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.

OBJECTIVE: To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum (ER) stress and mitochondrial pathway. METHODS: Different doses (12.5-800 µg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration (IC₅₀) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78 (GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid (4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside. RESULTS: Asperuloside of 325, 650, and 1300 µg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells (P<0.01). All doses of asperuloside significantly increased intracellular ROS levels, reduced mitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions (P<0.01). In addition, 10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis (P<0.05), and 650 µg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation, decreased apoptosis and cleaved-caspase-3, -4 and GRP78 protein expressions (P<0.05). CONCLUSION Our study revealed the role of asperuloside in cervical cancer, suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.
Female ; Humans ; Uterine Cervical Neoplasms/metabolism* ; Caspase 3/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Reactive Oxygen Species/metabolism* ; Endoplasmic Reticulum Chaperone BiP ; HeLa Cells ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Apoptosis ; Endoplasmic Reticulum Stress ; Cell Line, Tumor

Background: Cervical cancer is the fourth leading cause of cancer deaths in women worldwide and second in the Philippines. However, Pap smear test, a common screening test procedure for the detection of cervical cancer, remains underutilized, contributing to the increasing incidence of cervical cancer. Women's knowledge, attitudes, and practices (KAP) must be measured to ensure good, targeted interventions; and increase screening and detection of cervical cancer cases. Objectives: The study aims to determine the KAPof women in Surallah, South Cotabato, towards Pap smear. It also aims to help the local government, college administrators, and rural health unit create programs to enhance women's KAPin the municipality. Methodology: The study used a descriptive, cross-sectional design, employing questionnaires manually distributed to determine the KAPof women in Surallah, South Cotabato. Results: The study included 375 respondents. Most know the purpose and importance of a Pap smear but are in need of better understanding of the procedure and the timing of the test. Most of the respondents also had varied reactions toward the test toward the test; some had positive attitudes, and others had negative attitudes. The respondents didn't undergo the procedure despite having a good knowledge of it. Conclusion Most respondents correctly understood the importance of the procedure but needed to learn how it was done. They also have a fair to commendable attitude towards the test. However, despite these, the respondents still practice poorly due to misconceptions and misinformation
Health Knowledge, Attitudes, Practice ; Papanicolaou Test ; Uterine Cervical Neoplasms ; Surveys and Questionnaires

Female ; Humans ; Adenocarcinoma in Situ ; Uterine Cervical Neoplasms/pathology* ; Papillomavirus Infections ; Cervix Uteri/pathology* ; Adenocarcinoma/pathology* ; Papillomaviridae ; DNA, Viral

INTRODUCTION: Cervical cancer has a high disease burden in Singapore, and it is strongly associated with human papillomavirus (HPV) infections. Despite constant efforts to encourage vaccination, local HPV vaccine uptake remains low. Universal mass vaccination is a proven cost-effective method to reduce the cervical cancer disease burden. This paper reviews the newly implemented school-based HPV vaccination programme in Singapore and the factors that led to its success. METHODS: Fully subsidised HPV vaccinations were offered to all Secondary 1 female students on an opt-in basis, starting as a rollout dose in 2019. One-time catchup vaccination was also offered to female students in Secondary 2-5. Eligible recipients were identified using enrolment data provided by Ministry of Education schools. A total of 19,144 students across 139 schools were offered the rollout dose, and 20,854 students across 140 schools were offered the catchup doses. RESULTS: High vaccine uptake rates of 80.6%-87.3% were noted with the introduction of the school-based programme, translating to high vaccine coverage of 90.3%-93.4%. Only a small proportion of students (1.5%-1.9% per cohort) opted out. The rate of reported side effects, which were commonly known effects, was low at one in 1000. Among the students who reported side effects, those who received the second vaccine dose did so uneventfully. CONCLUSION High HPV vaccine coverage was achieved after implementation of the school-based immunisation programme. Timely assessment of knowledge lapses and targeted intervention, strong partnerships with stakeholders, constant on-site adaptation and positive social influence contributed to its success. This model can be applied to future school health programmes.
Humans ; Female ; Papillomavirus Vaccines/therapeutic use* ; Human Papillomavirus Viruses ; Papillomavirus Infections/prevention & control* ; Singapore ; Uterine Cervical Neoplasms/epidemiology* ; Vaccination ; Immunization Programs

Objective: To investigate the clinicopathological features and prognostic factors of lung metastasis in patients with cervical cancer after treatment. Methods: The clinicopathological data of 191 patients with lung metastasis of stage Ⅰa-Ⅲb cervical cancer (FIGO 2009 stage) treated in Sichuan Cancer Hospital from January 2007 to December 2020 were analyzed retrospectively. Kaplan Meier method and Log rank test were used for survival analysis, and Cox regression model was used for prognostic factors analysis. Results: Among 191 patients with lung metastasis of cervical cancer, pulmonary metastasis was found in 134 patients (70.2%) during follow-up examination, and 57 patients (29.8%) had clinical symptoms (cough, chest pain, shortness of breath, hemoptysis, and fever). The time from the initial treatment of cervical cancer to the discovery of lung metastasis was 1-144 months in the whole group, with a median time of 19 months. Univariate analysis of the prognosis of lung metastasis after treatment of cervical cancer showed that the diameter of cervical tumor, lymph node metastasis, positive surgical margin, disease-free interval after treatment of cervical cancer, whether it is accompanied by other metastasis, the number, location and maximum diameter of lung metastasis, and the treatment method after lung metastasis are related to the prognosis of patients with lung metastasis of cervical cancer. Multivariate analysis showed that the number of lung metastases and other site metastases in addition to lung metastases were independent factors affecting the prognosis of patients with lung metastases of cervical cancer (P<0.05). Conclusions: For patients with cervical cancer, attention should be paid to chest CT examination during follow-up to guard against the possibility of lung metastasis after treatment. Besides lung metastasis, other site metastasis and the number of lung metastasis are independent factors affecting the prognosis of patients with lung metastasis of cervical cancer. For patients with lung metastasis after treatment of cervical cancer, surgical treatment is an effective treatment. It is necessary to strictly grasp the surgical indications, and some patients can achieve long-term survival. For patients with lung metastasis of cervical cancer who are not suitable for resection of lung metastasis, the remedial treatment of chemotherapy with or without radiotherapy is still a recommended choice.
Female ; Humans ; Prognosis ; Uterine Cervical Neoplasms/pathology* ; Neoplasm Staging ; Retrospective Studies ; Lung Neoplasms/pathology* ; Survival Rate

Objective: To investigate the mechanism of S100A7 inducing the migration and invasion in cervical cancers. Methods: Tissue samples of 5 cases of cervical squamous cell carcinoma and 3 cases of adenocarcinoma were collected from May 2007 to December 2007 in the Department of Gynecology of the Affiliated Hospital of Qingdao University. Immunohistochemistry was performed to evaluate the expression of S100A7 in cervical carcinoma tissues. S100A7-overexpressing HeLa and C33A cells were established with lentiviral systems as the experimental group. Immunofluorescence assay was performed to observe the cell morphology. Transwell assay was taken to detect the effect of S100A7-overexpression on the migration and invasion of cervical cancer cells. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to examine the mRNA expressions of E-cadherin, N-cadherin, vimentin and fibronectin. The expression of extracellular S100A7 in conditioned medium of cervical cancer cell was detected by western blot. Conditioned medium was added into Transwell lower compartment to detect cell motility. Exosomes were isolated and extracted from the culture supernatant of cervical cancer cell, the expressions of S100A7, CD81 and TSG101 were detected by western blot. Transwell assay was taken to detect the effect of exosomes on the migration and invasion of cervical cancer cells. Results: S100A7 expression was positively expressed in cervical squamous carcinoma and negative expression in adenocarcinoma. Stable S100A7-overexpressing HeLa and C33A cells were successfully constructed. C33A cells in the experimental group were spindle shaped while those in the control group tended to be polygonal epithelioid cells. The number of S100A7-overexpressed HeLa cells passing through the Transwell membrane assay was increased significantly in migration and invasion assay (152.00±39.22 vs 105.13±15.75, P<0.05; 115.38±34.57 vs 79.50±13.68, P<0.05). RT-qPCR indicated that the mRNA expressions of E-cadherin in S100A7-overexpressed HeLa and C33A cells decreased (P<0.05) while the mRNA expressions of N-cadherin and fibronectin in HeLa cells and fibronectin in C33A cells increased (P<0.05). Western blot showed that extracellular S100A7 was detected in culture supernatant of cervical cancer cells. HeLa cells of the experimental group passing through transwell membrane in migration and invasion assays were increased significantly (192.60±24.41 vs 98.80±47.24, P<0.05; 105.40±27.38 vs 84.50±13.51, P<0.05) when the conditional medium was added into the lower compartment of Transwell. Exosomes from C33A cell culture supernatant were extracted successfully, and S100A7 expression was positive. The number of transmembrane C33A cells incubated with exosomes extracted from cells of the experimental group was increased significantly (251.00±49.82 vs 143.00±30.85, P<0.05; 524.60±52.74 vs 389.00±63.23, P<0.05). Conclusion: S100A7 may promote the migration and invasion of cervical cancer cells by epithelial-mesenchymal transition and exosome secretion.
Female ; Humans ; Uterine Cervical Neoplasms/pathology* ; HeLa Cells ; Fibronectins/metabolism* ; Culture Media, Conditioned ; Carcinoma, Squamous Cell/metabolism* ; Adenocarcinoma ; Cadherins/metabolism* ; RNA, Messenger/metabolism* ; Cell Movement ; Epithelial-Mesenchymal Transition/genetics* ; Cell Line, Tumor ; Cell Proliferation ; S100 Calcium Binding Protein A7/metabolism*

Objective: To explore the relationship between the expression of the T-cell activation suppressor-immunoglobulin variable region (VISTA) and the development of cervical squamous cell carcinoma (CSCC), and the impact on the prognosis of CSCC patients. Methods: Cervical tissue samples from 116 CSCC, including 23 cervical intraepithelial neoplasia (CIN) grade I, 23 CIN grade Ⅱ-Ⅲ, and 23 chronic cervicitis patients, were collected from the First Hospital of Soochow University between March 2014 and April 2019. The expression of VISTA in each group was detected by immunohistochemistry (IHC). Survival data of CSCC patients were obtained by follow-up. The survival analysis was performed by Kaplan-Meier method, and survival differences between groups were compared by Log rank test. Prognostic impact factors were analyzed using a multifactorial Cox proportional hazards model. Results: The positive rate of VISTA expression in CSCC group was 32.8% (38/116), and which of grade Ⅱ-Ⅲ was 17.4% (4/23). VISTA expression results showed no positive expression patients in the cervical intraepithelial neoplasia grade I and chronic cervicitis groups. The differences between the CSCC group and other groups were statistically significant (P<0.01). In 116 CSCC patients, VISTA expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis (P<0.01). The mean survival time of patients in the VISTA positive expression group was 30.7 months, and the 3-year survival rate was 44.7% (17/38). However, the mean survival time of the patients in the VISTA negative expression group was 49.1 months, and the 3-year survival rate was 87.2% (68/78). The Cox regression model found that VISTA expression positivity (P=0.001) and FIGO stage (P=0.047) were prognostic factors for CSCC, and patients with VISTA-positive CSCC had a 4.130-fold risk of death higher than those with VISTA-negative expression. Conclusions: The VISTA protein is highly expressed in CSCC tissues, and its expression level is closely related to the occurrence and development of CSCC. The expression of VISTA can be used as an independent predictor of CSCC prognosis and can provide a strong basis for the treatment of CSCC with immune checkpoint inhibitors.
Female ; Humans ; Carcinoma, Squamous Cell/pathology* ; Clinical Relevance ; Neoplasm Staging ; Prognosis ; Uterine Cervical Dysplasia/pathology* ; Uterine Cervical Neoplasms/pathology* ; Uterine Cervicitis/pathology*

Objective: To study the diagnostic value of different detection markers in histological categories of endocervical adenocarcinoma (ECA), and their assessment of patient prognosis. Methods: A retrospective study of 54 patients with ECA in the Cancer Hospital, Chinese Academy of Medical Sciences from 2005-2010 were performed. The cases of ECA were classified into two categories, namely human papillomavirus-associated adenocarcinoma (HPVA) and non-human papillomavirus-associated adenocarcinoma (NHPVA), based on the 2018 international endocervical adenocarcinoma criteria and classification (IECC). To detect HR-HPV DNA and HR-HPV E6/E7 mRNA in all patients, we used whole tissue section PCR (WTS-PCR) and HPV E6/E7 mRNA in situ hybridization (ISH) techniques, respectively. Additionally, we performed Laser microdissection PCR (LCM-PCR) on 15 randomly selected HR-HPV DNA-positive cases to confirm the accuracy of the above two assays in identifying ECA lesions. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of markers to identify HPVA and NHPVA. Univariate and multifactorial Cox proportional risk model regression analyses were performed for factors influencing ECA patients' prognoses. Results: Of the 54 patients with ECA, 30 were HPVA and 24 were NHPVA. A total of 96.7% (29/30) of HPVA patients were positive for HR-HPV DNA and 63.3% (19/30) for HR-HPV E6/E7 mRNA, and 33.3% (8/24) of NHPVA patients were positive for HR-HPV DNA and HR-HPV E6/E7 mRNA was not detected (0/24), and the differences were statistically significant (P<0.001). LCM-PCR showed that five patients were positive for HR-HPV DNA in the area of glandular epithelial lesions and others were negative, which was in good agreement with the E6/E7 mRNA ISH assay (Kappa=0.842, P=0.001). Analysis of the ROC results showed that the AUC of HR-HPV DNA, HR-HPV E6/E7 mRNA, and p16 to identify HPVA and NHPVA were 0.817, 0.817, and 0.692, respectively, with sensitivities of 96.7%, 63.3%, and 80.0% and specificities of 66.7%, 100.0%, and 58.3%, respectively. HR-HPV DNA identified HPVA and NHPVA with higher AUC than p16 (P=0.044). The difference in survival rates between HR-HPV DNA (WTS-PCR assay) positive and negative patients was not statistically significant (P=0.156), while the difference in survival rates between HR-HPV E6/E7 mRNA positive and negative patients, and p16 positive and negative patients were statistically significant (both P<0.05). Multifactorial Cox regression analysis showed that International Federation of Obstetrics and Gynecology (FIGO) staging (HR=19.875, 95% CI: 1.526-258.833) and parametrial involvement (HR=14.032, 95% CI: 1.281-153.761) were independent factors influencing the prognosis of patients with ECA. Conclusions: HR-HPV E6/E7 mRNA is more reflective of HPV infection in ECA tissue. The efficacy of HR-HPV E6/E7 mRNA and HR-HPV DNA (WTS-PCR assay) in identifying HPVA and NHPVA is similar, with higher sensitivity of HR-HPV DNA and higher specificity of HR-HPV E6/E7 mRNA. HR-HPV DNA is more effective than p16 in identifying HPVA and NHPVA. HPV E6/E7 mRNA and p16 positive ECA patients have better survival rates than negative.
Female ; Humans ; Papillomavirus Infections/diagnosis* ; Retrospective Studies ; Uterine Cervical Neoplasms/pathology* ; Prognosis ; Oncogene Proteins, Viral/genetics* ; Human Papillomavirus Viruses ; Adenocarcinoma/pathology* ; RNA, Messenger/genetics* ; Papillomaviridae/genetics* ; RNA, Viral/genetics*

Objective: To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. Methods: A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy). The median follow-up time was (96±12) months ( range time from 84 to 108 months). Results: (1) The data were divided into surgery combined with chemoradiotherapy group (surgery group) and concurrent chemoradiotherapy group (radiotherapy group), including 324 cases in the surgery group and 164 cases in the radiotherapy group. There were significant differences in Eastern Cooperation Oncology Group (ECOG) score, FIGO 2018 stage, large tumors (≥4 cm), total treatment time and total treatment cost between the two groups (all P<0.01). (2) Prognosis: ① for stage Ⅲc1 patients, there were 299 patients in the surgery group with 250 patients survived (83.6%). In the radiotherapy group, 74 patients survived (52.9%). The difference of survival rates between the two groups was statistically significant (P<0.001). For stage Ⅲc2 patients, there were 25 patients in surgery group with 12 patients survived (48.0%). In the radiotherapy group, there were 24 cases, 8 cases survived, the survival rate was 33.3%. There was no significant difference between the two groups (P=0.296). ② For patients with large tumors (≥4 cm) in the surgery group, there were 138 patients in the Ⅲc1 group with 112 patients survived (81.2%); in the radiotherapy group, there were 108 cases with 56 cases survived (51.9%). The difference between the two groups was statistically significant (P<0.001). Large tumors accounted for 46.2% (138/299) vs 77.1% (108/140) in the surgery group and radiotherapy group. The difference between the two groups was statistically significant (P<0.001). Further stratified analysis, a total of 46 patients with large tumors of FIGO 2009 stage Ⅱb in the radiotherapy group were extracted, and the survival rate was 67.4%, there was no significant difference compared with the surgery group (81.2%; P=0.052). ③ Of 126 patients with common iliac lymph node, 83 patients survived, with a survival rate of 65.9% (83/126). In the surgery group, 48 patients survived and 17 died, with a survival rate of 73.8%. In the radiotherapy group, 35 patients survived and 26 died, with a survival rate of 57.4%. There were no significant difference between the two groups (P=0.051). (3) Side effects: the incidence of lymphocysts and intestinal obstruction in the surgery group were higher than those in the radiotherapy group, and the incidence of ureteral obstruction and acute and chronic radiation enteritis were lower than those in the radiotherapy group, and there were statistically significant differences (all P<0.01). Conclusions: For stage Ⅲc1 patients who meet the conditions for surgery, surgery combined with postoperative adjuvant chemoradiotherapy and radical chemoradiotherapy are acceptable treatment methods regardless of pelvic lymph node metastasis (excluding common iliac lymph node metastasis), even if the maximum diameter of the tumor is ≥4 cm. For patients with common iliac lymph node metastasis and stage Ⅲc2, there is no significant difference in the survival rate between the two treatment methods. Based on the duration of treatment and economic considerations, concurrent chemoradiotherapy is recommended for the patients.
Female ; Humans ; Uterine Cervical Neoplasms/pathology* ; Neoplasm Staging ; Lymphatic Metastasis ; Lymph Node Excision ; Retrospective Studies ; Prognosis ; Chemoradiotherapy/methods* ; Carcinoma, Squamous Cell/pathology*