One-step nucleic acid amplification (OSNA) assay for detecting lymph node metastasis in cervical and endometrial cancer: a preliminary study

Shinichi Togami,Takashi Ushiwaka,Ikumi Kitazono,Shintaro Yanazume,Masaki Kamio,Akihide Tanimoto,Hiroaki Kobayashi 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.2

Objective: To evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay for the diagnosis of lymph node (LN) metastasis in uterine cancer. Methods: A total of 116 LNs from 30 patients with cervical and endometrial cancer, enrolled in this prospective study, were used. Excised LNs were cut into 4 to 6 blocks at 2 mm intervals, and nonadjacent blocks were alternately subjected to either histological examination or the OSNA assay. Results: The concordance rate between histological examination and the OSNA assay in cervical cancer and in endometrial cancer was 95.9% and 95.2%, respectively. The sensitivity, specificity, and negative predictive value of the OSNA assay were 80%, 97.7%, and 97.7% in cervical cancer, and 85.7%, 93.3%, and 98.2% in endometrial cancer, respectively. In cervical cancer, discordant results were observed in 2 out of 49 LNs (4.1%); 1 was OSNA assay-positive and histological examination-negative, and 1 was OSNA assay-negative and histological examination-positive. In endometrial cancer, discordant results were observed in 5 out of 67 LNs (7.5%); 4 were OSNA assay-positive and histological examination-negative, and 1 was OSNA assay-negative and histological examination-positive. Conclusion: The OSNA assay showed high concordance rate with histological examination, sensitivity, and specificity in uterine cancer, suggesting that it could enhance the accuracy of conventional pathological examination for the detection of LN metastasis by reducing false negative rate.

The prognostic value of lymph node ratio in stage IIIC cervical cancer patients triaged to primary treatment by radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy

Koray Aslan,Mehmet Mutlu Meydanli,Murat Oz,Yusuf Aytac Tohma,Ali Haberal,Ali Ayhan 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.1

Objective: The aim of this study was to determine the prognostic value of lymph node ratio (LNR) in women with 2018 International Federation of Gynecology and Obstetrics stage IIIC cervical cancer. Methods: In this retrospective dual-institutional study, a total of 185 node-positive cervical cancer patients who had undergone radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy were included. All of the patients received adjuvant chemoradiation after surgery. LNR was defined as the ratio of positive lymph nodes (LNs) to the total number of LNs removed. The patients were categorized into 2 groups according to LNR; LNR <0.05 and LNR ≥0.05. The prognostic value of LNR was evaluated with univariate log-rank tests and multivariate Cox regression models. Results: A total of 138 patients (74.6%) had stage IIIC1 disease and 47 (25.4%) patients had stage IIIC2 disease. With a median follow-up period of 45.5 months (range 3–135 months), the 5-year disease-free survival (DFS) rate was 62.5% whereas the 5-year overall survival (OS) rate was 70.4% for the entire study population. The 5-year DFS rates for LNR <0.05 and LNR ≥0.05 were 78.2%, and 48.4%, respectively (p<0.001). Additionally, the 5-year OS rates for LNR <0.05 and LNR ≥0.05 were 80.6%, and 61.2%, respectively (p=0.007). On multivariate analysis, LNR ≥0.05 was associated with a worse DFS (hazard ratio [HR]=2.12; 95% confidence interval [CI]=1.15–3.90; p=0.015) and OS (HR=1.95; 95% CI=1.01–3.77; p=0.046) in women with stage IIIC cervical cancer. Conclusions: LNR ≥0.05 seems to be an independent prognostic factor for decreased DFS and OS in stage IIIC cervical carcinoma.

High-risk human papillomavirus testing as a primary screening for cervical cancer: position statement by the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology

공태욱,김미선,김영한,김용범,김자연,김재원,박미혜,박주현,이정호,임명철,홍준석 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.1

Based on emerging data and current knowledge regarding high-risk human papillomavirus (hrHPV) testing as a primary screening for cervical cancer, the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology support the following scientific facts:• Compared to cytology, hrHPV screening has higher sensitivity and detects more cases of high-grade cervical intraepithelial neoplasia. • Qualified hrHPV testing can be considered as an alternative primary screening for cervical cancer to the current cytology method. • The starting age of primary hrHPV screening should not be before 25 years because of possible overtreatment in this age, which has a high human papillomavirus (HPV) prevalence but rarely progresses to cancer. The screening interval should be no sooner than every 3 years and no longer than every 5 years. • Before the introduction of hrHPV screening in Korea, research into comparative effectiveness of primary hrHPV screening for cervical cancer should be conducted to determine the appropriate HPV assay, starting age, and screening interval.

National screening programs for cervical cancer in Asian countries

Eiko Saitoh Aoki,Rutie Yin,Kemin Li,Neerja Bhatla,Seema Singhal,Dwiana Ocviyanti,Kumiko Saika,서민아,김미선,Wichai Termrungruanglert 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.3

Cervical cancer is still one of the most common female cancers in Asia and the leading cause of cancer-related deaths in low- and middle-income countries. Nowadays, national screening programs for cervical cancer are widely provided in Asian countries. We reviewed the National Cancer Screening Program (NCSP) in China, India, Indonesia, Japan, Korea, and Thailand. The NCSP were established at varying times, from 1962 in Japan to 2014 in Indonesia. The primary screening method is based on cytology in all countries except for India and Indonesia. In India and Indonesia, visual inspection of the cervix with acetic acid (VIA) is mainly used as a primary screening method, and a “see and treat” strategy is applied to women with a positive VIA result. The starting age of NCSP ranges from 18 years in China to 30 years in Thailand. The screening interval is 2 years in all countries except for China and Indonesia, in which it is 3 years. Uptake rates of NCSP vary from 5.0%–59.7%. Many women in low- and middle-income countries still do not participate in NCSP. To improve uptake rates and thereby prevent more cases of cervical cancer, Asian countries should continue to promote NCSP to the public using various approaches.

High expression of folate receptor alpha is associated with poor prognosis in patients with cervical cancer

Shu Yazaki,Yuki Kojima,Hiroshi Yoshida,Shigemasa Takamizawa,Rui Kitadai,Tadaaki Nishikawa,Tatsunori Shimoi,Kazuki Sudo,Ayumi Saito,Hitomi Sumiyoshi Okuma,Maki Tanioka,Emi Noguchi,Masaya Uno,Mitsuya Is 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.6

Objective: Folate receptor α (FRα) is a membrane protein expressed in various solid tumors but has limited expression in normal cells. Therefore, FRα is an attractive target for cancer treatment. This study aimed to investigate the relationship between FRα expression and the clinicopathological characteristics and survivals of cervical cancer. Methods: This retrospective study included patients with cervical cancer who underwent primary surgery between 2000 and 2020 at our institution. Immunohistochemical staining of FRα was performed using an anti-folate-binding protein/FBP antibody. FRα-positive staining was defined as ≥5% of tumor staining and FRα-high as ≥50% tumor staining with ≥2+ intensity. The association between FRα expression and survival was assessed using multivariate Cox regression analysis, adjusting for established prognostic factors. Results: Overall, 123 patients were identified, and 140 tumor samples, including 17 paired primary and metastatic samples, were evaluated. As histological types, 67 patients had squamous cell carcinoma (SCC), and 56 patients had non-SCC. All primary tumors were FRα-positive. High FRα expression was observed in 25% of the cases and differed according to histology (SCC vs. non-SCC, 14.9% vs. 37.5%, p=0.004). FRα expression was significantly higher in metastatic tumors than in primary (170 [IQR, 140–205] vs. 125 [IQR, 110–150], p=0.0006). High FRα expression was significantly associated with worse overall survival (hazard ratio, 6.73; 95% confidence interval, 2.21–20.53; p=0.001). Conclusion: In cervical cancer, FRα expression was elevated in metastatic tumors and high expression was associated with a worse prognosis. Our study supports the development of FRα-targeted therapy for advanced cervical cancer.

Prognostic factors of dose-response relationship for nodal control in metastatic lymph nodes of cervical cancer patients undergoing definitive radiotherapy with concurrent chemotherapy

Won Hee Lee,GwiEonKim,Yong Bae Kim 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.5

Objective: Regional control is occasionally unsatisfactory in cervical cancer, with the optimal radiation dose for nodal metastases in definitive radiotherapy (RT) with concurrent chemotherapy (CRT) remaining controversial. We investigated dose-response relationship for nodal local control in cervical cancer. Methods: We identified 115 patients with 417 metastatic nodes who received definitive CRT for cervical cancer with nodal metastases. External beam radiation therapy and brachytherapy plans were summated to determine total dose received by each node. Prognostic factors of nodal control and dose-response relationship were investigated using Cox-regression and restricted cubic spline function. Results: The 2-year progression-free survival rate was 69.4%. Among 43 patients with failures, 17 patients (37.5%) had regional failure included in first failure sites of which all except one were in-field only regional failures. Total 30 nodes showed recurrence at initial metastatic site after treatment. Neutrophil-to-lymphocyte ratio (NLR) ≥3.1, total radiation dose (minimum dose received by 98% of the target volume in equivalent dose in 2 Gy per fractions), and initial nodal volume ≥5.29 mL were poor prognostic factors (all p<0.050) of nodal local control. Restricted cubic spline functions revealed strongest dose-response relationship in high NLR (NLR ≥3.1) and initial nodal volume ≥5.29 mL subgroup. Conclusion: Initial nodal volume, radiation dose, and NLR were significant factors of nodal local control in cervical cancer; a stronger dose-response relationship was seen in bulky nodes with high NLR. Clinicians may consider these factors when determining the RT dose and the need for boost to nodal metastases in cervical cancer.

Kallikrein 5 overexpression is associated with poor prognosis in uterine cervical cancer

장지석,김나리,김지예,도성임,조연아,김현수,김용배 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.6

Objective: Kallikrein 5 (KLK5), which is frequently observed in normal cervico-vaginalfluid, is known to be related to prognosis in several solid tumors. We investigated theprognostic significance of KLK5 in uterine cervical cancer using tumor tissue microarray andimmunohistochemistry staining. Methods: We analyzed samples of 165 patients with uterine cervical cancer who receiveddefinitive radiation therapy between 2004 and 2012. We divided patients into two groupsstratified by their KLK5 activity by immunohistochemistry staining: negative/weak (0–1+)(n=120 patients) and moderate/strong (2–3+) group (n=45 patients). Patient and tumorcharacteristics, patterns of failure, and survival outcomes were compared. Univariable andmultivariable analyses were performed to identify prognostic factors. Results: Patients with KLK5 2–3+ were younger (median: 52 vs. 60 years) and had frequentparaaortic lymph node involvement (40.0% vs. 18.3%) than those with KLK5 0–1+. With amedian follow-up of 60.8 (interquartile range, 47.5–77.9) months, patients with KLK5 2–3+had inferior 5-year locoregional recurrence-free survival and distant metastasis-free survivalof 61.7% (vs. 77.5% in KLK5 0–1+ group) and 59.4% (vs. 72.8% in the KLK5 0–1+ group),respectively (all p<0.05). KLK5 2–3+ expression retained its significance after adjusting forother well-known prognostic factors of tumor size and stage in multivariable analysis. Conclusions: KLK5 overexpression is associated with the aggressiveness of cervical cancerand may underlie the diminished response to conventional treatments. Therefore, KLK5could be a reliable prognostic factor in cervical cancer.

Conditional relative survival of cervical cancer: a Korean National Cancer Registry Study

신동욱,배재만,하조현,정규원 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.1

Objective: Conditional relative survival (CRS) considers changes in prognosis over time andmay offer more useful estimates for survivors. We aimed to investigate CRS among patientswith cervical cancer stratified by various factors that influence survival probability. Methods: This nationwide retrospective study used data from the Korean Central CancerRegistry. We included 78,606 patients diagnosed with cervical cancer as their first cancer betweenJanuary 1, 1996 and December 31, 2015, and who were followed until December 31, 2016. CRS andthe conditional probabilities of death for the following 1 year were stratified by age at diagnosis,histology, cancer stage, treatment, year of diagnosis, and social deprivation index. Results: The 5-year relative survival rate at the time of diagnosis was 80.6% for all cases. Theprobability of surviving an additional 5 years conditioned on having already survived 1, 2,3, 4, and 5 years after diagnosis was 85.7%, 90.6%, 93.5%, 95.3%, and 94.3%, respectively. Patients with poorer initial survival estimates (older, advanced stage, non-squamous cellhistology) generally showed the largest increases in CRS over time. Patients aged ≥70years had the highest probability of death in the first year after diagnosis (24.5%), but theconditional probability of death in the 2nd, 3rd, 4th, and 5th years declined abruptly to13.1%, 7.5%, 5.4%, and 3.9%, respectively. Conclusions: The CRS rates for patients with cervical cancer improved over time, particularlyamong patients with poorer initial prognoses. Our estimates enable patients to make betterinformed decisions regarding follow-up care and their personal life.

Novel vaginoplasty technique involving the use of peritoneal flaps during laparoscopic radical hysterectomy for early-stage cervical cancer

Iori Kisu 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.2

Radical hysterectomy is often performed to treat early-stage cervical cancer in womenof reproductive age, and sexual dysfunction due to postoperative vaginal shortening is a major concern [1,2]. Vaginoplasty using various techniques is commonly performed in patients with congenital vaginal agenesis [3]. However, there are few reports of vaginoplasty being performed for vaginal shortening after radical hysterectomy in a patient with cervical cancer [4,5]. We demonstrate a novel vaginoplasty technique in which peritoneal flaps are used during laparoscopic radical hysterectomy to prevent postoperative vaginal shortening and consequent sexual dysfunction in patients with early-stage cervical cancer. A 37-year-old woman with early-stage cervical cancer who wished to perform sexual activity postoperatively underwent laparoscopic radical hysterectomy and vaginoplasty. After radical hysterectomy, the residual vaginal length was 4 cm. The dissected peritoneum of pouch of Douglas (posterior peritoneal flap) was sutured to the posterior vaginal stump. The supravesical peritoneum was dissected from the ventral to the dorsal side to create an anterior peritoneal flap, which was inverted, pulled down, and sutured to the anterior vaginal stump. The anterior peritoneal flap and suprarectal peritoneum were sutured to create a 10-cm neovaginal vault. Subsequently, a methacrylic resin mold was inserted into the neovagina to prevent postoperative neovaginal stenosis. The patient had sexual intercourse 3 months postoperatively. She was satisfied with the sexual activity and experienced no vaginal shortening or stenosis. Our novel vaginoplasty technique is feasible and effective for preventing sexual dysfunction by lengthening the vagina during laparoscopic radical hysterectomy for early-stage cervical cancer. Trial Registration: Japan Registry of Clinical Trials Identifier: jRCT1030210227

The trend and outcome of postsurgical therapy for high-risk early-stage cervical cancer with lymph node metastasis in Japan: a report from the Japan Society of Gynecologic Oncology (JSGO) guidelines evaluation committee

Masae Ikeda,Masako Shida,Shogo Shigeta,Satoru Nagase,Fumiaki Takahashi,Wataru Yamagami,Hidetaka Katabuchi,Nobuo Yaegashi,Daisuke Aoki,Mikio Mikami 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.3

Objective: The Japan Society of Gynecologic Oncology published the first guidelines for thetreatment of cervical cancer in 2007. The aim of this research was to evaluate the influence ofthe introduction of the first guideline on clinical trends and outcomes of patients with early stage cervical cancer who underwent surgery. Methods: This analysis included 9,756 patients who were diagnosed based on thepathological Tumor-Node-Metastasis (pTNM) classification (i.e., pT1b1, pT1b2, pT2b andpN0, pN1, pNX) and received surgery as a primary treatment between 2004 and 2009. Dataof these patients were retrospectively reviewed, and clinicopathological trends were assessed. The influence of the introduction of the guideline on survival was determined by using acompeting risk model. Results: For surgery cases, the estimated subdistribution hazard ratio (HR) by the competingrisk model for the influence of the guideline adjusted for age, year of registration, pTclassification, pN classification, histological type, and treatment methods was 1.024(p=0.864). Following the introduction of the first guideline in 2007, for patients with lymphnode metastasis, the use of chemotherapy (CT) as a postsurgical therapy increased, whereasthat of concurrent chemoradiotherapy (CCRT)/radiotherapy (RT) decreased (p<0.010). ForpN1 cases, the estimated subdistribution HR by the competing risk model for the influenceof the guideline was 1.094 (p=0.634). There was no significance in the postsurgical therapybetween CT and CCRT/RT (p=0.078). Conclusions: Survival of surgical cases was not improved by the introduction of theguidelines. It is necessary to consider more effective postsurgical therapy for high-risk early stage cervical cancer.