Search Results (613)

Background: Human papillomavirus (HPV) is the most common sexually transmitted infection and the primary etiological agent of cervical cancer. Despite the high global disease burden, the Middle East and North Africa (MENA) region faces substantial challenges in HPV prevention and control. This narrative review aimed to synthesize existing evidence on the prevalence, genotypic distribution, awareness, vaccination status, clinical outcomes, and the role of HPV in non-cervical malignancies in the MENA region. Methods: PubMed, Web of Science, Scopus, and Google Scholar were searched, and 122 studies were included. Findings were synthesized qualitatively and descriptively. Cohort studies, systematic reviews, and meta-analyses were prioritized to support inferences about associations and potential causal relationships. Results: HPV prevalence in the general female population of the MENA region ranged from 4.7% to 53.3%, exceeding 90% in high-risk groups and patients with malignancies. The most common genotypes were HPV16 and HPV18; however, distribution patterns varied across populations. Key risk factors included younger age, multiple sexual partners, early age at first sexual intercourse, smoking, and alcohol consumption. General awareness was low to moderate, and vaccination coverage was very low in most countries. Barriers included lack of knowledge, fear of side effects, religious concerns, and social stigma. Evidence also indicates an association between HPV and non-cervical malignancies (head and neck, esophageal, gastric, breast, and thyroid cancers), with HPV DNA detected in tumor tissues. Conclusions: HPV poses a significant public health challenge in the MENA region, characterized by high prevalence, genotypic diversity, limited knowledge and awareness, and unsatisfactory vaccination coverage. Expanding screening and vaccination through financial support, culturally and religiously appropriate education, and longitudinal studies to monitor genotypic changes and associations with other malignancies are essential measures to reduce the burden of HPV-related diseases in the region. Full article

Background/Objectives: The COVID-19 pandemic was a major challenge for healthcare systems and social life worldwide. During the pandemic, studies focused on examining structural changes in patient care and establishing new guidelines to manage COVID-19, but very few of them addressed patients’ perceptions and concerns regarding changes in cancer treatment during the pandemic. This study aimed to assess the changes in their therapy situation during three waves of the pandemic and the impact on their social life. Methods: This exploratory cross-sectional multicenter survey was conducted among patients with gynecological malignancies and breast cancer at gynecological oncology centers in Germany between October 2020 and February 2022. An anonymous paper-based 50-item questionnaire, available in German, assessed medical care, treatment modifications, mental health, and socioeconomic burden during the COVID-19 pandemic. Data were analyzed descriptively. Two subgroup analyses were conducted, comparing age groups ≤70 and >70 years, as well as patients with and without a migrant background. Results: Overall, 778 patients met the inclusion criteria of the survey (median age: 59; range: 24–93). In the majority of the patients (77.1%), the treatment schedules remained unchanged during COVID-19 pandemic. Treatment appointments were modified in a small number of patients (9.0%). Changes in therapy schedules were slightly more common among the second- and third-generation migrants and among patients ≤70 years. Despite the uncertainty of the COVID-19 pandemic, most patients (83.4%) kept their trust in the healthcare system. Acceptance of preventive measures was high, and 85.9% were willing to be vaccinated against COVID-19. Psychological symptoms such as worries and fear were reported by more than half of the participants during the last 2 weeks previous to the survey and more common among patients ≤70 years. Only 8.6% were more afraid of a COVID-19 infection than their cancer disease. Conclusions: Despite major challenges in cancer care due to the COVID-19 pandemic, access to cancer treatment and adequate management at gynecological oncology centers in Germany remained stable. The increased psychological burden in crises requires new infrastructure and should be addressed to improve patient care in future crises. The acceptance of taking preventive measures against COVID-19 was high among cancer patients. Full article

Background: Hormone receptor-positive breast cancer depends on estrogen and progesterone signaling, yet factors that modulate hormone receptor expression within tumors remain incompletely understood. Human cytomegalovirus (HCMV), a widespread herpesvirus detected in breast tumors, has been associated with reduced expression of estrogen receptor-α (ERα) and progesterone receptor (PR), but a direct causal relationship has not been established. Methods: ER+/PR+ breast cancer cell lines MCF-7 and T47D were infected with HCMV in vitro. ERα and PR protein levels were assessed by immunoblotting, and transcript levels of ESR1 and PGR were quantified by qPCR. To determine whether virus replication was required, parallel experiments used UV-inactivated HCMV. Results: HCMV infection resulted in a marked reduction in ERα and PR protein levels in both cell lines, accompanied by decreased ESR1 and PGR transcript levels by 48 h post-infection. Notably, UV-inactivated HCMV produced a comparable suppression of hormone receptor expression, indicating that viral gene expression and productive replication are not required for this effect. Conclusions: These findings indicate that HCMV exposure suppresses ERα and PR expression in breast cancer cells through a replication-independent mechanism. This effect suggests that viral components or host responses to infection may alter hormone receptor signaling within tumors, with potential implications for hormone receptor signaling and endocrine therapy responsiveness that warrant further investigation. Together, these results identify HCMV as a previously underrecognized modulator of hormone receptor pathways in breast cancer. Full article

Gynecological malignancies and breast cancer impose substantial health and economic burdens. This review examines how local and systemic microbiota may affect epithelial integrity, inflammation, estrogen metabolism, and immunity. The vaginal ecosystem is the most extensively studied female microbial niche. Cervical cancer serves as the most illustrative clinical example: loss of stable Lactobacillus crispatus dominance and increased prevalence of anaerobic bacteria (anaerobic dysbiosis) are associated with persistent HPV infection, which directly elevates the risk of cervical precancerous lesions. The estrobolome is particularly relevant in endometrial cancer, where intestinal bacterial beta-glucuronidase activity may increase estrogen reabsorption, particularly in obesity and metabolic disease. In ovarian cancer, microbiota is being studied as a possible risk modifier in BRCA1 carriers, but the evidence remains exploratory. In breast cancer, intratumoral bacteria may shape the immune microenvironment, particularly in triple-negative disease. The primary limitation of current research is methodological heterogeneity. Low-biomass samples, such as those from the ovary or endometrium, are highly susceptible to technical contamination. Most studies are cross-sectional and cannot establish causality. Current evidence supports microbiota as a modifier, not a standalone marker or a substitute for standard diagnosis and treatment. Its most plausible near-term role is in multiparameter risk or response models, pending standardized prospective validation. Full article

Background/Objectives: Korea has experienced rapid and heterogeneous shifts in cancer epidemiology since 1999. We aimed to characterize divergent incidence trajectories across the 24 major cancer types, quantify sex-specific burdens, and project case counts through 2030. Methods: Annual incidence data—including new case counts and age-standardized incidence rates (ASIRs) per 100,000 (2020 Korean standard population) stratified by sex—were extracted from the KCCR via the Korean Statistical Information Service (KOSIS) for 1999–2023. Annual percent change (APC) was estimated by log-linear regression with 95% confidence intervals (CIs). Holt–Winters damped exponential smoothing generated 2024–2030 projections with 95% prediction intervals (PIs). Changes in case ascertainment and coding over the study period were considered in interpretation. Results: Total incidence increased from 101,854 (1999) to 288,613 cases (2023), a 183.4% increase. Overall ASIR rose from 402.7 to 522.9 per 100,000. Of the 24 cancer types, 15 showed statistically significant increasing ASIR trends, 6 showed significant decreasing trends, and 3 showed no significant change. The highest-APC cancers were thyroid (+7.56%), prostate (+6.98%), testis (+5.39%), breast (+5.03%), and corpus uteri (+5.03%; all p < 0.001). The largest significant declines occurred in cervix uteri (−3.81%), larynx (−3.18%), liver (−2.90%), and stomach (−2.20%; all p < 0.001). Female ASIR increased from 294.7 to 488.9 per 100,000 (+65.9%); male ASIR increased from 573.3 to 587.0 per 100,000 (+2.4%). Total cancer incidence is projected to reach 307,091 (95% PI: 281,200–332,983) in 2026 and 330,213 (95% PI: 290,663–369,763) by 2030, with the steepest projected relative growth for prostate (+48.9%), kidney (+33.7%), and breast (+31.3%) cancers. Conclusions: Korean cancer epidemiology is undergoing a pronounced transition from infection-related toward metabolic, hormonal, and aging-related malignancies, with a marked and widening sex-specific divergence. Cancer-type-resolved projections through 2030 provide an evidence base for strategic capacity planning in Korean oncology. Full article

Background: Human papillomavirus (HPV) has traditionally been considered a sexually transmitted infection, yet accumulating evidence demonstrates that HPV can be acquired through multiple non-sexual routes. Understanding these alternative transmission pathways is critical for interpreting HPV detection in non-sexually active populations and for refining public health strategies. Methods: This review synthesizes current evidence on non-sexual HPV transmission routes, including vertical (transplacental, intrapartum), perinatal oropharyngeal colonization, fomite contamination, breast milk transmission, and horizontal non-sexual contact. We examine HPV prevalence data from female virgins, neonates, infants, and children, and evaluate metagenomic evidence positioning HPV as a component of the human virome across multiple body sites. Results: Published studies report that vertical transmission occurs in approximately 18.2% of HPV-positive mothers, with neonatal HPV positivity of 3.4% at birth and 100% genotype concordance in transmission pairs. Transplacental transmission has been documented in 10.2% of concordant mother–placenta–newborn triads. Reviewed studies report oropharyngeal colonization at birth reaching 58.2% following vaginal delivery, with 94.3% of colonized neonates clearing infection by 24 months. HPV DNA has been detected on fomites and medical devices, in breast milk (8.6–15%), and across body sites in healthy adults (skin 61.3%, vagina 41.5%, oral cavity 30%, gut 17.3%). Metagenomic studies identify HPV DNA in 68.9% of healthy individuals, with 109 distinct types detected. Female virgins show HPV prevalence ranging from 0–51.1% across studies. Conclusions: The reviewed evidence suggests that HPV exhibits characteristics of a ubiquitous virome component with multiple non-sexual acquisition routes. These findings have important implications for vaccination strategies, screening interpretation, infection control in healthcare settings, and counseling of pediatric cases and non-sexually active individuals. Full article

Background/Objectives: The safety of hypofractionated postmastectomy radiotherapy (HF-PMRT) in patients undergoing implant-based breast reconstruction remains uncertain because of concerns regarding radiation-related reconstructive complications. We conducted a systematic review and meta-analysis to compare reconstruction-related complications following HF-PMRT versus conventionally fractionated (CF) PMRT. Methods: PubMed, Cochrane Library, and EMBASE databases were searched through August 2025 following PRISMA guidelines. Studies comparing HF-PMRT with CF-PMRT in patients undergoing implant-based breast reconstruction were included. Outcomes were capsular contracture, implant or tissue expander removal, infection, and wound dehiscence. Risk of bias was assessed using RoB 2 and ROBINS-I tools. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using the Mantel–Haenszel method. Subgroup analyses were performed by reconstruction stage (tissue expander vs. permanent implant). Results: Seven studies (n = 2200 patients; 1153 HF, 1047 CF) were analyzed, comprising two randomized controlled trials and five retrospective cohort studies. HF-PMRT was associated with a significantly lower risk of capsular contracture (OR 0.65, 95% CI 0.47–0.92) and wound dehiscence (OR 0.39, 95% CI 0.16–0.94) than CF-PMRT. Implant or tissue expander removal (OR 0.90, 95% CI 0.67–1.22) or infection (OR 0.98, 95% CI 0.67–1.44) did not differ. In subgroup analyses, reduction in capsular contracture was most evident when PMRT was delivered during the tissue expansion phase. Conclusions: These findings suggest that moderate hypofractionation is a reasonable fractionation option for implant-based breast reconstruction, with no evidence of increased reconstructive complications, although the certainty of evidence was limited, and prospective validation is warranted. Full article

Background/Objectives: Korea has undergone rapid epidemiological transitions in cancer incidence over the past two decades. Using a 25-year nationwide dataset (1999–2023), we characterize long-term trends for 61 cancer types, examine inter-cancer correlations, and forecast incidence to 2028. Methods: Annual incidence counts, crude rates, and age-standardized incidence rates (ASIRs) stratified by sex were obtained from the Korea Central Cancer Registry (KCCR) via the Korean Statistical Information Service (KOSIS). Annual percent change (APC) was estimated using log-linear regression. Pearson correlation coefficients were computed among cancer-specific ASIRs, with false-discovery-rate (FDR) correction for multiple comparisons. Multiple and hierarchical regression evaluated the statistical association of individual cancer types with the overall cancer rate, and variance inflation factors (VIFs) were used to quantify multicollinearity. Time series forecasting used damped Holt–Winters exponential smoothing; forecast accuracy was assessed with rolling-origin cross-validation (RMSE, MAE, MAPE) and benchmarked against ARIMA. A sensitivity analysis excluding the pandemic years (2020–2021) tested the robustness of trend estimates. Five-year prevalence data (2007–2023) were analyzed from the KCCR prevalence module. Results: Total cancer incidence increased from 101,854 in 1999 to 288,613 in 2023, a 183% increase. The overall ASIR rose from 402.7 to 522.9 per 100,000 (2020 standard population). The three fastest-growing cancers were thyroid (APC +7.56%, p < 0.001), prostate (+6.98%, p < 0.001), and breast (+5.03%, p < 0.001). Stomach (APC −2.20%) and liver (−2.90%) cancers showed significant declines. Hierarchical regression showed that adding thyroid, breast, and prostate to lung and stomach increased explained variance from R² = 0.449 to 0.997; however, high VIF values (up to ~263) indicate substantial multicollinearity and compositional dependence, so these coefficients should not be read as independent causal contributions. Holt–Winters and ARIMA produced comparable accuracy (mean MAPE 4.6% vs. 4.7%). The five-year cancer prevalence pool reached 1,035,107 in 2023. Forecasting projects a total incidence of approximately 319,000 by 2028. Conclusions: Korean cancer epidemiology is undergoing a transition from infection-related cancers toward hormone-sensitive and screening-detectable malignancies. These findings support strategic resource allocation for high-growth cancers while maintaining vigilance over rising pancreatic and other emerging cancers. Full article

Context: Locally advanced fungating breast cancer complicated by hemorrhage or infection represents a complex clinical condition that often requires a rapid and coordinated multidisciplinary approach. Although international guidelines, such as those developed by ESMO and NCCN, provide well-defined principles for the management of locally advanced breast cancer, they offer limited recommendations regarding the management of complicated fungating forms. Methods: We conducted a structured narrative review of the literature using the PubMed, Scopus, and Web of Science databases, including studies published between December 2019 and March 2026. Studies addressing locally advanced breast cancer and fungating forms complicated by hemorrhage or infection were included. Results: Available data are heterogeneous and derive primarily from case reports, small case series and retrospective studies. Systemic therapy remains the cornerstone of oncologic control; however, the presence of acute complications often necessitates prioritization of local interventions depending on the patient’s clinical stability. Hemorrhage may be managed through arterial embolization, hemostatic dressings or radiotherapy, whereas infection requires local wound care and targeted antibiotic therapy. These interventions aim to control acute symptoms and stabilize patients, thereby facilitating the subsequent integration of oncologic treatment. Emergency surgical intervention is reserved for selected cases, particularly when conservative measures fail to control bleeding or in the presence of persistent sepsis. Conclusions: The management of fungating breast cancer should be individualized and guided by the clinical presentation within a multidisciplinary team setting rather than by a rigid therapeutic sequence. This paper proposes a pragmatic, symptom-oriented clinical framework integrating all currently available therapeutic modalities (systemic therapy, radiotherapy, interventional radiology, surgery, and supportive care) with the aim of supporting decision-making in complex clinical scenarios. Full article

Laparoscopically harvested pedicled omental flap (LHPOF) reconstruction is a minimally invasive autologous option for immediate breast reconstruction, but prior reviews have largely examined omental flaps broadly, combining open and laparoscopic harvests, free and pedicled transfers, and mixed reconstructive indications. This systematic review evaluated operative characteristics, peri-operative complications, and esthetic outcomes following LHPOF after oncologic breast surgery. MEDLINE, Cochrane and Embase were searched without language or date restrictions, with backward citation searching of included studies. Eligible studies included female patients undergoing immediate unilateral breast reconstruction with LHPOF after mastectomy or BCS. Twenty-two studies published between 2001 and 2025 were included, representing 1869 patients. Operative techniques were broadly consistent, most commonly involving transverse-colon-first omental harvest, preservation of the right gastroepiploic vessels, and tunnelling from the inframammary fold toward the xiphoid. Reported complications included omental fat necrosis, partial flap loss, hematoma, infection, epigastric bulging, and incisional or tunnel-site hernia. Esthetic outcomes were generally favourable but assessed using heterogeneous methods. Current evidence suggests this technique is feasible in selected patients and may offer favourable esthetic outcomes with limited donor-site morbidity. However, prospective comparative studies with standardized reporting are needed to define optimal patient selection, long-term safety, and esthetic durability. Full article

Ebola virus disease (EVD) has traditionally been considered an acute infection characterized by high mortality and severe systemic inflammation. However, growing evidence accumulated over the last decade has progressively challenged this view, demonstrating that Ebola virus may persist long after apparent clinical recovery within immune-privileged anatomical compartments, including the male genital tract, ocular tissues, central nervous system, and breast milk. Persistent viral reservoirs have been associated with prolonged RNA shedding, sexual transmission, recrudescence phenomena, and outbreak resurgence, highlighting the clinical and public health relevance of post-acute Ebola persistence. At the same time, increasing evidence suggests that EVD survivors frequently exhibit chronic inflammatory activation and long-lasting immune dysfunction. Persistent alterations involving cytokine signaling, T-cell responses, and antiviral immune regulation may contribute to incomplete viral clearance and reservoir maintenance. In this context, the potential interaction between Ebola virus persistence and HIV-associated immune dysregulation remains poorly explored despite the substantial geographical overlap between both infections in sub-Saharan Africa. This narrative review examines current evidence regarding Ebola virus persistence, immune-privileged reservoirs, survivor immune dysfunction, and persistence-associated transmission. Additionally, we discuss the biological plausibility that chronic immune activation, T-cell exhaustion, and impaired antiviral surveillance observed in people living with HIV (PWH) could theoretically influence persistence dynamics and long-term reservoir biology. Understanding these interactions may have implications for survivor monitoring, outbreak preparedness, and future research on post-acute viral reservoir diseases. Importantly, this review does not argue that HIV has been clinically established as a modifier of Ebola virus persistence. Rather, it examines Ebola virus persistence as an established post-acute phenomenon and considers whether HIV-associated immune dysregulation in people living with HIV (PWH) may represent a biologically plausible, but still untested, determinant of viral clearance and reservoir biology. Full article

Background: Cutibacterium avidum is an emerging opportunistic pathogen responsible for device-associated infections, including prosthetic joint and breast implant infections. Unlike its relative C. acnes, for which phage therapy has been explored, C. avidum infections are recalcitrant to antibiotics, and no infecting bacteriophages have been described to date. Here, we report the isolation and characterization of ΦCA1NRNZ, to the best of our knowledge, the first lytic phage described against C. avidum. Methods: ΦCA1NRNZ was obtained from wastewater sampling at the Sorek Treatment Facility in Jerusalem. Wastewater metagenomics, transmission electron microscopy, genome sequencing, host-range testing, efficiency of plating (EOP), aerobic and anaerobic lysis assays, and antibiofilm assays against mature C. avidum biofilms were performed. Results: Metagenomic analysis indicated low and transient detection of C. avidum-classified reads in wastewater. ΦCA1NRNZ was identified as a long-tailed Caudoviricetes with a ~320 nm virion. Its 33,712 bp dsDNA genome (GenBank PV441878.1) encodes 46 predicted proteins, shares 76.5% nucleotide identity with C. acnes phage ΦFD1, and contains divergent tail-fiber and host-recognition genes. No known bacterial virulence, toxin, human pathogenicity-associated, or antibiotic-resistance genes were identified. ΦCA1NRNZ lysed all 11 clinical C. avidum isolates tested under aerobic and anaerobic conditions, with EOP values of 0.11–5.55, mean 1.87, and showed no lytic activity against 25 C. acnes isolates. Against mature biofilms, ΦCA1NRNZ reduced total biomass by 28.4% (p = 0.014), reduced viable cell counts by approximately two logs, and increased extracellular ATP release (p < 0.001). Conclusions: The strict species specificity and significant in vitro antibiofilm activity of ΦCA1NRNZ support its potential for phage therapy of device-associated C. avidum infections. Full article

Oncolytic virotherapy offers a promising avenue for solid tumor treatment, yet single-agent approaches are frequently limited by insufficient tumor lysis and inadequate immune activation. Here we report that combined therapy with two recombinant variants of the oncolytic vaccinia virus, armed with either herpes simplex virus thymidine kinase (VV-HSVtk) or the interleukin 15 receptor subunit alpha (VV-mIL15Rα), leads to enhanced cytotoxicity and immune stimulation in a murine mammary adenocarcinoma model (4T1). In vitro, VV-HSVtk exhibited dose-dependent cytotoxicity markedly potentiated by ganciclovir (GCV) through HSVtk-mediated phosphorylation into a cytotoxic nucleoside analog, and co-culture of VV-infected tumor cells with donor-derived NK cells further increased oncolytic efficiency. In vivo, combined treatment with VV-HSVtk, VV-mIL15Rα, and GCV resulted in significant tumor regression and extended survival relative to monotherapy controls in 4T1 syngeneic mice. Histological examination revealed increased lymphocytic infiltration at tumor sites and absence of hepatic or splenic toxicity. Together, these data indicate that integrating direct viral cytotoxicity, HSVtk/GCV-mediated suicide gene therapy, and IL-15-pathway-targeted immunomodulation within an oncolytic vaccinia platform can improve antitumor efficacy in a stringent breast cancer model. Full article

Cytomegalovirus (CMV) remains one of the most relevant congenital and early-life infections in pediatrics because of its high global seroprevalence, lifelong latency, and potential for reactivation or reinfection. Biologically, the virus poses a particular threat during pregnancy, when maternal primary infection carries a substantially higher risk of transplacental transmission than non-primary infection, with fetal and neonatal consequences that vary according to gestational timing and host vulnerability. In children, CMV infection is common in the first years of life and may contribute to a broad spectrum of outcomes, ranging from asymptomatic infection to severe multisystem disease, neurodevelopmental impairment, and sensorineural hearing loss. Clinically, the document highlights the importance of timely maternal diagnosis, differentiation between primary and recurrent infection, and integration of prenatal, neonatal, radiological, and audiological assessment. Attention is given to symptomatic and asymptomatic newborns, preterm infants, and infants exposed through breast milk. The availability of antiviral strategies in pregnancy and infancy strengthens the rationale for early identification and risk stratification. Universal newborn screening emerges as a potentially valuable approach to improve case detection, enable prompt follow-up, and reduce long-term disability. Overall, a multidisciplinary and early-intervention framework is essential to optimize prevention, diagnosis, treatment, and long-term outcomes in pediatric CMV infections. Full article

Neonatal defense against pathogens relies on maternal antibodies transferred both through the placenta (IgG) and through breast milk (primarily secretory IgA). Maternal IgG antibodies are transferred across the placenta to the fetus mainly via the neonatal Fc receptor (FcRn), which is expressed at high levels in placental syncytiotrophoblasts, and results in the acquisition of maternal-fetal IgG. Transplacental transfer via the FcRn pathway can provide therapeutic proteins and protective antibodies following maternal vaccination. However, maternal IgG antibodies can bind to vaccine antigens such as measles, tetanus, and poliovirus, resulting in rapid clearance through FcgRIIB-mediated inhibition and inadequate B cell activation. In this way, they can inhibit de novo immune responses and significantly reduce vaccine response. On the other hand, the interference that breast milk-derived antibodies may have on vaccine-induced immunity is still largely unknown. Vaccination against influenza, pertussis, and COVID-19 during pregnancy or lactation has been shown to induce the production of protective, pathogen-specific, secretory IgA and IgG antibodies in breast milk. Conversely, studies found that breast milk-derived antibodies of vaccinated mothers reduced vaccine-induced immunity in breastfed infants by accelerating the clearance of vaccine antigen, resulting in reduced antigen availability and reduced plasma cell formation after vaccination. Additional factors in middle- and low-income countries, including environmental (increased microbiome diversity, environmental intestinal dysfunction, malnutrition, co-infections) and breastfeeding practices, may exacerbate the interference effect of maternal antibodies. Current evidence supports that breastfeeding is associated with a reduced immunological response exclusively to the rotavirus vaccine. However, the limited evidence base to date precludes definitive conclusions regarding the role of breast milk-derived antibodies in modulating vaccine-induced immunity. Nevertheless, the evidence suggests that although maternal antibodies may theoretically reduce vaccine immunogenicity, the overall protective benefits of breastfeeding outweigh any potential interference with vaccine responses. Full article