Search Results (651)

Cervical cancer screening plays a crucial role in preventing invasive disease through early detection of high-grade lesions. However, traditional cytology and histology often fail to reliably differentiate between transient HPV infections and those likely to progress. This study investigates the feasibility of integrating molecular HPV testing into histopathological workflows using FFPE tissue samples to improve diagnostic precision. A retrospective analysis was conducted on 55 FFPE cervical specimens from patients undergoing colposcopy with biopsy or conization. The workflow included automated DNA extraction and real-time PCR-based HPV genotyping with the Seegene Anyplex II HPV28 assay. HPV DNA was detected in 56.4% of samples, with 21 genotypes, including multiple high-risk types. High viral loads correlated with high-grade lesions, supporting the clinical value of HPV quantification. Compared to histology, molecular analysis reduced potential overdiagnosis by confirming HPV absence in morphologically suspicious but HPV-negative lesions. Integrating viral load and genotyping improved risk stratification, optimizing colposcopy referrals and reducing unnecessary follow-ups. This study introduces a novel, fully automated molecular workflow applicable to FFPE samples, enhancing cervical cancer screening beyond traditional methods. Although based on a limited sample, the findings support the method’s potential for broader implementation and further validation in multicenter settings. Full article

Background: Human papillomavirus (HPV) is the most prevalent sexually transmitted infection with significant health implications, especially for women living with human immunodeficiency virus (HIV). The variability in reported prevalence and genotype distribution of HPV among HIV-positive women across different regions in Africa necessitates a comprehensive and systemic examination. Methods: A systematic search was conducted across several databases. A random effect model was used to evaluate study heterogeneity through Q statistics and I² measures. Publication bias was assessed using funnel plots and Egger’s tests. Risk factors for HPV among HIV-positive women were summarized qualitatively. This review was registered with PROSPERO: CRD42024525123. Result: Twenty-three studies involving 9954 HIV-positive women were combined to estimate HPV prevalence. The overall prevalence of all HPV types was 49.4% (95% CI: 42.43, 56.38), with evidence of heterogeneity (Q = 520.92, df = 16, I² = 96.93%, p < 0.0001). The prevalence of high-risk HPV was 45.26% (95% CI: 31.02, 59.91), showing heterogeneity across studies (Q = 439.18, df = 10, p < 0.0001, I² = 97.72%). Low-risk HPV had a prevalence of 24.98% (95% CI: 12.27, 40.41), with variation among studies (Q = 134.39, df = 6, p < 0.0001, I² = 95.54%). The most frequent genotypes were 16, 18, 52, 33, and 35. A higher cluster of differentiation 4 (CD4) count is associated with a lower prevalence of HPV. Conclusions: The pooled HPV prevalence among HIV-positive women in Africa is lower compared to previous studies, but the slow decline poses challenges to meet the WHO’s goal of eliminating HPV-related cervical cancer by 2030. Therefore, enhanced prevention efforts, including HPV self-sampling, improved vaccination coverage, and early treatment interventions, are essential to meet the goal of eliminating HPV-related cervical cancer. Full article

Human papillomavirus (HPV) significantly contributes to anogenital cancers, with elevated risks among people living with HIV (PWH), particularly men who have sex with men (MSM). This study assessed anal HPV prevalence and associated risk factors in PWH in Mexico, focusing on the role of antiretroviral therapy (ART). Methods: A cross-sectional study at an HIV clinic in Mexico City (October 2023–December 2024) enrolled 214 MSM with HIV. The participants completed a validated risk factor questionnaire and provided anal samples for real-time PCR testing of 28 HPV genotypes. Logistic regression analyzed associations between HPV infection, ART regimens, and clinical/behavioral factors. Results: HPV prevalence was 89.3%, with HPV-16 (20.1%) being the most common high-risk genotype. Integrase inhibitor (INSTI) use was inversely associated with HPV-16 infection (OR: 0.42; 95% CI: 0.21–0.83; p = 0.011), while protease inhibitor use increased HPV-16 (OR: 2.16; 95% CI: 1.09–4.29; p = 0.025) and HPV-6 risks. Higher CD4+ counts (≥500 cells/mm³) and undetectable HIV viral load (<40 copies/mL) were protective against multiple HPV genotypes. Lower education and smoking increased HPV risk. Conclusions: This first Mexican study in the ART and HPV vaccination era highlights high anal HPV prevalence in PWH and suggests that INSTI-based regimens may reduce HPV-16 risk, informing ART selection for HPV prevention. Full article

16S rRNA next-generation sequencing (NGS) has significantly advanced cervicovaginal microbiome profiling, offering insights into the relationship between vaginal dysbiosis and HPV-associated carcinogenesis. However, reliance on a limited set of 16S hypervariable regions introduces inherent biases that impact results. This study developed standardized workflows for 16S/ITS NGS, with a focus on identifying methodological biases that influence microbial abundance and taxonomic specificity. Commercial NGS tools were employed, including the 16S/ITS QIAseq V1–V9 screening panel, ATCC vaginal microbial standard, and CLC Genomics Workbench integrated with a customized database (VAGIBIOTA) for analysis. The microbial communities of 66 cervical cytology samples were characterized. Among the regions tested, V3V4 exhibited the least quantitative bias, while V1V2 offered the highest specificity. Microbial profiles and Community State Types (CST) (I–V) were broadly consistent with prior studies, with Lactobacillus abundance clustering into three states: L.-dominant (CST I–III, V), L.-diminished (CST IV-A), and L.-depleted (CST IV-B). Differential abundance analysis revealed that anaerobic opportunistic pathogens dominant in CST IV-B (dysbiosis) were also enriched in HSIL and HPV-16 positive samples. Our findings revealed distinct differences in species identification across 16S rRNA hypervariable regions, emphasizing the importance of region selection in clarifying microbial contributions to HPV-associated carcinogenesis. Full article

Background: High concentrations of supplemental oxygen (FiO₂ > 0.6) are commonly used to treat acute hypoxemia in critically ill patients. However, the effects of High FiO₂ in patients with COVID-19 remain unclear, particularly regarding its impact on hypoxic pulmonary vasoconstriction (HPV) and ventilation–perfusion (V/Q) mismatch. Objective: This study aims to evaluate whether administering lower concentrations of inspired oxygen (FiO₂ < 0.6) is associated with improved outcomes—namely reduced need for mechanical ventilation and mortality—in patients with COVID-19 and severe pulmonary involvement. Methods: This retrospective observational cohort included 201 patients with confirmed COVID-19. Patients were grouped by mean FiO₂ during the first 24–48 h: High FiO₂ (≥0.60) or Low FiO₂ (<0.60). The primary outcome was the requirement for mechanical ventilation; the secondary outcome was in-hospital mortality. A composite endpoint (mechanical ventilation and in-hospital death) was also evaluated. Analyses included logistic regression and Kaplan–Meier survival with log-rank testing. Results: High FiO₂ (≥0.60) was associated with higher odds of the composite outcome (mechanical ventilation and in-hospital death). In multivariable analysis, Low FiO₂ remained associated with lower odds (adjusted OR 0.18; 95% CI 0.08–0.39; p < 0.001). Unadjusted rates were 43.1% vs. 16.1% for mechanical ventilation and 34.3% vs. 8.1% for in-hospital death (High vs. Low FiO₂; both p < 0.001). Event-free survival favored the Low FiO₂ group (log-rank p < 0.001). The model showed excellent discrimination (AUC 0.96; 95% CI 0.92–0.99). Conclusions: Higher early FiO₂ exposure was associated with worse clinical outcomes in severe COVID-19. These findings are consistent with physiological models in which excess oxygen may attenuate hypoxic pulmonary vasoconstriction and increase shunt/dead space. Prospective studies are warranted to assess causality and refine oxygen targets. Full article

Background/Objectives: Cervical cancer (CC), caused mainly by high-risk human papillomavirus (hrHPV), remains a global health challenge despite being preventable. The disease’s incidence and mortality rates significantly vary across regions, highlighting the need for effective screening programs. The World Health Organization prioritizes CC screening to monitor and eliminate the disease. The Screening for Cervical Cancer and Early Treatment (SCCET) project aligns with this goal by adhering to the 2012 National Program for Cervical Cancer Screening and implementing the European Guidelines of Quality Assurance. Methods: The SCCET initiative facilitates access to equitable and high-quality preventive medical services for Romanian women, incorporating the Babeș–Papanicolaou smear (Pap test) and/or hrHPV DNA screening. Focused on the Muntenia Region of South Romania, the project leverages a methodical approach to gather substantial medical data on hrHPV infection rates and cervical lesions, thereby improving health management for women in the screening program. Results: Through public information and educational campaigns about HPV and its link to CC, the SCCET project has significantly enhanced participation in the screening program. In the study conducted between September 2022 and March 2023, 14,385 women aged 30 to 64 years voluntarily participated; of these, 11,996 (83.4%) underwent primary hrHPV DNA screening and were tested using the PowerGene 9600 Plus Real-Time polymerase chain reaction (PCR) system and the commercial Atila BioSystems AmpFire^® HPV Screening 16/18/HR test, version 4.1. This substantial participation indicates a positive shift in public attitudes towards CC prevention and highlights the success of the project’s outreach efforts. The study revealed an overall prevalence of hrHPV infection of 12.24%; of these, the most common genotype was other hrHPV types (9.84%), followed by HPV 16 (2.3%) and HPV 18 (0.71%). Conclusions: The SCCET project’s recent data on primary hrHPV DNA screening showcases its pivotal role in advancing the management and prevention of CC in Romania. By providing accessible, high-quality screening services and fostering public education on HPV, the initiative has made significant strides toward reducing the burden of CC. This effort aligns with global public health goals, and providing updated information on the prevalence of hrHPV types will allow the development of personalized national screening and vaccination programs to eradicate CC. Full article

Background: The Human Papillomavirus (HPV) vaccine has been globally implemented to prevent HPV-associated diseases. Since its introduction in China in 2017, this vaccine has substantially reduced the burden of HPV-related health conditions. As more people get vaccinated these days, ongoing safety monitoring and evaluation have become critical. This helps to safeguard public trust in immunization programs and ensures the sustainability of immunization programs. Methods: Suspected adverse events following immunization (AEFIs) associated with HPV vaccination from 2017 to 2024 were extracted from the Chinese National Immunization Information System (CNIIS). Data on the number of HPV vaccine doses given came from the Immunization Planning Information Management System of Anhui Province. Descriptive statistical methods examined the distribution characteristics of AEFIs, and chi-square tests assessed differences in incidence rates. Results: From 2017 to 2024, the vaccine safety surveillance system in Anhui Province monitored a total of 1149 reports of AEFIs associated with the HPV vaccine. The reported overall rate of AEFIs was 16.32 per 100,000 doses. Specifically, the rates of common adverse reactions were 15.15 per 100,000 doses, while the rates for rare adverse reactions were 0.85 per 100,000. Among the common adverse reactions, the incidence rates of injection-site redness and swelling (diameter >5.0 cm), induration (diameter >5.0 cm), and fever (axillary temperature ≥38.6 °C) were 0.60, 0.33, and 1.34 per 100,000 doses, respectively. For rare adverse reactions, the reported incidence rates of allergic rash, allergic urticaria, and aseptic abscess were 0.50, 0.09, and 0.03 per 100,000 doses, respectively. Most AEFIs occurred within 24 h post-vaccination. Conclusions: The overall reported incidence of AEFIs following HPV vaccination in Anhui Province from 2017 to 2024 was low, with serious rare adverse reaction occurring infrequently. These findings suggest that the HPV vaccine has a favorable safety profile. Full article

Background/Objectives: Annona muricata (AM), commonly known as soursop or guanabana, has long been used in traditional medicine for its purported anticancer properties. However, scientific studies evaluating its potential enhancing or additive effects with conventional antineoplastic drugs (ADs) remain limited. This study aimed to assess the cytotoxic effects of an aqueous AM infusion alone and in combination with standard ADs in cancer cell lines, while also evaluating its safety in healthy cells. Additionally, we explored the potential molecular interactions of AM metabolites with therapeutic targets using silico modeling. Methods: An AM infusion (125 and 250 µg/mL) was tested on two cancer cell lines—MDA-MB-231 (human triple-negative breast cancer) and TC-1 (murine HPV16-positive cancer)—as well as healthy human leukocytes and a non-tumorigenic mouse lung cell line. Cell viability was assessed using the Alamar Blue™ assay. The combined effects of AM with multiple first-line ADs were evaluated. In silico molecular docking was performed with Molegro Virtual Docker to assess the interaction of AM metabolites (quercetin and hyperoside) with the A2B adenosine receptor. Additionally, the physicochemical properties of 13 AD were analyzed to explore correlations with cytotoxic outcomes. Results: AM infusion alone exhibited low cytotoxicity in both cancer and healthy cell types. However, when combined with ADs, it enhanced cytotoxic effects in cancer cells while sparing healthy cells at the evaluated concentrations. Docking studies revealed strong interactions between quercetin and hyperoside (major metabolites in the AM infusion) and the A2B receptor, supporting a possible mechanistic explanation for the observed effects. Conclusions: AM infusion may act as a chemical modulator, potentiating the effects of conventional ADs in cancer cells while preserving normal cell viability. These findings encourage further preclinical exploration of AM as a complementary agent in integrative oncology. Full article

Background: Cervical cancer ranks among the most prevalent tumors in low-income countries, with the Pap test as one of the primary screening tools. The Pap smear detects abnormal cells, the CLART test identifies specific HPV genotypes, and HPV self-sampling allows for self-collected HPV testing. This study aimed to evaluate the feasibility of the first smartphone-based health device for home-collection HPV testing. Methods: Enrolled patients during the gynecological examination underwent three different samplings: Pap smear, HPV DNA genotyping test CLART, and vaginal HPV-Selfy swab. Each patient received a kit including an activation code, vaginal swab, and instructions. After performing the self-sample, patients returned the kit to our laboratory. Both the samples collected by the gynecologist and those collected by the patients themselves were analyzed. Results: A total of 277 patients were enrolled, with 226 self-collected swabs received for analysis. The assay yielded valid results for both self-collected and clinician-collected swabs in 190 patients. When comparing these results with paired clinician-taken vaginal swabs, we observed an agreement of 95.2% (Cohen’s Kappa: 0.845). We report an agreement of 93.7% (Cohen’s Kappa: 0.798). Conclusions: The study demonstrated the feasibility of HPV-Selfy as a complementary tool in cervical cancer screening, especially where adherence to traditional surveillance is low. Full article

Background/Objectives: This study evaluated the in vitro probiotic potential of Lactiplantibacillus plantarum Probio87 (Probio87), focusing on its physiological robustness, safety, antimicrobial properties, and anticancer activity, with relevance to vaginal and cervical health. Methods: Tests included acid and bile salt tolerance, mucin adhesion, and carbohydrate utilization. Prebiotic preferences were assessed using FOS, GOS, and inulin. Antibiotic susceptibility was evaluated per EFSA standards. Antimicrobial activity of the cell-free supernatant (CFS) was tested against Staphylococcus aureus, Escherichia coli, and Candida species. Effects on Lactobacillus iners and L. crispatus were analyzed. Anticancer properties were assessed in HeLa, CaSki (HPV-positive), and C-33A (HPV-negative) cervical cancer cell lines through proliferation, apoptosis, angiogenesis, and cell cycle assays. Results: Probio87 showed strong acid and bile tolerance, efficient mucin adhesion, and broad carbohydrate utilization, favoring short-chain prebiotics like FOS and GOS over inulin. It met EFSA antibiotic safety standards. The CFS exhibited potent antimicrobial activity, including complete inhibition of Candida albicans. Probio87 selectively inhibited L. iners without affecting L. crispatus, indicating positive modulation of vaginal microbiota. In cervical cancer cells, the CFS significantly reduced proliferation and angiogenesis markers (p < 0.05), and induced apoptosis and cell cycle arrest in HPV-positive cells, with minimal effects on HPV-negative C-33A cells. Conclusions: Probio87 demonstrates strong probiotic potential, with safe, selective antimicrobial and anticancer effects. Its ability to modulate key microbial and cancer-related pathways supports its application in functional foods or therapeutic strategies for vaginal and cervical health. Full article

Cervical cancer remains a major health burden among women in sub-Saharan Africa, where screening is often limited. Persistent high-risk human papillomavirus (HR-HPV) infection is the principal cause, highlighting the need for accurate molecular diagnostics. This cross-sectional study evaluated the analytical performance of one mRNA assay, APTIMA^® HPV assay (APTIMA mRNA), and two DNA-based assays, the Abbott RealTime High Risk HPV assay (Abbott DNA) and Seegene Allplex™ II HPV28 assay (Seegene DNA), in 527 cervical samples from a South African tertiary hospital, focusing on 14 shared HR-HPV genotypes. Seegene DNA yielded the highest detection rate (53.7%), followed by Abbott DNA (48.2%) and APTIMA mRNA (45.2%). APTIMA mRNA showed a strong agreement with Abbott DNA (87.9%, κ = 0.80), 89.9% sensitivity, 91.2% NPV, and the highest accuracy (AUC = 0.8804 vs. 0.8681). The agreement between APTIMA mRNA and Seegene DNA was moderate (83.4%, κ = 0.70), reflecting target differences. Many DNA-positive/mRNA-negative cases likely represent transient infections, though some may be latent with reactivation potential, warranting a follow-up. In resource-constrained settings, prioritizing transcriptionally active infections through mRNA testing may enhance screening efficiency and reduce burden. Scalable, cost-effective assays with strong clinical utility are essential for broadening access and improving cervical cancer prevention. Further studies should assess the integration of mRNA testing into longitudinal screening algorithms. Full article

Introduction: Following up on treated high-grade cervical intraepithelial neoplasia (HSIL/CIN) lesions poses a challenge. Cervical cytology often has a high false-negative rate, while high-risk human papillomavirus (HR-HPV) DNA testing, though sensitive, lacks specificity. The detection of messenger RNA of the HR-HPV E6 and E7 oncoproteins (E6/E7 mRNA) is proposed as an indicator of viral integration, which is crucial for identifying severe lesions. Additionally, HPV vaccination could reduce recurrence rates in patients treated for high-grade cervical intraepithelial neoplasia. Objective: Our study aimed to assess the clinical utility of E6/E7 mRNA determination in the follow-up of HPV-immunized patients who were treated for HSIL/CIN. Methods: We conducted a retrospective observational study including 407 patients treated for HSIL/CIN. The recurrence rate and the validity parameters of E6/E7 mRNA testing were analyzed. Results: The recurrence rate for high-grade lesions was 1.7%. This low percentage might be related to the vaccination of patients who were not immunized before treatment. The sensitivity of the E6/E7 mRNA test was 88% at the first clinical visit, reaching 100% in the second and third reviews. Specificity was 91% at the first visit, 92% at the second, and 85% at the third. Regarding predictive values, the positive predictive value was 18% at the first visit, 10% at the second, and 14% at the third, while the negative predictive value was 100% across all follow-up visits. Conclusions: The E6/E7 mRNA test appears to be an effective tool for ruling out recurrence after treatment for HSIL/CIN lesions in HPV-immunized patients. Full article

Background: Effective triage of women testing positive for high-risk HPV DNA is essential to reduce unnecessary colposcopies while preserving cancer prevention. Cytology, the current standard, has limited specificity and reproducibility. The genotype-specific 7-type HPV E6/E7 mRNA test (PreTect HPV-Proofer’7), targeting HPV types 16, 18, 31, 33, 45, 52, and 58, detects transcriptionally active infections and may enhance risk stratification. Methods: Between 2019 and 2023, 34,721 women aged 25–69 underwent primary HPV DNA screening with the Cobas 4800 assay at the University Hospital of North Norway, within the national screening program. Of these, 1896 HPV DNA-positive women were triaged with liquid-based cytology with atypical squamous cells of undetermined significance or worse (≥ASC-US) and the 7-type HPV mRNA test. Histological outcomes were followed through October 2024. Diagnostic performance for CIN2+ was evaluated overall and by genotype. Results: CIN2+ prevalence was 13.3%. The mRNA test reduced test positivity from 50.3% to 33.4% while maintaining comparable sensitivity (70.6% vs. 72.2%) and improving specificity (72.3% vs. 53.0%) and PPV (28.1% vs. 19.1%). Genotype-specific PPVs were highest for HPV16 mRNA (47.7%), followed by HPV33 (39.2%) and HPV31 (32.2%), all exceeding corresponding DNA-based estimates. Conclusion: Genotype-specific HPV mRNA triage offers superior risk discrimination compared to cytology, supporting more targeted, efficient, and accessible cervical cancer screening. Full article

Human papillomavirus 18 (HPV18) is the second most oncogenic high-risk HPV genotype, after HPV16, and is responsible for about 15% of cervical cancer cases worldwide. The integration of high-risk HPV DNA into the host genome leads to the disruption of the E1 and/or E2 genes, which is considered a risk factor for viral-induced carcinogenesis. This study examined the disruption events of HPV18 E1 and E2 genes in precancerous cervical lesions to investigate the rates and sites of gene disruption in the Greek population. The complete E1 and E2 genes were amplified using three and four overlapping primer sets, respectively. Extensive analysis revealed that the disruption/deletion events of the E1 and E2 genes were detected in all grades of cytology-determined lesions, with high frequency. E2 gene disruption was significantly related to LSIL+ cases (Fisher’s exact test, p = 0.022). No significant association was found in the analysis of the E1 gene. Additionally, no preferential sites of E1/E2 gene disruption were detected. This is the first study to provide evidence of disruption events of the HPV18 E1 gene. The data from the current analysis suggest that disruption of the E2 gene could be a significant marker for the progression of cytology-determined cervical dysplasia. However, future studies are required to evaluate whether different geographic populations have particular profiles regarding the rates and sites of gene disruption to further determine population-specific biomarkers. Full article

Human papillomavirus (HPV) is a recognized oncogenic agent in several epithelial malignancies, though its role in esophageal squamous lesions remains unclear. Esophageal squamous papilloma and papillomatosis are rare, often benign lesions, but increasing evidence suggests possible associations with high-risk HPV genotypes and a non-negligible risk of dysplasia and malignant transformation. This narrative review summarizes current evidence on epidemiology, clinical features, histopathology, and diagnostic approaches, emphasizing advanced endoscopic imaging techniques that improve lesion detection and characterization. Management relies primarily on complete endoscopic resection with histological and virological evaluation. While small, non-dysplastic solitary lesions may not require routine surveillance, multifocal or high-risk HPV-positive cases warrant closer follow-up. Standardized HPV testing and long-term prospective studies are needed to better define the oncogenic potential and inform surveillance and treatment strategies. Full article