Search Results (800)

Cervical cancer remains a significant public health challenge, disproportionately affecting women in low- and middle-income countries (LMICs). Persistent infection with high-risk types of human papillomavirus (HPV), particularly HPV16 and HPV18, is the central cause of cervical carcinogenesis, driven by the viral oncoproteins E6 and E7, which disrupt the host tumor suppressors p53 and retinoblastoma protein (pRb). Advances in molecular understanding have catalyzed effective primary and secondary prevention strategies. Prophylactic HPV vaccination, especially the nonavalent formulation, has demonstrated high efficacy in reducing HPV infections and cervical precancer. Concurrently, HPV deoxyribonucleic acid (DNA) testing, self-sampling, and screen-and-treat protocols are transforming screening paradigms, particularly in resource-limited settings. However, global disparities in vaccine access, screening coverage, and health infrastructure persist, impeding progress toward the World Health Organization’s (WHO) 90–70–90 elimination targets. By synthesizing recent advances in virology, prevention strategies, and implementation innovations, such as therapeutic vaccines, artificial-intelligence (AI)-driven diagnostics, and mobile health solutions, this review sheds light on their potential to narrow these equity gaps. Full article

Background/Objectives: The diagnostic performance of CINtec^® PLUS can be influenced by numerous patient characteristics and risk factors. The aim of this retrospective study was to evaluate and model the risk factors associated with CINtec^® PLUS test positivity in patients undergoing cervical cancer screening and to assess their predictive performance for the prediction of cervical intraepithelial neoplasia (CIN) 2/3 using an unsupervised machine learning-based model. Methods: Medical data of 134 patients with human papillomavirus (HPV) infection who underwent CINtec^® PLUS testing were used to model the impact of risk factors on dual-stain cytology positivity and to evaluate the predictive performance for CIN2/3. Results: The gradient boosting classifier for the prediction of CINtec^® PLUS positivity using clinical risk factors had a precision of 75%, an overall accuracy of 0.62, and an area under the curve (AUC) value of 0.77. Body mass index and age were the most important variables in this model. HSIL, ASC-US, and other high-risk HPV strains increased the likelihood of a positive outcome. Overall AUC values for a positive test alone were 0.74 and 0.69 for CIN2 and CIN3 prediction, respectively. For CIN2 prediction, the XGBoost model performed well, with 71% sensitivity, 85% specificity, and an AUC value of 0.90. However, the model had 96% sensitivity, 25% specificity, and 0.58 AUC for CIN3 prediction. Conclusions: Patient characteristics and risk factors can influence CINtec^® PLUS positivity rates and they need to be carefully considered before choosing a specific management. Full article

Background/Objectives: High-risk human papillomavirus (HPV) is the principal etiological agent of cervical cancer, with distinct genotype-specific oncogenic potential. While HPV type 16 is most frequently implicated in carcinogenesis, the role of other genotypes and their interaction with sexually transmitted infections and cervico-vaginal dysbiosis is gaining recognition. This study aimed to assess the genotype-specific distribution of high-risk HPV among HPV-positive women from Southern Croatia and examine associations with age and co-infections with selected microbial pathogens. Methods: We conducted a retrospective cross-sectional study on 1211 HPV-positive women (out of 3098 tested) from Split and Dalmatia County between 2023 and 2024. Cervico-vaginal swabs were tested using molecular and culture-based methods for 14 high-risk HPV genotypes and several pathogens, including Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, Gardnerella vaginalis, and other microorganisms. In the analysis, each detected HPV genotype was also treated as a distinct line-level observation. Genotypes were grouped by phylogenetic and carcinogenic profiles, and statistical analyses—including chi-square tests and multinomial logistic regression—were performed to evaluate associations with age and co-infections. Results: Among high-risk HPV-positive women, the most frequently detected high-risk HPV genotypes were HPV 16 (23.3%), HPV 31 (22.4%), and HPV 51 (13.5%). Notably, HPV 18 was less prevalent (8.1%) and occurred at a similar frequency to HPV 58 and 68. Although younger age was significantly associated with high-risk HPV positivity (p < 0.001), no significant differences in HPV genotype group distribution were observed between age groups; however, C. trachomatis and Streptococcus agalactiae were significantly more prevalent in women aged ≤29 years (p < 0.001 and p = 0.029, respectively). Multinomial regression revealed that C. trachomatis was negatively associated with 16-related and lower-risk genotypes, while G. vaginalis showed a positive association with 16-related types. Conclusions: There is a complex interplay between high-risk HPV genotypes and microbial co-infections, which means the broader cervico-vaginal microbiome has to be considered in HPV risk assessment. The findings highlight the need for extended genotyping and microbial screening to inform regional prevention strategies. Full article

Cervical cancer remains a significant public health concern, ranking as the 10th most common cancer among women in Greece. Current screening programs primarily rely on cytology and HPV DNA testing; however, their positive predictive value (PPV) for detecting high-grade cervical intraepithelial neoplasia (CIN2+) remains limited. This study aimed to compare the clinical performance of the HPV mRNA test with that of the HPV DNA test, focusing on their PPV for detecting CIN1+ lesions in a cohort of Greek women. A total of 114 women undergoing routine cervical cancer screening were tested using an HPV DNA assay (detecting 41 HPV types), Pap smear, and were referred for colposcopy and biopsy when indicated. Among them, 29 women aged 18 to 65 years (mean age: 35.1 ± 10.8 years) who tested positive for one or more of the five high-risk HPV types (16, 18, 31, 33, 45) were further assessed using the PreTect HPV-Proofer^® mRNA assay. Of these 29 women, 11 (37.9%) had negative biopsy findings, 16 (55.2%) were diagnosed with CIN1, and 2 (6.9%) with CIN2, corresponding to a positive predictive value (PPV) of 55.2% for CIN1 and 6.9% for CIN2 with the HPV DNA test. Among the 17 women who tested positive for HPV mRNA, 13 were diagnosed with CIN1 and 2 with CIN2. Among the 12 women who tested negative for HPV mRNA, 3 had CIN1 and 9 had negative biopsy results. Based on these findings, the PPV of the HPV mRNA test for CIN1 was 76.5%, the negative predictive value (NPV) was 75.0%, and the clinical sensitivity for CIN1 was 81.3%. For CIN2, the PPV was 11.8%, while the clinical sensitivity and NPV were 100%. These findings highlight the potential of HPV mRNA testing to improve specificity in cervical cancer screening by more accurately identifying clinically significant lesions and reducing unnecessary colposcopies. Full article

Human Papillomavirus (HPV), particularly high-risk strains such as HPV16 and HPV18, is a leading cause of cervical cancer and a significant risk factor for several other epithelial malignancies. While the oncogenic mechanisms of viral proteins E6 and E7 are well characterized, the broader effects of HPV infection on host transcriptional regulation remain less clearly defined. This study explores the hypothesis that conserved genomic motifs within the HPV genome may act as molecular decoys, sequestering human transcription factors (TFs) and thereby disrupting normal gene regulation in host cells. Such interactions could contribute to oncogenesis by altering the transcriptional landscape and promoting malignant transformation.We conducted a computational analysis of the genomes of high-risk HPV types using MEME-ChIP for de novo motif discovery, followed by Tomtom for identifying matching human TFs. Protein–protein interactions among the predicted TFs were examined using STRING, and biological pathway enrichment was performed with Enrichr. The analysis identified conserved viral motifs with the potential to interact with host transcription factors (TFs), notably those from the FOX, HOX, and NFAT families, as well as various zinc finger proteins. Among these, SMARCA1, DUX4, and CDX1 were not previously associated with HPV-driven cell transformation. Pathway enrichment analysis revealed involvement in several key biological processes, including modulation of Wnt signaling pathways, transcriptional misregulation associated with cancer, and chromatin remodeling. These findings highlight the multifaceted strategies by which HPV may influence host cellular functions and contribute to pathogenesis. In this context, the study underscores the power of in silico approaches for elucidating viral–host interactions and reveals promising therapeutic targets in computationally predicted regulatory network changes. Full article

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

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

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

Background/Objectives: This study was designed to investigate the relationship between peripheral hematological inflammation markers, namely, neutrophil/lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), systemic immune inflammation index (SII), and systemic inflammatory response index (SIRI) and high-grade cervical lesions (CIN2+). Methods: A retrospective cohort analysis was conducted on 358 patients who underwent cervical excision procedures. Patients were divided into two groups: <CIN2 and CIN2+. Preoperative complete blood count data were used to calculate the inflammation indices. HPV genotypes were also recorded. Logistic regression and ROC analyses were performed to evaluate the predictive performance. Results: CIN2+ lesions were detected in 69.6% of participants. In the univariate analysis, only age and HPV 16 positivity (p < 0.005) showed a significant association with the presence of CIN2+. NLR, PLR, MLR, SII, and SIRI values did not show significant differences between groups (all p > 0.05). In the multivariate analysis, increasing age was independently associated with a decrease in the risk of CIN2+ (OR = 0.96, 95% CI: 0.94–0.99), while HPV 16 positivity was associated with an increase in risk (OR = 2.44, 95% CI: 1.43–4.18). ROC analysis showed that combining age and HPV 16 status improved the specificity (85.1%) of predicting CIN2+ compared to using age alone (42.2%). Conclusions: Peripheral haematological inflammation markers (NLR, PLR, MLR, SII, and SIRI) did not show predictive value in predicting CIN2+ lesions. However, age and HPV 16 infection were found to be independent predictors. These findings suggest that haematological indices may reflect systemic inflammatory responses but are not sufficient on their own for the detection of CIN2+. HPV genotyping is of critical importance for the early detection of high-grade lesions. Full article

Head and neck cancer (HNC) is the seventh most common cancer worldwide, with rising incidence particularly in oropharyngeal cancer subsites. Despite well-known risk factors, such as tobacco and alcohol consumption as well as human papillomavirus (HPV) infection, most HNCs are diagnosed at an advanced stage, resulting in poor prognosis. Early detection and screening are critical, especially in high-risk populations. Nevertheless, there is a lack of guidelines for a stratified HNC screening. A systematic literature review was conducted following PRISMA guidelines, using PubMed and ScienceDirect databases up to 30 June 2025. Search terms included “screening”, “early diagnosis”, and specific HNC subsites. A total of 199 records were screened, and 160 studies were included based on relevance and scientific rigor. The review concentrates on contemporary screening modalities, stratification of high-risk cohorts, emerging technologies, and cost-effectiveness evidence. Visual inspection and panendoscopy remain the standard tools for HNC screening, but have limited effectiveness and cost-efficiency. Opportunistic screening in high-risk individuals, especially in regions with high HNC prevalence, has shown benefits. Liquid biopsy techniques targeting HPV- and Epstein-Barr virus-related HNC demonstrate high sensitivity for early detection and recurrence monitoring. Novel imaging technologies like narrow-band imaging and Raman spectroscopy show promising diagnostic accuracy but require further validation. Most broad-based screening programs lack cost-effectiveness, while targeted strategies in high-risk groups appear more viable. Screening for HNC should be stratified by individual risk profiles and regional disease prevalence. Emerging technologies, particularly liquid and optical biopsy techniques, offer transformative potential. Future screening strategies must integrate technological advances into tailored, evidence-based protocols to improve early detection and patient outcomes in HNC. 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: 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/Objectives. Women living with human immunodeficiency virus (WLWH) have a six-fold higher risk of developing cervical cancer associated with high-risk human Papillomavirus (HR-HPV) than HIV-negative women. We herein assessed HR-HPV genotype distribution and plasma levels of the cancer antigen 125 (CA-125) in WLWH in a rural town in Gabon, in Central Africa. Methods. Adult WLWH attending the local HIV outpatient center were prospectively enrolled and underwent cervical visual inspection and cervicovaginal and blood sampling. HIV RNA load and CA-125 levels were measured from plasma using the Cepheid^® Xpert^® HIV-1 Viral Load kit and BioMérieux VIDAS^® CA-125 II assay, respectively. HPV detection and genotyping were performed via a nested polymerase chain reaction (MY09/11 and GP5+/6+), followed by sequencing. Results. Fifty-eight WLWH (median age: 52 years) were enrolled. Median CD4 count was 547 cells/µL (IQR: 412.5–737.5) and HIV RNA load 4.88 Log₁₀ copies/mL (IQR: 3.79–5.49). HPV prevalence was 68.96%, with HR-HPV detected in 41.37% of women. Among HR-HPV-positive samples, 87.5% (21/24) were genotypes targeted by the Gardasil vaccine, while 12.5% (3/24) were non-vaccine types. Predominant HR-HPV types included HPV-16 (13.8%), HPV-33 (10.34%), HPV-35 (5.17%), HPV-31, and HPV-58 (3.45%). Most participants had normal cervical cytology (62.07%), and a minority (14.29%) had elevated CA-125 levels, with no correlation to cytological abnormalities. Conclusions. In the hinterland of Gabon, WLWH are facing an unsuspected yet substantial burden of cervical HR-HPV infection and a neglected risk for cervical cancer. Strengthening cervical cancer prevention through targeted HPV vaccination, sexual education, and accessible screening strategies will help in mitigating associated risk. Full article

Cervical cancer (CC), often caused by persistent high-risk HPV infection, is a major health issue for Moroccan women. This study is the first in Morocco to examine how the cervico-vaginal microbiome differs across HPV-related clinical stages. Using 16S rRNA sequencing, the researchers analyzed samples from 247 women—100 healthy controls, 43 hr-HPV⁺ pre-cancer cases, and 104 post-treatment CC cases. In healthy women, Lactobacillus dominated (70%), but it significantly declined in the pre-cancer group (45%, p < 0.01) and remained low post-treatment (50%). Meanwhile, Pseudomonadota and Actinobacteriota increased in pre-cancer samples (up to 25–30%, p < 0.01). Although the alpha diversity remained stable, the beta diversity differed significantly across stages (p = 0.001), but not by HPV status. Post-treatment samples showed a sharp decline in Bacillota (logFC −5, p < 10⁻¹⁵) and increases in Campylobacterota and Fusobacteriota (logFC +6 to +21, p < 10⁻¹⁶). Functionally, chemo-heterotrophy and fermentation declined, while nitrogen fixation and phototrophy rose in pre-cancer cases. Host factors like late menarche, high parity, STIs, and contraceptive use correlated with specific microbiota shifts. Full article