Search Results (196)

Background/Objectives: Anal squamous cell carcinoma (SCCA) is a rare Human Papillomavirus (HPV)-related disease in the general population but its incidence is increasing among high-risk populations, i.e., men who have sex with men (MSM), HIV+ patients and women with a history of cervical/vulvar dysplasia. The objectives of this study were: (i) to investigate the prevalence of high-risk (HR) and low-risk (LR) anal HPV infections in a high-risk cohort; (ii) to correlate specific HPV genotypes with cytological and histological outcomes; and (iii) to assess the impact of cumulative HPV genotype burden. Methods: A retrospective study (2017–2022) was conducted on 550 high-risk patients. All patients underwent anal Pap tests (ThinPrep, Hologic) and HPV genotyping (Anyplex II HPV 28, Seegene), according to our screening protocol. High-Resolution Anoscopy (HRA) was performed on 430 patients; biopsy was performed in all cases with suspicious lesions. Results: The overall HR-HPV prevalence was 57.3%. Men showed a significantly higher prevalence of HR-HPV (59.9% vs. 47.4%) and cytological abnormalities (35.8% vs. 20.2%) compared to women. Notably, HPV 16, 58 and 45 accounted for 79% of AIN2+ (Anal Intraepithelial Neoplasia of grade 2 or higher) lesions. A significant cumulative HPV genotype burden effect, i.e., the number of HPV genotypes detected, was observed: patients with ≥3 HR-HPV types showed an increased risk of AIN2+ lesions (aOR 34.72; 95% CI 4.07–296.10) and AIN1+ lesions (aOR 16.26; 95% CI 4.54–58.30) respectively. The presence of ≥3 LR-HPV genotypes in HR-HPV-positive patients is associated with an increased risk of AIN1 lesions. Conclusions: HPV 16, 58 and 45 positivity and the cumulative HPV genotype burden could represent new potential indicators for risk stratification in high-risk populations. Future larger-scale prospective studies are needed to validate these preliminary results. Full article

High-risk human papillomavirus (HR-HPV) infection is the principal etiological factor in cervical cancer, with genotype distribution and cytological associations varying across populations. This retrospective study aimed to characterize the prevalence and genotype distribution of HR-HPV among 1747 Bulgarian women, including a subgroup of 1134 women with paired HPV polymerase chain reaction (PCR) and liquid-based cytology (LBC) results. The study population comprised women undergoing routine cervical screening (76.0%, n = 1328) and women tested because of clinical indications, including gynecological symptoms (24.0%, n = 419). The overall HR-HPV prevalence was 31.4% (549/1747) and was significantly higher among women tested for clinical indications than among those undergoing routine screening. HPV16 was the most frequently detected genotype, followed by multiple HR-HPV infections and other genotypes, including HPV31, HPV51, HPV66, HPV18, HPV45, HPV56, HPV68, and HPV33. Cytological abnormalities were identified in 24.7% (280/1134) of women with paired HPV and cytology results. HR-HPV positivity was strongly associated with abnormal cytology; however, 27.3% (233/854) of women with negative cytology were also HR-HPV positive. Integrating HPV genotyping with cytology may improve risk stratification and support more targeted clinical management. Despite the increasing use of LBC and HPV co-testing, comparative data describing HR-HPV genotype distribution and its relationship with cytological findings in screening and symptomatic populations remain limited. These findings provide epidemiological evidence on HR-HPV infection patterns in Bulgarian women and establish a foundation for future studies evaluating genotype-specific risks, disease progression, and population-based surveillance strategies. Full article

Kidney transplant recipients (KTRs) face a significantly elevated risk of persistent high-risk human papillomavirus (HR-HPV) infection and subsequent anal squamous cell carcinoma (ASCC) due to chronic immunosuppressive therapy impairing immunosurveillance. Despite the markedly increased risk of ASCC in this vulnerable cohort, standardized screening protocols and optimal clinical management guidelines are not exhaustive. Chronically compromised immunosurveillance permits prolonged HR-HPV carriage and viral genome integration, driving oncogenesis via the E6 and E7 oncoproteins. While calcineurin inhibitors exert pro-oncogenic effects, transitioning to mTOR inhibitors offers distinct antiproliferative and antiviral advantages. Early detection relies on risk-stratified screening utilizing digital anorectal examination, anal cytology, and high-resolution anoscopy. For managing anal intraepithelial neoplasia, traditional topical agents and minimally invasive ablative procedures are widely used, although high recurrence rates present a major clinical challenge. This review analyzes HPV pathogenesis and clinical management in KTRs, evaluating the impact of immunosuppressive regimens and exploring innovative diagnostic and therapeutic strategies. To address viral persistence without compromising the allograft, integrating novel non-invasive, target-specific nutraceuticals may represent an interesting complementary approach. Ultimately, mitigating post-transplant ASCC requires a multidisciplinary strategy that couples early localized screening with tailored systemic immunosuppression. Full article

Small cell carcinoma of the cervix (SCCC) is a rare yet highly aggressive subtype of cervical cancer (CC), characterized by early invasion, high metastatic potential, frequent recurrence, and extremely poor prognosis, which severely impairs women’s physical and mental health. Currently, high-risk human papillomavirus (hr-HPV, particularly HPV18) infection is recognized as one of the core drivers underlying the initiation and progression of SCCC. Malignant evolution is not triggered by a single infection event but is cooperatively regulated at multiple molecular levels, including HPV genome integration, critical gene mutations, and aberrant activation of multiple signaling pathways. In addition, SCCC exhibits an HPV-independent oncogenic pathway mainly mediated by somatic mutations in tumor protein 53 (TP53) and retinoblastoma 1 (RB1), thus forming a dual pathogenic mechanism. Based on current clinical understanding and molecular mechanisms, this paper reviews the molecular pathogenesis and subtypes of SCCC, reveals the associations between tumor heterogeneity, therapeutic resistance, and metastasis, and proposes potential novel targets for the treatment of SCCC. This study innovatively presents a closed-loop model of two-way empowerment between basic research and clinical application. It emphasizes that basic research should be oriented toward real clinical problems and highlights the reciprocal feedback of clinical practice on basic research, thereby achieving dynamic iteration and collaborative breakthroughs in both fields. Full article

Cervical cancer (CC) affects women worldwide, and more than 95% of cases are caused by persistent infection with high-risk human papillomavirus (HR-HPV), such as type 16, which promotes the progression of precancerous lesions to cancer. This study aimed to identify differentially expressed proteins (DEPs) in biopsies from patients with HPV16+ low-grade squamous intraepithelial lesions (LSILs) and from patients with HPV16+ squamous cell carcinoma (SCC) compared with those from HPV-negative normal cervical tissue (NCT HPV−) controls. The samples were analyzed by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) using a data-independent acquisition (DIA) approach. Data processing and differential protein expression analysis were performed with the DIA-NN software (Data-Independent Acquisition Neural Networks), followed by bioinformatics analyses, including Venn diagrams, pathway enrichment, functional interactome, The Cancer Genome Atlas (TCGA)-SCC data integration, and Western blot detection. In total, 1607 DEPs associated with cell adhesion and extracellular matrix proteins were identified in LSILs, whereas 1516 DEPs associated with catalytic and transport activities were identified in SCC; the proteins overexpressed in LSILs (332) were enriched in processes such as metabolism, immune response activation, and stress and cell death responses. In contrast, proteins overexpressed in SCC (205) were associated with the cell cycle, DNA damage, drug metabolism, proteasome degradation, methylation, and immune response. Interaction analyses highlighted proteins related to early proteins 1,5,6 and 7 (E1, E5, E6, and E7). In terms of the two DEPs, S100 calcium binding protein A10 (S100A10/p11) and thymidine phosphorylase (TYMP) were detected in patients with LSIL, HSIL, and SCC at the protein level, consistent with their higher transcript levels in public datasets. Given the small, exploratory cohort, these findings are hypothesis-generating, and validation in a larger, balanced, independent cohort is required. In conclusion, this study identified DEPs associated with the progression of premalignant lesions to SCC that may represent candidate biomarkers and therapeutic targets warranting further investigation. Full article

Objectives: To assess the prevalence of high-risk human papillomavirus (hrHPV) infection and selected genitourinary pathogens and to examine their co-detection patterns in sexually active adolescent females. Methods: In this single-center cross-sectional study, 167 consecutive outpatients aged 13–17 years with self-reported sexual initiation underwent multi-pathogen polymerase chain reaction (PCR) testing for hrHPV, Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU), Ureaplasma parvum (UP), and Mycoplasma genitalium (MG). Prevalence estimates are reported with 95% confidence intervals (CIs). Associations with hrHPV positivity were explored using univariable and parsimonious multivariable logistic regression; sensitivity analyses examined alternative age parameterization and exclusion of sparse variables. Results: The prevalence of hrHPV was 28.1% (47/167; 95% CI: 21.5–35.6). The prevalence of CT, UU, UP, and MG was 3.0%, 28.1%, 25.1%, and 0.6%, respectively. Any bacterial pathogen was detected in 61/167 participants (36.5%), while hrHPV–bacterial co-detection was observed in 24/167 (14.4%). In univariable analysis, UU was associated with hrHPV positivity (OR 2.55, 95% CI: 1.24–5.24; p = 0.013); this signal remained in the primary multivariable model (adjusted OR 2.46, 95% CI: 1.07–5.93; p = 0.035). A graded increase in hrHPV positivity was observed with increasing bacterial burden (p for trend = 0.018). Conclusions: Sexually active adolescent girls attending gynecologic outpatient care showed a substantial burden of hrHPV and bacterial genitourinary pathogen detection. This Central and Eastern European adolescent outpatient cohort contributes integrated multi-pathogen PCR-based epidemiologic data from a clinically relevant and underreported population. An exploratory association between UU and hrHPV positivity was observed; this signal is best interpreted as reflecting shared sexual exposure or the cervicovaginal microbial milieu rather than as evidence of an independent causal role for UU. The absence of vaccination status, behavioral, and longitudinal data represents a principal limitation. Prospective studies incorporating these variables are needed to clarify the epidemiology of hrHPV and co-detected pathogens in adolescents. Full article

Background/Objectives: Oral human papillomavirus (HPV) infection is emerging as a key driver of HPV-associated oropharyngeal cancer, especially in high-risk groups such as men who have sex with men (MSM) living with HIV (PLWH). However, evidence on oral HPV persistence and the impact of nine-valent HPV vaccination in adults remains limited. We conducted a prospective longitudinal study including 76 MSM PLWH, of whom 64 were nine-valent HPV-vaccinated and 12 unvaccinated. Methods: Oral rinse samples were collected at baseline (T0) and after 6 months (T6). HPV DNA detection and genotyping were performed using the Allplex™ HPV28 assay. Oral HPV dynamics (persistence, clearance, and incidence) were assessed for high-risk (HR) HPV, low-risk (LR) HPV, and vaccine-type HPV genotypes. Results: Baseline oral HPV prevalence was high (59.2%), with HR HPV detected in 43.4% of participants. HPV16 was the most frequent genotype at both T0 and T6. Among participants HPV-positive at baseline, persistence of HPV DNA was high and similar regardless of vaccination status (77.8%). However, incident vaccine-type oral HPV infection was significantly lower among vaccinated individuals than unvaccinated participants (6.3% vs. 33.3%; OR 0.13, 95% CI: 0.03–0.71; p = 0.0441). Finally, reporting ≥10 sexual partners in the previous year was significantly associated with baseline oral HPV positivity (p = 0.0298). Conclusions: In MSM PLWH, oral HPV infection is highly prevalent and persistent, underscoring that it may represent a reservoir for HPV-related oropharyngeal disease. In our small observational cohort, nine-valent HPV vaccination was associated with lower incident detection of vaccine-type oral HPV, supporting targeted vaccination and oral HPV surveillance in high-risk adult populations, while highlighting the need for larger longitudinal studies to confirm these findings and better define the magnitude and durability of vaccine-associated protection at the oral site. Full article

Persistent high-risk human papillomavirus infection is a critical prerequisite for cervical intraepithelial neoplasia and cervical cancer, yet viral factors alone do not fully explain why most infections clear while a subset persists and progresses. Emerging longitudinal, multi-omics, and mechanistic evidence supports a plausible model in which the cervicovaginal microbiota is not a passive bystander but a functional determinant of mucosal immunity, epithelial barrier integrity, and local metabolic tone. Lactobacillus-dominant community states, particularly those enriched in Lactobacillus crispatus, are generally associated with lower pH, regulated inflammatory signaling, stronger barrier function, and a higher likelihood of HPV clearance. In contrast, anaerobe-enriched dysbiosis is linked to elevated pro-inflammatory cytokines, altered antigen presentation, immune checkpoint signatures consistent with T-cell dysfunction, and metabolic shifts involving lactate depletion and accumulation of short-chain fatty acids and other metabolites that can influence epithelial and immune-cell programs. Importantly, the interaction is bidirectional: hrHPV can remodel the microenvironment by suppressing host defense peptides and perturbing mucosal barriers, thereby reducing Lactobacillus fitness and reinforcing dysbiosis in a feed-forward loop that favors persistence and oncogenic progression. This review integrates functional ecology, longitudinal clinical evidence, immunological and metabolic mechanisms, and translational implications, highlighting opportunities for microbiome-informed risk stratification and adjunctive interventions, as well as key gaps requiring standardized longitudinal multi-omics and rigorously designed clinical trials. Full article

Background/Objectives: Cervical self-sampling is increasingly used for high-risk human papillomavirus (hrHPV) testing, but evidence for integrated liquid-based cytology (LBC) and sexually transmitted infection (STI) testing is limited. This study evaluated the feasibility and diagnostic agreement of an integrated single-step self-sampling approach for LBC, hrHPV, and STI testing. Methods: In this prospective paired study, 520 Korean women for cervical cancer screening between December 2024 and February 2025 were enrolled. Each participant first underwent cervical self-sampling using Earlypap^®, followed by clinician-collected sampling. Paired specimens were analyzed for LBC, hrHPV, and STI detection. Percentage agreement and Cohen’s kappa coefficients (κ) were calculated. Results: Self-sampling was successful on the first attempt in 98.5% of participants, with 92.1% preferring it over clinician-collection. LSIL was detected in 2.3% of self-collected and 1.2% of clinician-collected specimens, and HSIL was detected in 0.4% of both specimen types. hrHPV positivity was 14.8% in self- and 12.9% in clinician-collected specimens. Ureaplasma spp. were frequently detected, and Candida albicans was identified in approximately 5% of specimens. Overall agreement was 91.7% (κ = 0.67) for LBC, 95.4% (κ = 0.79) for hrHPV, and 97.0% (κ = 0.72) for STI. Conclusions: Integrated cervical self-sampling using a single-step device demonstrated high feasibility and substantial agreement with clinician-based sampling, supporting its potential to improve screening efficiency and reduce participation barriers. Full article

Background: Persistent high-risk human papillomavirus (hrHPV) infection causes over 99% of cervical precancers and cancers worldwide, with HPV genotype 16 (HPV16) responsible for 50% of the cases. Latvia ranks among the top EU countries for cervical cancer incidence and mortality. In the general Latvian population, 4.2% of women are hrHPV-infected, mostly with HPV16. However, information on the circulating HPV16 isolates is missing. Objectives: To study the genomic variability of the Latvian HPV16 isolates, compare them with HPV16 in Europe and across the globe, reveal features associated with the severity of cervical disease and uncover eventual sequence changes due to the national HPV vaccination. Methods: DNA was extracted from the formalin-fixed paraffin-embedded cervical tissues of women diagnosed with cervical intraepithelial neoplasia (CIN) stages I-III and squamous cell carcinoma (SCC) grades 1–3, collected between 2012 and 2024. Samples positive for HPV16 were subjected to whole genome sequencing (WGS) on the Illumina platform (n = 16) or Sanger sequencing of the E6/E7 coding region (n = 31). A consensus HPV16 sequence was generated, and single nucleotide polymorphisms (SNPs) and eventual amino acid substitutions (AAS) were analysed. Results: Complete genomes of 16 HPV16 variants were reconstructed, with 13 related to the European sublineage A1 and 3 to the sublineage A2 references. Sequences showed high conservation; still 93 non-redundant variants were identified. The highest variability was observed for the capsid protein L2, and the lowest, for oncoprotein E7. The prevalence of SNPs and AAS in the Latvian HPV16 variants, specifically in capsid protein L1, did not increase with time, showing no effect of HPV vaccination. Associations between HPV16 sequence features and severity of cervical disease were limited to AAS E6:L90V, which was significantly more common in SCC grade 2/3 than in CINII/III cases (p = 0.015). Conclusions: Highly conserved HPV16 genomes circulating in Latvia harbour a series of unique as well as common nonsynonymous SNPs with respective AAS, with one, AAS E6:L90V, associating with disease severity. No HPV vaccine escape variants were detected. Deciphering complete genomes of HPV16 from CIN and SCC cases in Latvia informs public authorities performing HPV vaccination and is useful for the management of HPV-associated cervical diseases. Full article

Cervical cancer remains a major public health challenge worldwide and in Poland, where mortality rates are among the highest in the European Union. Persistent infection with high-risk human papillomavirus (hrHPV), particularly genotype HPV16, plays a central role in cervical carcinogenesis. This study aimed to evaluate the regional variability of hrHPV prevalence and genotype distribution in Poland and to assess its potential implications for cervical cancer incidence and prevention strategies. A systematic literature review was conducted using PubMed, Scopus, and Google Scholar to identify studies published up to May 2025 reporting hrHPV prevalence and genotypes among Polish women. Eligible studies included population-based cohorts, women undergoing screening, and patients with cervical lesions or cancer. The analysis revealed substantial heterogeneity in hrHPV prevalence and genotype distribution across regions and study populations. Nationwide data indicate high overall HPV prevalence (up to 50.9%), with HPV16 consistently dominating, followed by HPV31, HPV51, HPV52, and HPV66. Regional differences were observed, including a higher prevalence of HPV51 in southern Poland and HPV56 and HPV45 in central regions. Studies in women with abnormal cytology or cervical cancer showed markedly higher hrHPV prevalence (often >90%), with HPV16 predominating in high-grade lesions and invasive cancer. These findings confirm the dominant oncogenic role of HPV16 while highlighting significant regional variability in other hrHPV genotypes. Such differences may influence the effectiveness of screening and vaccination programs. Strengthening standardized, regionally stratified HPV surveillance is essential to optimize cervical cancer prevention and tailor public health interventions in Poland. Full article

Cervical cancer remains one of the most lethal cancers affecting women, with infection by high-risk Human Papillomavirus (HR-HPV), especially HPV-16, recognized as a primary cause. Phyllanthus urinaria, a plant that grows in Indonesia, has demonstrated notable both antiviral and anticancer properties. This study aimed to investigate the potential of P. urinaria as both an antiviral and anti-cervical cancer agent. The HPV-16 E6 protein was modeled using homology modelling, with model accuracy verified through torsional angle assessment and identification of conserved regions. Molecular docking was performed to examine E6–p53 interactions. Fraction of n-hexane compounds of P. urinaria were further evaluated for their interaction with E6 by molecular docking and molecular dynamics simulation. Additionally, in vitro cytotoxicity assays were conducted using HaCaT (normal keratinocyte) and HeLa (cervical cancer) cell lines. Compounds from P. urinaria were found to interact with E6 within conserved regions and these interactions were more stable conformationally than those observed for p53. In vitro assay demonstrated that P. urinaria exhibited moderate cytotoxicity against HeLa cells but had limited toxicity toward HaCaT cells. The n-hexane fraction of P. urinaria leaves exhibits anti-cervical cancer activity by inhibiting HPV-16 E6 and eliminating cervical cancer cells. Full article

Cervical cancer screening with high-risk human papillomavirus (HR-HPV) testing requires effective triage of HPV-positive women. Koilocytosis is a classic cytopathic effect of HPV infection, but its clinical significance in low-grade squamous intraepithelial lesions (LSILs) remains unclear. We retrospectively evaluated 157 HPV-positive women with LSIL cytology and follow-up data, including 140 women with concurrent biopsy results. Koilocytes were identified in 93/157 cases (59.2%) and were less frequent in HPV16/18-positive cases. Cervical intraepithelial neoplasia ≥ grade 2 (CIN2+) was detected in 9/84 koilocyte-positive cases (10.7%) and 16/56 koilocyte-negative cases (28.6%), whereas non-CIN findings were more common in koilocyte-positive cases. Koilocyte-positive cases also showed a longer time to regression from LSIL to negative for intraepithelial lesions or malignancy. These findings suggest that koilocytosis mainly reflects productive HPV infection and has limited utility for predicting CIN2+ in HPV-based screening triage. Excluding koilocytosis-driven low-grade cytological changes from triage positivity criteria may improve specificity and positive predictive value, supporting higher triage thresholds. Full article

Persistent high-risk human papillomavirus (hr-HPV) infection drives cervical carcinogenesis, yet improved molecular biomarkers are needed to define high-risk groups. Circulating microRNAs (miRNAs), stable in blood and involved in carcinogenic pathways, represent promising liquid biopsy biomarkers. This study assessed five miRNAs for distinguishing high-grade squamous cell intraepithelial lesions (HSILs) and cervical cancer from healthy controls and for HPV stratification. Circulating miRNAs were quantified in blood samples from 80 women (38 HSIL, 10 cervical cancer, and 32 controls). Relative expression by disease and HPV status was measured by RT-qPCR and normalized to miRNA-23a. Diagnostic performance of single and combined miRNAs was evaluated by logistic regression and ROC curve analysis. Three circulating miRNAs (miR-21, miR-205, and miR-218) were found to be significantly differentially dysregulated in the patient cohorts. A combination of the three markers showed the best diagnostic value for HSIL (AUC of 0.81, sensitivity of 79%, and specificity of 71%) and cancer (AUC of 0.81, sensitivity of 90%, and specificity of 65%). Whereas miR-205 was significantly associated with HPV16/18 in HSIL patients, the combined model had the highest diagnostic performance for multiple HPV infections. Circulating miRNA signatures show promise as liquid biopsy biomarkers for detecting cervical dysplasia and stratifying for HPV status in HSIL, warranting validation in larger prospective studies. Full article

Background and Objectives: The microbiome plays a pivotal role in male infertility, with distinct microbial species exerting both beneficial and deleterious effects on reproductive function. Sexually transmitted bacteria and several viruses, including human papillomavirus (HPV), have been identified in semen. This cross-sectional study aimed to examine the prevalence of single and co-infections of sexually transmitted bacteria (STB)—such as Chlamydia trachomatis, Mycoplasma spp., and Ureaplasma spp.—with various HPV subtypes in Greek male partners of infertile couples and to evaluate their potential impact on sperm parameters. In addition, the possible effect of cryopreservation on the maintenance of these pathogens was assessed. Materials and Methods: Eighty-two semen samples were initially collected from 82 individuals undergoing routine sperm analysis. In total, 80/82 (97.6%) participants proceeded to further analysis, as 2/82 (2.4%) were excluded due to poor DNA quality. Results: A total of 18/80 (22.5%) sperm samples tested positive for STB, with Ureaplasma spp. representing the most frequently detected pathogen. Co-infection of Ureaplasma spp. and Mycoplasma hominis was observed in 4/80 (5%) samples. Twelve samples (12/80, 15%) were positive for HPV, including low-risk (LR) and high-risk (HR) types, and HPV 16 was the predominant HR genotype. Notably, a co-infection of STB and HPV was not found in our specimens. STB-positive samples demonstrated significantly higher sperm concentration and improved progressive motility compared with STB-negative samples. HPV-positive samples exhibited lower sperm volume and concentration and increased non-progressive motility compared with HPV-negative samples. Following three months of cryopreservation, LR HPV and STB were no longer detectable, whereas HR HPV types remained detectable. Conclusions: These preliminary findings are interesting, as they could be useful for routine screening of HPV and STB in sperm samples preserved in sperm banks and highlight the need for future research. Full article