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The WHO (World Health Organization) conducted an elimination of cervical cancer program using triple pillar intervention strategy to target 90%-70%-90% of women before the year 2030, including (1) a full vaccination of HPV (human papillomavirus) vaccine to 90% of girls

The current review described a 55-year woman using 28 months to finish her surgery-based radiation-free multimodality treatment journey to fight International Federation of Gynaecology & Obstetrics (FIGO) 2018 clinical stage IIA2 (cT2aN0M0) squamous cell carcinoma (SCC) of the cervix. She received six cycles of perioperative adjuvant therapy, including three cycles of neoadjuvant therapy (NAT) and three cycles of postoperative adjuvant therapy by using combination of dose-dense chemotherapy (CT, weekly paclitaxel 80 mg/m2+triweekly cisplatin 40 mg/m2), immunotherapy (IO, triweekly pembrolizumab 200 mg) and half-dose anti-angiogenic agent (triweekly bevacizumab 7.5 mg/kg) plus interval radical surgery (radical hysterectomy + bilateral salpingo-oophorectomy + bilateral pelvic lymph node dissection + para-aortic lymph node sampling) and following maintenance therapy with monthly 22 cycles of half-dose of IO (pembrolizumab 100 mg) and concomitant 4 cycles of single-agent CT (paclitaxel 175 mg/m2) and 18 cycles of half-dose anti-angiogenic agent (bevacizumab 7.5 mg/kg). During the cervical SCC fighting journey, two unwanted adverse events (AEs) occurred. One was pseudo-progressive disease during the NAT treatment and pathology-confirmed upgrading FIGO stage IIIC1p (ypT2a1N1M0) after radical surgery and the other was the occurrence of hypothyroidism during the post operative adjuvant therapy. Based on this case we presented, we review the recent trend in the management of women with locally advanced cervical cancer (LACC) using the radiation-free but surgery-based multimodality strategy and highlight the strengths and limitations about perioperative adjuvant therapy with dose-dense CT + IO + half-dose anti-angiogenic agent and maintenance treatment of half-dose IO combining with short-term single agent CT and following long-term half-dose anti-angiogenic agent. All underscore the possibility that women with LACC have an opportunity to receive surgery-based RT-free multi-modality strategy to manage their diseases with satisfactory results. Additionally, the evolving role of IO plus CT with/without anti-angiogenic agent functioning as either primary treatment or adjuvant therapy for the treatment of advanced CC has been in process continuously. Moreover, the patient's positive response to IO, pembrolizumab as an example, both during the primary and maintenance therapy, highlights the importance of integrating IO into CT regimens for CC, especially in cases where conventional therapies, RT as an example, are insufficient or who do not want to receive RT-based treatment. The sustained disease-free status of the patient over several years reinforces the potential of IO to significantly increase long-term survival outcomes in CC patients, particularly for those with LACC.

Intrauterine adhesions (IUA) occurred in the reproductive-age women are a big economic and health problem, resulting in severe impairment of social, psychological and physical function of the female genital organs. IUA-related symptoms or signs are varied greatly from free of symptoms or ambiguous symptoms (an incidental finding during the intervention) to ceased menstruation and loss of fecundability. The underlying pathophysiology is not completely understood, but intrauterine damage with broken basal layers of the endometrium formatting scar tissues or fibrosis in the endometrium with subsequently causing partial or complete occlusion of the uterine cavity may be a well-accepted hypothesis. Previously, infection is the most common cause to develop IUA, but now, intrauterine surgery may be a critical cause contributing to the majority of cases of IUA. In the current review, update information about the etiology, epidemiology, pathophysiology, sequelae and prevention of IUA will be renewed. We emphasize the importance of awareness of IUA, and primary prevention should be considered in the routine clinical practice if intrauterine surgery has been applied, based on uncertainty of ideal treatment for the established IUA and unpredictable outcomes after IUA treatment. So far, evidence supports that hyaluronic acid with/without other strategy is the most valuable and effective method to reduce the formation and re-formation of IUA as well as to achieve the best fertility outcome.

A significant decline in both incidence and prevalence of cervical cancers after widespread-introducing cervical screening strategy by Papanicolau test (Pap test) has been found in the world, but cervical cancer is still one of the most common female cancers, reporting the fourth prevalence and also one of the leading causes to result in main women-associated morbidity and mortality, particularly for those women living in low- and middle-income countries. Cervical cancer is one of the most important health concerns directly destroying the global health-care system, partly because of not only increasing the disability either secondary to diseases themselves of victims or mediated by treatment-related adverse events to the survivors but also acting as a leading cause of death of diseased patients worldwide, alarming the urgent need to do something to minimize the catastrophic diseases-related heavy socioeconomic burden. It is fortunate that cervical cancer is a preventable disease, based on its strong association with human papillomavirus (HPV) infection (more than 95%), particularly for those high-risk HPV (HR-HPV) and its high possibility by detecting HPV infection before the development of cervical cancer as well as an effective prevention by HPV vaccination. That is why WHO (World Health Organization) considers cervical cancer as a public problem and attempts to accelerate the elimination of cervical cancer program by three-pillar approach (90:70:90% targets), including (1) 90% of girls are fully vaccinated with HPV vaccine by 15 years of age; (2) 70% of women are screened with a high-performance test by 35 and 45 years of age and precancerous lesions are treated early; and (3) 90% of women identified with cervical diseases receive appropriate and adequate treatment. Herein, this review focuses on the HPV vaccination as Part I, including global recommendations and Taiwan government's policy for HPV vaccination.

Objective To evaluate the efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms (VMS) associated with menopause in East Asian women. Methods In this phase 3, randomized, double-blind study, postmenopausal women with moderate to severe VMS (minimum average frequency in the 10 days before randomization, ≥7/day or 50/week) received fezolinetant 30 mg/day or placebo (weeks 1–12), followed by an open-label extension phase with fezolinetant 30 mg/day (weeks 13–24). The co-primary endpoints were the mean changes in the daily frequency and severity of VMS at weeks 4 and 12. Results Among 301 participants, the difference in the least squares mean change (95% confidence interval) from baseline in the daily frequency of moderate to severe VMS versus placebo was −0.65 (−1.41 to 0.12) at week 4 and −0.55 (−1.35 to 0.26) at week 12. The differences in the least squares mean change from baseline in the VMS severity score versus placebo were −0.06 (−0.14 to 0.03) and −0.13 (−0.27 to 0.01) at weeks 4 and 12, respectively. Serious adverse events occurred in 0.7% of participants receiving fezolinetant in weeks 1 to 12, compared with 1.3% of those receiving placebo. Conclusions Fezolinetant was generally safe but did not reduce the frequency or severity of VMS versus placebo in postmenopausal women in this study. ClinicalTrials.Gov Identifier: NCT04234204

In the Part I, we have discussed the background of CA125 and the development of anti-CA125 monoclonal antibody (MAb) to highlight the potential role of CA125 and anti-CA125 MAb in the management of women with advanced stage epithelial ovarian cancer (EOC). Glycosylation change either by N-link or by O-link of CA125 is supposed to play a role in the modification of immunity. Anti-CA125 MAb, which can be classified as OC 125-like Abs, M11-like Abs, and OV197-like Abs, is often used for diagnosing, screening, monitoring and detecting the mesothelin-related diseases of the abdominal cavity, particular for those women with EOC. Additionally, anti-CA125 MAb also plays a therapeutic role, named as OvaRex MAb-B43.13 (oregovomab), which has also been extensively reviewed in the Part I review article. The main mechanisms include (a) forming CA125 immune complexes to activate the antigen-presenting cells; (b) triggering induction of CA125-specific immune responses, including anti-CA125 Abs against various epitopes and CA125-specific B and T cell responses; and (c) triggering CD4 and CD8 T-cell responses specific for B43.13 to produce specific and non-specific immune response. With success in vitro, in vivo and in primitive studies, phase II study was conducted to test the effectiveness of chemoimmunotherapy (CIT) for the management of EOC patients. In the 97 EOC patients after optimal debulking surgery (residual tumor

Since government-provided annual cervical cytology testing for all Taiwanese women aged 30 years or older became available in 1995, both cervical cancer incidence and death have decreased significantly. However, with the 2018 introduction of the national immunization program for human papillomavirus (HPV) vaccination in all schoolgirls aged 13–15 years old, the positive predictive value of cytology testing is expected to decrease with rising vaccination rates, and therefore a transition to more sensitive HPV-based testing may be needed. This position paper, derived from discussions by a panel of experts in cervical cancer screening, provides short-, medium-, and long-term policy recommendations to manage the transition between cervical screening methods for Taiwan. The recommendations include concrete suggestions regarding testing procedures, standards, accreditation, monitoring, promotion, and implementation. It is hoped that comprehensive preparation and management of this transition will enable Taiwan to repeat the previous successes of the cervical cytology testing program.

The current standard therapy of epithelial ovarian cancer (EOC) is the combination of surgery (primary cytoreductive surgery or interval cytoreductive surgery) and platinum-based chemotherapy (mainly using paclitaxel and carboplatin either by neoadjuvant chemotherapy and/or by postoperative adjuvant chemotherapy) with/without adding targeted therapy (mainly using anti-angiogenesis agent- bevacizumab). After front-line chemotherapy, the advanced-stage EOC can be successfully controlled and three-quarters of patients can achieve a complete clinical remission. Unfortunately, nearly all patients will recur and progression-free survival (PFS) of these patients is seldom more than 3 years with a dismal median PFS of 12–18 months. With each recurrence, patients finally develop resistance to standard chemotherapy regimen, contributing to fewer than half of women who survive for more than 5 years after diagnosis with a median overall survival (OS) of 40.7 months. Due to the lower PFS and OS, particularly for those advanced-stage patients, novel therapeutic options during the front-line therapy are desperately needed to decrease the occurrence of recurrence, and the majority of them are still under investigation. It is well-known that overexpression of CA125 has been associated with attenuated cellular apoptosis, platinum chemotherapy resistance, tumor proliferation and disease progression, suggesting that anti-CA125 may play a role in the management of patients with EOC. The current review is a Part I which will focus on development of anti-CA125 monoclonal antibody, hoping that alternation of the front-line therapy by chemo-immunotherapy will be beneficial for prolonged survival of patients with EOC.

Ram sperm undergo a sequence of physiological and biochemical changes collectively termed as capacitation to perform oocyte fertilization. However, the protein changes induced by capacitation remain in need of further exploration. Thus, the present study investigated the comparative proteomic profiling in ram spermatozoa under non-capacitating (NC) and capacitating (CAP) conditions in vitro using a liquid chromatography–tandem mass spectrometry combined with tandem mass tag labeling strategy. As a results, 2050 proteins were identified and quantified; 348 of them were differentially abundant, with 280 of the proteins upregulated and 68 of the proteins downregulated between the CAP and NC spermatozoa, respectively. Functional enrichment analysis indicated that the differentially abundant proteins Prune Exopolyphosphatase 1, Galactose-1-Phosphate Uridylyltransferase, and ATP Citrate Lyase were strictly related to energy production and conversion, and Phosphoglycolate phosphatase, Glucosamine-6-Phosphate Deaminase 1 and 2 were related to metabolism, RNA processing, and vesicular transport pathways. Furthermore, the networks of protein–protein interaction indicated a strong interaction among these differential proteins in annotated pathways such as ubiquitin and transport metabolism. Our findings indicate that capacitation progress might be regulated through different pathways, providing insights into mechanisms involved in ram sperm capacitation and fertility.

Objective: To report a rare case of anti-N-Methyl-d-aspartate receptor encephalitis (anti-NMDARE) presented by mental and behavioral changes and seizures accompanied with respiratory failure. Case report: A 37-year-old multiparous woman was initially presented with abnormal mental behavior and the diagnosis of schizophrenia was made, but the disease progressed rapidly to general convulsion and acute respiratory failure. Although active treatment, including steroids, intravenous immunoglobulins (IVIGs) and plasma exchange was applied, no significant improvement was obtained. Transvaginal ultrasound and pelvic magnetic resonance image (MRI) were arranged and the results showed a suspicious cystic lesion (3 × 2.3 cm) at the right ovary. Laparoscopic unilateral salpingo-oophorectomy was performed and final pathology reported a matured cystic teratoma, suggesting that this patient had anti-NMDARE secondary to ovarian mature teratoma. After surgery, the clinical condition was dramatically improved and she recovered completely without sequelae. Conclusion: Although it is well-known about the relation between anti-NMDARE and ovarian mature teratoma, this small tumor may result in the missing diagnosis. Remind us to consider the possibility of any small ovarian cystic lesion-related anti-NMDARE in women with autoimmune encephalitis.

Sialic acids (SA) are a kind of nine-carbon backbone sugars, serving as important molecules in cell-to-cell or cell-to-extra-cellular matrix interaction mediated by either O-linked glycosylation or N-linked glycosylation to attach the terminal end of glycans, glycoproteins, and glycolipids. All processes need a balance between sialylation by sialyltransferase (STs) and desialylation by sialidases (also known as neuraminidases, NEU). Although there is much in uncertainty whether the sialyation plays in cancer development and progression, at least four mechanisms are proposed, including surveillance of immune system, modification of cellular apoptosis and cell death, alteration of cellular surface of cancer cells and tumor associated microenvironment responsible carcinogenesis, growth and metastases. The current review focuses on the role of glycosylation in gynecologic organ-related cancers, such as ovarian cancer, cervical and endometrial cancer. Evidence shows that sialylation involving in the alternation of surface components of cells (tumor and cells in the microenvironment of host) plays an important role for carcinogenesis (escape from immunosurveillance) and dissemination (metastasis) (sloughing from the original site of cancer, migration into the circulation system, extravasation from the circulatory system to the distant site and finally deposition and establishment on the new growth lesion to complete the metastatic process). Additionally, modification of glycosylation can enhance or alleviate the aggressive characteristics of the cancer behaviors. All suggest that more understandings of glycosylation on cancers may provide a new therapeutic field to assist the cancer treatment in the near future.

Endometriosis, manifested by pain and infertility, is a chronic inflammatory disease, associated with a large disability of daily living, causing a socio-economic diastrophic problem and burden. The main goal of therapy attempts to reduce pain, correct infertility and possibly avoid or delay occurrence of long-term endometriosis-associated sequelae, such as fibrosis, adhesion and malignant transformation. Although the advanced technology (minimally invasive diagnostic tools, magnetic resonance imaging, high-resolution vaginal ultrasound etc.) and the better understanding pathophysiology of endometriosis for development of new therapeutic strategy is continuous for both diagnosis and management of endometriosis, there is still presence of many debated issues, which commonly occur in routine clinical practice. For example, the timing and duration of medications may be one of most frequently discussed issues. In this part I, we would like to overview the general background knowledge (basic concept) about the endometriosis, and emphasize the role of clinical diagnosis and possible empirical medical treatment (therapeutic test) for the management of women with endometriosis.

Endometrial cancer (EC) has become one of rapidly increasing women's cancers, contributing to the most common cancer of the female genital tract in high- and middle-incomed countries, including Taiwan. In general, EC is believed its favorable outcome; however, high-grade endometrial cancers have a tendency to recur and also have a high risk to be presented as an advanced stage or accompanied with metastatic lesions, which result in a biggest therapeutic challenge. The standard therapy includes complete staging surgery (sentinel node sampling)/optimal debulking surgery, and subsequent adjuvant therapy, by either radiotherapy locally or systemic therapy as chemotherapy or targeted therapy, or in combination or in subsequential strategy is made based on the risk stratification using clinicopathological prognostic factors. All efforts are made to minimize the risk of recurrence and possible therapeutic failure. In this part I, we would like to overview the general background knowledge (basic concept) about the cancer of uterine corpus, and discuss the recent transformation to patients-tailored therapy based on modern molecular technology as the optimal strategy to balance the therapeutic efficacy and treatment-related toxicity. Optimally, it is possible to reach the best benefits.