RESUMO
Precise vaccination data is essential to accurately estimate the effectiveness of the human papillomavirus (HPV) vaccine against HPV-related cancers. In Japan, the number of subsidized HPV vaccinations can be tracked through registries, but the number of self-funded vaccinations has not been tracked. The number of individuals who chose to receive the vaccine at their own expense, despite being ineligible for public subsidies due to their age, is unknown and has been nominally considered to be zero. Our aim is to produce a more accurate estimate of this number using recently released proprietary data. First, we estimated the total number of self-funded HPV vaccinations occurring from 2010 to 2012 using public data from the Ministry of Health, Labour and Welfare and our previously reported data on the number of HPV vaccinations eligible for public subsidy. Second, using proprietary data from the vaccine manufacturer, we calculated the distribution of self-funded vaccination shots by age. Finally, we combined these data to estimate the number of self-funded HPV vaccinations by birth fiscal year (FY) relative to a yearly reference population. We found that 78,264 individuals born in FY1993 and 58,190 born in FY1992 self-funded their vaccinations, representing 13.6% and 10.0% of the reference population, respectively. Additionally, we found that 5%-10% of individuals born from FY1986 to FY1991 self-funded their vaccinations. Our study revealed for the first time that a certain number of individuals from the "HPV unvaccinated generation," ineligible for subsidies due to age restrictions, chose to self-fund their vaccinations.
RESUMO
DNA methylation is a pivotal epigenetic modification that defines cellular identity. While cell deconvolution utilizing this information is considered useful for clinical practice, current methods for deconvolution are limited in their accuracy and resolution. In this study, we collected DNA methylation data from 945 human samples derived from various tissues and tumor-infiltrating immune cells and trained a neural network model with them. The model, termed MEnet, predicted abundance of cell population together with the detailed immune cell status from bulk DNA methylation data, and showed consistency to those of flow cytometry and histochemistry. MEnet was superior to the existing methods in the accuracy, speed, and detectable cell diversity, and could be applicable for peripheral blood, tumors, cell-free DNA, and formalin-fixed paraffin-embedded sections. Furthermore, by applying MEnet to 72 intrahepatic cholangiocarcinoma samples, we identified immune cell profiles associated with cancer prognosis. We believe that cell deconvolution by MEnet has the potential for use in clinical settings.
RESUMO
In 2013, the national human papillomavirus (HPV) immunization program began. However, in June 2013, Japan's Ministry of Health, Labor and Welfare (MHLW) announced a "temporary" suspension of its recommendation for the human papillomavirus vaccine. Finally, in November 2021, the MHLW ended its suspension of the recommendation of the HPV vaccine. To address the 9-year gap in HPV vaccinations the suspension had caused, the MHLW conducted a program of catch-up vaccinations from April 2022 to March 2025. Finally, in April 2023, the 9-valent HPV vaccine was approved for both the routine and catch-up vaccination programs in Japan. In this study, we investigated the potential effects of the introduction of the 9-valent vaccine on the increased risk of cervical cancer in females born after fiscal year (FY) 2000. We estimated the lifetime relative risk of cervical cancer incidence and death using the improved routine and catch-up vaccination rates after the recent resumption of the governmental recommendation for women and girls to have the HPV vaccination. These relative risks were calculated using a lifetime risk of 1.000 for cervical cancer incidence and death for females born in FY 1993. We predicted that even if a 90% vaccination rate were to be achieved by FY 2024 with the 9-valent vaccine among women born between FY 2000 and FY 2005, the risk would remain higher than for the vaccination generation. Therefore, for women born between FY 2000 and FY 2005, it will be necessary to significantly improve the cervical cancer screening rate to compensate for this increased risk.
Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Detecção Precoce de Câncer , Japão/epidemiologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Comportamento de Redução do Risco , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Programas de ImunizaçãoRESUMO
BACKGROUND Although screening for uterine cervical cancer (UCC) and vaccination programs for human papilloma virus (HPV) have been implemented in many countries, women >65 years may not have access to or comply with cervical cancer screening. Women >65 years may present with advanced-stage cervical carcinoma with a poor outcome. Metastatic UCC is often diagnosed, and there are 2 types of metastases related to different treatments and survival rate: hematogenous metastasis and lymphatic metastasis. Hematogenous metastasis is relatively unusual, and it most commonly involves lung and bone locations. Orbital metastasis is an extremely rare hematogenous metastasis in patients with UCC. CASE REPORT A 70-year-old woman receiving dialysis presented to a local hospital due to general fatigue for 5 months. She was diagnosed with locally advanced UCC and underwent radiation therapy (RT). Twenty days after RT, skin masses appeared, and 34 days after RT, right exophthalmos induced by an orbital mass appeared. We diagnosed skin and orbital masses as metastases from UCC, and performed RT to the orbital tumor. The tumor shrank and the visual symptoms disappeared. Regrettably, the patient died of cancer 7 months after the orbital RT; however, no eye symptoms recurred until her death. CONCLUSIONS This report describes a rare presentation of UCC with metastasis to the orbit, and highlights that cervical cancer may still present at an advanced stage, particularly in older women. In this case, RT to the orbital metastasis from UCC was effective and contributed to the patient's quality of life.
Assuntos
Neoplasias Orbitárias , Neoplasias do Colo do Útero , Idoso , Feminino , Humanos , Detecção Precoce de Câncer , Recidiva Local de Neoplasia , Neoplasias Orbitárias/secundário , Qualidade de Vida , Diálise Renal , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Metástase NeoplásicaRESUMO
Randomized clinical trials assessing the efficacy of neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer have predominantly included women with high-grade serous carcinomas. The response rate and oncological outcomes of NACT for malignant ovarian germ cell tumors (MOGCT) are poorly understood. This study aimed to examine the effects of NACT on women with MOGCT by conducting a systematic review of four public search engines. Fifteen studies were identified, and a further descriptive analysis was performed for 10 original articles. In those studies, most women were treated with a bleomycin, etoposide, and cisplatin regimen, and one to three cycles were used in most studies. Four studies comparing NACT and primary debulking surgery showed similar complete response rates (n = 2; pooled odds ratio [OR] 0.90, 95% confidence interval [CI] 0.15-5.27), comparable overall survival (n = 3; 87.0-100% versus 70.0-100%), disease-free survival (n = 3; 87.0-100% versus 70.0-100%), recurrence rate (n = 1; OR 3.50, 95%CI 0.38-32.50), and adverse events rate from chemotherapy between the groups. In conclusion, NACT may be considered for the management of MOGCT; however, possible candidates for NACT use and an ideal number of NACT cycles remain unknown. Further studies are warranted to validate the efficacy of NACT in advanced MOGCT patients.
RESUMO
PURPOSE: In Japan, Japan's Ministry of Health, Labor, and Welfare decided to suspend govermental recommendation for HPV vaccination in FY 2013. The HPV vaccination rate for those born in FY 2000 or thereafter declined dramatically. In 2021, the "suspension of recommendation" ended. The catch-up vaccinations for the unvaccinated have been offered nationwide from FY 2022 to FY 2024. We aimed to quantify the vaccination intentions and characteristics of those young women now eligible for catch-up vaccination. METHODS: In February of 2022, we conducted an internet survey targeted women who were born in 1997-2004 but who had not yet been HPV vaccinated. RESULTS: We received 1,648 valid responses. 41.6% of the respondents wanted to uptake the catch-up HPV vaccination, 29.7% were undecided, and 28.7% did not want to be vaccinated. The intention to uptake catch-up HPV vaccination was associated with a good history of gynecological visits, intention to receive cervical cancer screening, sexual activity, degree of anxiety about cervical cancer, familiarity with problems associated with cervical cancer, experience with vaccination recommendations, and knowledge about cervical cancer (p < 0.05, respectively). In the vaccinated generation, the proportion of the group that did not want to be vaccinated was significantly higher (p < 0.05). In the vaccine-suspended generation, the proportion of the group that wanted to be vaccinated was significantly higher (p < 0.05). CONCLUSION: Our survey revealed that catch-up vaccination intentions differed depending on the vaccination environment. It is necessary for all organizations involved with HPV vaccination, such as government, medical institutions, and educational institutions, to make recommendations based on an understanding of the characteristics of the "vaccinated generation" and the "vaccine-suspended generation".
Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/prevenção & controle , Intenção , Japão , Infecções por Papillomavirus/prevenção & controle , Detecção Precoce de Câncer , Inquéritos e Questionários , Vacinação , Internet , Vacinas contra Papillomavirus/uso terapêuticoRESUMO
INTRODUCTION: Tumor cell spillage during the colpotomy has been suspected as one reason for poor oncologic outcomes in laparoscopic radical hysterectomy (LRH) for cervical cancer. To prevent such tumor spillage in LRH, we focused on use of a Gutclamper which is a device originally designed to clamp the colon and rectum during colorectal resections. MATERIALS AND SURGICAL TECHNIQUE: A woman with stage IB1 cervical cancer underwent LRH using the Gutclamper. The Gutclamper was inserted into the abdominal cavity via 5-mm trocar, the vagina was clamped, and an intracorporeal colpotomy was performed caudal to this device. DISCUSSION: The Gutclamper can be used to clamp the vaginal canal and avoid the exposure of cervical tumor, regardless of the surgeon's skills or patient conditions. An intracorporeal colpotomy using the Gutclamper can contribute to the standardization of LRH.
Assuntos
Carcinoma de Células Escamosas , Laparoscopia , Neoplasias do Colo do Útero , Feminino , Gravidez , Humanos , Neoplasias do Colo do Útero/cirurgia , Colpotomia , Constrição , Estudos Retrospectivos , Carcinoma de Células Escamosas/cirurgia , Estadiamento de Neoplasias , HisterectomiaRESUMO
The placenta has several crucial physiological functions that help maintain a normal pregnancy. Although approximately 2-4% of pregnancies are complicated by abnormal placentas, obstetric outcomes remain understudied. This study aimed to determine the outcomes and prevalence of patients with abnormal placentas by conducting a systematic review of 48 studies published between 1974 and 2022. The cumulative prevalence of circumvallate placenta, succenturiate placenta, multilobed placenta, and placenta membranacea were 1.2%, 1.0%, 0.2%, and 0.004%, respectively. Pregnancies with a circumvallate placenta were associated with an increased rate of emergent cesarean delivery, preterm birth (PTB), and placental abruption compared to those without a circumvallate placenta. The succenturiate lobe of the placenta was associated with a higher rate of emergent cesarean delivery, whereas comparative results were observed in terms of PTB, placental abruption, and placenta previa in comparison to those without a succenturiate lobe of the placenta. A comparator study that examined the outcomes of multilobed placentas found that this data is usually unavailable. Patient-level analysis (n = 15) showed high-rates of abortion (40%), placenta accreta spectrum (40%), and a low term delivery rate (13.3%) in women with placenta membranacea. Although the current evidence is insufficient to draw a robust conclusion, abnormal placentas should be recognized as a high-risk factor for adverse outcomes during pregnancy.
RESUMO
BACKGROUND: This study assesses the feasibility of minimally invasive surgery (MIS) for well-selected epithelial ovarian cancer (EOC) patients. METHODS: We performed a review of data prospectively collected from a single center from 2017 to 2022. Only patients with histologically confirmed EOC, with a tumor diameter of less than 10 cm, were eligible. We also performed a meta-analysis of similar studies comparing the outcomes of laparoscopy and laparotomy. We used MINORS (Methodological Index for Non-Randomized Studies) to assess the risk of bias and calculated the odds ratio or mean difference. RESULTS: Eighteen patients were included; 13 in re-staging group, four in PDS group, and one in IDS group. All achieved complete cytoreduction. One case was converted to laparotomy. The median number of removed pelvic lymph nodes was 25 (range 16-34), and 32 (range 19-44) for para-aortic nodes. There were two (15.4%) intraoperative urinary tract injuries. The median follow-up was 35 months (range 1-53). Recurrence was observed in one case (7.7%). Thirteen articles for early-stage ovarian cancer were included in our meta-analysis. Analysis of the pooled results found that MIS had a higher frequency of spillage (OR, 2.15; 95% CI 1.27-3.64). No differences were observed in recurrence, complications, or up-staging. CONCLUSIONS: Our experience supports the possibility of conducting MIS for EOC in well-selected patients. Except for spillage, our meta-analysis findings are consistent with previous reports, the majority of which were also retrospective. Ultimately, randomized clinical trials will be needed to authenticate the safety.
Assuntos
Laparoscopia , Neoplasias Ovarianas , Humanos , Feminino , Estudos Retrospectivos , Neoplasias Ovarianas/patologia , Carcinoma Epitelial do Ovário/cirurgia , Laparoscopia/métodos , Laparotomia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodosRESUMO
In November 2021, the government of Japan announced a reversal of its decision in 2013 to suspend the previous proactive recommendation for HPV vaccination. However, the program for young girls to receive routine and catch-up vaccinations has not necessarily developed as expected. We conducted a nationwide questionnaire survey by mail in September 2022. The survey was mailed to 133 municipalities consisting of all cities/wards of the Tokyo and Osaka Prefectures and all other prefectural capital cities. Responses were received from 82 municipalities (62.7%). Notification of routine HPV vaccinations had already been sent to 76 (92.7%) of the municipalities; 70 (85.4%) had been encouraged to promote catch-up vaccinations. The questionnaire forms for registration and pre-vaccination screening for routine immunization had been sent to 74.1% (60/81) of the municipalities and 68.8% (55/80) for catch-up immunizations. For catch-up vaccination, only 54 municipalities (65.9%) had detailed vaccination records for those eligible. In total, 10 municipalities (12.2%) had virtually no vaccination records because these had already been discarded. In addition, 61 municipalities (74.4%) had notified only women and girls eligible for a catch-up vaccination based on their vaccination record, whereas 25.6% (21/82) of the municipalities reported that they had sent, or would send, the notification to all women and girls within the targeted grades, including those who had already been vaccinated with three injections. The survey revealed disparities among the municipalities in their HPV vaccine notification processes. Future research on monitoring HPV vaccination rates and incidence rates of cervical cancer and precancerous lesions in each municipality will be desirable.
Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Cidades , População do Leste Asiático , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Disparidades em Assistência à Saúde , Japão , Cobertura VacinalRESUMO
Vasa previa carries a high risk of severe fetal morbidity and mortality due to fetal hemorrhage caused by damage to unprotected fetal cord vessels upon membrane rupture. Vasa previa is generally classified into types I and II. However, some cases are difficult to classify, and some studies have proposed a type III classification. This study aimed to review the current evidence on type III vasa previa. A systematic literature search was conducted, and 11 articles (2011-2022) were included. A systematic review showed that type III vasa previa accounts for 5.7% of vasa previa cases. Thirteen women with type III vasa previa were examined at a patient-level analysis. The median age was 35 (interquartile range [IQR] 31.5-38) years, and approximately 45% were assisted reproductive technology (ART) pregnancies. The median gestational week of delivery was 36 (IQR 34-37) weeks; the antenatal detection rate was 84.6%, and no cases reported neonatal death. The characteristics and obstetric outcomes (rate of ART, antenatal diagnosis, emergent cesarean delivery, gestational age at delivery, and neonatal mortality) were compared between types I and III vasa previa, and all outcomes of interest were similar. The current evidence on type III vasa previa is scanty, and further studies are warranted.
RESUMO
Laparoscopic radical hysterectomy (LRH) for cervical cancer has been reported to be similar oncologic outcome compared to abdominal radical hysterectomy (ARH) in many retrospective studies. In Japan, LRH has been covered by insurance since April 2018. In 2018, the same year that LRH became covered by insurance, Ramirez et al. at MD Anderson Cancer Center reported the results of a large phase III laparoscopic approach to cervical cancer trial (LACC trial) on the prognosis of open versus laparoscopic/robot-assisted minimally invasive radical hysterectomy. The results showed that minimally invasive approaches were associated with a higher rate of recurrence and death. At this point, it is not clear what is wrong with LRH and why it has a poorer prognosis compared to ARH. In this report, after the LACC report, we would like to review the current status of minimally invasive surgery for cervical cancer and future directions.
Assuntos
Laparoscopia , Neoplasias do Colo do Útero , Feminino , Humanos , Histerectomia/métodos , Japão , Laparoscopia/métodos , Estudos Retrospectivos , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Ensaios Clínicos Fase III como AssuntoRESUMO
INTRODUCTION: In laparoscopic surgery, the cooperation of the first assistant surgeon is essential for the creation and maintenance of an appropriate and safe surgical field. The aim of this study is a validation of the impact of our educational system for first assistant laparoscopic surgeon residency in a single university-affiliated teaching hospital. METHODS: Five residents were recruited for this study. We created a slide-set as an educational tool using Microsoft's PowerPoint that was in line with our surgical procedure to master the assistant skills of laparoscopic gynecologic surgery. Immediately after surgery, the attending doctor and residents reviewed videos of the first assistant's operative procedures. This study evaluated the effect of our educational checklist against the transition of evaluation scores before and after training in two groups of residents, those with minimal experience (Group 1) or with high experience (Group 2). RESULTS: Before receiving our training tool, there was an expected significant difference in the review scores of the two experience groups (29.1 ± 3.1 vs 48.7 ± 3.9, P = .01). After our modified training, the inexperienced residents of Group 1 received review scores comparable to or higher than those of the experienced residents of Group 2 (81.9 ± 5.9 vs 70.4 ± 7.5, P = .23). As they assisted with more surgeries, the concordance between the resident's self-assessment and the attending doctor's assessment scores significantly increased (P < .001). CONCLUSIONS: Our educational system for first assistant surgeons is effective for new residents, as it proved capable of imparting them with many of the same skill sets as much more experienced attending doctors.
Assuntos
Cirurgia Geral , Internato e Residência , Laparoscopia , Humanos , Feminino , Competência Clínica , Laparoscopia/educação , Procedimentos Cirúrgicos em Ginecologia , Cirurgia Geral/educaçãoRESUMO
Vasa previa is a rare fetal life-threatening obstetric disease classified into types I and II. This study aimed to examine the characteristics and obstetric outcomes of type II vasa previa. A systematic review was performed, and 20 studies (1998-2022) were identified. The results from six studies showed that type II vasa previa accounted for 21.3% of vasa previa cases. The characteristics and obstetric outcomes (rate of assisted reproductive technology (ART), antenatal diagnosis, emergent cesarean delivery, maternal transfusion, gestational age at delivery, and neonatal mortality) were compared between type I and II vasa previa, and all outcomes of interest were similar. The association between ART and abnormal placenta (bilobed placenta or succenturiate lobe) was examined in three studies, and the results were as follows: (i) increased rate of succenturiate lobes (ART versus non-ART pregnancy; OR (odds ratio) 6.97, 95% confidence interval (CI) 2.45-19.78); (ii) similar rate of abnormal placenta (cleavage-stage versus blastocyst embryo transfer); (iii) increased rate of abnormal placenta (frozen versus fresh embryo transfer; OR 2.97, 95%CI 1.10-7.96). Although the outcomes of type II vasa previa appear to be similar to those of type I vasa previa, the current evidence is insufficient for a robust conclusion.
RESUMO
In 2013, the Ministry of Health, Labor, and Welfare (MHLW) in Japan announced a suspension of the governmental recommendation for routine HPV vaccinations. In 2020, MHLW started individual notifications of HPV vaccine to the targeted girls. In April 2022, the governmental recommendation was restarted, and catch-up vaccinations started. We evaluated the benefits and limitations of the MHLW's new vaccination strategies by estimating the lifetime risk for cervical cancer for each birth FY under different scenarios to suggest a measure for the vaccine suspension generation. It was revealed that catch-up immunization coverage among the unvaccinated must reach as high as 90% in FY2022, when the program begins, in order to reduce the risk of the females already over the targeted ages to the same level or lower than that of women born in FY1994-1999 who had high HPV vaccination rates. For women whose vaccination coverage waned because of their birth FYs, strong recommendations for cervical cancer screening should be implemented.
RESUMO
BACKGROUND: In Japan, HPV vaccination rates has dramaticaly declined since 2013. Since mothers are the ones making the decision to vaccinate their daughters against HPV, we probed the mothers' intention to receive vaccinations for themselves and to vaccinate their daughters against HPV, and their reasoning. METHODS: An internet survey was conducted in March of 2021. Through the screening, 1576 participants were extracted from a survey panel and divided into 3 groups based on their daughter's birth fiscal year (Group 1: 1994 to 1999, Group 2: 2000 to 2003, Group3: 2004 to 2008). The chi-square test and residual analysis were used for the statistical analysis of comparison among the groups. Logistic regression analysis was used to identify independent variables with mothers intention to get their daughters vaccinated under specific situations. RESULTS: The percentage of respondents without anxiety regarding their daughter's general vaccination was significantly higher in Group 1 (p < 0.05). In the mothers of daughters born in or after 2000 when vaccination rates declined (Groups 2 and 3), a situation in which 'The daughter's best friends were vaccinated before her' made the mothers think positively about HPV vaccination, and to the same degree as a situation in which 'You received a notice from your local government recommending vaccination' (Group 2: 41.6% (214/514) and 40.5% (208/514), Group 3: 48.5% (257/530) and 47.0% (249/530)). CONCLUSION: If mothers who have had their daughters vaccinated were to recommend HPV vaccination to their close friends, 'the best friend effect' should promote others to be vaccinated.
Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Infecções por Papillomavirus/prevenção & controle , Neoplasias do Colo do Útero/diagnóstico , Amigos , Japão , Conhecimentos, Atitudes e Prática em Saúde , Vacinação , Mães , Inquéritos e Questionários , Vacinas contra Papillomavirus/uso terapêutico , Aceitação pelo Paciente de Cuidados de SaúdeRESUMO
Abnormal cord insertion (ACI) is associated with adverse obstetric outcomes; however, the relationship between ACI and assisted reproductive technology (ART) has not been examined in a meta-analysis. This study examines the association between ACI and ART, and delivery outcomes of women with ACI. A systematic review was conducted, and 16 studies (1990-2021) met the inclusion criteria. In the unadjusted pooled analysis (n = 10), ART was correlated with a higher rate of velamentous cord insertion (VCI) (odds ratio (OR) 2.14, 95% confidence interval (CI) 1.64-2.79), marginal cord insertion (n = 6; OR 1.58, 95%CI 1.26-1.99), and vasa previa (n = 1; OR 10.96, 95%CI 2.94-40.89). Nevertheless, the VCI rate was similar among the different ART types (blastocyst versus cleavage-stage transfer and frozen versus fresh embryo transfer). Regarding the cesarean delivery (CD) rate, women with VCI were more likely to have elective (n = 3; OR 1.13, 95%CI 1.04-1.22) and emergent CD (n = 5; OR 1.93, 95%CI 1.82-2.03). In conclusion, ART may be correlated with an increased prevalence of ACI. However, most studies could not exclude confounding factors; thus, further studies are warranted to characterize ART as a risk factor for ACI. In women with ACI, elective and emergent CD rates are high.
RESUMO
BACKGROUND: In Japan, in June 2013, The Ministry of Health, Labor and Welfare (MHLW) decided to temporarily suspend its official recommendation for the participation of girls in the national immunization program. The HPV vaccination rate in Japan soon declined to below 1%. In October 2020, the MHLW notified that the municipalities could and should begin to individually notify girls and their parents targeted for routine vaccination. We have examined how that type of individual notification has affected the number of vaccinations. METHODS: From 12 municipalities (with a combined total population of approximately 4.06 million), we collected vaccination data for all girls who attended grades 6 through 10 from April 2019 to March 2021. We analyzed the number of initial-round vaccinations that occurred by month and the timing and the subjects of the individual notifications. RESULTS: The annual vaccination rate for tenth-grade students in 2020 in the six municipalities that had implemented individual notification was 9.46% (342/3618), which was significantly higher than the rate of 3.22% (54/1676) in the three municipalities that had not implemented individual notification (p < 0.001). On the other hand, the annual vaccination rate for the sixth to ninth-grade students in 2020 in the six municipalities that had implemented individual notification was not significantly (p = 0.56) higher than the rate in the three municipalities that did not: 1.43% (197/13,785) versus 1.33% (83/6260), respectively. CONCLUSION: This study clearly demonstrates the importance of providing information for routine vaccination directly to the targets and their parents.
Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Feminino , Humanos , Programas de Imunização , Japão/epidemiologia , Governo Local , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , VacinaçãoRESUMO
BACKGROUND: Endometrial cancer (EC) is a common gynecologic malignancy and patients with advanced and recurrent EC have a poor prognosis. Although chemotherapy is administered for those patients, the efficacy of current chemotherapy is limited. Therefore, it is necessary to develop novel therapeutic agents for EC. In this study, we focused on lipolysis-stimulated lipoprotein receptor (LSR), a membrane protein highly expressed in EC cells, and developed a chimeric chicken-mouse anti-LSR monoclonal antibody (mAb). This study investigated the antitumor effect of an anti-LSR mAb and the function of LSR in EC. METHODS: We examined the expression of LSR in 228 patients with EC using immunohistochemistry and divided them into two groups: high-LSR (n = 153) and low-LSR groups (n = 75). We developed a novel anti-LSR mAb and assessed its antitumor activity in an EC cell xenograft mouse model. Pathway enrichment analysis was performed using protein expression data of EC samples. LSR-knockdown EC cell lines (HEC1 and HEC116) were generated by transfected with small interfering RNA and used for assays in vitro. RESULTS: High expression of LSR was associated with poor overall survival (hazard ratio: 3.53, 95% confidence interval: 1.35-9.24, p = 0.01), advanced stage disease (p = 0.045), deep myometrial invasion (p = 0.045), and distant metastasis (p < 0.01). In EC with deep myometrial invasion, matrix metalloproteinase (MMP) 2 was highly expressed along with LSR. Anti-LSR mAb significantly inhibited the tumor growth in EC cell xenograft mouse model (tumor volume, 407.1 mm3 versus 726.3 mm3, p = 0.019). Pathway enrichment analysis identified the mitogen-activated protein kinase (MAPK) pathway as a signaling pathway associated with LSR expression. Anti-LSR mAb suppressed the activity of MAPK in vivo. In vitro assays using EC cell lines demonstrated that LSR regulated cell proliferation, invasion, and migration through MAPK signaling, particularly MEK/ERK signaling and membrane-type 1 MMP (MT1-MMP) and MMP2. Moreover, ERK1/2-knockdown suppressed cell proliferation, invasion, migration, and the expression of MT1-MMP and MMP2. CONCLUSIONS: Our results suggest that LSR contributes to tumor growth, invasion, metastasis, and poor prognosis of EC through MAPK signaling. Anti-LSR mAb is a potential therapeutic agent for EC.
Assuntos
Neoplasias do Endométrio , Receptores de Lipoproteínas , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias do Endométrio/genética , Feminino , Humanos , Metaloproteinase 14 da Matriz , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Receptores de Lipoproteínas/genética , Receptores de Lipoproteínas/metabolismoRESUMO
BACKGROUND: In Japan, the government suspended HPV vaccine recommendation in 2013, resulting in dropping vaccination uptake to almost zero. We conducted four serial surveys on our colleague' attitude to HPV vaccination between 2014 and 2021. Here, we evaluate the result of the survey in 2021 and compare it to previous surveys. METHODS: The subjects were 567 obstetricians and gynecologists who had been trained in our university hospital or our affiliated hospitals. We used a questionnaire similar in format to those used in 2014, 2017, and 2019. RESULTS: A total of 340 doctors (60.0%) completed the survey. Among them, 93.2% (317/340) of respondents thought that the government should restart HPV vaccination recommendation, and that 63.2% (215/340) think male teenagers should also vaccinate against HPV. The percentage of teenaged daughters inoculated with HPV vaccination after Japanese government had suspended its recommendation was 43.5% (20/46), an increasing trend from the previous surveys. 39 out of the 46 daughters (84.8%) would be expected to receive full HPV vaccination after they take junior high school entrance examination or after 9-valent HPV vaccination is designated as a national routine-immunization. CONCLUSION: This study revealed increasing number of our colleagues think HPV vaccination is necessary for prevention of cervical cancer. The Japanese government's decision to resume its recommendation of the HPV vaccine in November 2021 will lead to a change in the public's thinking and behavior toward the HPV vaccine.