Jin Hwa Hong

Lymphocyte activation gene (LAG)-3 is a potential immunotherapeutic target for microsatellite stable, programmed death-ligand 1 (PD-L1)-positive endometrioid endometrial cancer

Immune checkpoint inhibitors have been widely used in the treatment of endometrial cancer (EC) with microsatellite instability-hypermutated (MSI-H). However, there is an unmet need for microsatellite stable (MSS) EC because of their modest activity. This study aimed to identify potential immune-related biomarkers in MSS EC. One hundred and twenty-three patients with EC who underwent hysterectomy were enrolled. MSI status was determined using MSI analysis and/or immunohistochemical staining for mismatch repair proteins. Immunohistochemical analysis of programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), PD-L2, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), cluster of differentiation 3 (CD3), CD8, lymphocyte activation gene-3 (LAG-3), indoleamine 2,3-dioxygenase 1 (IDO1), phosphatase and tensin homolog (PTEN), p53, AT-rich interactive domain-containing protein 1A (ARID1A), and β-catenin was performed using tissue microarray blocks. Among 123 patients, 95 (77.2%) were classified as having MSS. Within EC with MSS, PD-L1 positivity was significantly associated with positive PD-1 (p<0.001), CTLA-4 (p<0.001), CD3 (p=0.002), CD8 (p<0.001), and LAG-3 (p<0.001). In the univariate analysis, positive PD-1 (odds ratio [OR]=9.281; 95% confidence interval [CI]=2.560-33.653; p<0.001), CTLA-4 (OR=5.33; 95% CI=1.418-19.307; p=0.005), CD3 (OR=5.571; 95% CI=1.746-17.775; p=0.004), CD8 (OR=6.909; 95% CI=2.647-18.037; p<0.001), and LAG-3 (OR=9.75; 95% CI=1.947-48.828; p=0.005) were significantly associated with PD-L1 positivity in MSS EC. In the multivariate analysis, LAG-3 demonstrated a significant association with positive PD-L1 expression in MSS EC (OR=5.061; 95% CI=1.534-16.693; p=0.023). In patients with MSS EC harboring PD-L1, LAG-3 may be a potential immunotherapeutic target. Clinical trials investigating the role of anti-LAG-3 antibodies, alone or in combination with other immunotherapies, are warranted.

Genomic landscape of advanced endometrial cancer analyzed by targeted next-generation sequencing and the cancer genome atlas (TCGA) dataset

Recent studies have detailed the genomic landscape of endometrial cancer (EC); however, no study has focused on genetic alterations in advanced EC. We performed genomic profiling of patients with advanced EC using targeted next-generation sequencing (NGS). Archival tissue samples from 21 patients diagnosed with stage III and IV EC were obtained and subjected to NGS. Our data and the cancer genome atlas dataset were combined, and somatic mutation patterns were analyzed and compared according to the stage and histological type. Additionally, survival effects of specific mutated genes were analyzed. Somatic mutation patterns of 38 genes were identified in 263 EC samples, and the most commonly mutated genes were

Long-term risks of coronary heart disease and cerebrovascular disease in ovarian, uterine and cervical cancer survivors: a nationwide study in Korea

Only few studies have evaluated the incidence of coronary heart disease (CHD) and cerebrovascular disease (CVD) among gynaecologic cancer survivors. We selected 26,880 gynaecologic cancer patients who underwent health check-ups within 2 years after diagnosis using the Korean National Health Insurance Service Database. They were compared with 79,830 non-cancer controls. Cox regression models were used to estimate hazard ratios (HRs). There was no significant relationship between gynaecologic cancer survivors and CHD or CVD events. However, 10 years after diagnosing cancers, the risk of angina increased in cancer survivors (adjusted HR = 1.193, 95% CI: 1.013-1.406). After 1 year of diagnosis, cancer patients with no initial comorbidities showed an increased risk of all CHD and CVD events (adjusted HR = 1.101, 95% CI: 1.020-1.189) and CHD alone (adjusted HR = 1.168, 95% CI: 1.055-1.293) compared with controls. CHD risk was also higher in the cancer group with no comorbidities after 10 years of diagnosis (adjusted HR = 1.284, 95% CI: 1.020-1.615). Overall, the risk of CHD or CVD did not increase in gynaecologic cancer survivors. However, cancer patients without any comorbidities showed a higher risk of CHD compared with control, the risk persisting until 10 years after cancer diagnosis.Impact Statement

Comparing efficacy of high-dose rate brachytherapy versus helical tomotherapy in the treatment of cervical cancer

Boost radiation using brachytherapy (BT) is a standard treatment for local disease control in concomitant chemoradiation therapy (CCRT) for advanced cervical cancer. However, it is associated with gastrointestinal and genitourinary complications. Hence, this study investigates the feasibility of helical tomotherapy (HT) as an alternative to BT. Medical records of patients who underwent CCRT between 2000 and 2017 at a single institution were retrospectively reviewed. Patients with stage IIB-IVA cancers were selected based on the 2009 criteria of The International Federation of Gynaecology and Obstetrics. External beam radiation combined with chemotherapy was followed by either BT or HT. The propensity score matching of both groups was calculated using logistic regression analysis. Disease outcomes and treatment-related adverse events were compared between the 2 groups. The matched population included 70 BT patients and 35 HT patients. The 5-year progression-free survival rates for BT and HT were 72.6% and 72.5%, respectively (p=0.721). There was no difference in the overall survival rate between the two groups (p=0.203). The presence of acute and chronic gastrointestinal complications was also similar between the groups (p=0.460 and p=0.563, respectively). The chronic genitourinary toxicities were also comparable (p=0.105). HT boost treatment showed comparable disease outcomes with those observed with conventional BT in patients with advanced cervical cancer. HT could be a complementary boost protocol as a single modality or hybrid with BT in selected patients. Further studies with longer follow-up periods are warranted to confirm long-term outcomes.

Prevalence and Treatment of Vulvar Cancer From 2014−2018: A Nationwide Population-Based Study in Korea

Vulvar cancer is one of the rare gynecologic malignancies. Despite the recent increasing trend of vulvar cancer in western countries due to the increased infection of human papillomavirus, there has been no study for population-based incidence of vulvar cancer in Korea. We aimed to investigate the prevalence and treatment of vulvar cancer in South Korea between 2014 and 2018. Data from patients diagnosed and treated with vulvar cancer between 2014 and 2018 were obtained from the Health Insurance Review and Assessment Service/National Inpatient Sample (National In-Patient Sample) in South Korea. A total of 4,636,542 women were identified through the HIRA-NIS database from 2014 to 2018, of which 259 patients were diagnosed and treated for vulvar cancer. The mean age diagnosed with vulvar cancer was 62.82 (± 14.30) years in 2014, 64.19 (± 16.79) years in 2015, and 67.40 (± 14.41) years in 2016. In terms of treatment modalities, the most frequent treatment was surgery only without chemotherapy or radiation therapy. In the age-specific prevalence analysis, vulvar cancer was the most prevalent among those over 70 years old. According to multiple regression analysis, patients' age was significantly associated with the prevalence of vulvar cancer. Vulvar cancer was more prevalent in women with low socioeconomic status (SES) compared to those with high SES in 2018 (OR, 4.242; Considering the high prevalence of vulvar cancer in the elderly, it is necessary to establish a new strategy for early screening and treatment.

Accuracy of human papillomavirus tests on self-collected urine versus clinician-collected samples for the detection of cervical precancer: a systematic review and meta-analysis

The human papillomavirus (HPV) test is an effective screening tool to prevent cervical cancer. Urinary sampling for HPV detection improves the accessibility and participation of screening services and reduces the cost and burden on physicians. The clinical accuracy of urinary HPV test has yet to be determined via meta-analysis. This study assessed the clinical accuracy of these tests to detect cervical intraepithelial neoplasia (CIN) 2 or worse. Relevant studies were identified using the PubMed, Embase, and Cochrane databases. Research eligibility was based on the clinical accuracy of HPV test on clinician-collected samples as a comparator test, and urine as an index test. The reference standard was the presence of CIN2 or worse. The pooled absolute, relative sensitivity, and specificity of the urinary HPV test versus clinician-collected samples were assessed using a bivariate model. The pooled sensitivity of urinary HPV test was significantly lower than that of clinician-collected samples (ratio=0.84, 95% confidence interval [CI]=0.78-0.91). However, some polymerase chain reaction (PCR)-based HPV test such as GP5+/6+ (relative sensitivity=0.98, 95% CI=0.91-1.05), SPF10 (relative sensitivity=0.98, 85% CI=0.88-1.08) and non GP5+/6+ PCR (relative sensitivity=1.00, 95% CI=0.88-1.14) showed similar sensitivity in both the urine and clinician-collected samples. Our findings indicate that HPV test with some PCR-based assay on urine versus clinician-collected samples demonstrate similar clinical accuracy to detect CIN2 or worse. It suggests that urinary HPV test may present itself as a decent alternative screening tool for the detection of cervical pre-cancer. PROSPERO identifier: CRD42021227901.

Human papillomavirus testing as a primary screening tool for cervical cancer

Primary Cervical Cancer Screening by Self-sampling HPV Test

Cervical cancer seriously threatens women's health and HPV infection is the main cause of cervical cancer. Traditionally, Cervical cancer screening is based on cervical exfoliated cell samples collected by health care provider, which is labor consuming and the coverage and compliance are both relatively low in some areas. Non-invasive hrHPV self-sampling test appears to be more acceptable and may improve the HPV screening coverage. This study aims to evaluate the clinical performance of a newly developed urine/vaginal self-sampling hrHPV test in Cervical cancer screening.