Search Results (618)

Objectives: The aim of the study was to gauge the clinical usefulness of the Derkay scale in assessing the severity of voice dysfunction in patients with recurrent respiratory papillomatosis (RRP). Material and Methods: The study included 29 patients (8 women and 21 men) with a mean age of 40.2 years. To subjectively assess each patient’s voice, the Polish version of the Voice Handicap Index questionnaire was used. Acoustic parameters were calculated using the Multidimensional Voice Program, which included mean fundamental frequency (F0), frequency changes (% Jitter), amplitude changes (% Shimmer), noise-to-harmonic ratios (NHRs), and the soft phonation Index (SPI). The stage of RRP was assessed using the Derkay scale, together with the anatomical location of the lesion (from laryngeal endoscopy) and the impact RRP had on the general condition of the patient. Results: In women, Derkay clinical and total scores showed significant, positive, and strong correlations with almost all VHI-30 subscales (rho = 0.73–0.76). In men, the correlations were weaker (rho = 0.38–0.55) but were strong between the Derkay total score and F0 and total score and Jitter (rho = 0.63–0.65). Patients with human papilloma virus HPV-6 had significantly higher soft phonation index values (M = 11.97) compared to patients with HPV-11 (M = 6.91, U = 34.0; p = 0.019). Conclusions: The Derkay classification system correlates well with objective acoustic frequency measures and patient-reported voice outcomes. The system may be helpful in identifying patients at increased risk of voice dysfunction. It could be used to guide decisions about voice assessment and rehabilitation. Full article

Eosinophils are innate immune cells that infiltrate tissues in response to cell proliferation and necrosis, which occurs during normal injury repair, parasitic infections, allergies, and cancer. Their involvement in cancer is controversial particularly with regard to tumor-associated tissue eosinophilia (TATE) and a recently defined mechanism of extracellular trap cell death (ETosis), a particular type of eosinophil cell death that is distinct from both apoptosis and necrosis. This narrative review synthesizes the literature regarding the prognostic significance of TATE, focusing on eosinophil ETosis and the important role of transmission electron microscopy (TEM) in its detection and morphological characterization. The prognostic role of TATE is contradictory: in certain tumors, it is a favorable prognostic marker, while in others, it is unfavorable. However, recent research reveals that TATE is associated with a better prognosis in non-viral neoplasms, but it may correlate with a poor prognosis in virus-related neoplasms, such as human T-lymphotropic virus type 1 (HTLV-1)-associated lymphomas and HPV-positive carcinomas. Our ultrastructural investigations revealed distinct phases of eosinophil ETosis in gastric cancer, which were defined by chromatin decondensation, plasma membrane disruption, granule discharge, and development of extracellular traps. We observed synapse-like interactions between eosinophils, exhibiting ETosis or compound exocytosis, and tumor cells, which showed various degrees of cellular damage, ultimately leading to colloid-osmotic tumor cell death. TEM provides important insights into eosinophil-mediated cytotoxicity, requiring further investigation as potential immune effector mechanisms in non-viral tumors. TATE evaluation, together with the viral status of the neoplasia, may be useful to confirm its prognostic significance and consequently its therapeutic implication in specific cancers. Full article

Human papillomavirus (HPV) infection is a primary driver of cervical cancer. Integration of HPV into the human genome causes persistent expression of viral oncogenes E6 and E7, which promote carcinogenesis and disrupt host genomic function. However, the impact of integration on host gene expression remains incompletely understood. We used multimodal RNA sequencing, combining total RNA-seq and Cap Analysis of Gene Expression (CAGE), to clarify virus–host interactions after HPV integration. HPV-derived transcripts were detected in 17 of 20 clinical samples. In most specimens, transcriptional start sites (TSSs) showed predominant early promoter usage, and transcript patterns differed with detectable E4 RNA region. Notably, the high RNA expressions of E4 region and viral-human chimeric RNAs were mutually exclusive. Chimeric RNAs were identified in 13 of 17 samples, revealing 16 viral integration sites (ISs). CAGE data revealed two patterns of TSS upregulation centered on the ISs: a two-sided pattern (43.8%) and a one-sided pattern (31.3%). Total RNA-seq showed upregulation of 12 putative cancer-related genes near ISs, including MAGI1-AS1, HAS3, CASC8, BIRC2, and MMP12. These findings indicate that HPV integration drives transcriptional activation near ISs, enhancing expression of adjacent oncogenes. Our study deepens understanding of HPV-induced carcinogenesis and informs precision medicine strategies for cervical cancer. Full article

Background/Objectives: Human papillomavirus (HPV) infection is a well-established risk factor for oropharyngeal squamous cell carcinoma (OPSCC), where p16 immunohistochemistry serves as a surrogate marker. However, the role of HPV in sinonasal squamous cell carcinoma (SNSCC) remains less defined, and the reliability of p16 as a standalone surrogate is under debate. This study aimed to assess the concordance between p16 expression and HPV-DNA status in SNSCC and characterize clinicopathologic features in HPV-associated cases. Methods: We retrospectively analyzed 111 SNSCC cases diagnosed between 2008 and 2024 at two German centers. p16 status was determined by immunohistochemistry using site-specific antibody protocols. HPV-DNA testing and genotyping were performed via PCR and reverse hybridization. Clinical and histopathological data were collected and compared between HPV-positive and -negative tumors. Results: HPV-DNA was detected in 31/111 cases (27.9%), with HPV16 and HPV33 (Site A) and HPV 16 and HPV18 (Site B) being the most frequent subtypes. Discordance between p16 and HPV-DNA status was observed in 29.7% of cases, with site-specific discordance rates of 44.6% and 14.5%. Patients with HPV-positive tumors were younger than their HPV-negative counterparts. Conclusions: Our findings underscore the limitations of p16 as a single surrogate marker for detecting HPV-associated sinonasal cancer. Future research on the role of HPV in sinonasal cancer should integrate complementary testing methods (like p16Ink4A immunohistochemistry and HPV DNA/mRNA analysis) and aim for test standardization. Full article

Background/Objectives: Virus-like particle (VLP) vaccines based on human papillomavirus (HPV) L1 proteins have high efficacy for preventing cervical cancer and other HPV-associated diseases. The production yields of commercial HPV VLPs remain suboptimal. We aimed to improve HPV VLP production efficiency using a hyper-expression vector system for the expression of L1 proteins of four major HPV serotypes—HPV 6, 11, 16, and 18. Methods: HPV L1 proteins were expressed in Trichoplusia ni (Hi5) insect cells via a hyper-expression baculovirus vector system. Following cell lysis using a microfluidizer, VLPs were purified through a two-step chromatographic process. Particle morphology was characterized using transmission electron microscopy and dynamic light scattering. Immunogenicity was evaluated using a murine model; mice received three intramuscular injections of the purified quadrivalent VLPs. The resulting IgG and neutralizing antibody responses were compared with those elicited by the commercial quadrivalent vaccine, Gardasil. Results: The L1 proteins from HPV 6, 11, 16, and 18 were successfully expressed at high levels in Hi5 cells, forming uniformly sized VLPs with hydrodynamic diameters of 50–60 nm. The average production yield of the quadrivalent VLPs exceeded 40 mg/L, an improvement over conventional yields. The candidate VLPs elicited strong HPV-specific IgG and neutralizing antibody responses in mice, comparable to those induced by Gardasil. Conclusions: The hyper-expression baculovirus vector system enables high-yield production of HPV L1 VLPs with desirable structural and immunogenic properties. This approach holds promise for the cost-effective and scalable manufacturing of next-generation HPV VLP vaccines, facilitating broader global access to HPV immunization. Full article

Human papillomavirus (HPV) integration is recognized as a hallmark event in cervical carcinogenesis. However, it does not represent a routine phase of the viral life cycle but rather a stochastic occurrence, often constituting a dead-end pathway for the virus. High-risk human papillomavirus (hr-HPV) exhibits a greater propensity for integration. The progression from initial infection to genomic integration constitutes a dynamic multi-step oncogenic process in the development of cervical cancer (CC). This process involves viral entry, immune evasion, persistent infection, and ultimately integration. This article innovatively provides a comprehensive overview of this multi-stage mechanism: HPV, via the L1/L2 proteins, mediates internalization and establishes infection. Subsequently, under the influence of factors such as the host’s genetic background, vaginal microbiota imbalance, and immune evasion, the host’s DNA damage response (DDR) pathways are activated. Viral DNA integrates into host genome vulnerable sites (e.g., 3q28 and 8q24) through microhomology-mediated end joining (MMEJ) or other alternative pathways. Following integration, the expression of viral oncogenes persists, triggering host genomic rearrangements, aberrant epigenetic modifications, and immune microenvironment remodeling, all of which collectively drive cervical cancer progression. The study further reveals the clinical potential of HPV integration as a highly specific molecular biomarker, offering new perspectives for precision screening and targeted therapy. This dynamic model deepens our understanding of the HPV carcinogenic mechanism and provides a theoretical basis for intervention strategies. Full article

The papillomavirus (PV) life cycle is strictly controlled and can be divided into the following three distinct stages: initial infection, maintenance, and amplification. The papillomavirus E2 gene encodes a multifunctional protein responsible for regulating transcription and replication by recruiting viral and host factors to the viral DNA genome. Our lab has previously reported that tyrosine 102 may impact bovine (BPV) and human (HPV) viral replication in cell culture systems. This tyrosine is conserved in the E2 protein of the murine papillomavirus MmuPV1. To investigate how this amino acid impacts the MmuPV1 lifecycle in vivo, we generated potential phosphorylation mimetic (Y102E) and phosphorylation deficient (Y102F) mutants in the E2 open reading frame. The Y102F mutant protein supported both transcriptional activation and transient replication, while Y102E was defective. However, Y102E was capable of associating with E1 and the Brd4 C-terminal motif. When these E2-mutated MmuPV1 genomes were introduced into the skin of immunocompromised mice, only Y102F was capable of inducing papilloma development and production of infectious progeny virus. These findings demonstrate that while highly conserved, tyrosine at this position is not required by the virus. These data suggest that the chemical nature of the amino acid at this position can influence E2 activity and viral replication. Full article

Progressive immune damage associated with Human Immunodeficiency Virus (HIV) alters mucosal homeostasis, favouring oral microbial imbalance and the development of opportunistic infections. The aim of this study was to characterize the composition and structure of the oral microbiota in different clinical conditions of HIV infection. A cross-sectional study was conducted in 99 Mexican men divided into five groups: HIV-negative controls, newly diagnosed without antiretroviral treatment, virally suppressed, with oral candidiasis, and with HPV infection. Metagenomic DNA was obtained from salivary samples, and the V1–V3 region of the 16S rRNA gene was massively sequenced. Taxonomic profiles, alpha/beta diversity, differential abundance, microbial co-occurrence networks and degree of dysbiosis were analysed. The results showed distinctive profiles between the groups. Alpha and beta diversity was significantly higher in the groups with oral Candida and HPV lesions, reflecting a disturbance of microbial balance. Differential abundance analysis revealed an increase in Streptococcus, Veillonella, Lactobacillus and Actinomyces genera in HIV patients, while healthy subjects showed higher abundance of Neisseria, Treponema, and Rothia, associated with a eubiotico state. The group of patients with HPV lesions had the highest number of taxa with differential abundance, suggesting an ecological environment altered by the lesion. Analysis of co-occurrence networks revealed a progressive pattern of microbial complexity: controls presented simple networks with weak positive correlations, while HIV groups showed increased connection density and appearance of structured nuclei. The group of patients with HPV lesions presented the highest connectivity, with multiple strongly correlated cores and core nodes such as Prevotella melaninogenica and Shuttleworthia. The dysbiosis score increased progressively from healthy subjects to those with HPV lesions, indicating a gradient of oral microbial disruption. These findings suggest that HIV immunosuppression and the presence of oral lesions are associated with enhanced dysbiosis, although their individual contributions could not be independently assessed due to the absence of non-HIV lesion controls. The integration of microbial networks and dysbiosis scores could be useful for assessing mucosal and immune health in people with HIV and used as biomarkers of clinical progression. Full article

Background/Objectives: Cervical cancer is currently the fourth leading cause of cancer in women. It is primarily caused by Human Papilloma Virus (HPV) infections. Primary prevention methods, such as vaccines, and secondary prevention strategies, such as screening, have significantly reduced the burden of these diseases. The screening could be a crucial factor in the early diagnosis. This study aims to estimate the access of migrant and refugee populations to cervical cancer screening (CCS). Methods: A meta-analysis of scientific literature present in Pubmed and Scopus databases was conducted according to the PRISMA 2020 guidelines. Eighty-seven cross-sectional and five cohort unique studies were examined, to evaluate the participation of migrant and refugee populations to CCS programs in different world regions. Results: Statistical analysis was performed using STATA 14.2 software. Among cross-sectional studies, mean regular adherence to CCS for migrant and refugees resulted being 56% (95% CI 53–60), while participation at least once is 60% (95% CI 54–65). In cohort studies, regular adherence and participation at least once are, respectively, 55% (95% CI 50–59) and 56% (95% CI 52–61). Conclusions: The results of this review show how migrant and refugee populations have limited access to prevention interventions due to several socio-cultural factors. Our work calls for public health professionals’ efforts in order to promote more inclusive policies and prevention strategies towards those populations, aiming to reduce disparities and public health expenditures. Full article

Antigenicity and immunogenicity define a potent immunogen in vaccinology. Nowadays, there are simplified platforms to produce nanocarriers for small-peptide antigen delivery, derived from various infectious agents for the treatment of a variety of diseases, based on virus-like particles (VLPs). They have good cell-penetrating properties and protective action for target molecules from degradation. Human papillomavirus (HPV) causes anogenital warts and six types of cancer in infected women, men, or children, posing a challenge to global public health. The HPV capsid is composed of viral type-specific L1 and evolutionarily conserved L2 proteins. Produced in heterologous systems, the L1 protein can self-assemble into VLPs, nanoparticles sized around 50–60 nm, used as prophylactic vaccines. Devoid of the viral genome, they are safe for users, offering no risk of infection because VLPs do not replicate. The immune response induced by HPV VLPs is promoted by conformational viral epitopes, generating effective T- and B-cell responses. Produced in different cell systems, HPV16 L1 VLPs can be obtained on a large scale for use in mass immunization programs, which are well established nowadays. The expression of heterologous proteins was evaluated at various transfection times by transfecting cells with vectors encoding codon-optimized HPV16L1 and HPV16L2 genes. Immunological response induced by chimeric HPV16 L1/L2 VLP was evaluated through preclinical assays by antibody production, suggesting the potential of broad-spectrum protection against HPV as a prophylactic nanovaccine. These platforms can also offer promising therapeutic strategies, covering the various possibilities for complementary studies to develop potential preventive and therapeutic vaccines with broad-spectrum protection, using in silico new epitope selection and innovative nanotechnologies to obtain more effective immunobiologicals in combating HPV-associated cancers, influenza, hepatitis B and C, tuberculosis, human immunodeficiency virus (HIV), and many other illnesses. Full article

Background: A number of viruses are oncogenic. These include the human papilloma virus (HPV), Epstein–Barr virus (EBV), Kaposi sarcoma human herpes virus 2/human herpes virus 8 (KSHHV/HHV8), hepatitis B virus, (HBV), hepatitis C virus (HCV), Merkel cell polyoma virus (McPyV), and the human T-cell leukemia virus type 1 (HTLV-1). These viruses cause malignancies ranging from carcinomas, sarcomas, lymphomas, to leukemias. This review aims to study the effects and efficacy of vaccines against these viruses and the cancers they cause in their prevention and treatment. Methods: The literature in the past 30 years was searched employing Scopus and Google Scholar using the keywords “oncogenic viruses, HPV, EBV, KSHHV, HHV8, Polyoma virus, HTLV-1, COVID-19, carcinoma, sarcoma, lymphoma, leukemia, anti-virus vaccines”. Results: Prophylactic vaccines against the HPV and HBV are highly effective in preventing and reducing the incidence of uterine cervical and hepatocellular carcinomas. Prophylactic vaccines against other oncogenic viruses have been less successful, though efficacious in some experimental animals. Therapeutic vaccines are still mostly under evaluation and development. Conclusions: Identification of oncogenic viruses has rendered anti-viral vaccines conspicuous tools for preventing and treating cancers they cause. Many endeavors for the development of such vaccines have been met with limited success, apart from the very effective anti-HPV and anti-HBV vaccines in universal vaccination programs. With the development of new vaccine technologies, it is hoped that effective vaccines against other oncogenic viruses will be developed in the future. 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

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

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

Sexually transmitted infections (STIs) are a significant global health concern, affecting millions of people worldwide, particularly sexually active adolescents and young adults. These infections, caused by various pathogens, including bacteria, viruses, parasites, and fungi, can have profound implications for women’s reproductive health and fertility. This review explores the role of vaginal and uterine infections in women’s infertility, focusing on the most common pathogens and their impact on reproductive outcomes. Bacterial infections, such as those caused by intracellular bacteria (Mycoplasma, Ureaplasma, and Chlamydia), Neisseria gonorrhoeae, and bacterial vaginosis, are among the most prevalent causes of infertility in women. Studies have shown that these infections can lead to pelvic inflammatory disease, tubal occlusion, and endometrial damage, all of which can impair fertility. Mycobacterium tuberculosis, in particular, is a significant cause of genital tuberculosis and infertility in high-incidence countries. Viral infections, such as Human papillomavirus (HPV) and Herpes simplex virus (HSV), can also affect women’s fertility. While the exact role of HPV in female infertility remains unclear, studies suggest that it may increase the risk of endometrial implantation issues and miscarriage. HSV may be associated with unexplained infertility. Parasitic infections, such as trichomoniasis and schistosomiasis, can directly impact the female reproductive system, leading to infertility, ectopic pregnancy, and other complications. Fungal infections, such as candidiasis, are common but rarely have serious outcomes related to fertility. The vaginal microbiome plays a crucial role in maintaining reproductive health, and alterations in the microbial balance can increase susceptibility to STIs and infertility. Probiotics have been proposed as a potential therapeutic strategy to restore the vaginal ecosystem and improve fertility outcomes, although further research is needed to establish their efficacy. In conclusion, vaginal and uterine infections contribute significantly to women’s infertility, with various pathogens affecting the reproductive system through different mechanisms. Early diagnosis, appropriate treatment, and preventive measures are essential to mitigate the impact of these infections on women’s reproductive health and fertility. Full article