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

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 OBJECTIVES

This study assessed how 100 women (ages 18–45) in Quezon City understood HPV and their willingness to vaccinate.

MATERIALS AND METHODS

Researchers 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.

RESULTS

Results 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 RECOMMENDATION

In 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

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.

OBJECTIVES

This study aimed to determine the QOL of young women with cervical cancer treated with concurrent chemoradiation.

MATERIALS AND METHODS

A 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.

RESULTS

Seventy-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.

CONCLUSIONS

The 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

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

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.

OBJECTIVES

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.

STUDY DESIGN

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

POPULATION

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

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.

Human ; Cervical Cancer ; Uterine Cervical Neoplasms ; Human Papillomavirus ; Human Papillomavirus Viruses ; Vaccination

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 ; Female ; Pregnancy ; Adult ; Trophoblastic Tumor, Placental Site/pathology* ; Uterine Neoplasms/diagnosis* ; Prognosis ; Dilatation and Curettage ; Chorionic Gonadotropin/blood*

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 ; Female ; Pregnancy ; Leiomyomatosis/therapy* ; Uterine Neoplasms/therapy* ; Adult ; Retrospective Studies ; Fertility Preservation/methods* ; Hysterectomy ; Uterine Myomectomy/methods* ; High-Intensity Focused Ultrasound Ablation ; Pregnancy Outcome

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 ; Uterine Cervical Neoplasms/prevention & control* ; Female ; Early Detection of Cancer ; Global Burden of Disease ; China/epidemiology* ; Mass Screening ; Quality of Health Care ; Disease Management ; Adult ; Middle Aged

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* ; Autophagy/drug effects* ; HeLa Cells ; Uterine Cervical Neoplasms/therapy* ; Female ; Hyperthermia, Induced ; Spin Labels ; Endoplasmic Reticulum Stress/drug effects* ; Cyclic N-Oxides/pharmacology* ; Cell Survival/drug effects*

OBJECTIVES: To investigate the regulatory effects of Aurora-A in regulating proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells and the role of actin-related protein 2/3 complex subunit 4 (ARPC4) in mediating its effects. METHODS: The plasmids pCDH-NC, pCDH-Aurora-A, and shRNA-ARPC4 were used for inducing Aurora-A overexpression or ARPC4 knockdown in HeLa cells. The cells were divided into vector group, Aurora-A overexpression group, Aurora-A overexpression+ARPC4 knockdown group, and Aurora-A overexpression+NF‑κBp65 inhibitor group and transfected with the corresponding plasmids. The proliferation, colony-forming ability, migration and invasion of the treated Hela cells was evaluated using EdU immunofluorescence assay, crystal violet staining, scratch assay, Transwell assay, and Matrigel assay. Western blotting was performed to detect the changes in cellular expressions of EMT-related proteins and expression levels of NF-κBp65 and ARPC4. RESULTS: The expression of ARPC4 was significantly decreased in HeLa cells with Aurora-A knockdown and increased in Aurora-A-overexpressing cells. Aurora-A overexpression obviously promoted proliferation, migration, and invasion abilities of HeLa cells, and these effects was significantly antagonized by ARPC4 knockdown. In Aurora-A-overexpressing cells, the phosphorylation level of NF-κBp65 and the expression level of ARPC4 were increased significantly, and application of the NF‑κBp65 inhibitor obviously lowered the expression level of ARPC4. CONCLUSIONS Aurora-A overexpression upregulates the expression of ARPC4 by activating the NF-κBp65 signaling pathway, thereby promoting migration, invasion and EMT of HeLa cells.
Humans ; Uterine Cervical Neoplasms/metabolism* ; Female ; HeLa Cells ; Epithelial-Mesenchymal Transition ; Signal Transduction ; Cell Movement ; Neoplasm Invasiveness ; Cell Proliferation ; Aurora Kinase A/metabolism* ; Transcription Factor RelA/metabolism* ; Neoplasm Metastasis