The first-round results of a population based cohort study of HPV testing in Japanese cervical cancer screening: baseline characteristics, screening results, and referral rate

Kanako Kono,Tohru Morisada,Kumiko Saika,Eiko Saitoh Aoki,Etsuko Miyagi,Kiyoshi Ito,Hirokazu Takahashi,Tomio Nakayama,Hiroshi Saito,Daisuke Aoki 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.3

Objective: In 2013, a cohort study aimed to clarify the positive and negative effects ofintroducing the human papillomavirus (HPV) testing for population-based cervical cancerscreening has been launched in Japan. This study included four screenings during thesubsequent 7-year follow-up period. We aim to describe the results of the first round of thisstudy on cervical cancer screening here. Methods: This study began in September 2013 with recruitment completed in March 2016. Women aged 30–49 years were divided into 2 groups: those who received uterine cervicalcytology alone in the first year (control group), or those who received a combination ofcytology and HPV testing (intervention group), based on their age. After first screening,women with positive result of cytology or positive HPV test required referral. We summarizedthe results of the first round of cervical cancer screening. Results: Of the 25,074 women who were eligible for the study, 13,845 women (55.2%) werescreened with cytology alone; 11,229 women (44.8%) received a combination of cytologyand HPV testing. After screening, 407 women (2.9%) in the control group and 1,003 women(8.9%) in the intervention group required referral, respectively. Adding HPV testing increasedreferral rate significantly (p<0.001). Conclusion: After first screening, introduction of HPV testing appears to contribute tosignificantly higher referral rates, suggesting that the number of colposcopies as a detailedexamination may increase. These preliminary findings suggest that if HPV testing is introduced into screening, medical institutions need to be prepared for an increasing numberof follow-up examinations.

Effects of a fertility-sparing re-treatment for recurrent atypical endometrial hyperplasia and endometrial cancer: a systematic literature review

Isao Murakami,Hiroko Machida,Tohru Morisada,Yasuhisa Terao,Tsutomu Tabata,Mikio Mikami,Yasuyuki Hirashima,Yoichi Kobayashi,Tsukasa Baba,Satoru Nagase 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.4

Objective: To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial cancer (EC) following initial fertility-sparing treatment. Methods: A comprehensive systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Endometrial Cancer Committee. Multiple search engines, including PubMed/MEDLINE and the Cochrane Database, were searched in December 2021 using the keywords “Endometrial neoplasms,” “Endometrial hyperplasia,” “Endometrial intraepithelial neoplasia,” “Fertility preservation,” “Progestins,” AND “Recurrence.” Cases describing progestin re-treatment for recurrent EIN, AH and EC were compared with cases that underwent conventional hysterectomy. The primary outcomes were survival and disease recurrence, and the secondary outcome was pregnancy. Results: After screening 238 studies, 32 with results for recurrent treatment were identified. These studies included 365 patients (270 received progestin re-treatment and 95 underwent hysterectomy). Most progestin re-treatment involved medroxyprogesterone acetate or megestrol acetate (94.5%). Complete remission (CR) following progestin re-treatment was achieved in 219 (81.1%) cases, with 3-, 6- and 9-month cumulative CR rates of 22.8%, 51.7% and 82.6%, respectively. Progestin re-treatment was associated with higher risk of disease recurrence than conventional hysterectomy was (odds ratio [OR]=6.78; 95% confidence interval [CI]=1.99–23.10), and one patient (0.4%) died of disease. Fifty-one (14.0%) women became pregnant after recurrence, and progestin re-treatment demonstrated a possibility of pregnancy (OR=2.48; 95% CI=0.94–6.58). Conclusion: This meta-analysis suggests that repeat progestin therapy is an effective option for women with recurrent EIN, AH and EC, who wish to retain their fertility.

Validation of HPV triage in cytology- based cervical cancer screening for ASC-US cases using Japanese data

Eiko Saitoh Aoki,Kumiko Saika,Kazushige Kiguchi,Tohru Morisada,Daisuke Aoki 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.2

Objective: In Japan, cervical cancer screening consists of a cytology examination performed once every 2 years. We verified whether the risk of cervical intraepithelial neoplasia (CIN) 3 disease or higher (CIN3+) was equivalent to that of cytology negative cases (negative for intraepithelial lesion or malignancy [NILM]) for patients with a cytological diagnosis of “atypical squamous cells of undetermined significance (ASC-US)” who tested negative for human papillomavirus (HPV). Methods: Data from a total of 22,925 cases who had undergone cervical cancer screening at least twice or who had completed follow-up examinations after cervical screening at a single facility between April 2013 and April 2018 were analyzed. The cumulative incidence of CIN3+ was calculated for each category of initial cytology finding and HPV result (NILM, > ASC-US, ASC-US/HPV (unknown), ASC-US/HPV+, and ASC-US/HPV−). The statistical analysis was conducted using the Cox proportional hazards model. Results: The hazard ratio for the cumulative incidence of CIN3+ in 2 years relative to that for NILM cases was 2.7 (95% confidence interval=1.0–7.8) for > ASC-US cases, 0.5 (0.1–1.7) for ASC-US/HPV (unknown), 0.8 (0.3–2.4) for ASC-US/HPV+ cases, and 0.3 (0.1–1.0) for ASC-US/HPV− cases. Conclusion: Because the cumulative incidence of CIN3+ at 2 years for the ASC-US/HPV− cases was sufficiently low, compared with that of the NILM cases, we considered it reasonable and safe to perform HPV triage for ASC-US cases and to allow HPV-negative cases to return for their next screening in 2 years, which is the same follow-up schedule as that for NILM cases.

Cooperative interaction of Angiopoietin-like proteins 1 and 2 in zebrafish vascular development.

Kubota, Yoshiaki,Oike, Yuichi,Satoh, Shinya,Tabata, Yoko,Niikura, Yuichi,Morisada, Tohru,Akao, Masaki,Urano, Takashi,Ito, Yasuhiro,Miyamoto, Takeshi,Nagai, Norihiro,Koh, Gou Young,Watanabe, Sumiko,Sud National Academy of Sciences 2005 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.102 No.38

<P>Angiopoietin-like protein (Angptl) 1 and Angptl2, which are considered orphan ligands, are highly homologous, particularly in the fibrinogen-like domain containing the putative receptor binding site. This similarity suggests potentially cooperative functions between the two proteins. In this report, the function of Angptl1 and Angptl2 is analyzed by using morpholino antisense technology in zebrafish. Knockdown of both Angptl1 and Angptl2 produced severe vascular defects due to increased apoptosis of endothelial cells at the sprouting stage. In vitro studies showed that Angptl1 and Angptl2 have antiapoptotic activities through the phosphatidylinositol 3-kinase/Akt pathway, and coinjection of constitutively active Akt/protein kinase B mRNA rescued impaired vascular development seen in double knockdown embryos. These results provide a physiological demonstration of the cooperative interaction of Angptl1 and Angptl2 in endothelial cells through phosphatidylinositol 3-kinase/Akt mediated antiapoptotic activities.</P>

Angiogenic Role of LYVE-1-Positive Macrophages in Adipose Tissue

Cho, Chung-Hyun,Jun Koh, Young,Han, Jinah,Sung, Hoon-Ki,Jong Lee, Hyuek,Morisada, Tohru,Schwendener, Reto A.,Brekken, Rolf A.,Kang, Guson,Oike, Yuichi,Choi, Tae-Saeng,Suda, Toshio,Yoo, Ook-Joon,Koh, G Grune & Stratton 2007 Circulation research Vol.100 No.4

<P>Here we report the discovery of a characteristic dense vascular network (DVN) in the tip portion of epididymal adipose tissue in adult mice. The DVN is formed by angiogenesis rather than by vasculogenesis, and has functional blood circulation. This DVN and its subsequent branching may provide a new functional route for adipogenesis. The recruitment, infiltration, and accumulation of bone marrow-derived LYVE-1(+) macrophages in the tip region are crucial for the formation of the DVN. Matrix metalloproteinases (MMPs) and the VEGF-VEGFR2 system are responsible not only for the formation of the DVN, but also for the recruitment and infiltration of LYVE-1(+) macrophages into the epididymal adipose tissue tip region. SDF-1, but not the MCP-1-CCR2 system, is a critical factor in recruitment and ongoing retention of macrophages in this area. We also demonstrate that the tip region of epididymal adipose tissue is highly hypoxic, and thus provides a microenvironment conducive to the high expression and enhanced activities of VEGF, VEGFR2, MMPs, and SDF-1 in autocrine and paracrine manners, to create an ideal niche for the recruitment, retention, and angiogenic action of macrophages. These findings shed light on the complex interplay between macrophage infiltration, angiogenesis, and adipogenesis in the tip region of adult epididymal adipose tissue, and provide novel insight into the regulation of alternative outgrowth of adipose tissue.</P>