1.Role of Toll-like receptors in persistent infection of cervical high-risk human papillomavirus based on "latent pathogen theory".
Dan-Dan HONG ; Ting-Ting SHANG ; Hong-Yu GUO ; Wen-Ting ZUO ; Rui SUN ; Wen-Wen XU ; Qing-Ling REN
China Journal of Chinese Materia Medica 2025;50(7):1974-1979
Persistent infection with high-risk human papillomavirus(HR-HPV) is the primary etiological factor in cervical lesions and cervical cancer. Toll-like receptors(TLRs), as important pattern recognition receptors of the innate immune system, play a key role in the persistence of cervical HR-HPV infection. The "latent pathogen theory" in traditional Chinese medicine(TCM) holds that latent pathogens have both "latent" and "triggered" characteristics, which closely resemble the persistent infection and latent pathogenic potential of cervical HR-HPV. Guided by the "latent pathogen theory" and using contemporary immunological techniques, this paper explores the bidirectional immunomodulatory effects of TLRs in the persistence of cervical HR-HPV infection and their relationship with latent pathogens. The results indicate that TLRs play a crucial role in immune recognition and modulation. Dysregulation and overactivation of TLRs can induce chronic inflammation, allowing cervical HR-HPV to persist and evade immune detection. TLR dysfunction, coupled with a deficiency in healthy Qi that prevents the expulsion of pathogens, is a critical factor in the pathogenicity of latent pathogens. Restoring healthy Qi to modulate the immune functions of TLRs emerges as an important strategy for clearing cervical HR-HPV infection. By harmonizing the spleen and kidney and regulating immune balance, it is possible to reverse cervical HR-HPV infection, providing a scientific basis for clinical research.
Humans
;
Toll-Like Receptors/genetics*
;
Female
;
Papillomavirus Infections/genetics*
;
Papillomaviridae/immunology*
;
Persistent Infection/genetics*
;
Uterine Cervical Neoplasms/immunology*
;
Animals
;
Medicine, Chinese Traditional
;
Cervix Uteri/immunology*
;
Human Papillomavirus Viruses
2.Human papillomavirus carriage in the semen of men consulting for infertility: prevalence and correlations with sperm characteristics.
Armin PRIAM ; Antoine Le BOZEC ; Vasco Dias MEIRELES ; Fabien SAINT ; Rosalie CABRY ; Moncef BENKHALIFA ; Baptiste DEMEY ; Dorian BOSQUET
Asian Journal of Andrology 2025;27(2):196-203
We aim to study the semen carriage of human papillomavirus (HPV) and evaluate its association with patient characteristics. We conduct a single-center cohort study at Amiens University Hospital Center (Amiens, France). From May 1 to October 31, 2021, 461 men consulting for infertility and with semen analysis data were included. Each participant gave his written informed consent for the use of laboratory, demographic, clinical, and lifestyle data. A proportion of the semen samples were sent to a virology laboratory for HPV screening in a polymerase chain reaction (PCR) assay. In univariate and multivariate analyses with a logistic regression model, HPV + and HPV - groups were compared with regard to semen characteristics (including the DNA fragmentation index and the sperm decondensation index) and demographic, clinical, and lifestyle variables. Semen HPV carriage was detected in 22.3% of the patients. High-oncogenic-risk HPV genotypes were predominant (57.6%). Multivariate analysis showed that HPV carriage was significantly associated with the presence of at least one abnormal spermogram dinging (according to the 6 th World Health Organization criteria), with an adjusted odds ratio (OR) of 4.10 (95% confidence interval [CI]: 2.32-7.25, P < 0.001). A statistically significant association was also found for the type of infertility (OR: 1.61, 95% CI: 1.00-2.57, P = 0.05), the presence of varicocele (OR: 3.99, 95% CI: 1.48-10.71, P = 0.01), and a history of cryptorchidism, testicular ectopia, or monorchidism (OR: 3.54, 95% CI: 1.07-11.66, P = 0.04). Infection with a single HPV genotype or multiple HPV genotypes was significantly associated with at least one abnormal spermogram finding for all HPV oncogenic risk groups (OR: 3.93, 95% CI: 2.08-7.41, P < 0.001; and OR: 4.11, 95% CI: 1.58-10.68, P = 0.01, respectively). The association between sperm HPV carriage and the risk of infertility was statistically significant in a multivariate analysis (OR: 5.63, 95% CI: 3.16-10.01, P < 0.001) and after adjustment for the propensity score (OR: 6.10, 95% CI: 3.33-11.21, P < 0.001). Our results suggest that semen HPV carriage has an impact on male fertility. Sperm screening for HPV might be a useful addition to the work-up for male infertility.
Humans
;
Male
;
Adult
;
Infertility, Male/epidemiology*
;
Papillomavirus Infections/complications*
;
Semen/virology*
;
Semen Analysis
;
Prevalence
;
Papillomaviridae/genetics*
;
Cohort Studies
;
Spermatozoa/virology*
;
Middle Aged
;
France/epidemiology*
;
Human Papillomavirus Viruses
3.A Study of Flow Sorting Lymphocyte Subsets to Detect Epstein-Barr Virus Reactivation in Patients with Hematological Malignancies.
Hui-Ying LI ; Shen-Hao LIU ; Fang-Tong LIU ; Kai-Wen TAN ; Zi-Hao WANG ; Han-Yu CAO ; Si-Man HUANG ; Chao-Ling WAN ; Hai-Ping DAI ; Sheng-Li XUE ; Lian BAI
Journal of Experimental Hematology 2025;33(5):1468-1475
OBJECTIVE:
To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation.
METHODS:
Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0.
RESULTS:
A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×104 copies/ml, significantly higher than that in T cells (4.00×103 copies/ml, P <0.01) and NK cells (2.85×102 copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days).
CONCLUSION
In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans
;
Hematologic Neoplasms/virology*
;
Herpesvirus 4, Human/physiology*
;
Epstein-Barr Virus Infections
;
Hematopoietic Stem Cell Transplantation
;
Virus Activation
;
Lymphocyte Subsets/virology*
;
Flow Cytometry
;
Killer Cells, Natural/virology*
;
Male
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Female
;
B-Lymphocytes/virology*
;
Viral Load
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Adult
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T-Lymphocytes/virology*
;
Middle Aged
4.Anti-early antigen Epstein-Barr virus titer and atherosclerosis in relation to vascular endothelial growth factor (VEGF) polymorphism rs3025039 among older Japanese individuals.
Yuji SHIMIZU ; Hirotomo YAMANASHI ; Shin-Ya KAWASHIRI ; Yuko NOGUCHI ; Nagisa SASAKI ; Seiko NAKAMICHI ; Kazuhiko ARIMA ; Yasuhiro NAGATA ; Takahiro MAEDA
Environmental Health and Preventive Medicine 2025;30():83-83
BACKGROUND:
Epstein-Barr (EB) virus infection stimulates the production of vascular endothelial growth factor (VEGF), which contributes to the progression of angiogenesis. Angiogenesis plays an important role in the development of atherosclerosis. Since serum anti-early antigen EB virus IgG (EBV EA-IgG) titer is a sign of active EB virus infection, EBV EA-IgG titer could be associated with atherosclerosis. The number of minor (T) alleles in VEGF polymorphism rs3025039 has been reported to be inversely associated with serum VEGF concentration, suggesting that rs3025039 might have a strong influence on the association between EBV EA-IgG titer and atherosclerosis. By focusing on the role of VEGF in the development of atherosclerosis, this study aimed to investigate the association between active EB virus infection and atherosclerosis.
METHODS:
A cross-sectional study of 2,661 older Japanese individuals aged 60-89 years who participated in annual health check-ups during 2017-2019 was conducted. Logistic regression was used to evaluate the association between EBV EA-IgG titer and atherosclerosis in relation to rs3025039 genotype. The influence of rs3025039 (T) allele carrier status on the association between EBV EA-IgG titer and atherosclerosis was also evaluated by using logistic regression.
RESULTS:
Among rs3025039 CC-homozygotes, with the lowest EBV EA-IgG titer tertile as the reference, the multivariable odds ratio (95% confidence interval) was 1.11 (0.82, 1.50) for the medium tertile and 1.07 (0.78, 1.47) for the high tertile. Among rs3025039 (T) allele carriers, the corresponding values were 1.44 (0.88, 2.36) and 1.88 (1.15, 3.05), respectively. There was a significant interaction between rs3025039 (T) allele carrier status and the association between EBV EA-IgG titer and atherosclerosis (adjusted p = 0.0497).
CONCLUSION
EBV EA-IgG titer was significantly positively associated with atherosclerosis only among participants who are genetically less likely to have progressive angiogenesis. An angiogenesis-related genetic factor was revealed as a determinant of the association between EBV EA-IgG titer and atherosclerosis. These findings introduce a novel concept that could explain the association between viral infection and atherosclerosis.
Humans
;
Aged
;
Male
;
Middle Aged
;
Female
;
Japan/epidemiology*
;
Atherosclerosis/virology*
;
Aged, 80 and over
;
Vascular Endothelial Growth Factor A/genetics*
;
Epstein-Barr Virus Infections/virology*
;
Polymorphism, Single Nucleotide
;
Cross-Sectional Studies
;
Herpesvirus 4, Human
;
Antigens, Viral/immunology*
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Antibodies, Viral/blood*
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Immunoglobulin G/blood*
;
Genotype
;
East Asian People
5.Effectiveness of an educational intervention in increasing knowledge and willingness to vaccinate on human papillomavirus among women in barangay West Fairview, Quezon City
Lesly Mae D. Mara ; Camilla Thea S. Paraino ; Jebb Patrick Molina Delos Santos
Philippine Journal of Health Research and Development 2025;29(4):8-16
BACKGROUND
Cervical cancer, caused by human papillomavirus (HPV), is the second most common cancer among Filipino women. Despite vaccine availability, the Philippines has a low 60% immunization rate, driven by hesitancy and poor public awareness.
AIMS AND OBJECTIVESThis study assessed how 100 women (ages 18–45) in Quezon City understood HPV and their willingness to vaccinate.
MATERIALS AND METHODSResearchers used a pre–post interventional study and purposive sampling and Cochran’s formula for size calculation. Participants completed a pretest, a Department of Health/World Health Organization/Centers for Disease Control and Prevention-based digital educational intervention, a posttest, and a satisfaction survey. Data were gathered confidentially under informed consent.
RESULTSResults showed significant improvement in knowledge and willingness to vaccinate (P < 0.001), with almost all respondents expressing willingness. The intervention received high satisfaction ratings, proving the digital tool was effective and well-received.
CONCLUSION AND RECOMMENDATIONIn conclusion, this study demonstrated that a structured digital educational tool effectively bridges knowledge gaps and addresses vaccine hesitancy in a community setting. Findings emphasize the importance of targeted, community-level initiatives to reduce cervical cancer risk. Future research should include teens and males and use a larger randomized sample for definitive evidence.
Human ; Female ; Adolescent: 13-18 Yrs Old ; Young Adult: 19-24 Yrs Old ; Adult: 25-44 Yrs Old ; Middle Aged: 45-64 Yrs Old ; Uterine Cervical Neoplasms ; Human Papillomavirus Viruses ; Vaccination ; Women
6.Expert consensus on immunoprophylaxis of cervical cancer and other human papillomavirus- related diseases (2025 edition).
Chinese Journal of Epidemiology 2025;46(7):1107-1141
There have been recent, significant changes in strategies and policies for elimination of cervical cancer and advances in research of human papillomavirus (HPV)-related diseases and their prevention and control. Based on the latest national and international research, and building on a consensus published in 2019, we developed an expert consensus on immunoprophylaxis of cervical cancer and other human papillomavirus-related diseases (2025 edition) in order to provide clinicians, disease prevention and control professionals, and vaccination staff a reference for the prevention and control of cervical cancer and other HPV-related diseases and systematic, comprehensive evidence-based support for the scientific use of HPV vaccines to optimize their prevention effectiveness.
Humans
;
Uterine Cervical Neoplasms/virology*
;
Papillomavirus Vaccines/therapeutic use*
;
Papillomavirus Infections/prevention & control*
;
Female
;
Consensus
;
Papillomaviridae/immunology*
;
Vaccination
;
Human Papillomavirus Viruses
7.Progress of scRNA-seq technology in nasopharyngeal carcinoma research.
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(9):889-893
Nasopharyngeal carcinoma(NPC) is a distinct type of head and neck cancer closely associated with Epstein-Barr virus(EBV) infection and exhibits significant geographic variations in its incidence. Despite recent advancements in radiotherapy techniques and precision medicine for NPC, the overall survival rate remains unsatisfactory due to tumor metastasis, recurrence, and drug resistance. Single-cell RNA sequencing(scRNA-seq) is an emerging technology that allows for the analysis of gene expression at single-cell resolution, providing a clearer understanding of tumor cell subpopulations, the evolutionary trajectory of tumor cells, and the functional roles and interactions of cells within the tumor microenvironment. This provides new ideas for the development of precision medicine in NPC. Here, we review the applications of scRNA-seq in exploring the mechanisms of NPC pathogenesis, tumor heterogeneity, the tumor microenvironment, drug resistance, and therapeutic response.
Humans
;
Nasopharyngeal Neoplasms/genetics*
;
Tumor Microenvironment
;
Nasopharyngeal Carcinoma
;
Single-Cell Analysis
;
Sequence Analysis, RNA
;
Precision Medicine
;
Drug Resistance, Neoplasm
;
Epstein-Barr Virus Infections
;
Herpesvirus 4, Human
;
Single-Cell Gene Expression Analysis
8.Network Meta-analysis of Chinese patent medicines combined with recombinant human interferon α-2b in treatment of cervical human papillomavirus infections.
Kun MA ; Guan-Lan ZHONG ; Yue WANG ; Lin-Na MA ; Jie LUO
China Journal of Chinese Materia Medica 2024;49(24):6784-6802
The study employed network Meta-analysis to evaluate the efficacy and safety of Chinese patent medicines combined with recombinant human interferon α-2b(interferon) in the treatment of cervical human papillomavirus(HPV) infections. The relevant randomized controlled trial(RCT) published from inception to May 8, 2024 were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science. The modified Jadad scale and the Cochrane risk of bias tool were used to evaluate the quality of the included studies, and RevMan 5.4, R 4.3.3, and Stata 17 were used for data analysis. A total of 105 RCTs were included, involving 12 732 participants and 7 Chinese patent medicines: Baofukang Suppository, Compound Seabuckthorn Seed Oil Suppository, Huangqi Shengmai Decoction, Kangfu Gel, Kangfuyan Capsules, Kushen Gel, and Puling Penyankang Granules. Network Meta-analysis yielded the following results:(1)For improving the negative conversion rate of HPV, SUCRA top-ranked intervention was Puling Penyankang Granules + interferon.(2) For shortening vaginal discharge time, SUCRA top-ranked intervention was Compound Seabuckthorn Seed Oil Suppository + interferon.(3) For reducing the serum level of hypersensitive C-reactive protein(hs-CRP), SUCRA top-ranked intervention was Baofukang Suppository + interferon.(4) For elevating the serum level of CD~+_4 T cells, SUCRA top-ranked intervention was Baofukang Suppository + interferon.(5) For elevating the serum level of CD~+_8 T cells, SUCRA top-ranked intervention was Kangfuyan Capsules + interferon.(6) For improving the CD~+_4/CD~+_8 ratio, SUCRA top-ranked intervention was Compound Seabuckthorn Seed Oil Suppository + interferon.(7)In terms of reducing serum tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), recurrence rate at 6 months after treatment, and incidence of adverse events, there were no significant differences between the interventions when compared pairwise. The cluster analysis revealed that Puling Penyankang Granules + interferon, Baofukang Suppository + interferon, Kangfu Gel + interferon, and Huangqi Shengmai Decoction + interferon simultaneously improved the negative conversion rate of HPV and reduced the incidence of adverse events. The findings suggested that Chinese patent medicines combined with interferon were effective in treating cervical HPV infection by enhancing the negative conversion rate, shortening the vaginal discharge time, and improving the levels of hs-CRP and T lymphocyte subsets. However, due to the limitations of sample size and quality of the included studies, these conclusions require further validation by studies with larger sample sizes and higher quality.
Humans
;
Drugs, Chinese Herbal/therapeutic use*
;
Female
;
Papillomavirus Infections/virology*
;
Interferon alpha-2/administration & dosage*
;
Recombinant Proteins
;
Drug Therapy, Combination
;
Randomized Controlled Trials as Topic
;
Antiviral Agents/administration & dosage*
;
Interferon-alpha
;
Papillomaviridae/physiology*


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