Trends and future projections of cervical cancer-related outcomes in Japan: What happens if the HPV vaccine program is not implemented?

Contrary to other developed countries, in Japan, recent years have seen increases in cervical cancer incidence and mortality among young people. However, the human papillomavirus (HPV) vaccine program, a key measure for avoiding cervical cancer, has been virtually suspended. Temporal changes in cervical cancer profiles in this unique situation have not been fully investigated epidemiologically. Our study aimed to determine the current status and future trends of the incidence and mortality of cervical cancer and precancerous lesions in Japan. Mortality rates of cervical cancer during 1975 to 2016 and incidence rates of cervical cancer and cervical intraepithelial neoplasia (CIN) 3 during 1975 to 2013 were examined using vital statistics and population-based cancer registry data in Japan. Bayesian age-period-cohort analyses were performed to analyze temporal changes of the three cervical cancer-related outcomes. We also calculated projections to 2028 for the three outcomes, assuming that HPV vaccination coverage and screening rates in Japan would be maintained at the current level after the resumption of the national vaccination program. The risk of occurrence of the three outcomes showed similar changes by birth cohort, peaking in the mid-1890s to 1900s birth cohorts, declining sharply in the 1940s birth cohort, and persistently increasing in the 1950s and later birth cohorts. Projections to 2028 show increases in cervical cancer incidence and mortality in the 30 to 69 age group, with a particular increase in CIN3 incidence in the 25 to 49 age group, if HPV vaccine programs and screening are not effectively implemented. These findings revealed an increasing cervical disease burden among reproductive age females in Japan.

Characteristic of Endometrial Stromal Sarcoma by Algorithm of Potential Biomarkers for Uterine Mesenchymal Tumor.

The benign tumor uterine leiomyoma (UL) develops from the smooth muscle tissue that constitutes the uterus, whereas malignant tumor uterine sarcoma develops from either the smooth muscle tissue or stroma and is different from UL and endometrial cancer. Uterine sarcoma is broadly classified into three types: uterine leiomyosarcoma, endometrial stromal sarcoma (ESS), and carcinosarcoma. Although uterine leiomyosarcoma and ESS are both classified as uterine sarcoma, they significantly differ in terms of their sites of occurrence, symptoms, and treatment methods. Uterine leiomyosarcoma develops from the muscle tissue constituting the wall of the uterus and accounts for approximately 70% of all uterine sarcoma cases. In contrast, ESS develops from the stromal tissue beneath the endometrium and accounts for approximately 25% of all uterine sarcoma cases. ESS is classified as either low grade (LG) or high grade (HG). This case report aimed to highlight the importance of histopathologic examinations based on surgical specimens. Herein, we reported the case of a 45-year-old woman suspected of having submucosal leiomyoma of the uterus based on imaging results. Transvaginal ultrasonography and endometrial biopsy or partial dilation and curettage were performed. Contrast-enhanced magnetic resonance imaging (MRI) revealed a 32-mm mass projecting from the posterior wall of the uterus into the uterine cavity. T2-weighted imaging revealed a low signal within the mass; thus, submucosal UL was suspected. Histopathologic examination of surgical specimens obtained from a patient suspected of having submucosal UL after contrast-enhanced MRI indicated that the patient had ESS. Despite the remarkable advancements in medical imaging technology, the accuracy of contrast-enhanced MRI for detecting uterine mesenchymal tumors is limited. Therefore, histopathologic diagnosis based on surgical specimens should be performed when medical grounds for diagnosing a benign tumor on contrast-enhanced MRI are lacking.

Ovarian serous borderline tumors with recurrent or extraovarian lesions: a Japanese, retrospective, multi-institutional, population-based study.

BACKGROUND: Ovarian serous borderline tumors (SBT) are typically unilateral and are primarily treated using hysterectomy and bilateral salpingooophorectomy (SO). However, most young patients prefer fertility-sparing surgeries (FSS) with tumorectomy or unilateral SO. Micropapillary morphology and invasive implants have been designated as histopathological risk indicators for recurrence or metastasis, but their clinical impact remains controversial because of limitations like diagnostic inconsistency and incomplete surgical staging. METHODS: A nationwide multi-institutional population-based retrospective surveillance was conducted with a thorough central pathology review to reveal the clinical features of SBT. Of 313 SBT patients enrolled in the Japanese Society of Clinical Oncology's Surveillance of Gynecologic Rare Tumors, 289 patient records were reviewed for clinical outcomes. The glass slides of patients at stage II-IV or with recurrence or death were re-evaluated by three gynecological pathologists. RESULT: The 10-year overall and progression-free survival (PFS) rates were 98.6% and 92.3%. The median recurrence period was 40 months and 77.0% was observed in the contralateral ovary within 60 months. Patients aged ≤ 35 years underwent FSS more frequently and relapsed more (p < .001). A clinic-pathological analysis revealed diagnosis during pregnancy, FSS, and treatment at non-university institutes as well as advanced stage and large diameter were independent risk factors of recurrence. Among patients having pathologically confirmed SBTs, PFS was not influenced by the presence of micropapillary pattern or invasive implants. CONCLUSION: The recurrence rate was lower in this cohort than previous reports, but the clinical impacts of incomplete resection and misclassification of the tumor were still significant on the treatment of SBT.

Possibility of SARS-CoV-2 Infection in the Metastatic Microenvironment of Cancer.

According to a report from the World Health Organization (WHO), the mortality and disease severity induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are significantly higher in cancer patients than those of individuals with no known condition. Common and cancer-specific risk factors might be involved in the mortality and severity rates observed in the coronavirus disease 2019 (COVID-19). Similarly, various factors might contribute to the aggravation of COVID-19 in patients with cancer. However, the factors involved in the aggravation of COVID-19 in cancer patients have not been fully investigated so far. The formation of metastases in other organs is common in cancer patients. Therefore, the present study investigated the association between lung metastatic lesion formation and SARS-CoV-2 infectivity. In the pulmonary micrometastatic niche of patients with ovarian cancer, alveolar epithelial stem-like cells were found adjacent to ovarian cancer. Moreover, angiotensin-converting enzyme 2, a host-side receptor for SARS-CoV-2, was expressed in these alveolar epithelial stem-like cells. Furthermore, the spike glycoprotein receptor-binding domain (RBD) of SARS-CoV-2 was bound to alveolar epithelial stem-like cells. Altogether, these data suggested that patients with cancer and pulmonary micrometastases are more susceptible to SARS-CoV-2. The prevention of de novo niche formation in metastatic diseases might constitute a new strategy for the clinical treatment of COVID-19 for patients with cancer.

Pathological Evidence for Residual SARS-CoV-2 in the Micrometastatic Niche of a Patient with Ovarian Cancer.

In previous clinical studies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in cancer patients has a high risk of aggravation and mortality than in healthy infected individuals. Inoculation with coronavirus disease 2019 (COVID-19) vaccine reduces the risk of SARS-CoV-2 infection and COVID-19 severity. However, vaccination-induced anti-SARS-CoV-2 antibody production is said to be lower in cancer patients than in healthy individuals. In addition, the rationale for why the condition of patients with cancer worsens with COVID-19 is not well understood. Therefore, we examined the infection status of SARS-CoV-2 in the primary tumor and micrometastasis tissues of the patient with cancer and COVID-19. In this study, the expression of angiotensin-converting enzyme 2 (ACE2) was observed, and SARS-CoV-2 particles was detected in ovarian tissue cells in contact with the micrometastatic niche of the patient with high-grade serous ovarian cancer. We believe that the severity of COVID-19 in patients with cancer can be attributed to these pathological features. Therefore, the pathological findings of patients with advanced and recurrent ovarian cancer infected with SARS-CoV-2 may help decrease COVID-19 severity in patients with other cancer types.

Visceral-to-subcutaneous fat ratio is a possible prognostic factor for type 1 endometrial cancer.

BACKGROUND: Associations have been observed between obesity defined by the body mass index (BMI) and the incidence of endometrial cancer. However, the impact of obesity on the prognosis of endometrial cancer is not yet clear. Recently, visceral fat has been considered to have a greater impact on malignant disease in obese patients than subcutaneous fat. In this study, we investigated the association between prognostic factors of type 1 and type 2 endometrial cancer and obesity parameters. METHODS: The impacts of clinical factors on the progression-free survival (PFS) and overall survival (OS) were analyzed retrospectively in 145 primary endometrial cancer patients. The factors included age, BMI, pathological findings, Federation of Gynecology and Obstetrics (FIGO) stage, status of lymph node metastasis, and the amounts of visceral and subcutaneous fat obtained from computed tomography (CT) data. RESULTS: Only the visceral-to-subcutaneous fat ratio (V/S ratio) (cutoff value 0.5) corresponded to a significant difference in OS and PFS in type 1 endometrial cancer (p = 0.0080, p = 0.0053) according to the results of log-rank tests of Kaplan-Meier curves. The COX regression univariate analysis revealed that only the V/S ratio was a significant prognostic factor for PFS, but not OS (p = 0.033 and p = 0.270, respectively). CONCLUSION: A V/S ratio > 0.5 is a possible factor for poor prognosis in type 1 endometrial cancer. Further research is needed to investigate the preventive and therapeutic effects of reducing visceral fat on the prognosis of this type of cancer.

Oncological Properties of Intravenous Leiomyomatosis: Involvement of Mesenchymal Tumor Stem-Like Cells.

Uterine leiomyoma, also known as fibroids, is the most common benign neoplasm of the female genital tract. Leiomyoma is the most common uterine tumor. The leiomyoma subtypes account for approximately 10% of leiomyomas. Intravenous leiomyomatosis, a uterine leiomyoma subtype, is an intravascular growth of benign smooth muscle cells, occasionally with pelvic or extrapelvic extension. Uterine leiomyosarcoma, a malignant tumor, tends to metastasize hematogenously, and distant metastasis to the lungs and liver is common. Therefore, the oncological properties of this intravenous leiomyomatosis resemble those of the malignant tumor uterine leiomyosarcoma. Cancer stem cells migrate to distant organs via intravascular infiltration, leading to micrometastases. We examined the oncological properties of intravenous leiomyomatosis using molecular pathological techniques on tissue excised from patients with uterine leiomyoma. CD44-positive mesenchymal tumor stem-like cells were detected in both patients with intravenous leiomyomatosis and uterine leiomyosarcoma. The oncological properties of intravenous leiomyomatosis were found to be similar to those of uterine leiomyosarcoma. However, in intravenous leiomyomatosis, cyclin E and Ki-67-positive cells were rare and no pathological findings suspecting malignancy were observed. It is expected that establishing a treatment method targeting cancer stem cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis.

Correlation of anti-tumour drug resistance with epigenetic regulation.

During treatment, the development of drug-resistant tumours remains an important challenge in cancer treatment. Epigenetic changes have been reported as one of the mechanisms for anti-tumour drug resistance. In clinical practice, a combination of epigenetic-related drugs can be considered as a future selection of cancer therapeutic drugs.

Potential Novel Ovarian Cancer Treatment Targeting Myeloid-Derived Suppressor Cells.

Diagnosis by biopsy is difficult in the ovary since it is located deep in the abdomen. As a result, ovarian cancer is mostly found insidiously during exploratory laparotomy. Consequently, the early diagnosis of ovarian cancer is often difficult. The likelihood of peritoneal dissemination increases with the progress of ovarian cancer. With further progression, ovarian cancer metastasizes to the momentum, retroperitoneal lymph nodes, large intestine, small intestine, diaphragm, spleen, and other organs. Ovarian cancer has been considered a tumor that has a favorable response to chemotherapy, but more effective treatments are still being explored. Tumors use their own immune escape mechanism to evade host immunity. The immune checkpoint (IC) mechanism, one of the immune escape mechanisms, is established by programmed cell death-1 (PD-1)/PD-ligand-1 (PD-L1) communication. It has been shown that inhibiting PD-1/PD-L1 communication in various malignancies produces antitumor effects. However, the antitumor effect of ICI monotherapy on ovarian cancer is limited in actual clinical practice. In this review, we describe a novel cancer immunotherapeutic agent that targets myeloid-derived suppressor cells (MDSCs).

Mesonephric-like adenocarcinoma of the ovary in an elderly woman: A case report and a review of the literature.

Mesonephric-like adenocarcinoma (MLA) is a rare tumor that occurs in the uterine endometrium and ovary. It morphologically and immunohistochemically resembles cervical mesonephric adenocarcinoma (MA). Here, we present a case of MLA of the ovary along with a literature review. An asymptomatic 84-year-old woman presented with a pelvic mass, detected by computerized tomography. Magnetic resonance imaging demonstrated a polycystic mass with a solid component in the left adnexal region. The solid component showed low signal intensity on T2-weighted imaging and high signal intensity on diffusion-weighted imaging. We strongly suspected an ovarian malignant tumor; therefore, surgical resection of the uterus and adnexa was performed. Macroscopically, the tumor was predominantly solid with yellowish-tan cut surface. Microscopically, it showed a tubular pattern with intraluminal colloid-like material resembling MA. The tumor cells were negative for estrogen receptor, calretinin, and CD10 and positive for PAX8 and TTF-1. These findings are consistent with those of MLA.

Lymphoepithelioma-like carcinoma of uterine cervix: Preoperative diagnosis and course in three cases.

Lymphoepithelioma-like carcinoma of the uterine cervix is a rare variant of squamous cell carcinoma. Herein, we describe three cases of lymphoepithelioma-like carcinoma of the uterine cervix and review relevant literature. All three patients initially presented with postmenopausal bleeding. Gross appearances were endophytic with ulcerated mucosa in case 1, exophytic with polypoid morphology in case 2, and unremarkable even using colposcopy and hysteroscopy in case 3. Magnetic resonance imaging demonstrated well-demarcated cervical masses with high-intermediate intensity on T2-weighted images and high intensity on diffusion-weighted images in all three cases. In case 3, biopsy referring to local information from magnetic resonance images was required for preoperative diagnosis. We reviewed the literature of 59 lymphoepithelioma-like carcinoma cases in 19 papers published between 2001 and 2020. Preoperative diagnosis of lymphoepithelioma-like carcinoma is sometimes challenging, although magnetic resonance imaging findings may help determine the location of the tumor and obtain a successful biopsy.

Anti-VEGF therapy resistance in ovarian cancer is caused by GM-CSF-induced myeloid-derived suppressor cell recruitment.

BACKGROUND: The mechanism of resistance development to anti-VEGF therapy in ovarian cancer is unclear. We focused on the changes in tumour immunity post anti-VEGF therapy. METHODS: The frequencies of immune cell populations and hypoxic conditions in the resistant murine tumours and clinical samples were examined. The expression profiles of both the proteins and genes in the resistant tumours were analysed. The impact of granulocyte-monocyte colony-stimulating factor (GM-CSF) expression on myeloid-derived suppressor cell (MDSC) function in the resistant tumours was evaluated. RESULTS: We found a marked increase and reduction in the number of Gr-1 + MDSCs and CD8 + lymphocytes in the resistant tumour, and the MDSCs preferentially infiltrated the hypoxic region. Protein array analysis showed upregulation of GM-CSF post anti-VEGF therapy. GM-CSF promoted migration and differentiation of MDSCs, which inhibited the CD8 + lymphocyte proliferation. Anti-GM-CSF therapy improved the anti-VEGF therapy efficacy, which reduced the infiltrating MDSCs and increased CD8 + lymphocytes. In immunohistochemical analysis of clinical samples, GM-CSF expression and MDSC infiltration was enhanced in the bevacizumab-resistant case. CONCLUSIONS: The anti-VEGF therapy induces tumour hypoxia and GM-CSF expression, which recruits MDSCs and inhibits tumour immunity. Targeting the GM-CSF could help overcome the anti-VEGF therapy resistance in ovarian cancers.

VISTA expressed in tumour cells regulates T cell function.

BACKGROUND: V-domain Ig suppressor of T cell activation (VISTA) is a novel inhibitory immune-checkpoint protein. VISTA expression on tumour cells and the associated regulatory mechanisms remain unclear. We investigated VISTA expression and function in tumour cells, and evaluated its mechanism and activity. METHODS: VISTA in tumour cells was assessed by tissue microarray analysis, immunohistochemical staining and western blot. A series of in vitro assays were used to determine the function of tumour-expressed VISTA. In vivo efficacy was evaluated in syngeneic models. RESULTS: VISTA was highly expressed in human ovarian and endometrial cancers. Upregulation of VISTA in endometrial cancer was related to the methylation status of the VISTA promoter. VISTA in tumour cells suppressed T cell proliferation and cytokine production in vitro, and decreased the tumour-infiltrating CD8+ T cells in vivo. Anti-VISTA antibody prolonged the survival of tumour-bearing mice. CONCLUSIONS: This is the first demonstration that VISTA is highly expressed in human ovarian and endometrial cancer cells, and that anti-VISTA antibody treatment significantly prolongs the survival of mice bearing tumours expressing high levels of VISTA. The data suggest that VISTA is a novel immunosuppressive factor within the tumour microenvironment, as well as a new target for cancer immunotherapy.

Versican V1 in human endometrial epithelial cells promotes BeWo spheroid adhesion in vitro.

The endometrium extracellular matrix (ECM) is essential for embryo implantation. Versican, a large chondroitin sulfate proteoglycan that binds hyaluronan and forms large ECM aggregates, can influence fundamental physiological phenomena, such as cell proliferation, adhesion and migration. The present study investigated the possible role of versican in human embryo implantation. Versican V1 expression and secretion in human endometrial epithelial cells (EECs) was most prominent in the mid-secretory phase. Versican expression in EECs significantly increased after treatment with estrogen and progesterone, but not by estrogen alone. We also established versican V1-overexpressing Ishikawa (endometrial cancer cell line) cells (ISKW-V1), versican V3-overexpressing (ISKW-V3) and control GFP-overexpressing (ISKW-GFP) Ishikawa cells. By the in vitro implantation model, the attachment ratio of BeWo (choriocarcinoma cell line) spheroids to the monolayer of ISKW-V1, but not of ISKW-V3, was found significantly enhanced compared with attachment to the ISKW-GFP monolayer. The conditioned medium derived from ISKW-V1 (V1-CM) also promoted the attachment of BeWo spheroids to the ISKW monolayer. However, this attachment-promoting effect was abolished when V1-CM was pretreated with chondroitinase ABC, which degrades chondroitin sulfate. Therefore, out of the ECM components, versican V1 may facilitate human embryo implantation.

Prospects and Problems of Cancer Genome Analysis for Establishing Cancer Precision Medicine.

The genome represents a design for creating the body, with each one being different. In cancer genomic medicine, many genes are simultaneously examined using mainly cancer tissues (the oncogene panel test), and gene mutations are revealed. Cancer treatments are then initiated according to each individual's constitution and medical condition based on gene mutations. A system for cancer genome medical treatment is currently being developed. In the treatment of several types of cancer, the "oncogene test with an oncogene companion diagnosis" is already being performed as a standard test using cancer tissue to detect one or more gene mutations. On June 1, 2019, the cancer gene panel test was covered by the national health insurance system in Japan, and a system to initiate cancer genome medical treatment has begun. The prospects and problems associated with cancer genome medicine are discussed herein.

Validation of the 2018 FIGO cervical cancer staging system.

OBJECTIVE: To validate the revised 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system for cervical cancer, with a particular focus on stage IB and stage III disease. METHODS: Two retrospective cohort studies were conducted using The Surveillance, Epidemiology, and End Results Program between 1988 and 2014. The stage IB cohort consisted of node-negative FIGO stage IB1 (tumor size <2 cm), IB2 (2-3.9 cm), and IB3 (≥4 cm) cervical cancer. The stage III cohort consisted of FIGO stage IIIA, IIIB, and stage IIIC1 (any pelvic nodal metastasis) cervical cancer. Multivariable analysis was performed for cause-specific survival based on cancer stage. RESULTS: In the stage IB cohort (n = 8909), stage IB1 tumors were more likely to be adenocarcinoma and low-grade compared to other the groups (P < 0.001). On multivariable analysis, stage IB2 disease was independently associated with a nearly two-fold increased risk of cervical cancer mortality compared to stage IB1 disease (adjusted-hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.62-2.41, P < 0.001). In the stage III cohort (n = 11,733), stage IIIC1 was independently associated with improved cause-specific survival compared to stage IIIB disease (adjusted-HR 0.79, 95%CI 0.74-0.85, P < 0.001). Survival of stage IIIC1 disease significantly differed based on T = stage, (5-year rates: 74.8% for T1, 58.7% for T2, and 39.3% for T3) with a 35.3% difference in absolute survival (P < 0.001). CONCLUSION: The 2018 FIGO staging system for cervical cancer is useful to distinguish survival groups; stage IB1 and stage IB2 disease have distinct characteristics and survival outcomes, while survival in stage IIIC1 varies depending on local tumor factors.

The mesenchymal transition subtype more responsive to dose dense taxane chemotherapy combined with carboplatin than to conventional taxane and carboplatin chemotherapy in high grade serous ovarian carcinoma: A survey of Japanese Gynecologic Oncology Group study (JGOG3016A1).

OBJECTIVE: Recently, we established new histopathological subtypes of high-grade serous ovarian cancer (HGSOC) that include the mesenchymal transition (MT) type, the immune reactive (IR) type, the solid and proliferative (SP) type and the papillo-glandular (PG) type. Furthermore, we identified that the mesenchymal transcriptome subtype might be sensitive to taxane. We investigated whether these different histopathological subtypes of HGSOC require individualized chemotherapy for optimal treatment. METHODS: We conducted the Japanese Gynecologic Oncology Group (JGOG) 3016A1 study, wherein we collected hematoxylin and eosin slides (total n = 201) and performed a histopathological analysis of patients with HGSOC registered in the JGOG3016 study, which compared the efficacy of conventional paclitaxel and carboplatin (TC) and dose-dense TC (ddTC). We analyzed the differences in progression-free survival (PFS) and overall survival (OS) among the four histopathological subtypes. We then compared the PFS between the TC group and the ddTC group for each histopathological subtype. RESULTS: There were significant differences in both PFS and OS among the four histopathological subtypes (p = 0.001 and p < 0.001, respectively). Overall, the MT subtype had the shortest PFS (median 1.4 y) and OS (median 3.6 y). In addition, the MT subtype had a longer PFS in the ddTC group (median 1.8 y) than in the TC group (median 1.2 y) (p = 0.01). Conversely, the other types had no significant difference in PFS when the two regimens were compared. CONCLUSIONS: The MT type of HGSOC is sensitive to taxane; therefore, the ddTC regimen is recommended for this histopathological subtype.

Factors influencing the adoption of the sentinel lymph node technique for endometrial cancer staging: an international survey of gynecologic oncologists.

OBJECTIVE: To explore the factors influencing adoption of the sentinel lymph node (SLN) technique for endometrial cancer staging among gynecologic oncologists. METHODS: A self-administered, web-based survey was sent via email (April 20 through May 21, 2017) to all members of European Society of Gynecologic Oncologists, International Gynecologic Cancer Society, and Society of Gynecologic Oncologists. Surgical and pathologic practices related to SLN and reasons for not adopting this technique were investigated. RESULTS: Overall, 489 attending physicians or consultants in gynecologic oncology from 69 countries responded: 201 (41.1%), 118 (24.1%), and 117 (23.9%) from Europe, the USA, and other countries, respectively (10.8% did not report a country). SLN was adopted by 246 (50.3%) respondents, with 93.1% injecting the cervix and 62.6 % using indocyanine green dye. The National Comprehensive Cancer Network SLN algorithm was followed by 160 (65.0%) respondents (USA 74.4%, Europe 55.4%, other countries 71.4%). However, 66.7% completed a backup lymphadenectomy in high-risk patients. When SLN biopsy revealed isolated tumor cells, 13.8% of respondents recommended adjuvant therapy. This percentage increased to 52% if micrometastases were detected. Among the 243 not adopting SLN, 50.2% cited lack of evidence and 45.3% stated that inadequate instrumentation fueled their decisions. CONCLUSIONS: SLN with a cervical injection is gaining widespread acceptance for staging of endometrial cancer among gynecologic oncologists worldwide. Standardization of the surgical approach with the National Comprehensive Care Network algorithm is applied by most users. Management of isolated tumor cells and the role of backup lymphadenectomy for 'high-risk' cases remain areas of investigation.

Age-related survival disparity in stage IB and IIB cervical cancer patients.

AIM: Whether young cervical cancer patients have poorer prognosis compared to older ones has remained controversial over the past half century. The last three decades have seen a rise in morbidity and mortality among young Japanese women with cervical cancer. This reflects the fact that the importance of prevention has not been fully recognized due to limited clinical studies. We examined the relationship between age and prognosis in cervical cancer. METHODS: We retrospectively examined medical records of consecutive patients with International Federation of Gynecology and Obstetrics stage IB and IIB cervical cancer at a hospital in Japan. Patients were divided into two age groups: less than or equal to 39 years (adolescent and young adult [AYA] group) and greater than or equal to 40 years (older adult group). We compared prognosis and clinical factors associated with prognosis between AYA and older adult patients. RESULTS: Data from 182 patients (AYA n = 71; older adults n = 111) treated between 2004 and 2011 were analyzed. The proportion of loss to follow-up was 6.0%. Significant differences were observed in stage and lymph node metastasis between the two groups at baseline. However, despite the older adult group having a higher proportion of advanced cancer patients, the overall survival rate of stage IIB patients in the AYA group at the 3-year follow-up was significantly lower (AYA 53.6%, older adults 86.3%, P < 0.05). Multivariate analysis adjusted for clinical factors revealed that AYA patients had a 3.7-3.9 times greater mortality risk compared to older adults. CONCLUSION: AYA patients with stage IB and IIB cervical cancer may have a prognostic disadvantage.

Antitumor Effect of Nivolumab on Subsequent Chemotherapy for Platinum-Resistant Ovarian Cancer.

Platinum-resistant recurrent ovarian cancer is generally refractory to chemotherapy. Programmed cell death-1 (PD-1) signaling is a new target for antitumor therapy. The anti-PD-1 antibody nivolumab had a 10% durable complete response rate in our phase II clinical trial. However, how nivolumab affects sensitivity to subsequent chemotherapy remains unclear. We encountered several cases of unexpected antitumor response among patients who underwent palliative chemotherapy in the follow-up study of our phase II nivolumab trial (UMIN000005714). Several agents had an unexpected antitumor response in patients who were resistant or refractory to standard chemotherapeutic agents. In one patient, both pegylated liposomal doxorubicin (PLD) and nedaplatin (CDGP) resulted in partial response. In another patient, PLD and CDGP resulted in partial response and stable disease, respectively. These two patients remained alive on the cutoff date. These two cases raise the possibility that nivolumab might improve sensitivity to adequate chemotherapy for ovarian cancer.