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.Oncolytic virus-mediated base editing for targeted killing of cervical cancer cells.
Huanhuan XU ; Siwei LI ; Xi LUO ; Zuping ZHOU ; Changhao BI
Chinese Journal of Biotechnology 2025;41(4):1382-1394
Conventional cancer therapies, such as radiotherapy and chemotherapy, often damage normal cells and may induce new tumors. Oncolytic viruses (OVs) selectively target tumor cells while sparing normal cells. Most OVs used in clinical trials have been genetically engineered to enhance their ability to target tumor cells and activate immune responses. To develop a specific OV-based approach for treating cervical cancer, this study constructed an oncolytic adenovirus that delivered a base editor targeting oncogenes to achieve efficient killing of tumor cells through inhibiting tumor growth and directly lysing tumor cells. We utilized the human telomerase reverse transcriptase (TERT) promoter to drive the expression of adenovirus early region 1A (E1A) and successfully constructed the P-hTERT-E1A-GFP vector, which was validated for its activity in cervical cancer cells. Given the critical role of the MYC oncogene in the research of oncology, identifying efficient editing sites for the MYC oncogene is a key step in this study.Three MYC-targeting gRNAs were engineered and co-delivered with ABE8e base editor plasmids into HEK293T cells. Following puromycin selection, Sanger sequencing demonstrated differential editing efficiencies: MYC-1 (43%), MYC-2 (25%), and MYC-3 (35%), identifying MYC-1 as the most efficient editing locus. By constructing the P-ABEs-hTERT-E1A-GFP and P-MYC gRNA-hTERT-E1A-GFP vectors, we successfully packaged the virus and confirmed its specificity and efficacy. The experimental results demonstrate that this novel oncolytic adenovirus effectively inhibits the growth of HeLa cells in vitro, providing new experimental evidence and potential strategies for treating cervical cancer based on the HeLa cell model.
Humans
;
Uterine Cervical Neoplasms/pathology*
;
Oncolytic Viruses/genetics*
;
Female
;
HEK293 Cells
;
Oncolytic Virotherapy/methods*
;
Adenoviridae/genetics*
;
Gene Editing/methods*
;
Telomerase/genetics*
;
Adenovirus E1A Proteins/genetics*
;
Genetic Vectors/genetics*
;
HeLa Cells
3.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
4.Psychosocial and sexual function of young women less than 40 years old treated with concurrent chemoradiation for cervical cancer: A cross-sectional study testing quality of life.
Maria Rowena G. BASCOS ; Rey H. DELOS REYES
Philippine Journal of Obstetrics and Gynecology 2025;49(4):209-216
BACKGROUND OF THE STUDY
The treatment for cervical cancer among young women can result in adverse effects that contribute to a negative quality of life (QOL). The literature shows varied studies on the QOL of cervical cancer patients, but evidence on the local context is limited, particularly in young patients.
OBJECTIVESThis study aimed to determine the QOL of young women with cervical cancer treated with concurrent chemoradiation.
MATERIALS AND METHODSA prospective cross-sectional research design was employed. A total of 72 cervical cancer patients who were 40 years old and younger and treated with chemoradiation were recruited using complete enumeration. The study locale was in a tertiary government hospital, which is a training center for gynecologic oncology in the Philippines. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and EORTC QLQ of women with Cervical Cancer (CX24) served as data collection instruments. Descriptive statistics were utilized to describe and synthesize the data.
RESULTSSeventy-two young women with cervical cancer treated with concurrent chemoradiation reported a mean global health status score of 4.75, indicating a moderate QOL. However, functional domains were generally low, with the lowest scores in cognitive (1.71), social (1.64), and physical interference with social activities (1.96). The average symptom score was 2.10, reflecting moderate symptomatology. On the EORTC QLQ-CX24, most QOL aspects were rated low, except for body image (2.01), menopausal symptoms (2.31), and sexual worry (2.79). Sexual enjoyment scored the lowest at 1.16, with an overall average of 1.71.
CONCLUSIONSThe study highlights low-to-moderate QoL among young cervical cancer patients post-chemoradiation, underscoring the need for improved supportive care addressing physical, psychological, and social challenges caused by the disease and treatment modality.
Human ; Female ; Uterine Cervical Neoplasms ; Quality Of Life
5.A rare path in a common symptom: A case report on serous carcinoma of the cervix.
Reimalyn Doton AGUSTIN ; Ana Victoria Vallido DY ECHO
Philippine Journal of Obstetrics and Gynecology 2025;49(4):241-248
Although commonly seen in the ovary, fallopian tube, peritoneum, and endometrium, the serous carcinoma histology is considered a rare subtype when seen in the cervix. The prevalence of cervical adenocarcinoma, including serous carcinoma, varies between 5% and 15% of all cervical malignancies. A thorough literature study revealed only 113 cases of serous carcinoma of the cervix, highlighting its infrequency relative to other cervical cancer variants. As a subtype of adenocarcinoma, serous carcinoma of the cervix has aggressive characteristics and usually unfavorable prognosis, more so its clinicopathological characteristics are relatively unclear because of its rarity and limited number of cases and reviews seen in literature. This is a case of a 44-year-old G3P3 with a primary complaint of heavy vaginal bleeding. The diagnosis of serous carcinoma of the cervix was made by histopathological evaluation, confirmed by immunostaining. With physical examination and diagnostic imaging confirming an early stage disease, the patient successfully underwent primary surgical management.
Human ; Female ; Uterine Cervical Neoplasms
6.The effect of CD33+MDSC-mediated T lymphocyte function on the therapeutic efficacy of 125I particle implantation combined with arterial chemoembolization in the treatment of cervical cancer.
Yongjin HU ; Zanhong WANG ; Feng'e LI ; Weihong FENG ; Yupeng WANG
Chinese Journal of Cellular and Molecular Immunology 2025;41(10):905-912
Objective To explore the expression levels of CD33+ myeloid-derived suppressor cell (MDSC)-mediated T lymphocyte function and related inflammatory factors secreted by T lymphocyte subsets in patients with cervical cancer, and to analyze their correlation with the treatment efficacy of 125I particle implantation combined with arterial chemoembolization, as well as predictive value for treatment outcomes and interaction effects. Methods From January 1st, 2021 to January 1st, 2024, our hospital admitted 152 patients with advanced cervical cancer, who were confirmed by pathological examination. All patients received uterine artery chemoembolization combined with 125I particle implantation. The predictive value of CD33+MDSC levels for clinical treatment response in cervical cancer was assessed using receiver operating characteristic (ROC) curve analysis. Multivariate logistic regression analysis was performed to evaluate both multiplicative and additive interactions between CD33+MDSC and T lymphocytes in predicting clinical treatment failure of cervical cancer. Kaplan Meier method was used to analyze the survival differences between cervical cancer patients with high and low CD33+MDSC expression levels. Results Compared with the effective group, patients in the ineffective group had decreased expression levels of CD3+ T lymphocyte, CD4+ T lymphocyte, interleukin 2 (IL-2) and interferon γ (IFN-γ), while showing increased expression levels of CD33+MDSC, CD8+ T lymphocyte, IL-4 and IL-6, along with increased tumor necrosis factor α (TNF-α) levels, larger maximum tumor diameters, and a higher incidence of lymph node metastasis. The expression levels of CD33+MDSCs demonstrated good predictive performance for treatment efficacy in cervical cancer patients. The high CD33+MDSC expression group had a significantly shorter overall survival (OS) than the low CD33+MDSC expression group (6.0±1.0 months vs. 12.0±1.2 months; t=33.280). The interaction analysis revealed that CD33+MDSCs and CD8+ T lymphocytes were highly expressed, while CD3+ and CD4+ T lymphocytes were lowly expressed, which was associated with an increased risk of clinical treatment failure in cervical cancer patients. Conclusion CD33+MDSCs can inhibit CD3+ and CD4+ T lymphocytes. It can upregulate the expression of CD8+ T lymphocytes, form an immunosuppressive microenvironment, and reduce the treatment response rate of 125I particle implantation combined with arterial chemoembolization. CD33+MDSCs may serve as an independent biomarker for predicting the therapeutic efficacy and poor prognosis.
Humans
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Female
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Uterine Cervical Neoplasms/immunology*
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Middle Aged
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Chemoembolization, Therapeutic/methods*
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Sialic Acid Binding Ig-like Lectin 3/immunology*
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Adult
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T-Lymphocytes/immunology*
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Aged
;
Treatment Outcome
7.Global disease burden of cervical cancer and the association of screening coverage with quality of disease management.
Chang SUN ; Abdalle Abdi MUSTAFE ; Bingqing LIU ; Yuanying MA ; Weiguo LYU
Journal of Zhejiang University. Medical sciences 2025;54(3):281-288
OBJECTIVES:
To analyze the global disease burden of cervical cancer and the association between screening coverage and the quality of disease management.
METHODS:
The data of global burden of cervical cancer 2021 and the data of cervical cancer screening 2019 were obtained from IHME Global Burden of Disease (GBD) and the WHO global health observatory, respectively. The age-standardized disease burden index was calculated, the quality of care index (QCI) was determined with principal component analysis, and the correlation between QCI and cervical cancer screening coverage was examined with linear regression analysis by regions and populations.
RESULTS:
The burden of cervical cancer and the quality of management exhibited significant variability across countries with differing levels of social development. The indicators of cervical cancer burden in China were close to the average level of countries with higher socio-demographic index (SDI). The global QCI was 22.22 (10.50, 35.43), and that of China was 26.30. The global screening coverage rate for cervical cancer was 42% (12%, 86%) and that in China was 31%. After adjusting for the social development level of countries, the coverage level of cervical cancer screening was associated with QCI (β=0.27, P<0.01), with no difference between low and high SDI countries (P>0.05). The association was significantly stronger among 25-30 years old women (β=1.48, P<0.05).
CONCLUSIONS
There are discrepancies in both the disease burden of cervical cancer and the quality of disease management among countries with different socioeconomic levels, and there is still considerable room for improvement in China. Expanding coverage of cervical cancer screening may be an effective strategy to enhance the management quality of cervical cancer, particularly among younger women where the screening benefits are most pronounced.
Humans
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Uterine Cervical Neoplasms/prevention & control*
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Female
;
Early Detection of Cancer
;
Global Burden of Disease
;
China/epidemiology*
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Mass Screening
;
Quality of Health Care
;
Disease Management
;
Adult
;
Middle Aged
8.Synergistic inhibition of autophagic flux and induction of apoptosis in cervical cancer cells by Mito-TEMPO and hyperthermia.
Yu-Mei LI ; Qing-Li ZHAO ; Ryohei OGAWA ; Tatsuji MIZUKAMI ; Yu SONG ; Zheng-Guo CUI ; Jun-Ichi SAITOH ; Kyo NOGUCHI
Environmental Health and Preventive Medicine 2025;30():67-67
BACKGROUND:
Hyperthermia (HT), while a cancer treatment approach, isn't always effective alone. Therefore, identifying hyperthermia enhancers is crucial. We demonstrated that Mito-TEMPO ([2-[(1-Hydroxy-2,2,6,6-tetramethylpiperidin-4-yl) amino]-2-oxoethyl]-triphenylphosphanium, MT) acts as a potent thermosensitizer, promoting cell death in human cervical cancer (HeLa) cells.
METHODS:
Cells were pretreated with 0.4 mM MT for 5 minutes, followed by exposure to hyperthermia (42 °C for 60 minutes). The impacts of MT/HT on cell viability, proliferation, apoptosis, endoplasmic reticulum (ER) stress, apoptosis-related proteins and autophagy, autophagy-related proteins expression were measured. The relationships between autophagy and apoptosis were further investigated using the specific autophagy inhibitor chloroquine (CQ) and the autophagy inducer rapamycin (Rapa).
RESULTS:
The combined treatment reduced the mitochondrial membrane potential (MMP) and increased ROS production. It also upregulated the pro-apoptotic protein Bax and downregulated anti-apoptotic proteins such as Bcl-2 and MCL-1. As a result, Caspase-3 was activated. Additionally, the combined treatment upregulated the expression of p-PERK/PERK, ATF-4, CHOP proteins. Moreover, the combined treatment also increased the expression of LC3 II and p62, decreased expression of LAMP 1 and Cathepsin D and increased lysosomal pH, indicating coordinated changes in autophagy regulation. Notably, intensification of apoptosis induced by the combined treatment was observed with CQ, whereas attenuation was seen with Rapa.
CONCLUSIONS
MT effectively enhanced HT-induced apoptosis in HeLa cells. Elevated ER stress and interruption of autophagy flux are the possible underlying molecular mechanisms for this phenomenon. These findings suggested MT can act as a potential thermosensitizer, highlighting its versatility in cancer treatment strategies.
Humans
;
Apoptosis/drug effects*
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Autophagy/drug effects*
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HeLa Cells
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Uterine Cervical Neoplasms/therapy*
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Female
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Hyperthermia, Induced
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Spin Labels
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Endoplasmic Reticulum Stress/drug effects*
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Cyclic N-Oxides/pharmacology*
;
Cell Survival/drug effects*
9.Atypical placental site nodules: Five cases and literature review.
Yifu HE ; Wenqing YANG ; Yu ZHANG
Journal of Central South University(Medical Sciences) 2025;50(1):99-104
Atypical placental site nodules (APSN) are a rare form of trophoblastic disease in pregnancy. There is limited research on APSN, and treatment methods are controversial, with unclear prognosis. This study collected clinical and prognostic data of 5 patients diagnosed with APSN at Xiangya Hospital of Central South University from June 2008 to June 2023, aiming to provide a better understanding of the prognosis of APSN patients and offer scientific evidence for clinical treatment. The average age of the 5 APSN patients was 32.60 years, and all patients underwent dilation and curettage or hysteroscopic surgery or hysteroscopic surgery without hysterectomy. Except for one patient who was lost to follow-up after 30 days, the remaining 4 patients were followed up for 1.36 to 4.61 years. During the follow-up, gynecological ultrasound did not show abnormalities, and serum human chorionic gonadotropin (HCG) tests were negative, with no evidence of malignancy. A search of both English and Chinese databases yielded 8 articles reporting the diagnosis, treatment, and follow-up outcomes of APSN, with 37 cases cumulatively followed up. Among them, 2 (5.41%) cases developed epithelial trophoblastic tumors or placental site trophoblastic tumors during follow-up, but there is insufficient evidence to determine whether these tumors directly originated from APSN or were secondary to APSN. Currently, there is no direct evidence suggesting that APSN has the potential for malignant transformation. Patients with APSN who have completed their childbearing may consider preserving their uterus, but close follow-up is needed to further evaluate the prognosis.
Humans
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Female
;
Pregnancy
;
Adult
;
Trophoblastic Tumor, Placental Site/pathology*
;
Uterine Neoplasms/diagnosis*
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Prognosis
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Dilatation and Curettage
;
Chorionic Gonadotropin/blood*
10.Successful pregnancies following individualized treatment for diffuse uterine leiomyomatosis: A report of 5 cases.
Shudan CHEN ; Sili HE ; Ruizhen LI ; Chunxia CHENG
Journal of Central South University(Medical Sciences) 2025;50(6):1099-1105
OBJECTIVES:
Hysterectomy remains the only definitively effective treatment for diffuse uterine leiomyomatosis (DUL). However, no standardized management strategy exists for DUL patients wishing to preserve fertility. This study summarizes and analyzes 5 cases of individualized treatment in DUL patients desiring fertility preservation, aiming to provide a clinical reference for personalized management of similar patients.
METHODS:
We retrospectively analyzed the clinical data of 5 DUL patients with fertility intentions admitted to the Department of Obstetrics and Gynecology at Third Xiangya Hospital of Central South University. To preserve fertility, individualized treatment plans were selected based on clinical manifestations and fibroid distribution. One patient received high-intensity focused ultrasound (HIFU); one underwent hysteroscopic myomectomy (HM) combined with laparoscopic myomectomy (LRM); one underwent HIFU combined with HM and LRM; one received drug therapy combined with staged HM; and one underwent HIFU combined with staged HM and drug therapy. Treatment outcomes and pregnancy results were analyzed.
RESULTS:
After treatment, all 5 patients showed marked improvement in menstrual volume or dysmenorrhea symptoms and significant reduction in uterine volume; mild intrauterine adhesions occurred in 3 cases. All 5 patients achieved successful pregnancy. One patient with chronic hypertension developed severe preeclampsia at 34 weeks and underwent cesarean section, while the remaining 4 delivered at term by cesarean section. Three cases of placenta accreta and 2 cases of postpartum hemorrhage occurred. During long-term follow-up, one patient underwent hysterectomy 2 years postpartum due to increased menstrual volume, while the other 4 remained stable.
CONCLUSIONS
Individualized treatment tailored to DUL patients' conditions can preserve fertility, support successful pregnancy, and achieve favorable pregnancy outcomes.
Humans
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Female
;
Pregnancy
;
Leiomyomatosis/therapy*
;
Uterine Neoplasms/therapy*
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Adult
;
Retrospective Studies
;
Fertility Preservation/methods*
;
Hysterectomy
;
Uterine Myomectomy/methods*
;
High-Intensity Focused Ultrasound Ablation
;
Pregnancy Outcome


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