BACKGROUND

Cervical cancer remains to be the second leading cancer and cause of cancer-related deaths among Filipino women despite the use of the Papanicolaou screening. Latest research has shown that the human papillomavirus (HPV) is a necessary cause of cervical cancer. With major morbidity and high mortality rates associated with HPV infection and cervical cancer, several modes of primary and secondary forms of prevention have to be implemented. Among the primary modes of prevention is the administration of the preventive vaccine, which has consistently shown to decrease substantially HPV disease and cervical cancer rates in developed countries. In our country, before a successful vaccination, program is implemented, several sociocultural issues have to be addressed. Knowledge, attitude, and motivational factors are vital in determining acceptance of the vaccine. One relevant setting is exploring the willingness of mothers to get their female children vaccinated even before they become sexually active.

The aim of the study was to determine the association of the knowledge, attitude, and motivational factors of mothers on their willingness for their female children aged 9–13 years to undergo HPV vaccination at a tertiary government hospital.

This was a cross-sectional study that was carried out at a government institution.

The population consisted of 352 mothers with female children aged 9–13 years consulting the outpatient clinics at the department of obstetrics and gynecology at a tertiary government hospital.

A pretested and validated survey was given to 352 respondents. They were asked to answer a self-administered questionnaire that included sociodemographic, reproductive, sexual history variables, knowledge, and attitude, and motivational factors toward the disease and the associated vaccine.

Using the survey proportion estimation methods, the prevalence of women who were willing to enroll their daughters for HPV vaccination was 97.18% (n = 42, 95% confidence interval [CI]: 94.91 to 98.46%). It can be noted that only a third of the sample had high knowledge on the vaccine and its use 34.93% (n = 124, 95% CI: 30.25 to 39.92%). More women who reached college level (χ2: 5.67) and also those whose youngest child was between 11 and 13 years old (χ2: 8.82)-had higher knowledge scores than otherwise. Those who have an annual income of greater than or equal to P 60,000 (χ2: 16.55) and are non-Catholic (χ2: 18.77) – also appeared to have higher knowledge ratings on the questionnaire. Women who never to a few times a year attend church-related activities had higher knowledge scores compared to women who were more frequent goers (χ2: 16.33). For the attitude toward the vaccine, more mothers believed that getting the vaccine would not have an effect on a girl’s sexual activity and most agreed that they would not be viewed as bad parents. Most women also did not believe that religion would affect their willingness to vaccinate their children. There was an association in the degree of agreement between negative and positive attitudes from the Chi-square test performed (χ2: 7.44, P: 0.01). There were more agreeing responses from factors determining positive attitude and more disagreeing responses in the factors determining negative attitude. With regard to motivational factors, more women agreed that the cost was prohibitive and that they were more willing if only two doses would be required for their daughters. They were also not concerned about what other parents may think about getting the vaccine. Most answered that they were willing to follow their doctors’ recommendations and they have trust in vaccine manufacturers. Most women were also concerned that their daughters may get cervical cancer in the future. There was no difference in the proportion of agreeing responses between positive and negative motivating factors among the study participants (Z: 0.30, P: 0.79). This suggested that these factors could be important predictors of willingness to use vaccination on their children. Based on the crude odds ratios from the logistic regression, the likelihood of being willing to administer HPV vaccine to their children was almost twice as the knowledge score and scores on the positive attitude items increased, and was found to be statistically significant. At the same time, the odds of willingness increased by more than twice as the score on the negative attitude items decreased, and was also significant. There was no noted association for the other predictors of the association.

The role of knowledge and attitudes on the negative perceptions on the vaccine were important predictors of the willingness of mothers to have their female children vaccinated against HPV infection.

Congenital malformations of the uterus are rare. Pregnancies in these uterine abnormalities are usually associated with poor reproductive outcomes such as recurrent pregnancy losses, preterm birth and intrauterine growth restriction. Presented here is the case of a 21-year old G2P1(1001), who was diagnosed intraoperatively with a septate bicornuate uterus during her second Cesarean delivery. She had to undergo abdominal delivery for both her pregnancies due to malpresentation, and delivered live healthy babies with no gross structural defects. Pathophysiology and classification of congenital uterine malformations are discussed in the case, as well as the diagnostics and management for such conditions.
Human ; Female ; Young Adult: 19-24 yrs old ; Bicornuate uterus ; Septate Uterus ; Uterine anomalies

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

BACKGROUND: Cervical squamous cell carcinoma (CESC), the most common subtype of cervical cancer, is primarily caused by the high-risk human papillomavirus (HPV) infection and genetic susceptibility. Single-cell RNA sequencing (scRNA-seq) has been widely used in CESC research to uncover the diversity of cell types and states within tumor tissues, enabling a detailed study of the tumor microenvironment (TME). This technology allows precise mapping of HPV infection in cervical tissues, providing valuable insights into the initiation and progression of HPV-mediated malignant transformation. METHODS: We performed the scRNA-seq to characterize gene expression in tumor tissues and paired adjacent para-cancerous tissues from four patients with early-stage CESC using the 10× Genomics platform. The HPV infection and its subtypes were identified using the scRNA data and viral sequence mapping, and trajectory analyses were performed using HPV+ or HPV- cells. Interactions between different types of keratinized cells and their interactions with other cell types were identified, and pathways and specificity markers were screened for proliferating keratinized cells. The Cancer Genome Atlas (TCGA) dataset was used to verify the prognostic correlation between tumor-specific PI3+S100A7+ keratinocyte infiltration and CESC, and the localization relationship between PI3+S100A7+ keratinocytes and macrophages was verified by immunofluorescence staining. RESULTS: Various types of keratinocytes and fibroblasts were the two cell types with the most significant differences in percentage between the tumor tissue samples and paired adjacent non-cancerous tissue samples in the early stages of CESC. We found that PI3+S100A7+ keratinocytes were associated with early HPV-positive CESC, and PI3+S100A7+ keratinocytes were more abundant in tumors than in adjacent normal tissues in the TCGA-CESC dataset. Analysis of clinical information revealed that the infiltration of PI3+S100A7+ keratinocytes was notably higher in tumors with poor prognosis than in those with good prognosis. Additionally, multiplex immunofluorescence analysis showed a specific increase in PI3+S100A7+ expression within tumor tissues, with PI3+S100A7+ keratinocytes and CD163+ macrophages being spatially very close to each other. In the analysis of cell-cell interactions, macrophages exhibited strong crosstalk with PI3+S100A7+ proliferating keratinocytes in HPV-positive CESC tumors, mediated by tumor necrosis factor (TNF), CCL2, CXCL8, and IL10, highlighting the dynamic and tumor-specific enhancement of macrophage-keratinocyte interactions, which are associated with poor prognosis and immune modulation. Using CIBERSORTx, we discovered that patients with high infiltration of both PI3+S100A7+ proliferating keratinocytes and macrophages had the shortest overall survival. In the analysis of cell-cell interactions, PI3+S100A7+ proliferating keratinocytes and macrophages were found to be involved in highly active pathways that promote differentiation and structure formation, including cytokine receptor interactions, the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway, and TNF signaling pathway regulation. Further subtyping of fibroblast populations identified four subtypes. The C1 group, characterized by its predominance in tumor tissues, is a subtype enriched with cancer-associated fibroblasts (CAFs), whereas the C3 group is primarily enriched in adjacent non-cancerous tissues and consists of undifferentiated cells. Moreover, the distinct molecular and cellular differences between HPV16- and HPV66-associated tumors were demonstrated, emphasizing the unique tumor-promoting mechanisms and microenvironmental influences driven by each HPV subtype. CONCLUSIONS We discovered a heterogeneous population of keratinocytes between tumor and adjacent non-cancerous tissues caused by HPV infection and identified macrophages and specific CAFs that play a crucial role during the early stage in promoting the inflammatory response and remodeling the cancer-promoting TME. Our findings provide new insights into the transcriptional landscape of early-stage CESC to understand the mechanism of HPV-mediated malignant transformation in cervical cancer.
Humans ; Female ; Papillomavirus Infections/genetics* ; Uterine Cervical Neoplasms/genetics* ; Carcinoma, Squamous Cell/pathology* ; Keratinocytes/metabolism* ; Single-Cell Analysis/methods* ; Tumor Microenvironment/genetics*

BACKGROUND: Concurrent chemo-radiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer (LACC), but there are still many patients who suffer tumor recurrence. However, valuable predictors of treatment outcomes remain limited. This study aimed to assess the value of the serum immune biomarkers to predict the prognosis. METHODS: We reviewed cervical cancer patients treated with CCRT between January 2014 and May 2018 at Peking Union Medical College Hospital. The systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and lactate dehydrogenase (LDH) were calculated using blood samples. The relationship between immune markers and the treatment outcome was analyzed. The area under the receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency. The Cox proportional hazards model and log-rank were used to predict overall survival (OS) and disease-free survival (DFS). RESULTS: This study included 667 patients. Among them, 195 (29.2%) patients were defined as treatment failure, including 127 (19.0%) patients with pelvic failure, 94 (14.1%) distant failure, and 25 (3.7%) concurrent pelvic and distant failure. It revealed that the tumor stage, size, metastatic lymph nodes (MLNs), and serum immune biomarkers, such as SII, SIRI, and LDH, were significantly related to treatment outcomes. We demonstrated that the optimal cut-off of the SII, SIRI, and LDH were 970.4 × 10 9 /L, 1.3 × 10 9 /L, and 207.52 U/L, respectively. Importantly, this study presented that LDH level had the highest OR (OR = 4.2; 95% CI [2.3-10.8]). Furthermore, the OS and DFS for patients with pre-SII ≥970.5 × 10 9 /L were significantly worse than those with pre-SII <970.5 × 10 9 /L. Similarly, pre-SIRI ≥1.25 × 10 9 /L and pre-LDH ≥207.5 U/L were related to poor survival outcomes. CONCLUSIONS This study demonstrated that the baseline SII, SIRI, and LDH levels can be used to accurately and effectively predict the treatment outcomes after CCRT and long-term prognosis. Our results may offer additional prognostic information in clinical, which helps to detect the potential recurrent metastasis in time.
Humans ; Female ; Uterine Cervical Neoplasms/drug therapy* ; Middle Aged ; Adult ; Aged ; Chemoradiotherapy/methods* ; L-Lactate Dehydrogenase/blood* ; Treatment Outcome ; Disease-Free Survival ; Prognosis ; ROC Curve ; Biomarkers, Tumor/blood* ; Proportional Hazards Models

Humans ; Uterine Cervical Neoplasms/pathology* ; Female ; Patient Care Team ; Consensus ; China ; Neoplasm Staging ; Combined Modality Therapy ; Quality of Life ; Neoplasm Recurrence, Local/therapy* ; East Asian People

Humans ; Female ; Uterine Cervical Neoplasms/pathology* ; Carcinoma, Neuroendocrine/pathology* ; Consensus ; Prognosis ; Neoplasm Staging ; Cervix Uteri/pathology*

Intrauterine adhesion(IUA) is a common gynecological disease that is difficult to treat, and there is a lack of specific effective drugs and measures to prevent endometrial fibrosis. In this study, the mechanism of endometrial oxidative stress and fibrosis regulation was studied in an IUA rat model constructed by Bushen Huoxue Formula intervention of mechanical injury combined with infection. A total of 72 SPF SD female rats aged 8-10 weeks were randomly divided into blank control group, model control group, low-dose, medium-dose, and high-dose groups of Bushen Huoxue Formula, and estrogen groups. The rats in the estrous cycle of the model control group and the positive control group were simulated with surgical injury and infection, and the sham operation group was treated with on-off abdominal treatment. After successful modeling, the model control group was administered intragastrically with purified water of 15 μL·g~(-1) every day. The low-dose group was administered intragastrically with Bushen Huoxue Formula of 7.8 g·kg~(-1); the medium-dose group was administered intragastrically with Bushen Huoxue Formula of 15.6 g·kg~(-1), and the high-dose group was administered intragastrically with Bushen Huoxue Formula of 31.2 g·kg~(-1). The estrogen group was administered intragastrically with estradiol valerate of 4.2 mg·kg~(-1). After continuous intervention for 28 days, all rats were deprived of water and killed to collect blood and tissue. Hematoxylin-eosin(HE) staining calculated the number of uterine glands; Masson staining calculated the area of uterine collagen fibers. Combined with HE and Masson staining, semi-quantitative scores were performed on the degree of endometrial fibrosis. Immunohistochemistry was performed to detect the vascular endothelial growth factor(VEGF), stromal cell-derived factor-1(SDF-1), and transforming growth factor-β1(TGF-β1) expression in rats' uterine tissue. Enzyme-linked immunosorbent assay(ELISA) dected angiopoietin 1(IFN-γ), interleukin-1α(IL-1α), TGF-β1, tumor necrosis factor-α(TNF-α), collagen type Ⅳ(Ⅳ-Col), leukemia inhibitory factor(LIF), superoxide dismutase(SOD)、glutathione peroxidase(GSH-Px);The mRNA expressions of Smad2, Smad3, adisintegrin and metalloproteinase(ADAM17) and TGF-β1 were determined by qPCR. Notch and ADAM17 protein expression in rat uterus were determined by Western blot. The results showed that the area of uterine fibrosis was significantly reduced and the conditions of edema and adhesion were effectively alleviated after high-dose intervention of Bushen Huoxue Formula. The levels of inflammatory factors and Ⅳ-Col were significantly decreased, and the levels of LIF and antioxidant enzymes were significantly increased. The mRNA expressions of Smad2, Smad3, ADAM17 and TGF-β1 were significantly down-regulated. Immunohistochemical results showed that Bushen Huoxu Formula could effectively increase the positive expression of SDF-1 and reduce the positive expression of VEGF and TGF-β1. Western blot results showed that the protein expressions of Notch and ADAM17 in high-dose, medium-dose and low-dose of Bushen Huoxu Formula groups were significantly down-regulated in a dose-dependent manner. These results suggest that Bushen Huoxue Formula may inhibit fibrosis process through ADAM17/Notch signaling pathway, suggesting that Bushen Huoxuet Formula is one of the potential therapeutic methods for IUA.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Endometrium/pathology* ; Rats ; Fibrosis/metabolism* ; Oxidative Stress/drug effects* ; Humans ; Uterine Diseases/genetics* ; Vascular Endothelial Growth Factor A/genetics*

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

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 ; Female ; Uterine Cervical Neoplasms/immunology* ; Middle Aged ; Chemoembolization, Therapeutic/methods* ; Sialic Acid Binding Ig-like Lectin 3/immunology* ; Adult ; T-Lymphocytes/immunology* ; Aged ; Treatment Outcome