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

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.

Human papillomavirus vaccine effectiveness by age at first vaccination among Japanese women.

In Japan, the National Immunization Program against human papillomavirus (HPV) targets girls aged 12-16 years, and catch-up vaccination is recommended for young women up to age 26 years. Because HPV infection rates increase soon after sexual debut, we evaluated HPV vaccine effectiveness by age at first vaccination. Along with vaccination history, HPV genotyping results from 5795 women younger than 40 years diagnosed with cervical intraepithelial neoplasia grade 2-3 (CIN2-3), adenocarcinoma in situ (AIS), or invasive cervical cancer were analyzed. The attribution of vaccine-targeted types HPV16 or HPV18 to CIN2-3/AIS was 47.0% for unvaccinated women (n = 4297), but 0.0%, 13.0%, 35.7%, and 39.6% for women vaccinated at ages 12-15 years (n = 36), 16-18 years (n = 23), 19-22 years (n = 14), and older than 22 years (n = 91), respectively, indicating the greater effectiveness of HPV vaccination among those initiating vaccination at age 18 years or younger (P < .001). This finding was supported by age at first sexual intercourse; among women with CIN2-3/AIS, only 9.2% were sexually active by age 14 years, but the percentage quickly increased to 47.2% by age 16 and 77.1% by age 18. Additionally, the HPV16/18 prevalence in CIN2-3/AIS was 0.0%, 12.5%, and 40.0% for women vaccinated before (n = 16), within 3 years (n = 8), and more than 3 years after (n = 15) first intercourse, respectively (P = .004). In conclusion, our data appear to support routine HPV vaccination for girls aged 12-14 years and catch-up vaccination for adolescents aged 18 years and younger in Japan.

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

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.

[Toxicity of Takifugu exascurusCollected from the Sea of Kumano].

Marine pufferfish Takifugu exascurus is not approved for human consumption due to the lack of information on its toxicity. To clarify the toxicity of T. exascurus, ten live specimens were collected from the Sea of Kumano, Japan, and the toxicity and tetrodotoxin (TTX) concentration were determined using mouse bioassay and high performance liquid chromatography-fluorescence detection (HPLC-FLD), respectively. Toxicity was observed in the skin, liver, and ovaries, but the testes and muscle were non-toxic (<10 MU/g). On the other hand, HPLC-FLD revealed that TTX was detected in the muscle in two of the 10 specimens (1.4 and 1.5 MU/g). Based on the results, TTX is the main toxic component contributing to toxicity in T. exascurus.

Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan.

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012-2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2-3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type-specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type-specific RCs between CIN1 and CIN2-3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type-specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2-3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2-3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01-4.98), followed by HPV31 (2.51, 1.54-5.24), HPV18 (2.43, 1.59-4.32), HPV35 (1.56, 0.43-8.36), HPV33 (1.01, 0.49-3.31), HPV52 (0.99, 0.76-1.33), and HPV58 (0.97, 0.75-1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71-2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14-0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9-valent vaccine contributed to 89.7% (95% CI, 88.7-90.7) of CIN2-3/AIS and 93.8% (95% CI, 92.4-95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9-valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.

Production of donor-derived eggs after ovarian germ cell transplantation into the gonads of adult, germ cell-less, triploid hybrid fish†.

In animals, spermatogonial transplantation in sterile adult males is widely developed; however, despite its utility, ovarian germ cell transplantation is not well developed. We previously showed that the interspecific hybrid offspring of sciaenid was a suitable model for germ cell transplantation studies as they have germ cell-less gonads. However, all these gonads have testis-like characteristics. Here, we tested whether triploidization in hybrid embryos could result in germ cell-less ovary development. Gonadal structure dimorphism and sex-specific gene expression patterns were examined in 6-month-old triploid hybrids (3nHybs). Thirty-one percent of 3nHybs had germ cell-less gonads with an ovarian cavity. cyp19a1a and foxl2, ovarian differentiation-related genes, were expressed in these gonads, whereas dmrt1 and vasa were not expressed, suggesting ovary-like germ cell-less gonad development. Some (26%) 3nHybs had testis-like germ cell-less gonads. Ovarian germ cells collected from homozygous green fluorescent protein (GFP) transgenic blue drum (BD) (Nibea mitsukurii) were transplanted into 6-month-old 3nHybs gonads via the urogenital papilla or oviduct. After 9 months, the recipients were crossed with wild type BD. Among the six 3nHyb recipients that survived, one female and one male produced fertile eggs and motile sperm carrying gfp-specific DNA sequences. Progeny tests revealed that all F1 offspring possessed gfp-specific DNA sequences, suggesting that these recipients produced only donor-derived eggs or sperm. Histological observation confirmed donor-derived gametogenesis in the 3nHyb recipients' gonads. Overall, triploidization reduces male-biased sex differentiation in germ cell-less gonads. We report, for the first time, donor-derived egg production in an animal via direct ovarian germ cell transplantation into a germ cell-less ovary.

Four cases of Mayer-Rokitansky-Küster-Hauser syndrome treated via non-surgical vaginal reconstruction using uterine cervical dilators.

Vaginal creation is the standard treatment for Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Although non-surgical method is recommended as a first-line treatment in the American College of Obstetricians and Gynecologists guidelines for gynecological practice, it is not commonly performed in Japan. At our hospital, vaginal dilation using uterine cervical dilators (Hegar's dilator) is performed for patients with MRKH syndrome. We report four cases successfully treated with vaginal dilation. After the examination, patients were instructed to practice daily self-dilation at home. The initiation size was No. 13 with 10.5-mm diameter. After the vaginal cavity was dilated to a depth of 6 cm, the size of dilators was gradually increased until No. 30 with 25-mm diameter in a tip and 28-mm diameter in a trunk. The duration required to achieve the outcome was 5-22 months. All cases were successfully treated without any severe complication.

Reduction in HPV16/18 prevalence among young women with high-grade cervical lesions following the Japanese HPV vaccination program.

The Japanese government began a human papillomavirus (HPV) vaccination program for girls aged 12-16 years in 2010 but withdrew its recommendation in 2013 because of potential adverse effects, leading to drastically reduced vaccination uptake. To evaluate population-level effects of HPV vaccination, women younger than 40 years of age newly diagnosed with cervical intraepithelial neoplasia grade 1-3 (CIN1-3), adenocarcinoma in situ (AIS), or invasive cervical cancer (ICC) have been registered at 21 participating institutes each year since 2012. A total of 7709 women were registered during 2012-2017, of which 5045 were HPV genotyped. Declining trends in prevalence of vaccine types HPV16 and HPV18 during a 6-year period were observed in CIN1 (50.0% to 0.0%, Ptrend  < .0001) and CIN2-3/AIS (83.3% to 45.0%, Ptrend  = .07) only among women younger than 25 years of age. Overall, HPV vaccination reduced the proportion of HPV16/18-attributable CIN2-3/AIS from 47.7% to 33.0% (P = .003): from 43.5% to 12.5% as routine vaccination (P = .08) and from 47.8% to 36.7% as catch-up vaccination (P = .04). The HPV16/18 prevalence in CIN2-3/AIS cases was significantly reduced among female individuals who received their first vaccination at age 20 years or younger (P = .02). We could not evaluate vaccination effects on ICC owing to low incidence of ICC among women aged less than 25 years. We found HPV vaccination to be effective in protecting against HPV16/18-positive CIN/AIS in Japan; however, our data did not support catch-up vaccination for women older than 20 years. Older adolescents who skipped routine vaccination due to the government's suspension of its vaccine recommendation could benefit from receiving catch-up vaccination before age 20 years.

Germ cell-less hybrid fish: ideal recipient for spermatogonial transplantation for the rapid production of donor-derived sperm†.

An interspecific hybrid marine fish that developed a testis-like gonad without any germ cells, i.e., a germ cell-less gonad, was produced by hybridizing a female blue drum Nibea mitsukurii with a male white croaker Pennahia argentata. In this study, we evaluated the suitability of the germ cell-less fish as a recipient by transplanting donor testicular cells directly into the gonads through the urogenital papilla. The donor testicular cells were collected from hemizygous transgenic, green fluorescent protein (gfp) (+/-) blue drum, and transplanted into the germ cell-less gonads of the 6-month-old adult hybrid croakers. Fluorescent and histological observations showed the colonization, proliferation, and differentiation of transplanted spermatogonial cells in the gonads of hybrid croakers. The earliest production of spermatozoa in a hybrid recipient was observed at 7 weeks post-transplantation (pt), and 10% of the transplanted recipients produced donor-derived gfp-positive spermatozoa by 25 weeks pt. Sperm from the hybrid recipients were used to fertilize eggs from wild-type blue drums, and approximately 50% of the resulting offspring were gfp-positive, suggesting that all offspring originated from donor-derived sperm that were produced in the transplanted gfp (+/-) germ cells. To the best of our knowledge, this is the first report of successful spermatogonial transplantation using a germ cell-less adult fish as a recipient. This transplantation system has considerable advantages, such as the use of comparatively simple equipment and procedures, and rapid generation of donor-derived spermatogenesis and offspring, and presents numerous applications in commercial aquaculture.

Chemically Regulated ROS Generation from Gold Nanoparticles for Enzyme-Free Electrochemiluminescent Immunosensing.

In the present work, we report on an enzyme-free electrochemiluminescent (ECL) immunosensing scheme utilizing the catalytic generation of reactive oxygen species (ROS) from gold nanoparticles (AuNPs) (diameter ≥5 nm) dispersed in aqueous solutions of trishydroxymethylaminomethane (Tris). First, to examine this catalytic pathway in detail, the effects of various factors such as the AuNP size and concentration, dispersant type and concentration, and dissolved oxygen were investigated using the electrochemiluminescence (ECL) of luminol. It was found that the catalytic generation of ROS from AuNPs can be regulated chemically by altering conditions such as the type, concentration, and pH of the solution that the AuNPs are dispersed in. Under the best conditions studied in this work, the AuNPs displayed high catalytic activity toward ROS generation, with an estimated apparent turnover number per AuNP of 0.1 s-1, comparable to those of several common peroxide-producing enzymes. Following these studies, this phenomenon was applied to develop a one-step enzyme-free ECL immunosensor based on sandwiching the target analyte using antibody-conjugated magnetic beads (MB) and AuNPs. Using IgA as a model analyte, the developed immunosensor was able to detect the target in the range of 1 ng/mL to 10 µg/mL, with the lower detection limit being comparable to those of commercial assays for the same target. Altering the antibodies used to modify the MB and AuNPs could further improve the detection limit as well as expand the applicability of this immunoassay to the detection of other analytes.

Sensitive Detection of Glycated Albumin in Human Serum Albumin Using Electrochemiluminescence.

Monitoring of blood glucose content is vital for diabetes patients. The conventional widely used method involves an invasive procedure for blood sampling. In addition, blood glucose measured by this way is affected by immediate food consumption and it does not show accurate baseline blood glucose measurement. Thus, monitoring blood glucose by a noninvasive method that accurately reflects baseline blood glucose content is important. Glycated albumin (GA), a biomarker for diabetes indicating the average blood glucose over 2 weeks, can be used for semilong-term blood glucose monitoring. Detection of GA in saliva is a noninvasive method that alleviates the use of needles for diabetic patients; however, its content in saliva is in the nanomolar range. Therefore, the GA enzymatic detection method was combined with the ECL method for a highly sensitive detection of GA in human serum albumin and in the saliva sample. Here, the standard curve was constructed using model substrate, FZK, between 0.1 and 2 µM, and GA in human serum albumin was measured in this range. Also, we successfully demonstrated the detection limit of 0.1 µM GA in human serum albumin sample using ECL, which has seen improvement of about 70 times more than the colorimetric methods. The detection of GA in real saliva sample suggested that sample dilution of 5 times may be necessary to suppress the ECL quenching effect by impurities.

Expression of Tissue Factor in Epithelial Ovarian Carcinoma Is Involved in the Development of Venous Thromboembolism.

OBJECTIVES: Our 2007 study of 32 patients with ovarian cancer reported the possible involvement of tissue factor (TF) in the development of venous thromboembolism (VTE) before treatment, especially in clear cell carcinoma (CCC). This follow-up study further investigated this possibility in a larger cohort. METHODS: We investigated the intensity of TF expression (ITFE) and other variables for associations with VTE using univariate and multivariate analyses in 128 patients with epithelial ovarian cancer initially treated between November 2004 and December 2010, none of whom had received neoadjuvant chemotherapy. Before starting treatment, all patients were ultrasonographically screened for VTE. The ITFE was graded based on immunostaining of surgical specimens. RESULTS: Histological types were serous carcinoma (n = 42), CCC (n = 12), endometrioid carcinoma (n = 15), mucinous carcinoma (n = 53), and undifferentiated carcinoma (n = 6). The prevalence of VTE was significantly higher in CCC (34%) than in non-CCC (17%, P = 0.03). As ITFE increased, the frequencies of CCC and VTE increased significantly (P < 0.001 and P = 0.014, respectively). Multivariate analysis identified TF expression and pretreatment dimerized plasmin fragment D level as significant independent risk factors for VTE development. These factors showed particularly strong impacts on advanced-stage disease (P = 0.021). CONCLUSIONS: The 2007 cohort was small, preventing multivariate analysis. This study of a larger cohort yielded stronger evidence that the development of VTE in epithelial ovarian cancer may involve TF expression in cancer tissues.

[HPV Vaccination Program - The History and Recent Progress].

Four years have passed since HPV vaccination "crisis" occurred in June 2013. In Japan,a publicly funded HPV vaccination program for adolescent females aged 12-16 years began in December 2010. However,the Japanese government withdrew its recommendation for HPV vaccination in June, 2013 because news reports on potential adverse effects of HPV vaccines without any medical evidence appeared repeatedly. The vaccination coverage among adolescent females decreased quickly from around 70%in females born between 1994 and 1999 to only 1%in females born since 2001 over the country. The suspension of recommendation for vaccination has continued to the present,though there is no scientific or epidemiologic evidence to demonstrate the causal linkage between post-vaccination symptoms and the HPV vaccines. Very recently,an ecological investigation reported that similar symptoms also occur in unvaccinated adolescents in Japan. Medical organizations in Japan are also calling for a resumption of the HPV vaccination program. Now,the resumption of the recommendation needs a political judgment.

Clinicopathologic implications of DNA mismatch repair status in endometrial carcinomas.

OBJECTIVE: Endometrial carcinoma is the most common malignancy in women with Lynch syndrome caused by mismatch repair (MMR) deficiency. We investigated the clinicopathologic significance of deficient MMR and Lynch syndrome presumed by MMR analyses in unselected endometrial carcinomas. METHODS: We analyzed immunohistochemistry of MMR proteins (MLH1/MSH2/MSH6/PMS2) and MLH1 promoter methylation in primary endometrial carcinomas from 221 consecutive patients. Based on these results, tumors were categorized as sporadic or probable Lynch syndrome (PLS). Clinicopathologic variables and prognosis were compared according to MMR status and sporadic/PLS classification. RESULTS: Deficient MMR showed only trends towards favorable overall survival (OS) compared with intact MMR (p=0.13), whereas PLS showed significantly better OS than sporadic (p=0.038). Sporadic was significantly associated with older age, obesity, deep myometrial invasion, and advanced stage (p=0.008, 0.01, 0.02 and 0.03), while PLS was significantly associated with early stage and Lynch syndrome-associated multiple cancer (p=0.04 and 0.001). The trend towards favorable OS of PLS was stronger in advanced stage than in early stage (hazard ratio, 0.044 [95% CI 0-25.6] vs. 0.49 [0.063-3.8]). In the subset receiving adjuvant therapies, PLS showed trends towards favorable disease-free survival compared to sporadic by contrast with patients receiving no adjuvant therapies showing no such trend (hazard ratio, 0.045 [95% CI 0-20.3] vs. 0.81 [0.095-7.0]). CONCLUSIONS: The current findings suggest that analyzing MMR status and searching for Lynch syndrome may identify a subset of patients with favorable survival and high sensitivity to adjuvant therapies, providing novel and useful implications for formulating the precision medicine in endometrial carcinoma.

Fertility-sparing surgery for early stage epithelial ovarian cancer.

Discussion of fertility-sparing treatment is an important part of pretreatment counseling for young patients with early epithelial ovarian cancer. As a result of late childbearing nowadays, fertility preservation has become a major issue in ovarian cancer patients. The purpose of this review is to update current knowledge on fertility-sparing treatment for early stage epithelial ovarian cancer, which may be useful for pretreatment counseling for reproductive-age patients. The multicenter study data on the fertility-sparing treatment published by Japan Clinical Oncology Group in 2010 confirmed that fertility-sparing surgery is a safe treatment for Stage IA patients with non-clear cell histology and Grade 1 or 2 and suggested that Stage IA patients with clear cell histology and Stage IC patients with non-clear cell histology and Grade 1 or 2 can be candidates for fertility-sparing surgery followed by adjuvant chemotherapy. In the current review, we added the recent case series and review, and discussed the fertility-sparing treatment on young patients with early epithelial ovarian cancer. We need not to change the proposal by the Japan Clinical Oncology Group study, but we should wait for the results of an ongoing prospective study to strongly recommend the proposal of the Japan Clinical Oncology Group study.

Proposal for selection criteria of secondary cytoreductive surgery in recurrent epithelial ovarian, tubal, and peritoneal cancers.

BACKGROUND: The selection criteria for secondary cytoreductive surgery (SCS) in recurrent ovarian cancer are yet to be defined. The aim of this study was to propose the selection criteria through identifying predictive factors for successful SCS. METHODS: All patients who underwent SCS for recurrent epithelial ovarian, tubal, and peritoneal cancers between 1982 and 2012 at our institution were identified through our database. Potential prognostic factors were evaluated in univariate and multivariate analyses. Survival after SCS was examined by the grouping model based on the number of prognostic factors. RESULTS: We performed SCS in 80 consecutive patients, 48 (60 %) of whom achieved complete resection. Complete/incomplete resection significantly influenced survival (median 65 vs. 26 months; p = 0.0005). Among favorable prognostic factors determined before SCS, treatment-free interval >12 months, absent distant metastasis, solitary disease, and performance status 0 were independently associated with better survival (p = 0.0009, 0.00003, 0.0004, and 0.015, respectively). Patients with 3-4 of those factors had better survival than those with 2 or 0-1 factors (median 79, 26, and 19 months; p < 0.00001 and <0.0000000001, respectively). Complete resection of visible tumors was achieved in 79 % of patients with 3-4 factors, in 40 % of those with 2 factors, and in 33 % of those with 0-1 factor. Importantly, even when tumor removal was incomplete at SCS, median survival of patients with 3-4 factors was still quite favorable (83 vs. 67.5 months for complete/incomplete resection, respectively), while those of patients with 2 factors (41 vs. 25 months) and 0-1 factor (19 vs. 19 months) were not. CONCLUSION: We strongly recommend SCS for patients with 3-4 of the above favorable factors at recurrence. As for patients with 2 factors, SCS may be considered if complete resection is expected to be achieved. Prospective studies are warranted to validate our proposal.

Japan Society of Gynecologic Oncology guidelines 2013 for the treatment of uterine body neoplasms.

The third version of the Japan Society of Gynecologic Oncology guidelines for the treatment of uterine body neoplasms was published in 2013. The guidelines comprise nine chapters and nine algorithms. Each chapter includes a clinical question, recommendations, background, objectives, explanations, and references. This revision was intended to collect up-to-date international evidence. The highlights of this revision are to (1) newly specify costs and conflicts of interest; (2) describe the clinical significance of pelvic lymph node dissection and para-aortic lymphadenectomy, including variant histologic types; (3) describe more clearly the indications for laparoscopic surgery as the standard treatment; (4) provide guidelines for post-treatment hormone replacement therapy; (5) clearly differentiate treatment of advanced or recurrent cancer between the initial treatment and the treatment carried out after the primary operation; (6) collectively describe fertility-sparing therapy for both atypical endometrial hyperplasia and endometrioid adenocarcinoma (corresponding to G1) and newly describe relapse therapy after fertility-preserving treatment; and (7) newly describe the treatment of trophoblastic disease. Overall, the objective of these guidelines is to clearly delineate the standard of care for uterine body neoplasms in Japan with the goal of ensuring a high standard of care for all Japanese women diagnosed with uterine body neoplasms.

Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer.

The fourth edition of the Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer was published in 2015. The guidelines contain seven chapters and six flow charts. The major changes in this new edition are as follows-(1) the format has been changed from reviews to clinical questions (CQ), and the guidelines for optimal clinical practice in Japan are now shown as 41 CQs and answers; (2) the 'flow charts' have been improved and placed near the beginning of the guidelines; (3) the 'basic points', including tumor staging, histological classification, surgical procedures, chemotherapy, and palliative care, are described before the chapter; (4) the FIGO surgical staging of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer was revised in 2014 and the guideline has been revised accordingly to take the updated version of this classification into account; (5) the procedures for examination and management of hereditary breast and ovarian cancer are described; (6) information on molecular targeting therapy has been added; (7) guidelines for the treatment of recurrent cancer based on tumor markers alone are described, as well as guidelines for providing hormone replacement therapy after treatment.

Uterine cervical cancer volumetry using T2- and diffusion-weighted MR images in patients treated by primary surgery and neoadjuvant chemotherapy.

BACKGROUND: Tumor volumetry with magnetic resonance imaging (MRI) is very common; however, the accuracy of such measures remains unclear, especially after treatment. PURPOSE: To determine the accuracy of preoperative volume measurements of uterine cervical carcinomas resected with and without neoadjuvant chemotherapy (NAC) on T2-weighted (T2W) and diffusion-weighted (DWI) MRI. MATERIAL AND METHODS: Twenty-nine consecutive patients with surgically confirmed uterine cervical carcinoma were included in this study. MRI scans were performed before preoperative treatment in 17 patients and after two courses of NAC in 12 patients. In all patients, T2W images and DWI were obtained to measure the tumor diameters. The maximum diameter of the surgical specimens was macroscopically measured. The correlation coefficients between the measured tumor size using T2W imaging and DWI and the size measured on the surgical specimens were calculated for all specimens. RESULTS: The correlation coefficient of the three-dimensional (3D) tumor volume measurement using T2W imaging and DWI was 0.97 in the primary surgery group and was 0.96 in the NAC group. The 3D tumor volume measurement using MRI and the measurement of the actual surgical specimen was 0.55 for T2WI and 0.48 for DWI in the primary surgery group and 0.88 for T2WI and 0.95 for DWI in the NAC group. CONCLUSION: T2WI and DWI can provide accurate 3D tumor volume measurements of uterine cervical carcinomas in patients with and without preoperative chemotherapy, suggesting that tumor volumetry using 3 T MRI after uterus-preserving treatment is feasible.

Human leukocyte antigen class II DRB1*1302 allele protects against cervical cancer: At which step of multistage carcinogenesis?

We investigated the role of human leukocyte antigen (HLA) class II alleles in multistage cervical carcinogenesis. Cross-sectional analysis for HLA association with cervical cancer included 1253 Japanese women: normal cytology (NL, n = 341), cervical intraepithelial neoplasia grade 1 (CIN1, n = 505), CIN grade 2 or 3 (CIN2/3, n = 96), or invasive cervical cancer (ICC, n = 311). The HLA class II allele frequencies were compared by Fisher's exact test or the χ(2) -test. The Bonferroni adjustment corrected for multiple comparisons. Among the study subjects, 454 women with low-grade squamous intraepithelial lesion cytology were prospectively monitored by cytology and colposcopy every 3-4 months to analyze cumulative risk of CIN3 within the next 10 years in relation to HLA class II alleles. HLA class II DRB1*1302 allele frequency was similar between women with NL (11.7%) and CIN1 (11.9%), but significantly decreased to 5.2% for CIN2/3 and 5.8% for ICC (P = 0.0003). Correction for multiple testing did not change this finding. In women with low-grade squamous intraepithelial lesion cytology, the cumulative risk of CIN3 diagnosed within 10 years was significantly reduced among DRB1*1302-positive women (3.2% vs. 23.7%, P = 0.03). In conclusion, the two different types of analysis in this single study showed the protective effect of the DRB1*1302 allele against progression from CIN1 to CIN2/3.