Consistency in human papillomavirus type detection between self-collected vaginal specimens and physician-sampled cervical specimens.

With the rising need for accessible cervical cancer screening, self-sampling methods offer a promising alternative to traditional physician-led sampling. This study aims to evaluate the efficacy of the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high-risk HPV (hrHPV) types between samples collected by physicians and those self-collected by women using a self-sampling kit for validation. Women aged 21-65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician-sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self-sampling kit closely matched the physician-led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval [95% CI]: 0.72-0.79; agreement: 87.7%, 95% CI: 85.8-89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72-0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user-friendly alternative to traditional sampling methods. This suggests that self-sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.

Real-world efficacy and safety of low-dose pembrolizumab in patients with advanced and refractory gynecologic cancers.

OBJECTIVE: The approved standard dose of pembrolizumab (200 mg administrated every 3 weeks) for cancer treatment imposes a significant financial burden on patients. However, no study has analyzed the clinical outcomes of low-dose pembrolizumab among individuals diagnosed with gynecologic cancer. The primary objective of this study was to assess the effectiveness and safety of a low-dose pembrolizumab regimen in real-world clinical practice. METHODS: We retrospectively assessed the efficacy and safety data of patients with gynecologic malignancies who received pembrolizumab between 2017 and 2022 at Kaohsiung Chang Gung Memorial Hospital. Furthermore, we conducted a comparative analysis of the objective response rate (ORR) and progression-free survival (PFS) between patients with deficient mismatch repair (dMMR) and proficient MMR (pMMR). RESULTS: A total of thirty-nine patients were included and received pembrolizumab at fixed dosages of 50 mg (5.1%), 100 mg (84.6%) and 200 mg (10.3%) per cycle. Compared to the pMMR group, the dMMR group exhibited a tendency toward improved ORR (45.5% vs. 13.0%, p = 0.074), and notably, the median duration of response remained unreached. There was no significant difference in PFS between the dMMR and pMMR groups; however, the patients with dMMR in tumor tissue had a trend of better survival (p = 0.079). Incidence of immune-related adverse events (irAEs) of any grade was observed in 13 patients (33.3%), with 3 individuals (7.7%) experiencing grade 3 or 4 events. CONCLUSION: Low-dose pembrolizumab may be a cost-effective and safe treatment option without compromising clinical outcomes in patients with refractory gynecologic cancers.

A comparative analysis of MMR immunohistochemistry panels: Evaluating the utility of four-protein versus two-protein panels in endometrial cancer patients.

AIMS: This study aimed to assess the accuracy of a two-protein panel for mismatch repair (MMR) immunohistochemistry (IHC) compared to a four-protein panel in a cohort of endometrial cancer patients. METHODS: The study included patients diagnosed with endometrial cancer between January 2018 and December 2023 with patients underwent MMR IHC staining for the four-protein panel (MSH2, MSH6, MLH1, and PMS2) serving as the reference standard. Various combinations of two proteins were examined and evaluated for their accuracy against the four-protein panel. Sensitivity, negative predictive value (NPV), and negative likelihood ratio were calculated for each combination. McNemar's test was performed to assess discordance, and receiver operating characteristic (ROC) curves were generated to evaluate diagnostic accuracy. RESULTS: Of 593 patients, MMR deficiency defined as at least one protein loss was observed in 146 patients (24.62%). When compared with four-protein panel, the highest sensitivity was observed with the MSH6/PMS2 combination (99.32%), followed sequentially by MSH6/MLH1 (97.26%), MSH2/PMS2 (93.15%), MSH2/MLH1 (91.10%), MLH1/PMS2 (79.45%), and MSH2/MSH6 (21.92%). The MSH6/PMS2 combination also demonstrated the best NPV of 99.78% and negative likelihood ratio of 0.01, while MSH6/MLH1 showed satisfactory NPV of 99.11% and negative likelihood ratio of 0.03. McNemar's test revealed no statistical difference between the four-protein panel and the MSH6/PMS2 panel (p = 1.000), and the MSH6/MLH1 panel (p = 0.125). CONCLUSIONS: The two-protein panel, particularly MSH6/PMS2, offers high sensitivity and negative predictive value, suggesting its potential as a cost-effective alternative to the four-protein panel in MMR testing for endometrial cancer patients.

How Progesterone Receptor Expression Impacts Platinum Sensitivity in Ovarian Clear Cell Carcinoma: Insights from Clinical and Experimental Perspectives.

Ovarian clear cell carcinoma (OCCC) is often considered a relatively platinum-resistant malignancy. The aim of this study was to explore the influence of progesterone receptor (PR) expression levels on platinum sensitivity and survival outcomes in people with OCCC. A retrospective analysis was conducted with 80 people with OCCC who underwent surgery followed by adjuvant chemotherapy. PR expression was assessed via immunohistochemical (IHC) staining and quantified using the H score. The platinum sensitivity and survival outcomes of patients with weak and strong PR expression were compared. Additionally, cisplatin viability and migration experiments were conducted with OCCC cell lines (ES-2 and TOV-21G) with varying PR isoform expressions. Among the 80 patients, 62 were classified as having platinum-sensitive disease, while 18 had platinum-resistant disease. The mean total PR H- score of platinum-sensitive tumors was significantly higher than that of platinum-resistant tumors (p = 0.002). Although no significant differences in progression-free and overall survival were observed between patients with high and low PR expression, those with high PR expression tended to have longer survival. While PR protein was only weakly detectable in ES-2 and TOV-21G cells, a transfection of the PR-A or PR-B gene resulted in a strong expression of PR-A or PR-B, which led to significantly reduced proliferation and migration in ES-2 and TOV-21G cells. Furthermore, overexpression of PR-A or PR-B enhanced cisplatin cytotoxicity in these cell lines. In conclusion, strong PR expression was associated with improved platinum sensitivity and survival outcomes, consistent with our experimental findings. The potential of PR as a tumor sensitizer to cisplatin in OCCC warrants further investigation.

Estrogen/Progesterone Receptor Expression and Cancer Antigen 125 Level as Preoperative Predictors to Estimate Lymph Node Metastasis in Endometrioid Endometrial Cancer.

Loss of estrogen receptor/progesterone receptor (ER/PR) in endometrial cancer (EC) is associated with tumor progression and poor outcomes. Elevated pretreatment cancer antigen 125 (CA 125) level is a risk factor for lymph node metastasis (LNM). We evaluated whether the combination of ER/PR expression and CA 125 level could be used as a biomarker to predict LNM. We retrospectively investigated patients with endometrioid EC who underwent complete staging surgery during January 2015 to December 2020. We analyzed ER/PR status using immunohistochemical staining, and quantified its expression using the sum of both ER/PR H-scores. Receiver operating characteristic curves were used to identify optimal cutoff values of H-score and CA 125 levels for predicting LNM. A nomogram for predicting LNM was constructed and validated by bootstrap resampling. In 396 patients, the optimal cutoff values of the ER/PR H-score and CA 125 were 407 (area under the receiver operating characteristic curve: 0.645, P=0.001) and 40 U/mL (area under the receiver operating characteristic curve: 0.762, P<0.001), respectively. Multivariate analysis showed that CA 125 ≥40 UmL (odds ratio: 10.02; 95% CI: 4.74-21.18) and ER/PR H-score <407 (odds ratio: 4.20; 95% CI: 1.55-11.32) were independent predictors. An LNM predictive nomogram was constructed using these 2 variables and our model yielded a negative predictive value and negative likelihood ratio of 98.3% and 0.14, respectively. ER/PR expression with pretreatment CA 125 levels can help estimate LNM risk and aid in decision-making regarding the need for lymphadenectomy in patients with endometrioid EC.

Comprehensive Clinicopathologic Analysis for Mismatch Repair Protein Expression in Unselected Endometrial Carcinoma Patients With an Emphasis on the Role of MLH1 Deficiency.

Screening for mismatch repair (MMR) deficiency in unselected patients with endometrial carcinoma (EC) and the clinicopathologic descriptions of ECs with MMR deficiency have been well demonstrated in Western populations, but studies on Asian populations are relatively scarce. In this study, we described the clinicopathologic features of ECs according to MMR status in unselected Taiwanese patients. We also conducted subgroup analysis of MMR-deficient (dMMR) cases according to the presence or absence of MLH1. Patients diagnosed with ECs between January 2017 and February 2020 at our institution were included. Immunohistochemistry analysis of MLH1, PMS2, MSH2, and MSH6 proteins on endometrial primary tumors and clinicopathologic variables were assessed retrospectively. A total of 231 EC patients were enrolled, of whom 50 (21.6%) had dMMR tumors. Of these 50 cases, 39 had tumors that lacked MLH1 expression and 11 were positive for MLH1. The overall dMMR group was significantly related to older age, parity, and high histologic grade compared with the MMR-proficient (pMMR) group. ECs with MLH1 deficiency were obviously associated with several poor pathologic features, including high histologic grade, lymph node metastasis, and lymphovascular space invasion. Moreover, we first reported that parity and the late age at menopause are strongly correlated with MLH1-related dMMR EC group compared with pMMR group. In conclusion, triaging EC patients into pMMR, MLH1-related dMMR and non-MLH1-related dMMR groups by immunohistochemistry analysis may help clinicians to predict disease behavior and guide further management. The strong association between parity and MLH1-related dMMR ECs warrants further investigation on the underlying mechanism.

Evaluation of sexual dysfunction in gynecologic cancer survivors using DSM-5 diagnostic criteria.

BACKGROUND: In gynecologic cancer survivors, female sexual dysfunction (FSD) remains under-investigated. We attempted to estimate the prevalence of FSD associated with distress in gynecologic cancer survivors using diagnostic and statistical manual of mental disorders fifth edition (DSM-5) diagnostic criteria and to identify women at risk for FSD. METHODS: We conducted a cross-sectional analysis of premenopausal women aged 20-50 with various gynecologic cancers at least one year after treatment between January 2017 and December 2019. Data of sociodemographics and physical conditions were collected via face-to-face interview during outpatient clinic visits. The domains we used to define FSD were based on DSM-5 diagnostic criteria. Statistical analysis was carried out using Student's t test, Chi-square test and multiple logistic regression. RESULTS: A total of 126 gynecologic cancer survivors with a mean age of 42.4 years were included for analysis and 55 of them (43.7%) were diagnosed as having FSD associated with distress based on DSM-5 criteria. More than half of women (65.1%) reported decreased sexual satisfaction after cancer treatment. According to DSM-5 definition, the most common female sexual disorders were sexual interest/arousal disorder (70.9%), followed by genitopelvic pain/penetration disorder (60.0%), and orgasmic disorder (20.0%). In multiple logistic regression model, endometrial cancer diagnosis was the only independent factor predicting less influence of cancer treatment on FSD (OR 0.370; 95% CI 0.160, 0.856). CONCLUSION: The first study to use DSM-5 criteria for estimation of FSD prevalence. This enables clinicians to identify which women are actually needed to seek medical help. A prevalence of 43.7% of FSD associated with distress was found in a group of gynecologic cancer survivors with the most common being sexual interest/arousal disorder. Endometrial cancer survivors were at low risk for developing FSD after treatment.

Synchronous/metachronous endometrial and colorectal malignancies in Taiwanese women: a population-based nationwide study.

INTRODUCTION: Endometrial cancer (EC) and colorectal cancer (CRC) may share a common genetic background. In a subset of patients, the two malignancies can coexist either at the time of diagnosis (synchronous) or develop consequently (metachronous). The purpose of this nationwide, population-based study was to investigate the occurrence and clinical outcomes of synchronous/metachronous EC/CRC in Taiwanese women. MATERIALS AND METHODS: Data for women diagnosed with EC and/or CRC between 2007 and 2015 were retrospectively retrieved from the nationwide Taiwan Cancer Registry. Mortality data were obtained from the National Death Registry. Women with synchronous/metachronous EC/CRC versus EC or CRC were compared in terms of clinical characteristics and outcomes. RESULTS: Of the 62,764 Taiwanese women diagnosed with EC and/or CRC during the study period, 167 (0.3%) had synchronous/metachronous EC/CRC. Among them, 72 cases (43.1%) presented with EC followed by CRC, 66 (39.5%) with CRC followed by EC, and 29 (17.4%) with synchronous EC/CRC. Kaplan-Meier estimates for time-to-event data revealed that the 2-year risk rates of developing a metachronous tumor of interest (CRC or EC) in women diagnosed with an initial EC and CRC were 39.6% and 42.1%, respectively. The 5-year overall survival rates of women with metachronous EC/CRC who had an initial diagnosis of EC, CRC, and synchronous EC/CRC were 73.9%, 70.9%, and 37.0%, respectively. CONCLUSIONS: Endometrial cancer is the most common first tumor in Taiwanese women with metachronous EC/CRC. The 2-year risk rates of developing a metachronous tumor of interest (CRC or EC) in women diagnosed with an initial EC and CRC are not negligible. Surveillance for CRC is recommended for all women diagnosed with EC. The clinical outcomes of synchronous EC/CRC are markedly less favorable.

Effects of Icodextrin Solution (Adept®) on Ovarian Cancer Cell Proliferation in an In Vitro Model.

Background and objective: Anti-adhesion barriers are currently used during ovarian cancer surgery to decrease adhesion-related morbidity. Adept® (4% icodextrin) solution, a liquid anti-adhesion material, has been widely used during gynecologic surgeries, though the risk of this barrier for oncologic surgery is controversial. The aim of this study was to determine the effect of Adept® solution on the proliferation of ovarian cancer cells. Materials and methods: We assessed the dose- and time-dependent effects of icodextrin on the growth and proliferation of OVCAR-3 and A2780 human ovarian tumor cell lines in vitro. Cell growth was determined by cell number counting. Expressions of cell cycle-regulation proteins (cyclin D1 and cyclin B1) were determined using Western blot analysis. Results: Adept® did not significantly increase ovarian cancer cell growth when tested at various concentrations (0, 1, 5, 10, 15, and 20%, equal to 0, 0.04, 0.2, 0.4, 0.6 and 0.8% icodextrin) and different time points (1-3 days) compared to control cells. Moreover, the protein levels of cyclin D1 and B1 were not overexpression-elevated in icodextrin-treated ovarian cancer cells, either with an increasing concentration or with an increasing treated time. These results demonstrated that Adept® does not activate the growth or proliferation of ovarian cancer cells in either a dose- or time-dependent manner. Conclusions: This study supports the use of Adept® solution as a safe anti-adhesion barrier for ovarian cancer surgery, though further in vivo studies are necessary.

Factors associated with the inconsistent diagnosis between frozen section and permanent pathologic examination in borderline ovarian tumors.

AIM: The predictive accuracy of frozen sections for borderline ovarian tumors (BOTs) is suboptimal. The aim of this study was to determine the diagnostic accuracy of BOTs and factors associated with an upgrade to a permanent pathological diagnosis of invasive carcinoma in patients diagnosed with BOTs by frozen section. METHODS: We conducted a retrospective study between 2011 and 2018 at Kaohsiung Chang Gung Memorial Hospital (KCGMH). Two hundred and twenty-five records of eligible patients with a diagnosis of BOT by frozen section or permanent diagnosis were reviewed. Positive predictive value and the diagnostic accuracy of frozen sections were calculated. Univariate and multivariate analyses were used to determine the clinicopathological factors associated with an upgrade of the diagnosis from a borderline tumor to malignancy. RESULTS: The agreement between frozen section and permanent pathological diagnoses was 63.1%, and the positive predictive value was 72.1%. The multivariate analysis revealed that CA-125 level > 136 U/mL (odds ratio [OR] = 2.96, 95% confidence interval [CI] = 1.3-6.9; p = 0.012), and tumor histologic type (clear cell/endometrioid vs. mucinous; OR:32.8, 95% CI = 6.9-154.8, p < 0.001; clear cell/endometrioid vs. serous: OR 48.1, 95% CI = 8.8-261.8, p < 0.001) were independent risk factors for an upgrade of the permanent diagnosis from a BOT to ovarian carcinoma. CONCLUSION: An elevated CA-125 level (over 136 U/mL) and tumor histologic type (clear cell and endometrioid subtypes) were associated with an upgrade in the diagnosis of ovarian tumor from a BOT on frozen section to a permanent diagnosis of malignancy.