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Search Results (1,903)

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Keywords = human papillomavirus (HPV)

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12 pages, 235 KB  
Article
Factors Associated with Recommendation of Non-Routine Childhood Vaccines Among Healthcare Workers in Türkiye
by Asiye Burcu Kuş, Adnan Barutçu and Sena Kara Öncü
Vaccines 2026, 14(8), 670; https://doi.org/10.3390/vaccines14080670 (registering DOI) - 2 Aug 2026
Abstract
Background: Healthcare workers play a critical role in parental vaccine decision-making and the uptake of non-routine childhood vaccines. This study aimed to evaluate healthcare workers’ knowledge, attitudes and behaviors regarding non-routine childhood vaccines, including rotavirus, meningococcal, human papillomavirus (HPV) and influenza vaccines. Methods: [...] Read more.
Background: Healthcare workers play a critical role in parental vaccine decision-making and the uptake of non-routine childhood vaccines. This study aimed to evaluate healthcare workers’ knowledge, attitudes and behaviors regarding non-routine childhood vaccines, including rotavirus, meningococcal, human papillomavirus (HPV) and influenza vaccines. Methods: This cross-sectional study was conducted between October 2025 and March 2026 among healthcare workers in Türkiye. Data were collected using a structured questionnaire and the Attitudes Towards Vaccine Scale (ATVS), distributed through convenience and snowball sampling methods. Results: A total of 345 healthcare workers participated in the study. Recommendation behaviors differed significantly according to vaccine type (p < 0.001). Rotavirus and meningococcal vaccines were more frequently recommended than HPV and influenza vaccines. Although influenza vaccine had the highest awareness rate, it demonstrated the lowest recommendation rate and the lowest support for inclusion in the national immunization schedule. Physicians had significantly higher knowledge levels and vaccination attitude scores than non-physician healthcare workers (p < 0.001). ATVS scores were positively correlated with recommendation behaviors (ρ = 0.35, p < 0.001) and self-vaccination tendency (ρ = 0.34, p < 0.001). In multivariable analyses, higher vaccination attitude scores independently predicted greater self-vaccination tendency (OR = 1.07, 95% CI: 1.04–1.11, p < 0.001). Cost was the most commonly reported barrier to vaccine implementation. Conclusions: Positive attitudes toward non-routine childhood vaccines among healthcare workers do not necessarily translate into consistent recommendation behaviors across all vaccine types. Strategies targeting healthcare worker education, equitable vaccine access and standardized vaccine counseling practices may improve uptake and recommendation of optional childhood vaccines in Türkiye. Full article
(This article belongs to the Section Vaccines and Public Health)
11 pages, 243 KB  
Article
Clinical Significance of Vulvar Condyloma as a Marker of Concurrent High-Risk Cervical HPV Infection and Abnormal Cervical Cytology
by Eda Güner Özen, Süleyman Özen, Özgün Akbaş, Ahkam Göksel Kanmaz and Yaşam Kemal Akpak
Diagnostics 2026, 16(15), 2439; https://doi.org/10.3390/diagnostics16152439 (registering DOI) - 2 Aug 2026
Abstract
Background/Objectives: Human papillomavirus (HPV) infection is the principal etiological factor in cervical cancer and its precursor lesions. Although vulvar condyloma is typically associated with low-risk HPV types, high-risk HPV genotypes may coexist. This study evaluated the association between vulvar condyloma, cervical cytological abnormalities, [...] Read more.
Background/Objectives: Human papillomavirus (HPV) infection is the principal etiological factor in cervical cancer and its precursor lesions. Although vulvar condyloma is typically associated with low-risk HPV types, high-risk HPV genotypes may coexist. This study evaluated the association between vulvar condyloma, cervical cytological abnormalities, high-risk HPV positivity, and cervical histopathological outcomes. Methods: This retrospective observational study included 407 women evaluated at the Department of Obstetrics and Gynecology, Izmir City Hospital, between January 2025 and January 2026. Patients underwent cervical cytology, HPV testing, vulvar examination, and colposcopic biopsy when clinically indicated. Patients were categorized according to the presence or absence of histopathologically confirmed vulvar condyloma. Logistic regression analyses were performed to identify factors associated with vulvar condyloma. Results: Vulvar condyloma was identified in 180 patients (44.2%). Abnormal cervical cytology was recorded in 66/180 patients (36.7%) with vulvar condyloma and 41/227 patients (18.1%) without condyloma (p < 0.001). High-risk HPV positivity was observed in 104/180 (57.8%) and 86/227 (37.9%) patients, respectively (p < 0.001). In multivariate analysis, adjusted ORs were 2.30 for HPV16 positivity (95% CI 1.36–3.89, p = 0.002), 3.29 for HPV18 positivity (95% CI 1.40–7.73, p = 0.006), and 2.01 for abnormal cervical cytology (95% CI 1.24–3.25, p = 0.005). Recorded CIN2+ was 15/180 (8.3%) in the condyloma-positive group and 7/227 (3.1%) in the condyloma-negative group in the overall cohort; in the biopsy-restricted analysis, CIN2+ was 15/82 (18.3%) and 7/41 (17.1%), respectively. Conclusions: Vulvar condyloma was independently associated with abnormal cervical cytology and high-risk HPV infection, particularly HPV16/18 positivity. These robust associations suggest that vulvar condyloma may represent a clinically visible marker of concurrent cervical HPV-related disease. Careful cervical evaluation is warranted in women presenting with vulvar condyloma, whereas CIN2+ findings should be interpreted cautiously until confirmed in larger prospective cohorts with standardized histopathological verification. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
16 pages, 577 KB  
Article
The Role of Adjuvant Nonavalent HPV Vaccination After LLETZ in Patients with Isolated CIN2: A Controlled Cohort Study
by Vincenzo Pinto, Miriam Dellino, Marco Cerbone, Edoardo Di Naro, Achiropita Lepera, Silvio Tafuri, Gerardo Cazzato and Ettore Cicinelli
Pathogens 2026, 15(8), 814; https://doi.org/10.3390/pathogens15080814 (registering DOI) - 1 Aug 2026
Abstract
Background: Women treated for cervical intraepithelial neoplasia grade 2 (CIN2) face an increased risk of disease recurrence due to persistent or newly acquired human papillomavirus (HPV) infections, suggesting a potential role for adjuvant HPV vaccination. While a growing body of literature evaluates the [...] Read more.
Background: Women treated for cervical intraepithelial neoplasia grade 2 (CIN2) face an increased risk of disease recurrence due to persistent or newly acquired human papillomavirus (HPV) infections, suggesting a potential role for adjuvant HPV vaccination. While a growing body of literature evaluates the outcomes of HPV vaccination following a large loop excision of the transformation zone (LLETZ) for high-grade squamous intraepithelial lesions (CIN2–3), data specifically focused on isolated CIN2 remain limited. This study aims to evaluate the clinical efficacy of the nonavalent HPV vaccine (9vHPV) as an adjuvant strategy to reduce CIN2+ recurrence in women undergoing LLETZ for histologically confirmed, isolated CIN2. Methods: Between November 2017 and November 2024, women undergoing LLETZ for histologically confirmed CIN2 received their first dose of adjuvant 9vHPV within one month of surgery. Patients who achieved double-negative co-testing (Pap test and high-risk HPV DNA test) at the 6-month post-LLETZ follow-up were included in the study group. Conversely, patients with at least one positive test result at 6 months were excluded to rule out residual disease. The study group underwent a subsequent Pap smear at 12 months and a full co-test at 18 months post-surgery; upon achieving negative results through the 18th month, patients returned to the organized screening program. The primary outcome was the recurrence rate, defined as histologically confirmed CIN2+ occurring more than 6 months post-treatment. It was compared against an unvaccinated historical control group treated with LLETZ prior to the study period. The secondary outcome evaluated the prevalence of HPV genotypes at baseline and at the time of recurrence. Results: In the vaccinated group, 3 women (2.03%) experienced CIN2+ recurrence compared to 6 women (5.71%) in the unvaccinated control group. This represents an absolute risk difference of 3.69% and a relative risk reduction of 64.6%, though the difference did not reach statistical significance via Fisher’s exact test (p = 0.165). In the study group, two recurrences were detected at 18 months (associated cytologies: ASC-H and LSIL; genotypes: HPV 51/53 and 16, respectively) and one at four years (cytology: HSIL; genotype: HPV 33/58). In the control group, recurrences occurred at 12 months (n = 3), 18 months (n = 2), and four years (n = 1). Associated cytology revealed HSIL in three cases, ASC-H in one case, LSIL in one case, and ASCUS in the final case. The corresponding HPV genotypes were 16 (two cases), 18, 51, 31 and 56 (co-infection), and one case of high-risk HPV, not further genotyped. Conclusions: Adjuvant 9vHPV administration after LLETZ for isolated CIN2 was associated with a clinically substantial lower absolute recurrence rate (2.03% vs. 5.71%, corresponding to a 64.6% relative risk reduction). Although this reduction did not achieve statistical significance (p=0.165) due to our small sample size and a low baseline recurrence rate in this isolated cohort, the effect size is highly comparable to broader CIN2+ studies. The study was likely underpowered to prove statistical significance, and larger multi-center studies are required to confirm the statistical value of adjuvant vaccination specifically in isolated CIN2 lesions. Full article
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17 pages, 988 KB  
Review
The Role of Sex Hormone Receptors in the Squamous Cell Carcinoma of the Uterine Ectocervix: A Review and Future Directions
by Mun-Kun Hong and Dah-Ching Ding
Diagnostics 2026, 16(15), 2424; https://doi.org/10.3390/diagnostics16152424 - 31 Jul 2026
Viewed by 77
Abstract
Cervical cancer (CxCa) remains a major global gynecological malignancy causally linked to high-risk human papillomavirus (HPV) infection. However, HPV alone is insufficient for carcinogenesis; sex hormones and their receptors serve as essential cofactors. This review aims to synthesize current knowledge on the role [...] Read more.
Cervical cancer (CxCa) remains a major global gynecological malignancy causally linked to high-risk human papillomavirus (HPV) infection. However, HPV alone is insufficient for carcinogenesis; sex hormones and their receptors serve as essential cofactors. This review aims to synthesize current knowledge on the role of cervical histoarchitecture and hormonal microenvironments in ectocervical squamous cell carcinoma (SCC), and to explore how receptor-mediated signals contribute to malignant transformation and metastatic spread. The review examines the expression patterns of estrogen receptor α (ERα) and progesterone receptor (PR) in the uterine cervix, which is a hormone-responsive tissue. It discusses how these receptors fluctuate throughout the menstrual cycle and evaluates evidence from HPV-transgenic mouse models and human tissue analyses. The findings converge on a compelling model: stromal ERα drives pro-carcinogenic paracrine signaling, epithelial PR suppresses neoplastic transformation, and stromal PRB confers antimetastatic protection. These insights highlight the complex interplay between hormonal signals and SCC development in the ectocervix. Future therapeutic exploitation of these mechanistic insights—including selective estrogen receptor modulators, selective progesterone receptor modulators, and PR status-guided chemoprevention—holds considerable promise. This review provides a coherent framework for translating laboratory findings into clinical diagnostics and targeted interventions. Full article
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27 pages, 1670 KB  
Review
Basic Clinical Bidirectional Empowerment: Synergistic Breakthrough in Molecular Mechanisms and Clinical Management of Small Cell Cervical Carcinoma
by Mengjia Huang and Shuang Li
Int. J. Mol. Sci. 2026, 27(15), 6783; https://doi.org/10.3390/ijms27156783 - 29 Jul 2026
Viewed by 126
Abstract
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 [...] Read more.
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
(This article belongs to the Section Molecular Genetics and Genomics)
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49 pages, 2747 KB  
Review
Immunological Determinants of Oncogenic Virus-Driven Cancers in Africa: Mechanisms, Co-Infections and Public Health Challenges
by Victor Ayodele Aliyu, Olalekan Chris Akinsulie, Babatunde Ibrahim Olowu, Ibrahim Idris, Favour Akinfemi Ajibade, Pius I. Babawale, Oluwawemimo Adebowale, Charles Egede Ugwu, Chizaram Blessing Ukauwa, Onyedikachi Emmanuel Itumo, Peter Arinze Oge, Sammuel Shahzad, Chizobam Lilian Chukwu, Toyin Florence Ayandokun, Joy Taiye Aliyu, Peace Kehinde Aliyu, Jesuferanmi Mary Akinsulie, Muhammad Ipoola Adeyemi and Olamilekan Gabriel Banwo
Pathogens 2026, 15(8), 800; https://doi.org/10.3390/pathogens15080800 - 28 Jul 2026
Viewed by 205
Abstract
Oncogenic viruses contribute to approximately 20% of human cancers globally, with their impact falling disproportionately on populations in Sub-Saharan Africa. In this region, cervical cancer, hepatocellular carcinoma, endemic Burkitt lymphoma, and Kaposi sarcoma represent major causes of cancer-related morbidity and mortality, driven by [...] Read more.
Oncogenic viruses contribute to approximately 20% of human cancers globally, with their impact falling disproportionately on populations in Sub-Saharan Africa. In this region, cervical cancer, hepatocellular carcinoma, endemic Burkitt lymphoma, and Kaposi sarcoma represent major causes of cancer-related morbidity and mortality, driven by persistent infection with human papillomavirus (HPV), hepatitis B and C viruses (HBV/HCV), Epstein–Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), and human T-lymphotropic virus-1 (HTLV-1). This review synthesizes current insights into the immunological mechanisms that underpin viral carcinogenesis in Africa, emphasizing how defective viral clearance, chronic immune activation, and immune evasion arise from the convergence of region-specific co-infections, host genetic diversity, and environmental exposures. We examine the mechanistic roles of HIV-associated CD4+ T cell depletion, malaria-induced perturbation of antiviral T cell immunity, helminth-driven T helper 2 polarization, and tuberculosis-associated inflammatory signaling in promoting viral persistence and malignant transformation. In addition, the influence of the extensive diversity of African human leukocyte antigens (HLA) and cytokine gene polymorphisms on antiviral immune responses and cancer susceptibility was discussed. We also assessed how virus-associated tumors establish profoundly immunosuppressive microenvironments characterized by impaired antigen presentation and the dominance of immune checkpoint pathways. Finally, we examined how gaps in vaccination, screening, and diagnostic capacity intersect with immunological vulnerability across Africa, contributing to the burden of infection-associated cancers. These challenges position Africa as a critical setting for developing targeted, genotype-inclusive public health interventions and reducing global cancer disparities through advances in immunoprevention and immunotherapy. Full article
(This article belongs to the Section Viral Pathogens)
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18 pages, 531 KB  
Article
A Tale of Two Cohorts: Comparing HPV Vaccination Barriers and Facilitators Among HIV-Negative and HIV-Positive Women in Tennessee
by Alina Cernasev, Karissa Cliff, Emily Nagel, Hunter Smith, Alex Johnson and Tracy M. Hagemann
Int. J. Environ. Res. Public Health 2026, 23(8), 977; https://doi.org/10.3390/ijerph23080977 - 28 Jul 2026
Viewed by 190
Abstract
Background: Human papillomavirus (HPV) continues to cause an estimated 4000 preventable cancer deaths each year in the United States. Given the prevalence of HPV-related disease and suboptimal vaccination rates, this study explores perceptions of HPV vaccination among HIV-negative females and females living with [...] Read more.
Background: Human papillomavirus (HPV) continues to cause an estimated 4000 preventable cancer deaths each year in the United States. Given the prevalence of HPV-related disease and suboptimal vaccination rates, this study explores perceptions of HPV vaccination among HIV-negative females and females living with HIV in Tennessee. Methods: This prospective, observational qualitative study consisted of narrative interviews which were conducted with HIV-negative and HIV-positive participants, focusing on their perceptions of HPV and its vaccine. Interviews were conducted by phone, and the verbatim transcripts were inductively coded by three researchers. The inductive codes were then grouped into categories based on similarities which facilitated the emergence of themes. Results: A total of 40 participants were interviewed between July 2024 and December 2024. Narrative analysis revealed three themes: (1) “I had never heard of it until I saw the flier.” Gaps in Understanding of HPV and Its Health Implications, (2) Navigating Adolescent Health Decisions and Emotional Influence, and (3) Barriers to Uptake—Skepticism, Trust, and the Need for Tailored Information. Two subthemes emerged: Cohort-Specific Skepticism, and Parental Influence and Communication Gaps. Conclusions: This study revealed significant gaps in HPV knowledge and vaccination uptake among HIV-negative women and women living with HIV in Tennessee. Provider communication was key to vaccine decisions, but clear recommendations were often missed in clinical encounters. Full article
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20 pages, 6118 KB  
Article
HPV16 E7-Associated SERPINB3 Suppression and MYC-Related Epithelial Plasticity in Head and Neck Squamous Cell Carcinoma
by Zengchen Liu, Siwei Zhang, Tianyang Liu, Yanjing Li, Rui Li, Huan Liu, Dongcun Wang, Yunyan Tang, Heng Ma, Yuting Zhang, Lanlan Wei and Ming Chu
Cancers 2026, 18(15), 2420; https://doi.org/10.3390/cancers18152420 - 27 Jul 2026
Viewed by 762
Abstract
Background: Human papillomavirus (HPV) infection defines a distinct subtype of head and neck squamous cell carcinoma (HNSCC). Although HPV-positive (HPV+) HNSCC generally shows better overall survival than HPV-negative (HPV−) disease, it is frequently associated with cervical lymph node metastasis. However, the epithelial cell [...] Read more.
Background: Human papillomavirus (HPV) infection defines a distinct subtype of head and neck squamous cell carcinoma (HNSCC). Although HPV-positive (HPV+) HNSCC generally shows better overall survival than HPV-negative (HPV−) disease, it is frequently associated with cervical lymph node metastasis. However, the epithelial cell states and viral gene-associated mechanisms underlying HPV−related metastatic progression remain incompletely understood. This study aimed to identify metastasis-associated epithelial subpopulations in HPV+ HNSCC and explore the potential role of HPV16 E7 in regulating metastatic programs. Methods: Public single-cell RNA-sequencing datasets from paired primary and metastatic HNSCC samples were integrated and analyzed to characterize malignant epithelial subpopulations. Copy number variation (CNV) inference, clustering, pathway enrichment, stemness scoring, and trajectory analysis were performed to define metastasis-associated epithelial states. TCGA transcriptomic data and tissue-based validation were used to support candidate gene screening. In vitro functional assays were performed using SERPINB3-knockdown and HPV16 early gene-overexpressing CAL27 cell models. Results: Single-cell analysis identified stem-like metastatic epithelial subpopulations in HPV+ and HPV− HNSCC. In HPV+ metastatic lesions, an ALDH2+/LAMB3+ epithelial subpopulation showed elevated epithelial–mesenchymal transition activity and stem-like features. SERPINB3 displayed a dynamic expression pattern during HPV+ metastatic progression. Functional assays showed that SERPINB3 knockdown enhanced CAL27 cell migration and invasion and was associated with activation of MYC- and epithelial–mesenchymal transition-related transcriptional programs. Among HPV16 early genes, E5, E6, E6*, and E7 showed different degrees of SERPINB3 suppression, while E7-expressing cells exhibited distinct transcriptional alterations associated with epithelial plasticity and metastatic-related programs. Conclusions: This study identifies a stem-like metastatic epithelial state in HPV-associated HNSCC and suggests a potential HPV16 early gene-SERPINB3-MYC-related regulatory mechanism involved in metastatic epithelial plasticity. Full article
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20 pages, 1885 KB  
Article
Proteomic Analysis of TCGA Data Reveals Limited Prognostic Value of p53 but Suggests BAX as a Potential Survival Marker in Cervical Carcinoma
by Sebastian M. Toennießen-Klein, Dennis Rangno, Abhirami Sunil, Maria Bozko and Przemyslaw Bozko
Int. J. Mol. Sci. 2026, 27(15), 6717; https://doi.org/10.3390/ijms27156717 - 27 Jul 2026
Viewed by 160
Abstract
Cervical carcinoma is predominantly driven by high-risk human papillomavirus (HPV) infection, in which functional inactivation of p53 occurs mainly through viral oncoproteins rather than mutations in the TP53 gene. This raises questions concerning the prognostic relevance of TP53 gene status and p53 protein [...] Read more.
Cervical carcinoma is predominantly driven by high-risk human papillomavirus (HPV) infection, in which functional inactivation of p53 occurs mainly through viral oncoproteins rather than mutations in the TP53 gene. This raises questions concerning the prognostic relevance of TP53 gene status and p53 protein levels in this tumor type. This study aimed to systematically evaluate the prognostic significance of TP53 mutation status, p53 protein abundance, and selected downstream p53-regulated proteins in cervical carcinoma, with particular focus on tumors carrying wild-type TP53. Clinical and proteomic data from 162 cervical carcinoma patients were retrieved from The Cancer Genome Atlas (TCGA). Protein levels (p53, BAX, p21/CDKN1A, and TIGAR) were assessed using reverse-phase protein array (RPPA) data. Survival analyses were performed using Kaplan–Meier estimates with log-rank testing after stratification into quartile-based expression groups. The vast majority of tumors (~93%) harbored wild-type TP53, and the TP53 mutation status showed no association with patient survival. In tumors with wild-type TP53, p53 protein levels did not significantly correlate with overall survival, indicating a limited prognostic value. In contrast, elevated levels of the pro-apoptotic protein BAX showed a clear tendency to be associated with poorer overall and progression-free survival, suggesting BAX as a potential prognostic marker in this specific molecular context. The expression of p21/CDKN1A showed no prognostic relevance, while high TIGAR levels displayed a slight trend toward poorer survival, although without reaching statistical significance. In summary, in HPV-driven cervical carcinoma, neither the TP53 mutation status nor the p53 protein abundance reliably predict patient outcome. Instead, selected downstream effectors of p53 signaling—particularly BAX—may provide more informative prognostic insights in tumors retaining wild-type TP53. These findings highlight the importance of assessing functional outputs of p53 signaling rather than the p53 status alone in this disease context. Full article
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30 pages, 18970 KB  
Article
Molecular Insights from Differential Proteomic Profiling of Premalignant Cervical Lesions and Cervical Cancer
by Diana Laura Gonzalez-Tolentino, Olga Lilia Garibay-Cerdenares, Sergio Encarnación-Guevara, Ángel Gabriel Martínez-Batallar, Ramiro Alonso-Bastida, Jeovanis Gil, Jorge Organista-Nava, Luz del Carmen Alarcón-Romero, Marco Antonio Leyva-Vázquez and Berenice Illades-Aguiar
Pathogens 2026, 15(8), 793; https://doi.org/10.3390/pathogens15080793 - 26 Jul 2026
Viewed by 185
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Recent Advances in Human Papillomavirus Research)
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24 pages, 2697 KB  
Review
Nanomaterials for the Prevention, Detection, and Treatment of Pharyngeal Human Papillomavirus Infection: A Translational Roadmap
by Lorena Adriana Paun, Mihai Dumitru, Diana Gabriela Iacob, Oana Maria Patrascu, Daniela Vrinceanu, Rares Oanca, Alexandru-Darius Dragomir-Serboiu, Andreea Marinescu and Monica-Mihaela Cirstoiu
Materials 2026, 19(15), 3187; https://doi.org/10.3390/ma19153187 - 26 Jul 2026
Viewed by 226
Abstract
Pharyngeal infection with high-risk human papillomavirus (HPV), particularly HPV16, is biologically distinct from cervical infection because it occurs within the specialized lymphoepithelial environment of Waldeyer’s ring. This review evaluates nanoparticle materials for the prevention, detection, and treatment of pharyngeal HPV, with an emphasis [...] Read more.
Pharyngeal infection with high-risk human papillomavirus (HPV), particularly HPV16, is biologically distinct from cervical infection because it occurs within the specialized lymphoepithelial environment of Waldeyer’s ring. This review evaluates nanoparticle materials for the prevention, detection, and treatment of pharyngeal HPV, with an emphasis on structure–property–function relationships, mucosal performance, and translational feasibility. Lipid nanoparticle platforms, polymeric nanoparticle platforms, inorganic systems, and hybrid platforms are compared with respect to composition, particle size distribution, surface charge, colloidal stability, biodegradability, payload compatibility, release behavior, and manufacturing complexity. Evidence suggests that lipid and polymeric systems are the most credible near-future candidates for mucosal vaccination and localized nucleic acid delivery because they offer the best balance between controllable fabrication, analytical tractability, and biologically plausible performance in mucus-exposed tissue. By contrast, the development of inorganic theranostics and CRISPR-enabled platforms remains at an earlier stage because repeated mucosal dosing, retention in lymphoid tissue, and combined product regulation impose substantial burdens. A translational roadmap is proposed in which material selection is guided by clinically relevant quality attributes, standardized saliva- and mucus-relevant assays, human tonsil organoid testing, and early attention to manufacturability, safety, and regulatory strategy. The field is promising, but direct pharyngeal HPV data remain limited; accordingly, there is an urgent need for comparative studies that connect nanoparticle architecture to measurable outcomes such as tonsillar deposition, epithelial uptake, immune activation, and local tolerability. Full article
(This article belongs to the Section Biomaterials)
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26 pages, 3058 KB  
Article
Building Physician Capacity for HPV Vaccine Uptake in India: Mixed-Methods Implementation Outcomes of a Train-the-Trainer Model Using RE-AIM
by Ashleigh Flowers, Shaylen Foley, Swati Saxena, Sutapa Biswas, Priya Ganeshkumar, Purna Kurkure, Upendra Kinjawadekar, Sara Comstock, Nina DaSilva Batista and Meenu Anand
Vaccines 2026, 14(8), 654; https://doi.org/10.3390/vaccines14080654 - 25 Jul 2026
Viewed by 465
Abstract
Background: India accounts for one-fifth of global cervical cancer deaths, yet Human Papillomavirus (HPV) vaccination coverage remains low despite the World Health Organization (WHO) recommendations to initiate vaccination at age 9. With the national HPV vaccination campaign in 2026 and its approval [...] Read more.
Background: India accounts for one-fifth of global cervical cancer deaths, yet Human Papillomavirus (HPV) vaccination coverage remains low despite the World Health Organization (WHO) recommendations to initiate vaccination at age 9. With the national HPV vaccination campaign in 2026 and its approval for integration into India’s Universal Immunization Programme (UIP), strengthening physician knowledge, beliefs, and confidence in recommending the vaccine is critical. Methods: In 2023, the American Cancer Society and Cancer Foundation of India catalyzed two national medical societies, the Federation of Obstetric and Gynaecological Societies of India and the Indian Academy of Pediatrics, to educate physicians on HPV vaccination using a train-the-trainer (ToT) model. A mixed-methods evaluation, using the RE-AIM Framework, included pre- and post-training surveys assessing changes in knowledge, beliefs, confidence, and intent, as well as monthly engagement surveys and project reports analyzed using descriptive and inferential statistics. A fidelity assessment evaluated consistency of training delivery. Twenty in-depth interviews explored physician reactions and implementation of learnings, analyzed using a rapid approach. Results: A total of 18,206 physicians were trained. The post-training respondent group demonstrated higher HPV vaccination knowledge scores and more favorable responses in confidence, beliefs, and intent than the pre-training respondent group. The fidelity assessment demonstrated consistent delivery overall, with some variability in role play facilitation. Interviews highlighted increased physician confidence, peer knowledge sharing, and community engagement following the training. Medical societies reported strong program adoption and plans for continued efforts. Conclusions: A ToT physician training cascaded through medical societies is a feasible strategy to prepare physicians to recommend the HPV vaccine and address parental concerns at scale. Full article
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22 pages, 1339 KB  
Article
The Cervical Cancer Paradox in Eastern Europe: How Knowledge and Institutional Trust Shape HPV Vaccination Attitudes in Romania
by Ionel-Daniel Nati, Carmen Mihaela Mihu, Dan Mihu, Razvan Ciortea, Doru Diculescu, Mihaela Oancea, Carmen Bucuri, Maria Patricia Roman, Cristina Mihaela Ormindean, Viorela Suciu, Dumitru Rares Ciocoi-Pop and Andrei Mihai Malutan
Med. Sci. 2026, 14(4), 431; https://doi.org/10.3390/medsci14040431 - 25 Jul 2026
Viewed by 401
Abstract
Background: Although cervical cancer is a highly preventable malignancy, Romania continues to report critical mortality rates. This paradox is largely attributable to the suboptimal implementation of clinical guidelines and a passive, “opt-in” administrative framework. This cross-sectional study investigates the cognitive and behavioural determinants—specifically, [...] Read more.
Background: Although cervical cancer is a highly preventable malignancy, Romania continues to report critical mortality rates. This paradox is largely attributable to the suboptimal implementation of clinical guidelines and a passive, “opt-in” administrative framework. This cross-sectional study investigates the cognitive and behavioural determinants—specifically, human papillomavirus (HPV) knowledge, institutional trust in healthcare systems, and digital misinformation exposure—that modulate female attitudes toward HPV immunisation. Methods: An observational cross-sectional study was conducted between December 2025 and March 2026 across four obstetrics and gynaecology clinics. Data were collected via digital questionnaires administered to adult female patients aged 18 to 65 years. The assessment tool evaluated four primary domains: HPV knowledge, perceived vaccine safety, immunisation intention, and the degree of exposure to social media misinformation. Results: The cohort demonstrated a substantially low vaccination rate (28.6%). Statistical analysis elucidated significant positive correlations between HPV knowledge, trust in health authorities, and vaccination intention. Furthermore, reliance on official information sources strongly correlated with perceived vaccine safety. Conversely, exposure to negative online content exhibited a weak negative association with knowledge levels, yet it did not directly influence vaccination intention. Conclusions: Health literacy and institutional trust emerge as fundamental pillars for HPV vaccine acceptance. To overcome patient vaccine hesitancy, the national healthcare system must initiate a strategic paradigm shift, prioritising the neutralization of digital misinformation and transitioning from a passive model to a proactive, “opt-out” infrastructure. Full article
(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)
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18 pages, 1980 KB  
Article
HPV Genotype Landscape in Anal Squamous Cell Carcinoma Across Primary, Recurrent, and Metastatic Tumor Specimens
by Rose Seiberth, Hans Michael Kvasnicka, Tina Senff, David Brodmann, Florian Gebauer, Lars Bönicke and Daniel Gödde
Cancers 2026, 18(15), 2396; https://doi.org/10.3390/cancers18152396 - 25 Jul 2026
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Abstract
Background/Objectives: Anal squamous cell carcinoma (SCCA) is an HPV-driven malignancy with rising incidence, yet systematic HPV genotyping across recurrences and metastases is lacking. We characterized the complete HPV genotype distribution across the disease course. Methods: We retrospectively analyzed 213 tumor specimens from 136 [...] Read more.
Background/Objectives: Anal squamous cell carcinoma (SCCA) is an HPV-driven malignancy with rising incidence, yet systematic HPV genotyping across recurrences and metastases is lacking. We characterized the complete HPV genotype distribution across the disease course. Methods: We retrospectively analyzed 213 tumor specimens from 136 patients (82 female, 54 male) with histologically confirmed SCCA, spanning primary, recurrent, and metastatic disease (2009–2019 and from 2020 onwards). Patients contributed one or more specimens depending on the number of sampled disease events; specimens comprised 138 primary biopsies, 55 recurrence biopsies, 2 re-recurrence biopsies, and 18 distant metastases. HPV genotyping was conducted using a validated 28-type multiplex real-time PCR assay (Anyplex™ II HPV28, Seegene Inc.). Results: HPV DNA was detected in 179/213 specimens (84.0%; 95% CI 78.9–88.7) and 125/136 patients (91.9%; 95% CI 86.8–96.3). Across 269 HPV type detections, 24 distinct types were identified, with HPV 16 predominating both per-specimen (90.5%) and per-detection (60.2%) values. Non-HPV-16/18 high-risk types accounted for one in four high-risk detections (54/219; 24.7%; 95% CI 19.4–30.8). HPV positivity differed significantly by specimen type: 90.6% in primary biopsies versus 70.9% in recurrences (p = 0.001) and 72.2% in metastases (p = 0.038). Co-infections occurred in 24.6% of HPV-positive specimens (95% CI 18.5–31.6), with up to eight types. In metastases, the spectrum narrowed to 4 of 24 types; two harbored HPV 33 as the sole high-risk type. Conclusions: SCCA harbors a substantially broader HPV type spectrum than previously recognized. One in four high-risk detections lies beyond HPV 16/18, and high-risk types other than HPV 16 were the sole high-risk genotype detected in individual metastatic specimens. HPV positivity rates are significantly lower across specimen types, while the metastatic type spectrum converges on a few high-risk genotypes. Broad-spectrum HPV genotyping beyond types 16 and 18 warrants adoption as standard practice in SCCA diagnostics and surveillance, and potential stratification for HPV-directed therapies. Full article
(This article belongs to the Section Infectious Agents and Cancer)
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26 pages, 1678 KB  
Review
Non-Sexual Transmission of Papillomavirus: Is It Part of Our Virome?
by Sandro La Vignera and Rosita A. Condorelli
Viruses 2026, 18(8), 812; https://doi.org/10.3390/v18080812 - 24 Jul 2026
Viewed by 288
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue The Life Cycle of Human Papillomaviruses)
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