Details of a Researcher - Iwata, Takashi

Papers - Iwata, Takashi

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Gastric-type adenocarcinoma of the uterine cervix: clinical features and future directions.

Nishio H, Matsuda R, Iwata T, Yamagami W

Japanese journal of clinical oncology 2024.02

ISSN 0368-2811

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Proposal for the optimal staging of extramammary Paget's disease: A retrospective analysis of 57 cases with distant metastasis.

Funakoshi T, Nakamura Y, Hirai I, Kobayashi K, Fukuda K, Iwata T

Experimental dermatology 33 ( 2 ) e15017 2024.02

ISSN 0906-6705

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SCD1 inhibition enhances the effector functions of CD8+ T cells via ACAT1-dependent reduction of esterified cholesterol

Sugi T., Katoh Y., Ikeda T., Seta D., Iwata T., Nishio H., Sugawara M., Kato D., Katoh K., Kawana K., Yaguchi T., Kawakami Y., Hirai S.

Cancer Science (Cancer Science) 115 ( 1 ) 48 - 58 2024.01

ISSN 13479032

We previously reported that the inhibition of stearoyl-CoA desaturase 1 (SCD1) enhances the antitumor function of CD8+ T cells indirectly via restoring production of DC recruiting chemokines by cancer cells and subsequent induction of antitumor CD8+ T cells. In this study, we investigated the molecular mechanism of direct enhancing effects of SCD1 inhibitors on CD8+ T cells. In vitro treatment of CD8+ T cells with SCD1 inhibitors enhanced IFN-γ production and cytotoxic activity of T cells along with decreased oleic acid and esterified cholesterol, which is generated by cholesterol esterase, acetyl-CoA acetyltransferase 1 (ACAT1), in CD8+ T cells. The addition of oleic acid or cholesteryl oleate reversed the enhanced functions of CD8+ T cells treated with SCD1 inhibitors. Systemic administration of SCD1 inhibitor to MCA205 tumor-bearing mice enhanced IFN-γ production of tumor-infiltrating CD8+ T cells, in which oleic acid and esterified cholesterol, but not cholesterol, were decreased. These results indicated that SCD1 suppressed effector functions of CD8+ T cells through the increased esterified cholesterol in an ACAT1-dependent manner, and SCD1 inhibition enhanced T cell activity directly through decreased esterified cholesterol. Finally, SCD1 inhibitors or ACAT1 inhibitors synergistically enhanced the antitumor effects of anti-PD-1 antibody therapy or CAR-T cell therapy in mouse tumor models. Therefore, the SCD1–ACAT1 axis is regulating effector functions of CD8+ T cells, and SCD1 inhibitors, and ACAT1 inhibitors are attractive drugs for cancer immunotherapy.

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Phase I and II randomized clinical trial of an oral therapeutic vaccine targeting human papillomavirus for treatment of cervical intraepithelial neoplasia 2 and 3.

Kawana K, Kobayashi O, Ikeda Y, Yahata H, Iwata T, Satoh T, Akiyama A, Maeda D, Hori-Hirose Y, Uemura Y, Nakayama-Hosoya K, Katoh K, Katoh Y, Nakajima T, Taguchi A, Komatsu A, Asai-Sato M, Tomita N, Kato K, Aoki D, Igimi S, Kawana-Tachikawa A, Schust DJ.

JNCI Cancer Spectr 7 ( 6 ) 2023.11

Accepted

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Human papillomavirus vaccine impact on invasive cervical cancer in Japan: Preliminary results from cancer statistics and the MINT study

Onuki M., Takahashi F., Iwata T., Nakazawa H., Yahata H., Kanao H., Horie K., Konnai K., Nio A., Takehara K., Kamiura S., Tsuda N., Takei Y., Shigeta S., Matsumura N., Yoshida H., Motohara T., Yamazaki H., Nakamura K., Hamanishi J., Tasaka N., Ishikawa M., Hirashima Y., Kudaka W., Mori-Uchino M., Kukimoto I., Fujii T., Watanabe Y., Noda K., Yoshikawa H., Yaegashi N., Matsumoto K.

Cancer Science (Cancer Science) 114 ( 11 ) 4426 - 4432 2023.11

ISSN 13479032

The first prophylactic vaccine against human papillomavirus (HPV) 16 and HPV18 was licensed in Japan in 2009. HPV vaccine effectiveness against high-grade cervical lesions has been demonstrated among young Japanese women, but evidence of its effects on invasive cervical cancer (ICC) is lacking. Using data from two different cancer registries, we compared recent trends of new ICC cases by age group using Poisson regression analysis. We also analyzed time trends in HPV16/18 prevalence among 1414 Japanese women aged <40 years newly diagnosed with ICC in the past decade. Based on the population-based cancer registry, the incidence of ICC among young women aged 20–29 years showed a significant decline from 3.6 to 2.8 per 100 000 women-years during 2016–2019, but no similar decline was observed for older age groups (p < 0.01). Similarly, using data from the gynecological cancer registry of the Japan Society of Obstetrics and Gynecology, the annual number of ICCs among women aged 20–29 years also decreased from 256 cases to 135 cases during 2011–2020 (p < 0.0001). Furthermore, a declining trend in HPV16/18 prevalence in ICC was observed only among women aged 20–29 years during 2017–2022 (90.5%–64.7%, p = 0.05; Cochran–Armitage trend test). This is the first report to suggest population-level effects of HPV vaccination on ICC in Japan. Although the declining trend in HPV16/18 prevalence among young women with ICC supports a causal linkage between vaccination and results from cancer registries, further studies are warranted to confirm that our findings are attributable to vaccination.

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Clinical availability and characteristics of multigene panel testing for recurrent/advanced gynecologic cancer

Kitazawa S., Chiyoda T., Nakamura K., Sakai K., Yoshihama T., Nishio H., Kobayashi Y., Iwata T., Banno K., Yamagami W., Nishihara H., Aoki D.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 28 ( 11 ) 1554 - 1562 2023.11

ISSN 13419625

Background: Japan’s health insurance covers multigene panel testing. This study aimed to determine the potential availability and utility of gene panel testing clinically in gynecologic oncology. Methods: We analyzed the characteristics of patients with gynecologic cancer who underwent gene panel testing using FoundationOne® CDx or OncoGuide™ NCC Oncopanel between November 2019 and October 2022. Results: Out of 102 patients analyzed, 32, 18, 43, 8, and 1 had cervical, endometrial, ovarian cancers, sarcoma, and vaginal cancer, respectively. Druggable gene alteration was found in 70 patients (68.6%; 21 with cervical cancer, 15 with endometrial cancer, 28 with ovarian cancer, 5 with sarcoma, and 1 with other). The most common druggable gene alteration was PIK3CA mutation (n = 21), followed by PTEN mutation (n = 12) and high tumor mutation burden (TMB-H) (n = 11). TMB-H was detected in 5 patients with cervical cancer, 5 with endometrial cancer, and 1 with endometrial stromal sarcoma. Eleven patients (10.8%) received molecularly targeted therapy according to their gene aberrations. Gene panel testing was mostly performed when the second-line treatment was ineffective. Of all 102 patients, 60 did not have recommended treatment, and 15 died or had worsened conditions before obtaining the test results. Conclusion: Through multigene panel testing, although many patients had druggable gene alterations, 10.8% of them received the recommended treatment. TMB-H was mainly observed in cervical/endometrial cancer, suggesting its potential as a therapeutic biomarker of immune checkpoint inhibitors. Furthermore, patients’ prognosis and performance status should be considered before performing the test.

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Intra-Patient Genomic Variations of Human Papillomavirus Type 31 in Cervical Cancer and Precancer

Kogure G., Tanaka K., Matsui T., Onuki M., Matsumoto K., Iwata T., Kukimoto I.

Viruses (Viruses) 15 ( 10 ) 2023.10

Human papillomavirus type 31 (HPV31) is detected less frequently in cervical cancer than two major causative types, HPV16 and HPV18. Here, we report a comprehensive analysis of HPV31 genome sequences in cervical lesions collected from Japanese women. Of 52 HPV31-positive cervical specimens analyzed by deep sequencing, 43 samples yielded complete genome sequences of around 7900 base pairs and 9 samples yielded partially deleted genome sequences. Phylogenetic analysis showed that HPV31 variant distribution was lineage A in 19 samples (36.5%), lineage B in 28 samples (53.8%), and lineage C in 5 samples (9.6%), indicating that lineage B variants are dominant among HPV31 infections in Japan. Deletions in the viral genome were found in the region from the E1 to L1 genes, but all the deleted genomes retained the E6/E7 genes. Among intra-patient nucleotide variations relative to a consensus genome sequence in each sample, C-to-T substitutions were most frequently detected, followed by T-to-C and C-to-A substitutions. High-frequency, intra-patient mutations (>10%) in cervical cancer samples were found in the E1, E2, and E7 genes, and all of them were nonsynonymous substitutions. The enrichment of high-frequency nonsynonymous substitutions strongly suggests that these intra-patient mutations are positively selected during the development of cervical cancer/precancer.

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Successful radiotherapy for recurrent obstructive pancreatitis secondary to pancreatic metastasis from cervical squamous-cell carcinoma

Nakajima Y., Iwasaki E., Kayashima A., Machida Y., Kawasaki S., Horibe M., Kawaida M., Masugi Y., Iwata T., Kanai T.

Clinical Journal of Gastroenterology (Clinical Journal of Gastroenterology) 16 ( 5 ) 755 - 760 2023.10

ISSN 18657257

Metastatic pancreatic cancer is a rare condition and cases of pancreatic metastasis from cervical cancer are infrequently reported. Furthermore, the incidence rates of pancreatic tumors as the cause of pancreatitis and of pancreatitis in patients with pancreatic tumors are similarly low. Pancreatitis may occur when a tumor obstructs the pancreatic duct. This condition may be difficult to manage and significantly reduces the quality of life because of severe abdominal pain. Here, we present a rare case of obstructive pancreatitis caused by pancreatic metastasis from cervical squamous-cell carcinoma, pathologically confirmed using endoscopic ultrasonography-guided fine-needle biopsy and treated with palliative irradiation to achieve rapid therapeutic relief. It is important to obtain appropriate tissue samples, confirm the pathological diagnosis, and compare the pathological findings with those of the primary tumor to select the appropriate treatment for obstructive pancreatitis caused by a metastatic pancreatic tumor.

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Serum Free Fatty Acid Changes Caused by High Expression of Stearoyl-CoA Desaturase 1 in Tumor Tissues Are Early Diagnostic Markers for Ovarian Cancer.

Katoh K, Katoh Y, Kubo A, Iida M, Ikeda Y, Iwata T, Nishio H, Sugawara M, Kato D, Suematsu M, Hirai S, Kawana K

Cancer research communications 3 ( 9 ) 1840 - 1852 2023.09

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難治性子宮頸癌に対する腫瘍浸潤リンパ球輸注療法

岩田卓, 野上侑哉, 西尾浩, 松井友哉, 菅原正貴, 陳冠良, 青木大輔

Japanese Journal of Gynecological Oncology (Japan Society of Gynecologic Oncology) 41 ( 2 ) 84 - 93 2023.04

ISSN 13478559

進行子宮頸癌は極めて難治性で，有効な新規治療法の開発が望まれている．腫瘍浸潤リンパ球輸注療法（TIL療法）は米国国立衛生研究所（NIH）で開発された養子免疫療法で，進行子宮頸癌において約20％の完全奏効（CR）が報告されている．注目すべき特徴はCRとなった症例では，その後の再発が低率で，治癒が期待できるとされていることである．また，免疫チェックポイント阻害薬の無効例であっても高い効果が報告されている．TIL療法の手順では，まず最初に患者自身の腫瘍を切除して浸潤リンパ球を抽出し，培養28日目に活性を有するリンパ球を選択する．このリンパ球をフィーダー細胞である健常人由来の末梢血単核球と共培養して14日で約1,000倍に増殖させ（急速拡大培養），骨髄抑制処置を行った患者に輸注する．輸注後は抗腫瘍効果を増強するためIL-2を8時間ごと5回投与する．我々は，2021年10月より先進医療の枠組みのもと，第3種再生医療として進行子宮頸癌症例を対象としたTIL療法の第2相臨床試験を実施している（jRCTc031200283）．先進医療と並行して前臨床試験を実施し，医師主導治験への導出を目指す．

子宮頸部高度異形成(CIN3)に対して円錐切除vs.レーザー照射(非切除)　円錐切除

岩田卓

アンチ・エイジング医学 19 ( 2 ) 156 - 159 2023.04

Evaluation of CD4+ cells infiltration as a prognostic factor in cervical intraepithelial neoplasia 2

Chen G., Iwata T., Sugawara M., Nishio H., Katoh Y., Kukimoto I., Aoki D.

Journal of Gynecologic Oncology (Journal of Gynecologic Oncology) 34 ( 1 ) e2 2023.01

ISSN 20050380

Objective: To identify candidate predictors for the prognosis of cervical intraepithelial neoplasia 2 (CIN2) lesions and evaluate the prognostic value of the local immune response. Methods: One hundred fifteen CIN2 patients were enrolled. The percentage of p16-, minichromosome maintenance complex component 2-or apolipoprotein B mRNA editing enzyme catalytic subunit 3G (APOBEC3G)-positive cells was determined immunohistochemically. Tumor-infiltrating lymphocytes (TILs) in intertumoral lesions were scored using an automated system. CIN3 disease progression and regression rates were estimated by the Kaplan–Meier method. A case-control study was conducted to screen CIN2 prognostic factors in 10 regression and 10 progression patients. Selected factors were examined in a cohort study to determine their prognostic value for CIN2. Results: Among all participants, the cumulative progression and regression rates at 60 months were 0.477 and 0.510, respectively. In the case-control study, p16-and APOBEC3G-positive cells were higher in the progression group (p=0.043, p=0.023). Additionally, CD4+ cell infiltration was enhanced in the regression group (p=0.023). The cohort study revealed a significantly increased progression rate in patients with elevated p16-positive cells (p<0.001), and increased CD4+ TIL infiltration was associated with better regression (p=0.011). Kaplan– Meier analysis according to human papillomavirus (HPV) positivity revealed a greater CIN3 development risk in HPV16-positive patients than in HPV16-negative cases. Finally, multivariate analysis identified HPV16 infection and CD4+ TIL infiltration as independent prognostic factors in CIN2 regression. Conclusion: CD4+ TIL infiltration in intertumoral lesions was related with CIN2 regression. Our findings suggest CD4+ TIL infiltration may be useful for the triage of CIN2 patients.

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当科で経験した子宮頸部胃型粘液性癌12例の検討

木村由実子, 西尾浩, 千代田達幸, 松井友哉, 岩田卓, 椎名美季, 大野あゆみ, 横田めぐみ, 田中守, 青木大輔

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 72 ( 1 ) 19 - 24 2023.01

Accepted, ISSN 2186-0599

子宮頸部胃型粘液性癌はハイリスクHPV感染との関連が低く稀な組織型であり,予後不良な疾患とされる.本研究では当科で経験した子宮頸部胃型粘液性癌について検討を行った.対象症例は12例であり,年齢の中央値は50歳(range:33～60歳),観察期間の中央値は16ヵ月(range:3～29ヵ月),臨床進行期(FIGO 2008)はIB1期6例,IB2期4例,IIB期1例,IVA期1例であった.初回治療として,手術を行った症例は12例中9例,同時化学放射線療法(concurrent chemoradiation therapy:CCRT)を行った症例は3例であった.手術を行った9症例のうち5例(56%)は術前の細胞診および組織診において浸潤癌の所見を認めなかった.12例中5例(42%)に再発を認め,うち4例は治療終了後12ヵ月以内に再発し,いずれも腹膜播種によるものであった.子宮頸部胃型粘液性癌は予後不良な組織型であり,治療後早期に再発する可能性を念頭に置き,慎重な経過観察を行う必要がある.(著者抄録)

Whole-genome analysis of human papillomavirus 67 isolated from Japanese women with cervical lesions

Kogure G., Onuki M., Hirose Y., Yamaguchi-Naka M., Mori S., Iwata T., Kondo K., Sekizawa A., Matsumoto K., Kukimoto I.

Virology Journal (Virology Journal) 19 ( 1 ) 157 2022.12

Background: Human papillomavirus (HPV) type 67 is phylogenetically classified into Alphapapillomavirus species 9 (alpha-9) together with other carcinogenic types (HPV16, 31, 33, 35, 52 and 58), but is the only alpha-9 type defined as possibly carcinogenic. This study aimed to determine whole-genome sequences of HPV67 isolated from Japanese women with cervical cancer or cervical intraepithelial neoplasia (CIN) to better understand the genetic basis of the oncogenic potential of HPV67. Methods: Total cellular DNA isolated from cervical exfoliated cells that were single positive for HPV67 (invasive cervical cancer, n = 2; CIN3, n = 6; CIN 2, n = 1; CIN1, n = 2; the normal cervix, n = 1) was subjected to PCR to amplify HPV67 DNA, followed by next generation sequencing to determine the complete viral genome sequences. Variant lineages/sublineages were assigned through viral whole-genome phylogenetic analysis. The transcriptional activity of the virus early promoter was assessed by luciferase reporter assays in cervical cancer cell lines. Results: Phylogenetic analyses of HPV67 genomes from Japan (n = 12) revealed that 11 belonged to lineage A (sublineage A1, n = 9; sublineage A2, n = 2) and one belonged to lineage B. All cancer cases contained sublineage A1 variants, and one of these contained an in-frame deletion in the E2 gene. The long control region of the HPV67 genome did not induce transcription from the virus early promoter in HeLa cells, but showed weak transcriptional activity in CaSki cells. Conclusions: The single detection of HPV67 in cervical cancer and precancer specimens strongly suggests the carcinogenic potential of this rare genotype. The phylogenetic analysis indicates a predominance of lineage A variants among HPV67 infections in Japan. Since only 23 complete genome sequences of HPV67 had been obtained until now, the newly determined genome sequences in this study are expected to contribute to further functional and evolutionary studies on the genetic diversity of HPV67.

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Pembrolizumab plus chemotherapy in Japanese patients with persistent, recurrent or metastatic cervical cancer: Results from KEYNOTE-826

Nishio S., Yonemori K., Usami T., Minobe S., Yunokawa M., Iwata T., Okamoto A., Aoki Y., Itamochi H., Takekuma M., Harano K., Yamamoto K., Maruko T., Ugai H., Tekin C., Colombo N., Fujiwara K., Hasegawa K., Ushijima K.

Cancer Science (Cancer Science) 113 ( 11 ) 3877 - 3887 2022.11

ISSN 13479032

Pembrolizumab plus chemotherapy with or without bevacizumab demonstrated prolonged progression-free survival (PFS) and overall survival (OS) versus chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer in the phase 3, randomized, double-blind, placebo-controlled KEYNOTE-826 study. We report outcomes in patients enrolled in Japan. Patients received pembrolizumab 200 mg or placebo Q3W for up to 35 cycles plus chemotherapy (paclitaxel 175 mg/m2 + cisplatin 50 mg/m2 or carboplatin AUC 5) with or without bevacizumab 15 mg/kg. Dual primary endpoints were PFS per RECIST v1.1 by investigator assessment and OS in the global population; these were evaluated in patients with tumors with PD-L1 combined positive score (CPS) ≥1, all-comers, and PD-L1 CPS ≥10. Fifty-seven patients from Japan were randomized (pembrolizumab plus chemotherapy, n = 35; placebo plus chemotherapy, n = 22). Pembrolizumab plus chemotherapy improved PFS versus placebo plus chemotherapy in patients with PD-L1 CPS ≥1 (n = 51; hazard ratio [HR; 95% CI], 0.36 [0.16–0.77]), all-comers (n = 57; 0.45 [0.22–0.90]), and patients with PD-L1 CPS ≥10 (n = 25; 0.36 [0.12–1.07]). HRs (95% CI) for OS were 0.38 (0.14–1.01), 0.41 (0.17–1.00), and 0.37 (0.10–1.30), respectively. Incidence of grade 3–5 AEs was 94% in the pembrolizumab group and 100% in the placebo group. Consistent with findings in the global KEYNOTE-826 study, pembrolizumab plus chemotherapy with or without bevacizumab may prolong survival versus placebo plus chemotherapy with or without bevacizumab and had a manageable safety profile in Japanese patients with persistent, recurrent, or metastatic cervical cancer.

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がん微小環境における脂質代謝の制御は、抗腫瘍免疫応答を増強し、抗PD-1抗体の効果を増強する

加藤侑希, 谷口智憲, 岩田卓, 川名敬, 河上裕

Reproductive Immunology and Biology (日本生殖免疫学会) 37 ( 1-2 ) 23 - 31 2022.11

ISSN 1881-607X

抗PD-1/PD-L1阻害薬は、治療前に腫瘍抗原特異的なCD8陽性T細胞が腫瘍組織に浸潤している腫瘍(hot tumor)では、がん細胞などが発現するPD-L1によるエフェクターCD8陽性T細胞抑制の解除により、がん細胞を排除できる。しかし、多くの症例ではCD8陽性T細胞浸潤が少なく(cold tumor)、抗PD-1/PD-L1阻害薬単独投与の効果は限定的であり、この治療抵抗性機序を解明して治療効果を増強する方法の開発が期待されている。我々は、様々なヒトがんの網羅的遺伝子発現解析により、cold tumorの中には、脂肪酸不飽和化酵素であるStearoyl-CoA desaturase 1(SCD1)の高発現をはじめとする、脂質代謝異常が深く関与するサブタイプが存在することを見出した。そこで、本研究では、脂肪酸代謝の抗腫瘍免疫応答への関与及び、それを標的としたがん免疫療法の可能性を検討した。まず、各種マウスがん細胞株を移植したマウス腫瘍モデルを用いて、SCD1阻害剤投与により、抗腫瘍免疫応答を増強できるかを検討した。その結果、SCD1阻害剤投与群において、腫瘍内樹状細胞(DC)のCD80/CD86やCD83の発現上昇、およびその浸潤増加が認められた。更に、CD8陽性T細胞の腫瘍内浸潤数の増加も観察され、所属リンパ節及び腫瘍組織内で、腫瘍抗原特異的T細胞の誘導が増強された。腫瘍内浸潤CD8陽性T細胞におけるPD-1などの共刺激分子の発現もSCD1阻害剤投与群において増強されていたので、SCD1阻害剤と抗PD-1抗体の併用療法の効果を評価した。その結果、抗PD-1抗体単独投与ではほとんど効果を示さないがん細胞株においても、両薬の併用によって相乗的な抗腫瘍効果が観察され、完全奏効例も認められた。SCD1阻害剤のin vitroでの免疫細胞に対する効果を評価したところ、DC及びCD8陽性T細胞に直接作用し、その機能を増強することも明らかとなった。以上より、がん微小環境における脂質代謝の制御により、cold tumorをhot tumorに変え、免疫チェックポイント阻害薬の治療効果を向上させる可能性が示された。(著者抄録)

Regional differences in human papillomavirus type 52 prevalence among Japanese women with cervical intraepithelial neoplasia†

Kukimoto I., Onuki M., Yamamoto K., Yahata H., Aoki Y., Yokota H., Konnai K., Nio A., Takehara K., Kamiura S., Tsuda N., Takei Y., Shimada M., Nakai H., Yoshida H., Motohara T., Yamazaki H., Nakamura K., Okunomiya A., Tasaka N., Ishikawa M., Hirashima Y., Shimoji Y., Mori M., Iwata T., Takahashi F., Yoshikawa H., Yaegashi N., Matsumoto K.

Japanese journal of clinical oncology (Japanese journal of clinical oncology) 52 ( 10 ) 1242 - 1247 2022.10

ISSN 0368-2811

Although geographical differences in the distribution of human papillomavirus genotypes have been observed worldwide, no studies have reported on national differences in the prevalence of human papillomavirus types in Japan. Here, we report a cross-sectional study to explore regional differences in the prevalence of human papillomavirus types among Japanese women with cervical intraepithelial neoplasia or invasive cervical cancer. Using human papillomavirus genotyping data from the nationwide prospective study on human papillomavirus vaccine effectiveness, we compared the frequency of detection of 15 high-risk and two low-risk human papillomavirus types in each disease category between the women who visited hospitals located in eastern Japan and those who visited hospitals located in western Japan. The risk of cervical intraepithelial neoplasia progression was assessed by calculating a prevalence ratio of each human papillomavirus type for cervical intraepithelial neoplasia grade 2/3 versus grade 1. Among the human papillomavirus types studied, human papillomavirus 52 was detected significantly more frequently in western hospitals than in eastern hospitals in cervical intraepithelial neoplasia grade 1 patients, but was less frequent in cervical intraepithelial neoplasia grade 2/3. The prevalence of particular human papillomavirus types was not significantly different between patients in hospitals in eastern Japan and those in hospitals in western Japan for invasive cervical cancer. In both eastern and western hospitals, a higher risk of cervical intraepithelial neoplasia progression was observed in patients infected with human papillomavirus 16, 31 or 58. In contrast, there was a significantly higher prevalence of human papillomavirus 52 infection in women with cervical intraepithelial neoplasia grade 2/3 than in those with cervical intraepithelial neoplasia grade 1 in eastern hospitals (prevalence ratio, 1.93; 95% confidence interval, 1.48-2.58), but not in western hospitals (prevalence ratio, 1.03; 95% confidence interval, 0.83-1.30). Regional differences of human papillomavirus 52 prevalence in cervical intraepithelial neoplasia lesions may exist and emphasize the importance of continuous monitoring of human papillomavirus type prevalence throughout the country in order to accurately assess the efficacy of human papillomavirus vaccines.

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特集 AYA世代の女性ヘルスケア-対応と実際- Ⅳ.婦人科腫瘍・婦人科疾患への対策 1.子宮頸部病変の妊孕性温存手術

田中恒成, 岩田卓

産婦人科の実際 (金原出版) 71 ( 10 ) 1101 - 1105 2022.09

ISSN 05584728

Development of a prognostic prediction support system for cervical intraepithelial neoplasia using artificial intelligence-based diagnosis

Takahashi T., Matsuoka H., Sakurai R., Akatsuka J., Kobayashi Y., Nakamura M., Iwata T., Banno K., Matsuzaki M., Takayama J., Aoki D., Yamamoto Y., Tamiya G.

Journal of Gynecologic Oncology (Journal of Gynecologic Oncology) 33 ( 5 ) e57 2022.09

ISSN 20050380

Objective: Human papillomavirus subtypes are predictive indicators of cervical intraepithelial neoplasia (CIN) progression. While colposcopy is also an essential part of cervical cancer prevention, its accuracy and reproducibility are limited because of subjective evaluation. This study aimed to develop an artificial intelligence (AI) algorithm that can accurately detect the optimal lesion associated with prognosis using colposcopic images of CIN2 patients by utilizing objective AI diagnosis. Methods: We identified colposcopic findings associated with the prognosis of patients with CIN2. We developed a convolutional neural network that can automatically detect the rate of high-grade lesions in the uterovaginal area in 12 segments. We finally evaluated the detection accuracy of our AI algorithm compared with the scores by multiple gynecologic oncologists. Results: High-grade lesion occupancy in the uterovaginal area detected by senior colposcopists was significantly correlated with the prognosis of patients with CIN2. The detection rate for high-grade lesions in 12 segments of the uterovaginal area by the AI system was 62.1% for recall, and the overall correct response rate was 89.7%. Moreover, the percentage of high-grade lesions detected by the AI system was significantly correlated with the rate detected by multiple gynecologic senior oncologists (r=0.61). Conclusion: Our novel AI algorithm can accurately determine high-grade lesions associated with prognosis on colposcopic images, and these results provide an insight into the additional utility of colposcopy for the management of patients with CIN2.

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Risk assessment in the patients with uterine cervical cancer harboring intermediate risk factors after radical hysterectomy: a multicenter, retrospective analysis by the Japanese Gynecologic Oncology Group

Shigeta S., Shimada M., Tsuji K., Nagai T., Tanase Y., Matsuo K., Kamiura S., Iwata T., Yokota H., Mikami M.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 27 ( 9 ) 1507 - 1515 2022.09

ISSN 13419625

Background: Adjuvant therapy is usually considered for surgically treated patients with uterine cervical cancer harboring intermediate risk (IR) factors such as large tumor diameter, stromal invasion to the outer half, and lymphovascular space invasion (LVSI). However, the indications and types of adjuvant therapy for the IR group remain controversial. This study aimed to analyze the differences in patient outcomes in the IR group to provide novel insights for tailoring adjuvant therapy. Methods: Data from 6192 patients with cervical cancer who underwent radical hysterectomy at 116 institutions belonging to the Japanese Gynecologic Oncology Group were reviewed. Results: In total, 1688 patients were classified into the IR group, of whom 37.3% did not receive adjuvant therapy. Conversely, approximately equal proportions of the remaining patients received adjuvant radiotherapy, concurrent chemoradiotherapy, and chemotherapy. Patients with all three risk factors showed worse overall survival than those with one or two risk factors. In addition to LVSI, non-squamous cell carcinoma histology, and vaginal invasion were identified as independent risk factors for both recurrence and mortality in multivariate analyses. Tumor diameter greater than 40 mm and surgical center volume were identified as independent risk factors for recurrence. Stromal invasion to the outer half and ovarian metastasis were identified as independent risk factors for mortality. Conclusions: This study revealed the significant differences in prognosis in the IR group. The indications for adjuvant therapy should be further studied, focusing on conventional risk factors and other pathological findings.

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