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Search Results (610)

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Keywords = high-risk human papillomavirus

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23 pages, 990 KB  
Review
The Microbiome–Mitochondria–Extracellular Vesicle Axis in HPV Persistence and Cervical Carcinogenesis
by Efthalia Moustakli, Stylianos Makrydimas, Emmanouil D. Oikonomou, Agni Nakou, Eleni Albani and Nektaria Zagorianakou
Genes 2026, 17(6), 655; https://doi.org/10.3390/genes17060655 (registering DOI) - 1 Jun 2026
Abstract
Persistence of human papillomavirus (HPV) infection leading to cervical carcinogenesis can be attributed to the action of high-risk HPVs, but there are still some unclear factors involved in the mechanisms of either viral clearance or persistence. Although many infections may be self-limiting and [...] Read more.
Persistence of human papillomavirus (HPV) infection leading to cervical carcinogenesis can be attributed to the action of high-risk HPVs, but there are still some unclear factors involved in the mechanisms of either viral clearance or persistence. Although many infections may be self-limiting and cleared successfully by the immune response of the infected individuals, other infections result in persistent HPV infection. Recent studies indicate that microbiota in the gut and cervicovaginal tract modulate host immune status, mucosal inflammation, and epithelial barrier integrity. All these factors determine susceptibility to persistent infection. Inflammation, overproduction of reactive oxygen species (ROS), genomic instability, and impaired antiviral transcription pathways are associated with dysbiosis. In parallel, redox imbalance contributes to mitochondrial dysfunction, impairing mitochondrial antiviral signaling (MAVS)-dependent interferon responses and attenuating induction of interferon-stimulated genes. Additionally, extracellular vesicles (EVs) further promote immune evasion, metabolic programming, and epigenetic regulation by facilitating the intercellular exchange of viral constituents, microRNAs, and signaling molecules. Through this interconnected network of mechanisms, microbial dysbiosis, mitochondrial disruption, and EV signaling collectively shape a niche conducive to persistence. Unlike previous reviews that primarily examine microbiome alterations, oxidative stress (OS), mitochondrial dysfunction, extracellular vesicles, or immune responses as separate processes, this review integrates clinical and omics findings into a systems-based conceptual framework of HPV persistence. By emphasizing the potential interactions among these interconnected biological systems, we aim to identify points of biological convergence, generate mechanistic hypotheses, and highlight opportunities for future biomarker development and therapeutic intervention. Full article
(This article belongs to the Special Issue Genomic and Molecular Determinants of HPV-Related Reproductive Health)
18 pages, 669 KB  
Review
Is There Geographic Variation in Poland in the Distribution of Specific High-Risk HPV Genotypes in Normal Cervical Epithelium, Dysplastic Lesions, and Cervical Cancers?
by Beata Biesaga, Anna Mucha-Małecka, Anna Kruczak and Wiktor Szatkowski
Cancers 2026, 18(11), 1774; https://doi.org/10.3390/cancers18111774 - 28 May 2026
Viewed by 147
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Human Papillomavirus (HPV) and Related Cancer)
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16 pages, 5866 KB  
Article
Computational and Cytotoxicity Evaluation of Phyllanthus Urinaria-Derived Compounds as Potential Anti-Cervical Cancer Agents via HPV-16 E6 Oncoprotein Inhibition
by Andi Darma Putra, Safika Safika, Fadilah Fadilah, Kartiwa Hadi Nuryanto, Aldi Tamara Rahman, Lasmini Syariatin, Naufal Syafiq Darmawan, Kevin Nathaniel Cuandra, Firda Puspita and Gatot Purwoto
Int. J. Mol. Sci. 2026, 27(11), 4780; https://doi.org/10.3390/ijms27114780 - 26 May 2026
Viewed by 234
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Antiviral Mechanisms of Natural/Synthetic Compounds)
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12 pages, 4109 KB  
Article
Detection of HPV DNA in Cervical Intraepithelial Neoplasia Using In Situ Hybridization
by Marcin Przybylski, Sonja Millert-Kalińska, Dominik Pruski, Mateusz de Mezer, Monika Krzyżaniak, Robert Jach, Jakub Żurawski and Paweł Kurzawa
J. Clin. Med. 2026, 15(10), 3974; https://doi.org/10.3390/jcm15103974 - 21 May 2026
Viewed by 175
Abstract
Background: Human papillomavirus (HPV)-related diseases remain a major global health problem, with cervical intraepithelial neoplasia (CIN) representing a key precursor to cervical cancer. Identification of high-risk HPV genotypes is essential for early diagnosis and appropriate management. This study aimed to evaluate the [...] Read more.
Background: Human papillomavirus (HPV)-related diseases remain a major global health problem, with cervical intraepithelial neoplasia (CIN) representing a key precursor to cervical cancer. Identification of high-risk HPV genotypes is essential for early diagnosis and appropriate management. This study aimed to evaluate the usefulness of in situ hybridization (ISH) for detecting HPV DNA in formalin-fixed, paraffin-embedded (FFPE) cervical tissue and to compare automated signal detection with manual histopathological assessment. Methods: This prospective, non-randomized study included 83 women undergoing diagnostic procedures for abnormal cytology or confirmed CIN between 2022 and 2023. Tissue specimens obtained during a loop electrosurgical excision procedure (LEEP) were examined using two ISH probes: ISH II for low-risk HPV types 6 and 11, and ISH III for high-risk HPV genotypes. Staining patterns and distributions were evaluated and correlated with molecular HPV testing and histopathological outcomes. Results: ISH II distribution was significantly associated with the presence of HPV type 6 or 11 (p < 0.001), although stain structure itself was not. ISH III stain structure was significantly associated with high-risk HPV genotypes (p = 0.020). A positive ISH II result predicted low-risk HPV infection with a sensitivity of 62.5% and specificity of 64.0%, while ISH III predicted high-risk HPV infection with a sensitivity of 86.36% but lower specificity (23.53%). Overall diagnostic accuracy was 63.86% for ISH II and 73.49% for ISH III. Conclusions: ISH proved to be a reproducible method for detecting HPV in archived cervical tissue, enabling assessment even years after specimen collection. Although PCR-based methods remain more widely used due to higher sensitivity and less invasive sampling, ISH provides valuable morphological context and may serve as a complementary diagnostic tool, particularly when only archival tissue is available. Full article
(This article belongs to the Special Issue Clinical Advances in HPV-Related Disease)
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23 pages, 550 KB  
Article
Health Outcome Determinants of Human Papillomavirus Vaccination in Adult Women in Spain
by Jesús de la Fuente-Valero, Javier Rejas-Gutiérrez, Marta del Pino, Carmen González-Granados, Raquel Oliva-Sánchez, Beatriz Procas-Ramón, Mar Ramírez-Mena, Aaron Cohen-Castiel, Javier Calvo-Torres, María Fasero, Pluvio J. Coronado and on behalf of the HPV-Know Collaborative Group, SPAIN-GOG
Vaccines 2026, 14(5), 460; https://doi.org/10.3390/vaccines14050460 - 21 May 2026
Viewed by 176
Abstract
Background/Objectives: Health outcome determinants affecting Human Papillomavirus (HPV) vaccination among the adult female population are scarce in Spain. This study aimed to describe the health outcomes and determinants of HPV vaccination in women 18–65 years attending lower genital tract outpatient clinics across regions [...] Read more.
Background/Objectives: Health outcome determinants affecting Human Papillomavirus (HPV) vaccination among the adult female population are scarce in Spain. This study aimed to describe the health outcomes and determinants of HPV vaccination in women 18–65 years attending lower genital tract outpatient clinics across regions of Spain. Methods: This was a cross-sectional, multicenter, non-interventional, descriptive, and comparative nationwide study. Sociodemographic characteristics and health outcomes included obstetric, gynecological and HPV vaccination antecedents, together with patient-reported outcomes related to HPV infection. Statistical analysis included multivariate logistic regression models. Results: Among 2004 adult women recruited, 1907 (95.2%) were eligible for analysis. Vaccine uptake was 48.8%; 81.6% among women who were ever HPV positive (adjusted OR = 2.16 [95% CI: 1.59–2.93], p < 0.001), but 65.9% among women with an active infection, which acted as a negative factor for vaccination (OR = 0.63 [0.45–0.87], p = 0.005), as did increasing age (OR = 0.92 [0.90–0.93], p < 0.001); the higher the age, the lower the adjusted likelihood of being vaccinated. HPV knowledge and adequate physician-provided information were weakly associated with vaccination likelihood. A history of conization (OR = 7.48 [5.34–10.47], p < 0.001), use of contraception (OR = 1.49 [1.13–1.96], p = 0.004), infection with high-risk or unknown-risk HPV genotypes (OR = 1.86 [1.23–2.82], p = 0.003 and OR = 1.68 [1.17–2.42], p = 0.006, respectively), and Spanish nationality (OR = 2.46 [1.68–3.61], p < 0.001) were identified as factors associated with a higher vaccination likelihood. Conclusions: This study found that HPV vaccination uptake is improvable. Previous HPV infection favored vaccination; however, active infection and increasing age acted against vaccination. HPV knowledge and adequate healthcare professional information appeared to favor vaccination, along with, most notably, a history of cervical surgery (conization), contraceptive use, or infection with high-risk or unknown-risk HPV genotypes. Spanish women had a higher likelihood of receiving HPV vaccination than foreign residents. Full article
(This article belongs to the Section Human Papillomavirus Vaccines)
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14 pages, 1166 KB  
Article
Cost-Effectiveness of Nationwide HPV Vaccination in Girls in Kazakhstan: A UNIVAC-Based Analysis
by Raikhan Nissanova, Markhabat Kassenov, Vladislava Suchshikh, Perizat Akshalova, Zhandos Abay, Vladimir Kirpichenko, Aiken Karabassova, Saira Kaimoldina, Zhibek Zhetpisbay, Elvira Bashenova and Ainur Nurpeisova
Vaccines 2026, 14(5), 453; https://doi.org/10.3390/vaccines14050453 - 19 May 2026
Viewed by 285
Abstract
Background: Cervical cancer, largely attributable to persistent infection with high-risk human papillomavirus (HPV), remains a major public health burden worldwide, including in Kazakhstan, where limited screening coverage and low public awareness contribute to substantial incidence and mortality. This study evaluated the cost-effectiveness [...] Read more.
Background: Cervical cancer, largely attributable to persistent infection with high-risk human papillomavirus (HPV), remains a major public health burden worldwide, including in Kazakhstan, where limited screening coverage and low public awareness contribute to substantial incidence and mortality. This study evaluated the cost-effectiveness and epidemiological impact of a nationwide HPV vaccination programme for 10-year-old girls in Kazakhstan using the quadrivalent Gardasil-4 vaccine. Methods: A 10-year modelling analysis (2025–2035) was conducted using the World Health Organization (WHO)-endorsed Universal Vaccination Impact and Cost-Effectiveness Assessment (UNIVAC) tool adapted to Kazakhstan-specific epidemiological and economic parameters. Vaccination coverage was projected at 98.0% for the first dose and 96.5% for the second dose. Incremental cost-effectiveness ratios (ICERs) and disability-adjusted life years (DALYs) averted were estimated from governmental and societal perspectives. Sensitivity analyses assessed uncertainty in vaccine coverage, vaccine costs, and epidemiological inputs. Results: Over the 10-year period, the vaccination programme was projected to reduce HPV-related disease cases by 68.2% (from 112,198 to 35,628) and deaths by 68.3% (from 15,921 to 5056), while averting 67,445 DALYs. The ICER was estimated at US$ 533 per DALY averted from the governmental perspective and US$ 1169 from the societal perspective. Projected healthcare cost savings reached US$ 42.8 million, driven largely by reductions in 21,748 hospitalisations and 13,706 outpatient visits. These findings remained robust in probabilistic sensitivity analysis, with the probability of cost-effectiveness increasing as the willingness-to-pay threshold rose. Conclusions: UNIVAC-based modelling suggests that introduction of a national HPV vaccination programme for 10-year-old girls in Kazakhstan using Gardasil-4 could substantially reduce cervical cancer burden and related mortality while generating considerable healthcare savings. These findings support the cost-effectiveness of nationwide HPV vaccination in Kazakhstan. Full article
(This article belongs to the Special Issue Prevention of Human Papillomavirus (HPV) and Vaccination)
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13 pages, 340 KB  
Article
Increasing HPV Vaccination Among Early Adolescents Using a Game-Based Digital Intervention: A Randomized Controlled Trial
by Angela Chia-Chen Chen, Lihong Ou, Elizabeth Reifsnider, Kimberly Arcoleo, Ashish Amresh and Michael Todd
Vaccines 2026, 14(5), 448; https://doi.org/10.3390/vaccines14050448 - 18 May 2026
Viewed by 227
Abstract
Background/Objectives: Human papillomavirus (HPV) vaccination coverage among adolescents remains below public health targets despite strong evidence of vaccine effectiveness in preventing HPV-related cancers. Digital interventions (e.g., serious games) may improve HPV vaccine uptake, but evidence for effects on vaccination behavior remains limited. Methods: [...] Read more.
Background/Objectives: Human papillomavirus (HPV) vaccination coverage among adolescents remains below public health targets despite strong evidence of vaccine effectiveness in preventing HPV-related cancers. Digital interventions (e.g., serious games) may improve HPV vaccine uptake, but evidence for effects on vaccination behavior remains limited. Methods: This secondary analysis of a randomized controlled trial evaluated a co-designed, game-based digital intervention to increase HPV vaccine initiation among unvaccinated youth aged 11–14 years and their parents. The sample included 64 parent–adolescent dyads (33 intervention and 31 usual care dyads). The primary outcome was HPV vaccine initiation at 2-month follow-up. Results: A significantly greater proportion of adolescents in the intervention group initiated HPV vaccination compared with controls (88.5% vs. 46.2%; χ2(1) = 10.58, p = 0.001; risk difference = 0.423, 95% CI = [0.196, 0.650]). No significant between-group baseline differences were observed in parent HPV vaccination intention, knowledge, or psychosocial perceptions, although adolescent vaccination intention was higher in the intervention group. In adjusted logistic regression controlling for adolescent baseline HPV vaccination intention, intervention participants remained significantly more likely to initiate vaccination than controls (OR = 9.31, 95% CI = 2.13–40.70, p = 0.003). Intervention acceptability was high, with most parents and adolescents reporting that the game was easy to use, engaging, and relevant to vaccination decision-making. Conclusions: These findings provide preliminary evidence that a brief, family-centered, game-based digital intervention may help increase HPV vaccination initiation among adolescents. Larger trials with longer follow-up are needed to assess vaccine series completion and effectiveness across diverse settings. Full article
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22 pages, 893 KB  
Systematic Review
Circulating Biomarkers in Localized Anal Squamous Cell Carcinoma Across Treatment Timepoints: A Systematic Review
by Oluwatayo Adeoye, Abdulsabur Sanni, Khujasta Gul, Jakob Hamilton, Ahmed A. Abdelhakeem, Michael Rutenberg, Zhaohui Jin, Umair Majeed, Jeremy C. Jones and Conor D. O’Donnell
Cancers 2026, 18(10), 1626; https://doi.org/10.3390/cancers18101626 - 18 May 2026
Viewed by 383
Abstract
Background/Objectives: Locoregional anal squamous cell carcinoma (ASCC) is usually cured with chemoradiotherapy; however, some patients relapse, require salvage abdominoperineal resection or develop metastatic disease. Approximately 90% of cases are driven by high-risk human papillomavirus, most commonly HPV16. Conventional surveillance using clinical examination and [...] Read more.
Background/Objectives: Locoregional anal squamous cell carcinoma (ASCC) is usually cured with chemoradiotherapy; however, some patients relapse, require salvage abdominoperineal resection or develop metastatic disease. Approximately 90% of cases are driven by high-risk human papillomavirus, most commonly HPV16. Conventional surveillance using clinical examination and imaging may have limited sensitivity and specificity and is not individualized by recurrence risk. Circulating biomarkers (CBs), particularly circulating tumor DNA (ctDNA), have emerged as promising methods for real-time disease monitoring. We systematically reviewed available evidence evaluating CBs across treatment timepoints in localized ASCC. Methods: A PROSPERO-registered review (ID: 1133987) was conducted according to PRISMA guidelines. PubMed, EMBASE, Cochrane CENTRAL, Web of Science, and major conference proceedings (ASCO, ESMO, ASTRO) were searched on 30 November 2025. We included prospective or retrospective studies (≥10 patients) with stage I–III disease treated with curative-intent chemoradiotherapy that reported CBs, assay characteristics, and at least one clinical outcome. Studies with predominantly localized cohorts were included even if small proportions of metastatic patients were present, provided results relevant to curative-intent populations could be interpreted. Data were synthesized narratively by timepoint (baseline, mid-treatment, end of treatment, post-treatment/surveillance) and assay type given methodological heterogeneity. Results: Fifteen studies were included. CB assays comprised four categories: viral HPV ctDNA assays, tumor-informed ctDNA assays, non-specific total cell-free DNA (cfDNA) quantification, and circulating tumor cell (CTC)-based assays. Baseline detection rates varied by assay type. Viral HPV ctDNA assays demonstrated detection rates of 59–100%, while tumor-informed ctDNA assays showed rates of 79–89%. Across studies, higher CB detection rates and levels were generally associated with greater tumor burden, including more advanced T and N stage disease. Mid-treatment ctDNA clearance identified patients with excellent locoregional control and progression-free survival, whereas persistent ctDNA was associated with treatment failure. End-of-treatment and surveillance ctDNA positivity predicted recurrence within individual cohorts, with reported sensitivities of 80–90%, specificities of 95–99%, and molecular lead times preceding clinical or radiographic detection. In contrast, non-tumor-specific cfDNA dynamics showed more variable prognostic associations and were less consistently linked to tumor burden. Conclusions: Across heterogeneous assays, CB dynamics provide clinically meaningful prognostic information in localized ASCC, particularly when measured during treatment and early surveillance. Viral HPV and tumor-informed ctDNA may have the potential to guide follow-up intensity and inform future escalation or de-escalation strategies; however, prospective, standardized trials are needed to define actionable thresholds and test ctDNA-guided management. Full article
(This article belongs to the Special Issue Circulating Tumour DNA and Liquid Biopsy in Oncology)
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13 pages, 1112 KB  
Article
Koilocytosis in LSIL Cytology Has Limited Predictive Value for CIN2+ in HPV-Positive Women: Implications for Risk-Based Cytology Triage
by Yukimi Misawa, Shuichi Mizuno, Saeka Honda, Ruku Shinohara, Koki Kikuchi, Rei Settsu, Kaori Okayama, Masahiko Fujii, Mizue Oda and Mitsuaki Okodo
Pathogens 2026, 15(5), 537; https://doi.org/10.3390/pathogens15050537 - 15 May 2026
Viewed by 275
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Human Papillomavirus Infection and Its Role in Carcinogenesis)
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11 pages, 561 KB  
Systematic Review
Prevalence and Risk Factors of Potentially Malignant Oral Lesion in Prison Population: A Systematic Review
by Erika Roncarati, Saverio Ceraulo, Antonio Barbarisi, Gianluigi Caccianiga, Francesco Carinci and Dorina Lauritano
Dent. J. 2026, 14(5), 302; https://doi.org/10.3390/dj14050302 - 14 May 2026
Viewed by 204
Abstract
Background: Potentially malignant oral disorders (OPMDs) and oral carcinomas represent a significant oncological concern in incarcerated populations, where multiple modifiable risk factors such as tobacco use, illicit drug consumption, oncogenic human papillomavirus infections, and poor oral hygiene coexist with limited access to preventive [...] Read more.
Background: Potentially malignant oral disorders (OPMDs) and oral carcinomas represent a significant oncological concern in incarcerated populations, where multiple modifiable risk factors such as tobacco use, illicit drug consumption, oncogenic human papillomavirus infections, and poor oral hygiene coexist with limited access to preventive and routine dental care. This combination may increase the risk of delayed diagnosis and malignant transformation. Objective: This PRISMA-compliant systematic review aimed to evaluate the prevalence of OPMDs and associated risk factors in prison populations, with a particular focus on identifying gaps in the current evidence. Methods. A systematic literature search was conducted in PubMed, Scopus and Cochrane Library using predefined search strategies. The final search yielded 24 records, which were screened according to PRISMA 2020 guidelines. After title and abstract screening, 10 full-text articles were assessed for eligibility, and 5 cross-sectional studies were included in the qualitative synthesis following independent review. Results: The included studies revealed a substantial burden of oral mucosal lesions in incarcerated populations. Premalignant lesions were reported in a significant proportion of inmates, with oral submucous fibrosis particularly prevalent in some cohorts. Additionally, a high prevalence of oral high-risk HPV infection and widespread oral manifestations were observed. Tobacco use, often combined with betel quid, alcohol, or illicit drugs, emerged as the primary and consistently associated risk factor for oral lesions. Conclusions: Prison populations appear to represent a high-risk group for OPMDs due to the combined effect of behavioral and structural risk factors. However, the limited number of available studies, their cross-sectional design, and methodological heterogeneity prevent definitive conclusions. Further longitudinal and methodologically robust studies are needed to better define prevalence patterns and support targeted screening and prevention strategies in correctional settings. Full article
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20 pages, 1968 KB  
Review
Squamous Cancers and Precancers of the Vulva: Emerging Diagnostic, Prognostic and Predictive Biomarkers in Pathology
by Somayah Alsolami, Jennifer Ji and Lynn Hoang
Cancers 2026, 18(10), 1518; https://doi.org/10.3390/cancers18101518 - 8 May 2026
Viewed by 359
Abstract
Vulvar squamous cell carcinoma (VSCC) and its precursor lesions are relatively rare malignancies of the gynecologic tract. In recent years, international organizations and pathologic reporting guidelines endorse the subdivision of VSCC into human papillomavirus (HPV)-associated and HPV-independent types. There is also growing evidence [...] Read more.
Vulvar squamous cell carcinoma (VSCC) and its precursor lesions are relatively rare malignancies of the gynecologic tract. In recent years, international organizations and pathologic reporting guidelines endorse the subdivision of VSCC into human papillomavirus (HPV)-associated and HPV-independent types. There is also growing evidence for the further separation of HPV-independent into p53 abnormal and p53 wild-type cancers. Although the diagnosis and subclassification of VSCC is often straightforward, using immunohistochemical markers such as p16 and p53 as surrogate markers for high-risk HPV infection and TP53 mutation respectively, rare and unusual scenarios exist that can complicate VSCC classification. Herein we discuss these challenging scenarios in VSCC classification, as well as emerging VSCC prognostic biomarkers such as cyclin D1. In addition, the pathologic diagnosis of VSCC precursor lesions, particularly those of HPV-independent type, are frequently challenging to distinguish from benign conditions of the vulva. We discuss the recent literature describing the added diagnostic value of immunohistochemical biomarkers p53, CK17, CK13, SOX2, GATA3, GLUT1 and others, which may be particularly helpful when morphology is inconclusive. It is anticipated that with improved VSCC classification and precursor recognition, avenues for more tailored therapeutic strategies and earlier therapeutic intervention can be achieved. Full article
(This article belongs to the Special Issue Prognostic and Predictive Markers in Gynecological Cancers)
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17 pages, 818 KB  
Article
Circulating microRNA Profiles as Diagnostic Tools for High-Grade Cervical Lesions and HPV Genotype Stratification
by Annika Tamenang, Vanessa Vohl, Charlotte Schwartz, Jolanthe Kropidlowski, Anna Jaeger, Katharina Hintelmann, Eik Vettorazzi, Yvonne Goy, Cordula Petersen, Sven Peine, Klaus Pantel, Barbara Schmalfeldt, Linn Woelber, Harriet Wikman and Katharina Effenberger
Cells 2026, 15(9), 849; https://doi.org/10.3390/cells15090849 - 6 May 2026
Viewed by 410
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Cellular and Molecular Insights into Gynecologic Tumors)
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13 pages, 472 KB  
Article
The Influence of Sexually Transmitted Bacteria and Human Papillomavirus on Sperm Parameters: Data from a Preliminary Study
by Maria Samara, Eleni Thodou, Christina Messini, Efthalia Moustakli, Maria Anagnostou, Athanasios Zikopoulos, Alexandros Daponte, Ioannis Georgiou and George Anifandis
Medicina 2026, 62(5), 874; https://doi.org/10.3390/medicina62050874 - 3 May 2026
Viewed by 255
Abstract
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 [...] Read more.
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
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13 pages, 1070 KB  
Communication
Clinical Implications of p16 Evaluation in a Purposively Sampled Cohort of High-Risk Breast Cancer Phenotypes
by Sorana Caterina Anton, Alin Horațiu Nedelcu, Carmen Rodica Anton, Ionela Daniela Morariu, Ancuța Lupu, Gabriel Dăscălescu, Alin Ciobîcă, Vasile Valeriu Lupu, Anton Knieling, Dragoș Valentin Crauciuc, Carp Eduard, Mihaela Tirnovanu, Iurie Dondiuc, Ciprian Ilea and Emil Anton
Int. J. Mol. Sci. 2026, 27(9), 4097; https://doi.org/10.3390/ijms27094097 - 3 May 2026
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Abstract
The overexpression of cyclin-dependent kinase inhibitor p16 (INK4a) is widely recognized as a surrogate marker for high-risk human papillomavirus (HPV) in anogenital malignancies, but its significance in invasive breast carcinoma is complex and remains frequently debated. While historically investigated as a viral proxy, [...] Read more.
The overexpression of cyclin-dependent kinase inhibitor p16 (INK4a) is widely recognized as a surrogate marker for high-risk human papillomavirus (HPV) in anogenital malignancies, but its significance in invasive breast carcinoma is complex and remains frequently debated. While historically investigated as a viral proxy, emerging evidence suggests that elevated p16 levels in breast tissue may instead reflect intrinsic cell-cycle dysregulation and retinoblastoma (Rb) pathway disruption, though direct molecular confirmation is lacking in this area of research. This study aims to evaluate the role of p16 as an indicator of tumor aggressiveness for high-risk phenotypes. We conducted a retrospective study of 100 female patients with invasive breast carcinoma. Employing a purposive sampling strategy rather than a consecutive series, we analyzed a targeted cohort consisting predominantly of triple-negative breast cancer (TNBC) and high-grade tumors to evaluate biomarker patterns specifically in advanced disease contexts. Immunohistochemical assessment was performed using a standardized cumulative nuclear and cytoplasmic scoring system, with expression thresholds defined by receiver operating characteristic (ROC) curve analysis optimized for histological grade. p16 overexpression was a predominant characteristic of these aggressive tumors and was identified in 68% of cases. Statistical evaluation revealed a robust and significant correlation between p16 overexpression and the triple-negative molecular subtype, as well as a marked inverse relationship with estrogen receptor (ER) status. Although p16 levels were frequently associated with specific aggressive phenotypes, no statistically significant difference in overall survival was observed between expression groups, a finding attributable to the uniformly high-risk nature of the selected cohort. This study suggests an association between p16 expression levels and aggressive tumor features, although the study design limits causal inferences. A non-significant trend towards p16 overexpression was observed in ductal carcinomas compared to lobular subtypes, while high p16 expression was noted exclusively in G3 tumors within this selected cohort, a finding influenced by the purposive sampling strategy and the ROC-based cutoff definition. Tumor necrosis was more prevalent in p16-overexpressing tumors. Furthermore, p16 levels showed a strong inverse relationship with estrogen receptor (ER) status, as they were significantly elevated in ER-negative and triple-negative tumors compared to luminal phenotypes. Full article
(This article belongs to the Section Molecular Oncology)
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25 pages, 7238 KB  
Article
Genome-Wide DNA Methylation Profiling Reveals Ancestry-Associated Epigenetic Reprogramming in Cervical Intraepithelial Neoplasia
by Mohamed Masoud, Charu Shastri, Rajarshi Banerjee, Saanvi Dasgupta, Hector Chavarria-Bernal, Karan P. Singh, Jennifer Y. Pierce and Santanu Dasgupta
Int. J. Mol. Sci. 2026, 27(9), 3986; https://doi.org/10.3390/ijms27093986 - 29 Apr 2026
Viewed by 480
Abstract
Cervical cancer (CC) is an alarming global health problem, with predominantly higher incidence, lethal progression, and mortality among women of African ancestry (AA) than women of European ancestry (EA). Although persistent high-risk human papillomavirus (HPV) integration and infection are the key etiological factors, [...] Read more.
Cervical cancer (CC) is an alarming global health problem, with predominantly higher incidence, lethal progression, and mortality among women of African ancestry (AA) than women of European ancestry (EA). Although persistent high-risk human papillomavirus (HPV) integration and infection are the key etiological factors, currently available evidence implicates epigenetic reprogramming as a prime contributor to ancestry-associated differences in CC pathogenesis. To address these disparities, we performed genome-wide DNA methylation profiling of HPV-positive cervical intraepithelial neoplasia (CIN) lesions from AA (n = 15) and EA (n = 15) women. Differential methylation analysis identified a distinct epigenomic landscape in AA-CIN lesions, with widespread hypermethylation and hypomethylation at promoter-associated and regulatory CpG sites. Pathway enrichment analyses highlighted dysregulation of ECM-receptor interaction, focal adhesion, PI3K-Akt, MAPK, Ras, Rap1, and RUNX-dependent transcriptional networks. Comparative analysis across CIN grades (CIN1–CIN3) revealed progressive epigenetic reprogramming affecting cell cycles, cytoskeletal dynamics, signaling, and metabolic pathways. Among hypermethylated tumor suppressor genes, SH3GL2 and ARHGAP25 showed significantly higher methylation in AA lesions, accompanied by concomitant loss of their protein expression. MBD1, a methylation-binding regulator, was upregulated in AA-CIN lesions, coinciding with global loss of 5-hydroxymethylcytosine (5hmC), suggesting enhanced transcriptional repression. In contrast, EA lesions retained protein expression and 5hmC levels. Collectively, these findings indicate that early, ancestry-specific epigenetic modifications target tumor suppressor pathways and converge on oncogenic signaling, cytoskeletal remodeling, and cell–cell adhesion. Our study provides mechanistic insight into CC health disparities, identifying SH3GL2 and ARHGAP25 hypermethylation as potential biomarkers, and highlighting epigenetic regulation as a contributor to disparate CC progression in AA women. Full article
(This article belongs to the Special Issue New Advances in Cervical Cancer and Its Therapy)
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