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15 pages, 1293 KB  
Article
Chlamydia trachomatis Infection and Its Association with Human Papillomavirus Among Adolescent Girls and Young Women of Eastern Cape, South Africa
by Olufunmilayo O. Akapo and Zizipho Z. A. Mbulawa
Epidemiologia 2025, 6(4), 79; https://doi.org/10.3390/epidemiologia6040079 - 12 Nov 2025
Abstract
Background/Objectives: Adolescent girls and young women (AGYW) have a high burden of sexually transmitted infections (STIs). This study examined the prevalence of Chlamydia trachomatis, its association with human papillomavirus (HPV), and other associated factors among AGYW of rural communities. Methods: Secondary data [...] Read more.
Background/Objectives: Adolescent girls and young women (AGYW) have a high burden of sexually transmitted infections (STIs). This study examined the prevalence of Chlamydia trachomatis, its association with human papillomavirus (HPV), and other associated factors among AGYW of rural communities. Methods: Secondary data on C. trachomatis, HPV, and linked questionnaires from 214 sexually active AGYW were used. Self-collected vaginal specimens were previously tested using the Allplex™ STI Essential Assay and Roche Linear Array HPV genotyping assay. Results: The overall prevalence of C. trachomatis was 29.4% (63/214), and it was not influenced by age. The majority of the AGYW were C. trachomatis negative and HPV positive (52.4%, 111/212), followed by being C. trachomatis and HPV co-infected (23.6%, 50/212), C. trachomatis and HPV co-negative (18.4%, 39/212) and least were C. trachomatis positive and HPV negative (5.7%, 12/212). There was an increased prevalence of being HPV infected among C. trachomatis individuals than being C. trachomatis positive among HPV positive individuals (RR: 2.60, 95% CI: 2.00–3.38, p < 0.0001). C. trachomatis positive AGYW had a significantly higher association of HPV types targeted by Cervarix® HPV vaccine (HPV-16 and/or -18) than C. trachomatis negatives (RR: 2.58, 95% CI: 1.37–4.82, p = 0.005), targeted by Gardasil®4 HPV vaccine (HPV-6, -11, -16 and/or -18; RR: 2.21, 95% CI: 1.32–3.65, p = 0.005) and Gardasil®9 HPV vaccine (HPV-6, -11, -16, -18, -31, -33, -45, -52 and/or -58; RR: 1.92, 95% CI: 1.37–2.67, p < 0.001). Conclusions: There was a high burden of C. trachomatis and HPV coinfection. C. trachomatis coinfection influenced HPV genotype prevalence and distribution, including those that are targeted by the current commercial HPV vaccines, suggesting that the high burden of C. trachomatis among AGYW may pose challenges to the ongoing HPV vaccination program. Integrated STI screening and prevention strategies are needed in rural South African settings. Full article
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15 pages, 947 KB  
Article
Correlation of HPV Status with Colposcopy and Cervical Biopsy Results Among Non-Vaccinated Women: Findings from a Tertiary Care Hospital in Kazakhstan
by Talshyn Ukybassova, Gulzhanat Aimagambetova, Kuralay Kongrtay, Kuat Kassymbek, Milan Terzic, Sanimkul Makhambetova, Makhabbat Galym and Nazira Kamzayeva
Vaccines 2025, 13(11), 1151; https://doi.org/10.3390/vaccines13111151 - 11 Nov 2025
Abstract
Background/Objectives: Cervical cancer is one of the most frequent malignancies among women in Kazakhstan, where human papillomavirus (HPV) vaccination was initiated in 2024. Despite the implementation of vaccination and cytology-based screening programs, diagnostic limitations remain, and local evidence linking HPV infection to [...] Read more.
Background/Objectives: Cervical cancer is one of the most frequent malignancies among women in Kazakhstan, where human papillomavirus (HPV) vaccination was initiated in 2024. Despite the implementation of vaccination and cytology-based screening programs, diagnostic limitations remain, and local evidence linking HPV infection to clinical outcomes is scarce. This study aimed to evaluate the correlation between HPV status, cervical cytology results, colposcopic impression, and biopsy results in a non-vaccinated female population. Methods: A cross-sectional study was conducted at the University Medical Center, Astana, between November 2024 and March 2025. A total of 396 women of reproductive age were enrolled. Cervical samples underwent liquid-based cytology and high-risk HPV testing with the RealBest assay. Colposcopy was performed following abnormal cervical cytology results, and colposcopy-guided biopsies were obtained where indicated. Sociodemographic characteristics were assessed, and associations between HPV genotype and clinical outcomes were analyzed using descriptive and inferential statistics. Results: HPV infection was detected in 140 women (35.4%). HPV-16 was the most common genotype (11.4%), followed by HPV-52 (6.6%) and HPV-33 (5.3%). Among 198 women evaluated by colposcopy, abnormal findings were observed in 72.2%, with HPV-16 showing a significant association with higher-grade abnormalities (p < 0.001). Biopsies were available for 40 participants: 12 had CIN I, 12 had CIN II, 10 had CIN III, and 4 had carcinoma in situ. HPV-16 was the only genotype significantly linked to CIN II/III lesions. Conclusions: HPV-16 was strongly associated with abnormal colposcopic findings and high-grade histology, underscoring its oncogenic importance. The prevalence of HPV-52 and HPV-33 further supports the need for HPV nonavalent vaccination. These findings highlight the importance of HPV-based screening, genotype-specific triage, and expanded vaccination to reduce cervical cancer incidence in Kazakhstan. Full article
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12 pages, 646 KB  
Article
Heterogeneity in Prevalence, Incidence, and Clearance of Anal Human Papillomavirus Among HIV-Negative and HIV-Positive Men Who Have Sex with Men in China: An Observational Cohort Study
by Tian Tian, Zhen Lu, Jingjing He, Leiwen Fu, Wenhui Yu, Zewen Zhang, Zhen Chen, Huachun Zou and Jianghong Dai
Vaccines 2025, 13(11), 1144; https://doi.org/10.3390/vaccines13111144 - 7 Nov 2025
Viewed by 190
Abstract
Background: Men who have sex with men (MSM) are at high risk for anal human papillomavirus (HPV) infection, with HIV-positive MSM bearing the highest disease burden. Longitudinal data on anal HPV infection among HIV-negative and HIV-positive MSM are limited. We assessed and compared [...] Read more.
Background: Men who have sex with men (MSM) are at high risk for anal human papillomavirus (HPV) infection, with HIV-positive MSM bearing the highest disease burden. Longitudinal data on anal HPV infection among HIV-negative and HIV-positive MSM are limited. We assessed and compared the prevalence, incidence, and clearance of anal HPV infection among HIV-negative and HIV-positive MSM in Xinjiang, China. Methods: Sexually active HIV-positive and HIV-negative MSM aged 18 years and older have been enrolled in an ongoing observational cohort study of HPV since 1 September 2016, in Xinjiang, China. Participants were followed up on every 6 months with anal HPV testing and questionnaires regarding sexual behaviors. We compared HPV prevalence, incidence, and clearance between HIV-positive and HIV-negative MSM. Prevalence ratios (PRs), incidence rate ratios (IRRs), and clearance rate ratios (CRRs) for HIV-negative and HIV-positive MSM were calculated. Results: A total of 1425 MSM, including 131 HIV-positive and 1294 HIV-negative individuals, with a median age of 29 years (interquartile range [IQR]: 24 to 36), were included in our analysis. Compared with HIV-negative MSM, HIV-positive MSM demonstrated significantly higher prevalence across both individual and grouped HPV genotypes. Specifically, the prevalence of grouped HPV genotypes (any, high-risk, low-risk, 9v, 4v, HPV16/18, and HPV 6/11) was consistently elevated in HIV-positive individuals. PRs for individual HPV types 31, 45, 34, 44, 53, and 81 were 2.47 (95% CI: 1.16–5.25), 2.47 (1.10–5.54), 4.94 (1.25–19.52), 3.29 (1.08–10.06), 2.02 (1.01–4.04), and 2.66 (1.18–6.01), respectively. Furthermore, the incidence of most individual HPV genotypes were higher, while the clearance rates were lower among HIV-positive MSM. Specifically, IRRs for HPV types 31, 33, 45, 55, and 66 were 2.12 (1.19–3.75), 2.19 (1.24–3.90), 2.32 (1.17–4.59), 3.02 (1.15–7.93), and 2.44 (1.18–5.05), respectively. CRRs for HPV types 51 and 58 were 0.33 (0.21–0.52) and 0.60 (0.45–0.79), respectively. Conclusions: HPV prevalence, incidence, and clearance of anal HPV exhibited heterogeneity between HIV-positive and HIV-negative MSM. HPV vaccination and condom promotion programs should be recommended for HIV-positive MSM to mitigate the burden of HPV infection in this vulnerable population. Full article
(This article belongs to the Section Vaccines and Public Health)
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9 pages, 1631 KB  
Communication
Recent Trends in Prevalence of HPV Infection in Nasopharyngeal Carcinoma in Japan
by Luyao Liu, Nobuyuki Hirai, Satoru Kondo, Makiko Moriyama-Kita, Ryotaro Nakazawa, Shigetaka Komura, Makoto Kano, Daisuke Uno, Manabu Inaba, Takayoshi Ueno, Yosuke Nakanishi, Kazuhira Endo, Hisashi Sugimoto and Tomokazu Yoshizaki
Microorganisms 2025, 13(11), 2514; https://doi.org/10.3390/microorganisms13112514 - 31 Oct 2025
Viewed by 266
Abstract
Nasopharyngeal carcinoma (NPC) is a malignant tumor in which the etiologic contribution of Epstein–Barr virus (EBV) is well established. However, similar to that of oropharyngeal carcinoma, some papers reported that human papilloma virus (HPV) contributed to the development of NPC in non-endemic regions. [...] Read more.
Nasopharyngeal carcinoma (NPC) is a malignant tumor in which the etiologic contribution of Epstein–Barr virus (EBV) is well established. However, similar to that of oropharyngeal carcinoma, some papers reported that human papilloma virus (HPV) contributed to the development of NPC in non-endemic regions. Previously, we conducted a study on HPV infection in patients with NPC between 1996 and 2015 in our department. The current study aims to evaluate the incidence and role of HPV infection in NPC pathogenesis using samples of NPC after 2015. Paraffin-embedded tumor samples from 26 patients with NPC who were treated at our department between 2015 and 2022 were analyzed. HPV polymerase chain reaction, p16 immunohistochemistry, HPV genotyping, and in situ hybridization for EBV-encoded RNA were performed to determine the viral infection status. Of the 26 patients, 19 (73%) were EBV-positive and HPV-negative, 1 (4%) was EBV-negative and HPV-positive, and 6 (23%) were negative for both EBV and HPV. The detection rate of HPV has slightly increased from 3% to 4% over the past decade. Although Japan is a non-endemic region for NPC, HPV infection is exceedingly rare and may have a limited role in NPC development in Japan. However, the detection rate of HPV has not significantly changed in the past decade, further supporting the view that HPV has a relatively small impact on the pathogenesis of NPC in Japan. Full article
(This article belongs to the Section Virology)
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16 pages, 852 KB  
Review
Global Perspectives on HPV Vaccination: Achievements, Challenges, and Lessons from the Brazilian Experience
by Antonio Braga, Caroline Alves de Oliveira Martins, Gabriela Paiva, Érica de Almeida Barboza, Marcela Chagas, Gustavo Yano Callado, Edward Araujo Júnior, Jorge de Rezende-Filho, Isabel Cristina Chulvis do Val Guimarães, Roberta Granese, Gloria Calagna and Susana Cristina Aidé Viviani Fialho
Vaccines 2025, 13(11), 1106; https://doi.org/10.3390/vaccines13111106 - 29 Oct 2025
Viewed by 643
Abstract
Background: The introduction of prophylactic HPV vaccination has transformed cervical cancer prevention worldwide, yet many low- and middle-income countries face persistent challenges in implementation, coverage gaps, and vaccine hesitancy. This article presents a narrative review of global and Brazilian HPV vaccination programs, highlighting [...] Read more.
Background: The introduction of prophylactic HPV vaccination has transformed cervical cancer prevention worldwide, yet many low- and middle-income countries face persistent challenges in implementation, coverage gaps, and vaccine hesitancy. This article presents a narrative review of global and Brazilian HPV vaccination programs, highlighting achievements, pitfalls, and lessons for future strategies. Methods: We reviewed peer-reviewed literature and official reports from WHO, PAHO, CDC, Brazilian institutions, and others, focusing on programmatic performance, coverage trends, and vaccine acceptance. Results: In high-income settings such as Australia and the United Kingdom, school-based vaccination programs have driven sharp declines in HPV prevalence, genital warts, and precancerous lesions, in some cases approaching elimination thresholds. The United States has made progress but continues to struggle with disparities in uptake linked to socioeconomic and cultural factors. In India and several African nations, recent evidence supports single-dose regimens as a cost-effective and logistically feasible strategy. In Brazil, HPV vaccination was introduced in 2014 via the National Immunization Program (PNI), initially targeting girls aged 9–13 years through school campaigns. First-dose coverage exceeded 80% in the first year but subsequently declined, with full-schedule completion rates dropping below 60%. Contributing factors include misinformation, weakening of school-based delivery, and pandemic-related disruptions. Brazil later expanded eligibility to boys and immunocompromised populations and, more recently, extended catch-up vaccination to older adolescents. Conclusions: HPV vaccination has the potential to substantially reduce cervical cancer incidence globally. However, sustained impact depends not only on infrastructure and universal access but also on consistent school-based delivery, adaptive policies such as single-dose regimens, and robust communication strategies to counter misinformation. Brazil’s experience offers both inspiration and caution, providing lessons for countries striving to meet the WHO 90-70-90 targets. Full article
(This article belongs to the Collection HPV-Vaccines)
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17 pages, 462 KB  
Review
Human Papillomavirus: An Old New History
by Nicole West, Valentina Boz, Nunzia Zanotta, Carolina Cason, Giuseppina Campisciano, Alessandra Casuccio, Daniele Gianfrilli, Teresa Maria Assunta Fasciana, Giuseppina Capra, Maria Cristina Salfa, Franz Sesti, Barbara Suligoi, Francesca Valent, Laura Brunelli and Manola Comar
Pathogens 2025, 14(10), 1043; https://doi.org/10.3390/pathogens14101043 - 14 Oct 2025
Viewed by 885
Abstract
Human papillomavirus (HPV) represents the most common sexually transmitted infection worldwide and a major public health challenge. Nearly all sexually active individuals will acquire HPV during their lifetime, with the highest prevalence observed in adolescents and young adults shortly after sexual debut. More [...] Read more.
Human papillomavirus (HPV) represents the most common sexually transmitted infection worldwide and a major public health challenge. Nearly all sexually active individuals will acquire HPV during their lifetime, with the highest prevalence observed in adolescents and young adults shortly after sexual debut. More than 200 genotypes have been described, ranging from low-risk types, mainly responsible for benign lesions, to high-risk types, which are associated with cervical, anogenital, and head and neck cancers. While most infections are transient and spontaneously cleared by the immune system, persistent high-risk HPV can lead to precancerous lesions and malignant transformation, often in synergy with other sexually transmitted pathogens or in the context of microbiome imbalance. The introduction of vaccines and advanced screening technologies has substantially modified prevention strategies. Vaccination coverage remains heterogeneous, with persistent gaps particularly among males due to cultural, social, and educational barriers. Schools are increasingly recognized as strategic environments to promote awareness, sex education, and gender-neutral vaccination. Innovative approaches such as microbiome modulation, therapeutic vaccines, and liquid biopsy biomarkers are emerging as promising perspectives. This review aims to provide an updated overview of HPV epidemiology, clinical impact, prevention strategies, and future frontiers, with special attention to adolescents as a priority target group. Full article
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16 pages, 1001 KB  
Article
Prevalence of High-Risk Human Papillomaviruses (HPV) in Slovenian Women Attending Organized National Cervical Cancer Screening 14 Years After Implementation of the National HPV Vaccination Program
by Mateja Lasič, Anja Oštrbenk, Špela Smrkolj, Klara B. Bohinc, Ana Pflaum and Mario Poljak
Vaccines 2025, 13(10), 1050; https://doi.org/10.3390/vaccines13101050 - 13 Oct 2025
Viewed by 1042
Abstract
Background/Objectives: To assess overall and type-specific HPV vaccine effectiveness in central and eastern Europe (CEE), the age-stratified prevalence of cervical HPV infection was determined among Slovenian women aged 20 to 64 attending a cervical cancer screening program 14 years after implementation of [...] Read more.
Background/Objectives: To assess overall and type-specific HPV vaccine effectiveness in central and eastern Europe (CEE), the age-stratified prevalence of cervical HPV infection was determined among Slovenian women aged 20 to 64 attending a cervical cancer screening program 14 years after implementation of a national HPV vaccination program, which was then compared with 2009–2010 pre-vaccination data using the same methodological approach. Methods: Cervical samples of 4419 women were tested in 2023–2025 using the clinically validated Alinity m HR HPV Assay, and individual HPV types were determined by the Allplex HPV HR Detection assay. Results were compared with 2009–2010 pre-vaccination data generated using the same assay on an age-range matched cohort of women. Results: The overall prevalence of the 14 Alinity-targeted HPV types was 10.0% in 2023–2025 versus 13.3% in 2009–2010 (p < 0.001). HPV16 prevalence declined from 3.5% to 1.5% (p < 0.001), and HPV18 prevalence from 1.1% to 0.5% (p = 0.005). In women aged 20 to 24 with 40% uptake of quadrivalent HPV vaccine, overall HPV prevalence dropped from 25.3% to 12.8% (p < 0.001). No single case of HPV16/HPV18 infection was detected among vaccinated women. Conclusions: The first large-scale, systematic, and methodologically consistent study of HPV vaccine effectiveness in CEE showed a substantial reduction in high-risk HPV prevalence after implementation of the national program, with the greatest decline among women aged 20 to 24, who harbored the highest HPV burden in the pre-vaccination era. These locally acquired data will considerably inform public health strategies on cervical cancer elimination in CEE. Full article
(This article belongs to the Special Issue HPV Vaccination and Primary HPV Screening)
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32 pages, 9450 KB  
Systematic Review
Systematic Review and Meta-Analysis of microRNA-7-5p Expression and Biological Significance in Head and Neck Squamous Cell Carcinoma
by Rikki A. M. Brown, Michael Phillips, Andrew J. Woo, Omar Kujan, Stephanie Flukes, Louise N. Winteringham, Larissa C. Dymond, Fiona Wheeler, Brianna Pollock, Dianne J. Beveridge, Elena Denisenko and Peter J. Leedman
Cancers 2025, 17(19), 3232; https://doi.org/10.3390/cancers17193232 - 4 Oct 2025
Viewed by 773
Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy with poor clinical outcomes. microRNA-7-5p (miR-7-5p) has been described as both a tumour suppressor and an oncomiR depending on the tissue context, but its role in HNSCC remains unclear. This [...] Read more.
Background: Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy with poor clinical outcomes. microRNA-7-5p (miR-7-5p) has been described as both a tumour suppressor and an oncomiR depending on the tissue context, but its role in HNSCC remains unclear. This study aimed to clarify the clinical significance and biological function of miR-7-5p in HNSCC by integrating data from multiple sources. Methods: A systematic review of the literature was conducted to identify studies analysing miRNA expression in human head and neck tissues. A meta-analysis of individual patient data from Gene Expression Omnibus (GEO), ArrayExpress, and The Cancer Genome Atlas (TCGA) was performed to assess miR-7-5p expression in tumours and normal tissues, and its associations with clinical parameters and prognostic outcomes. Bioinformatics analyses were used to predict miR-7-5p target genes, classify hub genes, and perform gene ontology enrichment analysis. MicroRNA in situ hybridisation (miRNA ISH) and real-time quantitative PCR (RT-qPCR) were conducted on tissue samples, HNSCC cell lines, and an in vitro model of oral oncogenesis to validate miR-7-5p expression patterns. Results: miR-7-5p was significantly upregulated in tumours compared to normal tissues and associated with larger tumour size, HPV-negative status, poor disease-specific survival, and shorter progression-free intervals. Bioinformatics analysis highlighted miR-7-5p target genes enriched in pathways related to cell growth, survival, and tumourigenesis. Despite evidence supporting the anti-cancer role of exogenous miR-7-5p in preclinical models, the observed endogenous upregulation in tumours suggests that miR-7-5p expression may represent a compensatory or stress-responsive mechanism during tumourigenesis, rather than acting as a primary oncogenic driver. Conclusions: This study provides new insights into the complex role of miR-7-5p in HNSCC, supporting its potential as both a biomarker and a therapeutic target. Understanding the context-specific functions of miR-7-5p is essential for its development as an RNA-based therapeutic in HNSCC. Full article
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12 pages, 909 KB  
Article
Human Papillomavirus Prevalence in the Prostate and Seminal Vesicles: Does This Virus Have an Etiological Role in the Development of Prostate Cancer?
by Rei Shinzawa, Kazuyoshi Shigehara, Hiroki Nakata, Shingo Takada, Kotaro Fukukawa, Yuki Kato, Tomomi Nakagawa, Shohei Kawaguchi, Kouji Izumi and Atsushi Mizokami
Viruses 2025, 17(10), 1304; https://doi.org/10.3390/v17101304 - 26 Sep 2025
Viewed by 540
Abstract
Human papillomavirus (HPV) is common in both sexes and is also detected in male urine and semen. However, its exact origin and its etiological role in the male genital tract remain unclear. A total of 157 formalin-fixed paraffin-embedded tissues from 156 primary prostate [...] Read more.
Human papillomavirus (HPV) is common in both sexes and is also detected in male urine and semen. However, its exact origin and its etiological role in the male genital tract remain unclear. A total of 157 formalin-fixed paraffin-embedded tissues from 156 primary prostate cancer lesions and one metastatic lesion were analyzed. HPV-DNA was detected using a nested PCR, and HPV genotyping was performed using flow-through hybridization for positive cases. In situ hybridization (ISH) was used to localize HPV-DNA, whereas HPV-E6/E7 mRNA ISH and p16INK4a immunohistochemistry were conducted on high-risk (HR) HPV-positive samples. A nested PCR analysis demonstrated that HPV-DNA was detected in 9.6% of prostate cancers and 0% of seminal vesicles. HR-HPV was observed in 4.5% of the samples. Unknown type was the most common genotype. Of the genotypes which could be identified in the genotyping assay, HPV44 was the most prevalent. HPV prevalence was significantly higher in patients with high-grade groups. Among 15 HPV-positive cases, HPV-DNA was found in 9 cancerous and 10 non-cancerous lesions. E6/E7 mRNA was expressed in 6 of 7 HR-HPV-positive cases, while p16INK4a expression was weak or absent in all cases. HPV can infect prostate tissue and may contribute to carcinogenesis in some cases, but p16INK4a was not a consistent surrogate for E7 expression. Full article
(This article belongs to the Special Issue Human and Animal Papillomavirus: Infections, Genetics, and Vaccines)
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28 pages, 3125 KB  
Review
Molecular Insights into HPV-Driven Head and Neck Cancers: From Viral Oncoproteins to Precision Therapeutics
by Mustafa Ozdogan, Gizem Tutkun, Muharrem Okan Cakir and Gholam Hossein Ashrafi
Viruses 2025, 17(9), 1276; https://doi.org/10.3390/v17091276 - 20 Sep 2025
Viewed by 1812
Abstract
Human papillomavirus (HPV) plays a major role in the development of head and neck cancers (HNCs), particularly oropharyngeal squamous cell carcinoma. This review highlights the key molecular mechanisms of HPV-driven carcinogenesis, focusing on the oncogenic E6 and E7 proteins and their disruption of [...] Read more.
Human papillomavirus (HPV) plays a major role in the development of head and neck cancers (HNCs), particularly oropharyngeal squamous cell carcinoma. This review highlights the key molecular mechanisms of HPV-driven carcinogenesis, focusing on the oncogenic E6 and E7 proteins and their disruption of tumor suppressor pathways and epigenetic regulation. We discuss the rising prevalence of HPV-related HNCs, their distinct clinical features, and diagnostic approaches such as p16 immunohistochemistry and HPV DNA/RNA detection. HPV-positive tumors show better prognosis and response to treatment, prompting interest in therapy de-escalation. Emerging strategies including immune checkpoint inhibitors, therapeutic vaccines, CRISPR-based gene editing, and ctDNA monitoring are advancing precision oncology in this field. We also examine the preventive potential of HPV vaccination and ongoing research into its role across various HNC subtypes. A deeper understanding of HPV’s molecular impact may guide more effective, targeted, and less toxic interventions. Full article
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14 pages, 4010 KB  
Article
Development of a Microfluidic Point-of-Care Platform for HPV Detection Based on Helicase-Dependent Amplification
by Everardo González-González, Elda A. Flores-Contreras, Gerardo de Jesús Trujillo-Rodríguez, Mariana Lizbeth Jiménez-Martínez, Iram P. Rodríguez-Sánchez, Adriana Ancer-Arellano, Salomon Alvarez-Cuevas, Margarita L. Martinez-Fierro, Iván A. Marino-Martínez and Idalia Garza-Veloz
Trop. Med. Infect. Dis. 2025, 10(9), 272; https://doi.org/10.3390/tropicalmed10090272 - 19 Sep 2025
Viewed by 768
Abstract
Human papillomavirus (HPV) is the most prevalent sexually transmitted infection worldwide and a leading cause of cervical cancer, accounting for over 300,000 deaths annually, primarily due to high-risk genotypes HPV-16 and HPV-18. Conventional molecular diagnostic methods, such as polymerase chain reaction (PCR), require [...] Read more.
Human papillomavirus (HPV) is the most prevalent sexually transmitted infection worldwide and a leading cause of cervical cancer, accounting for over 300,000 deaths annually, primarily due to high-risk genotypes HPV-16 and HPV-18. Conventional molecular diagnostic methods, such as polymerase chain reaction (PCR), require expensive instrumentation and well-equipped laboratories, which limits their applicability in low-resource or decentralized settings. To address this challenge, the aim of this study was to develop a prototype point-of-care (POC) diagnostic platform based on helicase-dependent amplification (HDA) integrated into a microfluidic device for the specific detection of HPV-16 and HPV-18. The proposed POC platform comprises a disposable poly (methyl methacrylate) (PMMA) microfluidic device, a portable warming mat for isothermal amplification at 65 °C, and a compact electrophoresis chamber for fluorescence-based visualization using SYBR Safe dye, with an approximate total cost of $320 USD. Platform validation was performed on 33 samples, demonstrating amplification of target sequences in less than 60 min with only 20 µL of reaction volume, a limit of detection (LOD) of 15 copies (cp) per reaction, a sensitivity of 95.52%, and a specificity of 100%. This portable and scalable platform constitutes a cost-effective and reliable tool for the detection of HPV, supporting global health initiatives, including those driven by the World Health Organization (WHO), aimed at eliminating cervical cancer as a public health threat, as it can be implemented in decentralized or resource-limited settings. Full article
(This article belongs to the Special Issue Molecular Epidemiology of Human Papillomavirus Infection)
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24 pages, 1439 KB  
Article
Oral Viral DNA Profiling in Obesity, Adenomatous Polyposis, and Colorectal Cancer Identifies Human β-Papillomavirus Types as Potentially Sex-Related and Modifiable Cancer Risk Indicators
by Veronica Fertitta, David Israel Escobar Marcillo, Grete Francesca Privitera, Manuela Del Cornò, Valeria Guglielmi, Annamaria Agnes, Barbara Varano, Luca Colangeli, Lorenzo Ferri, Sandrine McKay-Chopin, Paolo Sbraccia, Roberto Persiani, Alfredo Pulvirenti, Zdenko Herceg, Massimo Tommasino, Tarik Gheit, Paola Fortini and Lucia Conti
Cancers 2025, 17(18), 3024; https://doi.org/10.3390/cancers17183024 - 16 Sep 2025
Viewed by 685
Abstract
Background/Objectives: Colorectal cancer (CRC) is the third most common cancer and a leading cause of death worldwide. Identifying non-invasive, early indicators of CRC risk remains essential and could help reduce its health burden. Excess adiposity and chronic inflammation are major predisposing factors [...] Read more.
Background/Objectives: Colorectal cancer (CRC) is the third most common cancer and a leading cause of death worldwide. Identifying non-invasive, early indicators of CRC risk remains essential and could help reduce its health burden. Excess adiposity and chronic inflammation are major predisposing factors for precancerous adenomatous polyposis (AP) and CRC, while diet- or surgery-induced weight loss was associated with a reduced risk. Viral infections also represent cancer risk factors through direct or synergic mechanisms, though no definitive causal link has been established for CRC. Moreover, interest is growing on the role of oral viruses as predictors of disease. Methods: In this study, highly sensitive and specific Luminex-based screening assays were used to perform a comprehensive characterization of oral infections by Human Herpes (HHV), Polyoma (HPyV) and Papilloma (HPV) Viruses in CRC patients (N = 50), healthy controls (N = 46; normal weight, NW = 26; overweight, OW = 20), and high-risk individuals with obesity (N = 35) or adenomatous polyposis (AP, N = 22). Results: We observed increased HPyV prevalence in AP, and higher single and multiple β-HPV infection rates in AP and CRC compared to controls. A panel of β-HPV genotypes, including oncogenic HPV5, was overrepresented in CRC and high-risk groups, and some of them showed an association with the male sex. The prevalence of most infections decreased in the obese cohort following bariatric surgery, alongside weight loss and reduction of inflammatory markers. Furthermore, oral infections by viral types previously detected in CRC tissue and adjacent mucosa also declined after surgery. Conclusions: Altogether, these findings suggested a role for oral β-HPV types as potential sex- and lifestyle-related, modifiable indicators of cancer risk. Full article
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21 pages, 5667 KB  
Article
Clinical Significance of Tumor Infiltrating T-Helper and Regulatory Cells in Bulgarian Cervical Cancer Patients
by Angel Yordanov, Polina Damyanova, Mariela Vasileva-Slaveva, Konstantina Karakadieva, Stoyan Kostov and Velizar Shivarov
Biomedicines 2025, 13(9), 2206; https://doi.org/10.3390/biomedicines13092206 - 9 Sep 2025
Viewed by 668
Abstract
Background and Objectives: Cervical cancer (CC), primarily caused by human papillomavirus (HPV) infection, is the most common gynecological cancer and a leading cause of cancer-related death in women. The immune microenvironment, particularly CD4+ T-helper cells and FOXP3 (forkhead box P3)+ regulatory T cells [...] Read more.
Background and Objectives: Cervical cancer (CC), primarily caused by human papillomavirus (HPV) infection, is the most common gynecological cancer and a leading cause of cancer-related death in women. The immune microenvironment, particularly CD4+ T-helper cells and FOXP3 (forkhead box P3)+ regulatory T cells (Tregs), plays a crucial role in tumor progression. However, the exact relationship between immune cell infiltration and clinical outcomes in CC is not fully understood. This study aimed to examine the association between CD4+ T-helper cells, FOXP3+ Tregs, and clinical/pathological parameters in CC patients. Methods: We conducted a retrospective analysis of 150 patients with T1-stage cervical cancers diagnosed between 2015 and 2021. Tumor samples were evaluated using immunohistochemistry (IHC) to assess CD4+ and FOXP3+ TILs in intratumoral and stromal regions. Additionally, deconvoluted transcriptomic data from the TCGA cohort were used to assess immune infiltration within the tumor immune microenvironment (TIME). Results: High infiltration of CD4+ T-helper cells was significantly associated with better overall survival (OS) in node-negative CC patients (p = 0.0006). However, no significant prognostic value was found for Tregs. CD4+ cells were more prevalent in patients with well-differentiated tumors (G1 and G2) and lower levels of CD4+ infiltration were found in squamous cell carcinoma (SCC) compared to other histological subtypes. Multivariate regression analysis showed that only tumor size (T1b3) and undifferentiated tumor morphology (G3) were significantly associated with poorer OS. In contrast, infiltration of CD4+ or FOXP3+ cells did not significantly correlate with OS after adjusting for clinical factors. Competing risk analysis for death from cancer showed no significant associations with immune cell infiltration levels. Conclusions: This study underscores the complex relationship between immune cell infiltration and clinical outcomes in CC. While CD4+ T-helper cell infiltration is associated with improved prognosis in node-negative cases, further research is necessary to clarify the role of Tregs and other immune components in the tumor microenvironment. These findings suggest potential avenues for therapeutic strategies, including immune checkpoint inhibitors, in CC. Full article
(This article belongs to the Collection Feature Papers in Immunology and Immunotherapy)
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22 pages, 750 KB  
Article
Association of HPV in the Genesis of Head and Neck Squamous Cell Carcinoma: A Case–Control Study in a Bulgarian Cohort
by Elitsa Deliverska, Vessela Raykova, Stanislav Yordanov, Daniel Markov, Svetoslav Slavkov, Viktor Lenkov and Zdravka Pashova-Tasseva
Cancers 2025, 17(17), 2907; https://doi.org/10.3390/cancers17172907 - 4 Sep 2025
Viewed by 875
Abstract
Background/Objectives: Head and neck squamous cell carcinoma (NHSCC) is a significant global health burden, with human papillomavirus (HPV) recognized as a major etiological factor in a growing proportion of cases. The interaction between HPV status, tumor characteristics, and other risk factors remains an [...] Read more.
Background/Objectives: Head and neck squamous cell carcinoma (NHSCC) is a significant global health burden, with human papillomavirus (HPV) recognized as a major etiological factor in a growing proportion of cases. The interaction between HPV status, tumor characteristics, and other risk factors remains an important focus for both prevention and clinical management. This study aimed to investigate the association between HPV and OPSCC in a Bulgarian cohort, with emphasis on the influence of behavioral and clinical factors, as well as basic tumor features. Methods: Eighty-nine participants were enrolled, including 50 patients with histologically confirmed NHSCC and 39 healthy controls. Clinical examinations and histopathological verification were conducted for all cases. Brush smear and oral rinse samples were collected for HPV testing, in line with molecular detection protocols, specifically PCR-based assays for viral DNA. Demographic data, behavioral risk factors, and information on concomitant diseases were obtained and analyzed in relation to HPV status. Results: Differences were identified between HPV-positive and HPV-negative NHSCC cases in relation to tumor characteristics, including clinical presentation and histological differentiation. Additional analyses demonstrated associations between certain behavioral factors, comorbidities, and the risk of NHSCC. Conclusions: This study provides data on HPV prevalence, related tumor features, and associated risk factors in OPSCC within a Bulgarian population. These findings highlight descriptive trends related to HPV status but indicate no robust statistical associations in this cohort. Full article
(This article belongs to the Section Cancer Epidemiology and Prevention)
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11 pages, 517 KB  
Review
Molecular Screening for Cervical Cancer
by Toni Ricardo Martins and José Eduardo Levi
Genes 2025, 16(9), 1041; https://doi.org/10.3390/genes16091041 - 2 Sep 2025
Viewed by 871
Abstract
Background/Objectives: Cervical cancer (CC), a highly prevalent female neoplasia, has been prevented through repeated cervicovaginal cytology, the so-called Pap test, across women’s lifespans. The now undebatable role of Human Papillomaviruses in the etiology of CC and the development of high-throughput automated molecular [...] Read more.
Background/Objectives: Cervical cancer (CC), a highly prevalent female neoplasia, has been prevented through repeated cervicovaginal cytology, the so-called Pap test, across women’s lifespans. The now undebatable role of Human Papillomaviruses in the etiology of CC and the development of high-throughput automated molecular amplification diagnostic platforms is allowing for the replacement of the Pap test with HPV testing. The objective of this review is to contextualize the current strategies for cervical cancer screening using molecular assays. Methods: The many existing screening tools relying on molecular markers and their advantages and drawbacks are discussed. Results: Testing for oncogenic Human Papillomavirus DNA is presently the mainstay strategy for molecular screening, replacing cervicovaginal cytology. Conclusions: The presence of HPV-DNA is the most sensitive marker for cervical cancer and its precursor lesions. However, its adoption has led to an increase in the number of screening-positive subjects, generating extra demand for triage resources. New algorithms and technologies are fast being developed to address this need, moving toward risk-based management. Full article
(This article belongs to the Special Issue Molecular Assays for Mutation and Infectious Agent Detection)
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