Sung Ran Hong

Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients.

Here, we demonstrate that electroporation-enhanced immunization with a rationally designed HPV DNA vaccine (GX-188E), preferentially targeting HPV antigens to dendritic cells, elicits a significant E6/E7-specific IFN-γ-producing T-cell response in all nine cervical intraepithelial neoplasia 3 (CIN3) patients. Importantly, eight out of nine patients exhibit an enhanced polyfunctional HPV-specific CD8 T-cell response as shown by an increase in cytolytic activity, proliferative capacity and secretion of effector molecules. Notably, seven out of nine patients display complete regression of their lesions and viral clearance within 36 weeks of follow up. GX-188E administration does not elicit serious vaccine-associated adverse events at all administered doses. These findings indicate that the magnitude of systemic polyfunctional CD8 T-cell response is the main contributing factor for histological, cytological and virological responses, providing valuable insights into the design of therapeutic vaccines for effectively treating persistent infections and cancers in humans.

Rate of vertical transmission of human papillomavirus from mothers to infants: Relationship between infection rate and mode of delivery

BackgroundIn contrast to consistent epidemiologic evidence of the role of sexual transmission of human papillomavirus (HPV) in adults, various routes may be related to HPV infection in infants. We have assessed the extent of HPV infection during the perinatal period, and the relationship between mode of delivery and vertical transmission.ResultsA total of 291 pregnant women over 36 weeks of gestation were enrolled with informed consent. Exfoliative cells were collected from maternal cervix and neonatal buccal mucosa. HPV infection and genotypes were determined with an HPV DNA chip, which can recognise 24 types. The HPV-positive neonates were re-evaluated 6 months after birth to identify the presence of persistent infection. HPV DNA was detected in 18.9 % (55/291) of pregnant women and 3.4 % (10/291) of neonates. Maternal infection was associated with abnormal cytology (p = 0.007) and primiparity (p = 0.015). The infected neonates were all born to HPV-positive mothers. The rate of vertical transmission was estimated at 18.2 % (10/55) which was positively correlated with maternal multiple HPV infection (p = 0.003) and vaginal delivery (p = 0.050), but not with labour duration and premature rupture of membranes. The rate of concordance of genotype was 100 % in mother-neonate pairs with vertical transmission. The neonatal HPV DNAs found at birth were all cleared at 6 months after delivery.ConclusionsVertical transmission of HPV DNA from HPV infected mother to the neonate increased when the infant was delivered through an infected cervix. However, the absence of persistent infection in infants at 6 months after delivery may suggest temporary inoculation rather than true vertical infection.

ORIGINAL ARTICLE: Peripheral Blood NK Cells Reflect Changes in Decidual NK Cells in Women With Recurrent Miscarriages

Citation Park DW, Lee HJ, Park CW, Hong SR, Kwak‐Kim J, Yang KM. Peripheral blood NK cells reflect changes in decidual NK cells in women with recurrent miscarriages. Am J Reprod Immunol 2010; 63: 173–180

Expression of Kisspeptin and its Receptor GPR54 in the First Trimester Trophoblast of Women with Recurrent Pregnancy Loss

Citation Park D‐W, Lee S‐K, Hong SR, Han A‐R, Kwak‐Kim J, Yang KM. Expression of kisspeptin and its receptor GPR54 in the first trimester trophoblast of women with recurrent pregnancy loss (RPL). Am J Reprod Immunol 2012; 67: 132–139

Ovarian sclerosing stromal tumors: gray scale and color Doppler sonographic findings.

Sclerosing stromal tumors are rare benign ovarian stromal tumors, which have distinctive clinical and pathologic features. The tumors occur predominantly in the second and third decades and are histologically characterized by the pseudolobular pattern of the cellular and hypocellular areas, marked vascularity, and heterogeneity of the cellular area. We analyzed 7 cases of sclerosing stromal tumors, which showed a typical sonographic appearance. On sonograms, sclerosing stromal tumors were solid and cystic and contained multiple round or cleftlike cysts. Ascites was rare. On transvaginal color Doppler sonograms, sclerosing stromal tumors were very hypervascular in the peripheral solid area and internal intercystic space and showed low‐impedance flow. We conclude that sclerosing stromal tumors should be considered in young women with menstrual irregularity who have hypervascular solid and cystic adnexal masses.

Practice guidelines for the early detection of cervical cancer in Korea: Korean Society of Gynecologic Oncology and the Korean Society for Cytopathology 2012 edition

The consensus guideline development committee of Korean Society of Gynecologic Oncology was reconvened in March 2012. The committee consisted of 36 experts representing 12 university hospitals and professional organizations. The objective of this committee was to develop standardized guidelines for cervical cancer screening tests for Korean women and to distribute these guidelines to every clinician, eventually improving the quality of medical care. Since the establishment of the consensus guideline development committee, evidence-based guidelines have either been developed de novo considering specific Korean situations or by adaptation of preexisting consensus guidelines from other countries. Recommendations for cervical cancer screening tests, management of atypical squamous and glandular cells, and management of low-grade and high-grade squamous intraepithelial lesions were developed. Additionally, recommendations for human papillomavirus DNA testing and recommendations for adolescent and pregnant women with abnormal cervical screening test results were also included.

MicroRNA expression profiling and Notch1 and Notch2 expression in minimal deviation adenocarcinoma of uterine cervix.

BackgroundMicroRNA (miRNA) expression is known to be deregulated in cervical carcinomas. However, no data is available about the miRNA expression pattern for the minimal deviation adenocarcinoma (MDA) of uterine cervix. We sought to detect deregulated miRNAs in MDA in an attempt to find the most dependable miRNA or their combinations to understand their tumorigenesis pathway and to identify diagnostic or prognostic biomarkers. We also investigated the association between those miRNAs and their target genes, especially Notch1 and Notch2.MethodsWe evaluated miRNA expression profiles via miRNA microarray and validated them using.real-time PCR assays with 24 formalin-fixed, paraffin-embedded tissue blocks of MDA and 11 normal proliferative endocervical tissues as control. Expression for Notch1 and 2 was assessed by immunohistochemistry.ResultsMiRNA-135a-3p, 192-5p, 194-5p, and 494 were up-regulated, whereas miR-34b-5p, 204-5p, 299-5p, 424-5p, and 136-3p were down-regulated in MDA compared with normal proliferative endocervical tissues (all P <0.05). Considering the second-order Akaike Information Criterion consisting of likelihood ratio and number of parameters, miR-34b-5p showed the best discrimination power among the nine candidate miRNAs. A combined panel of miR-34b-5p and 194-5p was the best fit model to discriminate between MDA and control, revealing 100% sensitivity and specificity. Notch1 and Notch2, respective target genes of miR-34b-5p and miR-204-5p, were more frequently expressed in MDA than in control (63% vs. 18%; 52% vs. 18%, respectively, P <0.05). MiR-34b-5p expression level was higher in Notch1-negative samples compared with Notch1-positive ones (P <0.05). Down-regulated miR-494 was associated with poor patient survival (P = 0.036).ConclusionsMDA showed distinctive expression profiles of miRNAs, Notch1, and Notch2 from normal proliferative endocervical tissues. In particular, miR-34b-5p and 194-5p might be used as diagnostic biomarkers and miR-494 as a prognostic predictor for MDA. The miR-34b-5p/Notch1 pathway as well as Notch2 might be important oncogenic contributors to MDA.

Adenoma malignum of the uterine cervix: imaging features with clinicopathologic correlation

Background Adenoma malignum, also known as minimal deviation adenocarcinoma, is a subtype of mucinous adenocarcinoma of the cervix. Purpose To evaluate the clinical, pathologic, and imaging features of the adenoma malignum of the uterine cervix. Material and Methods We retrospectively analyzed the CT and MRI findings in 13 patients: size, endoluminal fluid, appearance of the solid and cystic component, margin, enhancement, characteristics of locules of the cystic lesion, tumor spread, and associated ovarian lesion. Clinical and pathologic features were determined in 24 patients. Results The mean of the major tumor diameter was 4.1 cm (range, 2.2-6.5 cm). In the imaging features, 77% of 13 tumors demonstrated endoluminal fluid. All tumors showed enhancing solid components; 62% were multicystic and 38% had solid lesions. Most solid lesions exhibited an irregular margin (80%). The locules of the multicystic lesions tended to have smooth margins (75%), to have an average major diameter of ≤1 cm (88%), and to be 11 -20 in number (75%). The solid lesions were associated with invasion and metastases (60%). Clinically, 38% of 24 patients had watery discharge and 13% had Peutz-Jeghers syndrome, while pathologically, most patients were low stage (I or II) (83%). Over the 2-year follow-up of 17 patients, 82% was free from disease. The patients with more aggressive tumors or an unfavorable prognosis that manifested as tumor recurrence or metastasis tended to have invasion, watery discharges, high stages (III or IV) (100%) and solid lesions, metastases, and associated ovarian lesions (67%). Conclusion Awareness of imaging features as well as clinicopathologic manifestations of adenoma malignum can aid in accurate diagnosis, treatment, and prediction of prognosis.

Adenoma malignum of the uterine cervix: ultrasonographic findings in 11 patients

To evaluate the ultrasonographic features of adenoma malignum, a minimal deviation adenocarcinoma of the uterine cervix.

Treatment with Medroxyprogesterone Acetate Plus Levonorgestrel-releasing Intrauterine System for Early-stage Endometrial Cancer in Young Women: Single-arm, Prospective Multicenter Study: Korean Gynecologic Oncology Group Study (KGOG2009)

A prospective multicenter trial has been started in Korea to investigate the treatment efficacy of a levonorgestrel-releasing intrauterine system plus medroxyprogesterone acetate in young women with early-stage endometrial cancer. A number of studies have reported the effectiveness of hormonal therapy using systemic progestin in women clinically diagnosed with early endometrial adenocarcinoma at Stage IA, Grade 1, who want to maintain reproductive potential. In addition, several recent studies reported the use of a levonorgestrel-releasing intrauterine system to treat patients at a high risk of perioperative complications who cannot tolerate systemic progesterone because of its adverse effects. However, there has been no prospective multicenter trial that investigated the effectiveness of treatment with systemic progesterone in combination with intrauterine progesterone in young women with endometrial cancer. Young patients with histologically confirmed Grade 1 endometrioid adenocarcinoma that is presumably confined to the endometrium, who desired to preserve their fertility potential, undergo levonorgestrel-releasing intrauterine system insertion and are administered medroxyprogesterone acetate at a dosage of 500 mg/day concurrently. The follow-up and treatment response assessment were implemented at a 3-month interval with office endometrial aspiration biopsy with the levonorgestrel-releasing intrauterine system in place, and dilatation and curettage after removal of the levonorgestrel-releasing intrauterine system. The primary endpoint is the complete response rate. The secondary endpoint is to estimate the consistency of the results of the office endometrial aspiration biopsy with the levonorgestrel-releasing intrauterine system in the uterus and a dilatation and curettage after removal of the levonorgestrel-releasing intrauterine system.