biopsy samples, as well as their association with lesion severity. A total of 276 FFPE cervical tissue samples were evaluated. Viral DNA was detected by real-time PCR. The samples were histopathologically classified as normal/non-dysplastic, low-grade (LSIL), and high-grade (HSIL) lesions. HR-HPV DNA was detected in 112 samples (40.6%), with the highest prevalence observed in the 30–39 age group (51.2%). Among the HPV-positive cases, 46.5% (52/112) had single-type infections, 32.1% (36/112) had multiple-type infections, and 21.4% (24/112) were untypable. Together, these categories accounted for all HPV-positive samples. The most common genotype was HPV-16 (16.7%). HHV-8 and HSV-2 DNA were not detected. HSV-1 DNA was detected in only three non-dysplastic, HPV-negative cervical samples. In conclusion, HR-HPV DNA was detected in 40.6% of cervical biopsy samples and showed a significant association with increasing histological severity, highlighting its critical role in the progression of cervical lesions. Although the absence of HHV-8 and HSV-2 suggests a limited contribution of these viruses to cervical disease, the use of a single real-time PCR assay limits the ability to draw generalized conclusions regarding their clinical relevance. Further large-scale, multicenter studies employing both tissue-based and serological approaches are needed to validate these findings and to better understand the dynamics of viral co-infections in cervical disease. Full article

Background/Objectives: Contrast agents can damage renal tissue through multiple mechanisms, particularly by increasing reactive oxygen species (ROS), which contribute to DNA oxidation, lipid peroxidation, and endothelial injury. This prospective, comparative study aimed to evaluate the changes in ROS-related gene expressions—NFKB1, SIRT1, NFE2L2, and FOXO1—in patients who developed contrast-induced nephropathy (CIN) following coronary angiography versus those who did not. Methods: A total of 48 patients undergoing primary percutaneous coronary intervention were enrolled. Twenty-three patients who developed CIN (Group 1) were compared to 25 matched controls without CIN (Group 2) based on age, gender, and comorbidities. Blood and serum samples were collected 72 h post-contrast exposure to assess biochemical markers and mRNA expression levels of the target genes. Results: The mean age was similar between the groups (63 ± 7 vs. 62 ± 6 years; p > 0.05), as was gender distribution. Group 1 showed significant increases in serum creatinine and reductions in e-GFR post-procedure. Importantly, NFKB1, NFE2L2, and FOXO1 mRNA expression levels were significantly upregulated in CIN patients—by 5.7-, 5.8-, and 4.97-fold, respectively, while SIRT1 expression was downregulated by 0.76-fold (p < 0.05). Conclusions: These findings indicate enhanced activation of inflammatory and oxidative stress pathways in CIN patients, particularly through the NF-κB signaling axis. Conversely, reduced SIRT1 expression suggests diminished antioxidant protection. The study highlights that ROS-related gene expression changes may serve as potential biomarkers for CIN progression. Further studies at the protein level are needed to clarify cytokine roles in these pathways. Full article