Evaluating Opt-In Vaginal Human Papillomavirus Self-Sampling: Participation Rates and Detection of High-Grade Lesions (CIN2+) among Unscreened Japanese Women Aged 30-39.

Cervical cancer incidence is increasing among Japanese women, which is partly attributed to low screening rates. This study examined the implementation of opt-in human papillomavirus (HPV) self-sampling among Japanese women aged 30-39 years who had not undergone cervical cancer screening, focusing on those requiring preconception care. The responses to the opt-in approach and effectiveness in detecting cervical squamous intraepithelial neoplasia 2 or worse (CIN2+) were evaluated. Participants used the Evalyn® Brush for self-sampling, with HPV testing conducted using the Cobas 4800 system (version 2.2.0). Out of 3489 eligible, unscreened women from four municipalities in Fukui Prefecture, only 10.6% (370/3489) requested the self-sampling kit. Of these, 77.3% (286/370) returned the kit (HPV testing rate: 8.2% (286/3489)). The HPV positivity rate was 13.7% (39/285), yet only 61.5% (24/39) of those with positive HPV results proceeded to cytology testing. Subsequently, three cases of CIN2+ were detected (10.5/1000). While this study demonstrated a reasonable kit return rate and indicated the capability of opt-in HPV self-sampling to detect CIN2+ cases in unscreened women, the low ordering rate of kits and suboptimal compliance for follow-up cytology testing highlight significant challenges. The findings suggest the need for more effective strategies to enhance participation in cervical cancer screening programs.

The study protocol of the evaluation for the preventive efficacy of the HPV vaccine for persistent HPV16/18 infection in Japanese adult women: the HAKUOH study.

BACKGROUND: In general, human papillomavirus (HPV) vaccines have demonstrated efficacy in young women worldwide, but there is limited evidence on the efficacy of the quadrivalent HPV6/11/16/18 vaccine in adult women and no evidence of its effectiveness in Japanese adult women in particular. This study aims to evaluate the efficacy of the quadrivalent HPV6/11/16/18 vaccine for persistent HPV16/18 infection in Japanese women aged 27-45 years. METHODS: This is an interventional, nonrandomized, non-double-blind prospective cohort study designed to compare the rates of persistent HPV16/18 infection between the vaccinated arm and unvaccinated arm. The subjects will consist of all women aged 27-45 years who have normal cytology results confirmed by cervical cancer screening from May 2019 to March 2021. The follow-up time is two years. The subjects will be divided into two groups: the vaccinated group and the unvaccinated group. The study will need to enroll 600 vaccinated participants (experimental arm) and 2200 unvaccinated participants (control arm). DISCUSSION: The findings of this trial (HAKUOH study) might provide the first local evidence on the subject and be significantly useful not only to medical academia but also to the Japanese Ministry of Health, Labour and Welfare. The findings could contribute to public health improvement by providing local supportive knowledge on the prevention of HPV infection through HPV vaccination in young adult women in Japan, where active recommendations have been suspended for a long time due to adverse effects. TRIAL REGISTRATION: Trial registration number: NCT04022148 . Registration began on December 1, 2019.

Evaluation of the concordance in HPV type between self- and physician-collected samples using a brush-based device and a PCR-based HPV DNA test in Japanese referred patients with abnormal cytology or HPV infection.

BACKGROUND: To adopt HPV self-sampling in Japan, we assessed the concordance between self- and physician-collected human papillomavirus (HPV) samples from Japanese patients and examined the performance of HPV self-sampling for cervical intraepithelial neoplasia grade 2 or worse (CIN2+). METHODS: Patients who had previously tested negative for intraepithelial lesions or malignancy/HPV-positive, and patients with atypical squamous cells of undetermined significance or worse (ASCUS+) cytology were eligible for this cross-sectional study. Participants performed HPV self-sampling using an Evalyn brush, which was submitted at the Fukui Prefectural Health Care Association. The Evalyn brush heads were stored in ThinPrep vials. The physician, however, performed HPV and cell sampling using an endocervical brush and immediately stored the brush heads in ThinPrep vials. All participants underwent colposcopy and biopsy. Histopathological diagnoses were made by pathologists at Fukui University Hospital. HPV infection was confirmed using a PCR-based Cobas 4800 HPV DNA test. Cytological analysis was performed at Fukui Prefectural Health Care Association. RESULTS: HPV-positive rates for physician-collected samples and self-collected samples were 51 and 50%, respectively. The perfect match rate of HPV type between the groups was 88% (κ = 0.76). HPV16/18 showed higher agreement rates than other HPVs (99%, kappa 0.96 and 89% kappa 0.77, respectively). Both groups showed 100% sensitivity to CIN2+, but specificity was 57.0 and 58.1%, respectively. CONCLUSION: For HPV typing, a good concordance rate was seen between self- and physician-collected samples. Self-sampling showed high sensitivity for CIN2+. Self-sampling using the Evalyn brush and Cobas 4800 may be feasible for screening Japanese individuals.

Evaluation of the benefit and use of the new terminology in endometrial cytology reporting system.

OBJECTIVE: The introduction and establishment of a new classification system for endometrial cytology, the "New Terminology in Endometrial Cytology (NTEMC) system," which is based on the Bethesda System for uterine cervical cytology, has recently been reported. However, the clinical management for new categories in the NTEMC system, particularly atypical endometrial cells (ATEC), has not been clarified. The objective of the present study is to determine how the ATEC category should be treated and whether the introduction of the system has decreased the number of unnecessary endometrial biopsies. METHODS: Fifty-nine cases were diagnosed as "suspicious positive" according to the three-tier reporting (TTR) system, which was adopted in Japan. The specimens were re-evaluated according to the NTEMC system. Thirty-seven of the 59 patients underwent endometrial biopsy. We correlated the pathological diagnosis with the NTEMC system category. RESULTS: The 59 cases were classified according to the NTEMC system as follows: 36 cases were classified as ATEC of undetermined significance (ATEC-US), 21 cases were classified as ATEC for which atypical endometrial hyperplasia or worse cannot be excluded (ATEC-A), and 2 cases were classified as endometrial hyperplasia. The ratio of atypical endometrial hyperplasia or malignancy in ATEC-US category was significantly lower than that in ATEC-A category. Fifteen cases in ATEC-US category did not show atypical endometrial hyperplasia lesions or malignancy after 3 months. CONCLUSIONS: These data suggest that patients with ATEC-US results can be followed up for at least three months, and the introduction of the NTEMC system decreased the number of unnecessary endometrial biopsies.

Surgical Apgar Score predicts 30-day morbidity in elderly patients who undergo non-laparoscopic gynecologic surgery: A retrospective analysis.

INTRODUCTION: The aim of this study was to determine whether a preoperative health status index and intraoperative data could predict perioperative morbidity and mortality in women over the age of 65 years undergoing surgery for gynecologic disorders. METHODS: The medical records of 68 female patients who were ≥65 years of age and who underwent surgery under general anesthesia in our institute from January 2014 to December 2015 were retrospectively reviewed. Preoperative data were extracted from a database and included comorbidities, American Society of Anesthesiologists physiological status classification, the Charlson Comorbidity Index, the Subjective Global Assessment 2011 revision, the subjects' risk of falling, body mass index, and age. The intraoperative factors investigated included the type of surgery and the Surgical Apgar Score (SAS). Major postoperative complications were defined as > Grade 3 based on the Clavien-Dindo classification version 2.0. RESULTS: Of the 68 elderly gynecological patients, 6 (8.8%) developed serious Grade 3 or worse complications within 30 days of surgery. The only factor that significantly affected postoperative complications was the SAS, an index of the patient's intraoperative condition. The optimum cut-off SAS for the occurrence of complications was determined by the receiver operating characteristic curve to be ≤ 6 points; a score ≤6 points predicted the development of postoperative complications with 66.7% sensitivity and 79.0% specificity. CONCLUSION: In this study, the SAS predicted the development of serious complications in elderly gynecological patients within 30 days of surgery more accurately than did other comorbidities, preoperative assessments, and type of surgery.

A Novel Diagnostic Strategy Using 16α-[18F]-Fluoro-17-ß-Estradiol (18F-FES) PET/MRI to Achieve Complete Resection of Intravenous Leiomyomatosis in Reproductive-Age Women.

Intravenous leiomyomatosis is a life-threatening leiomyoma that grows into the extrauterine venous system. A high recurrence rate has been reported in reproductive-age women who undergo only tumor excision to preserve fertility. Precise diagnosis of tumor extension is essential to achieve complete resection. A 24-year-old woman presented with hypermenorrhea. Contrast-enhanced MRI showed an intramural myoma with worm-like extension into the right parametrium. F-FES PET/MRI accurately depicted the extension with strong FES activity into the right uterine vein, whereas F-FDG PET/MRI excluded the possibility of malignancy. These modalities can be a novel strategy to manage such cases of intractable intravenous leiomyomatosis.

18F-FDG/18F-FES standardized uptake value ratio determined using PET predicts prognosis in uterine sarcoma.

We investigated whether 16α-[18F]-fluoro-17ß-estradiol (18F-FES) and 18F-fluoro-deoxyglucose (FDG) uptake measured using positron emission tomography (PET) predicted prognosis in 18 patients with different histological subtypes of uterine sarcoma. Standardized uptake values (SUVs) and 18F-FDG/18F-FES SUV ratios were determined, and their correlations with progression-free (PFS) and overall survival (OS) were examined. Ten patients died from local recurrence or metastasis, and one more experienced recurrence, during the at least 36-month follow-up period. Patients with higher 18F-FDG SUVs (> 5.5) had worse OS (p = 0.007) and tended toward worse PFS (p = 0.11), while patients with lower 18F-FES SUVs (≤ 1.5) had worse PFS (p = 0.03) and tended toward worse OS (p = 0.19). Patients with 18F-FDG/18F-FES ratios > 2.6 had worse PFS (p = 0.009) and OS (p = 0.005). The 5-year PFS and OS rates were 75% and 88% for patients with lower ratios, but were only 10% and 20% for those with higher ratios. These results suggest that pretreatment tumor 18F-FDG/18F-FES ratio is useful for predicting the prognosis of uterine sarcoma patients.

Different Prognostic Implications of 18F-FDG PET Between Histological Subtypes in Patients With Cervical Cancer.

This study aimed to investigate whether the predictive values of intensity- and volume-based PET parameters are different between histological subtypes in patients with cervical cancer. Ninety patients, 65 with squamous cell carcinoma (SCC) and 25 with non-SCC (NSCC), who underwent pretreatment ¹8F-FDG PET/CT and pelvic MRI, were studied retrospectively. In addition to SUVmax and SUVmean, metabolic-tumor-volume (MTV) was determined by thresholding of 40% SUVmax and total-lesion-glycolysis (TLG) was calculated. Clinical factors and PET metabolic indices were compared between SCC and NSCC. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method with cut-offs determined by ROC analyses to stratify SCC and NSCC patients separately. Factors associated with survival were assessed with univariate and multivariate analyses using the Cox regression model. No significant differences were observed in clinical factors other than tumor size or ¹8F-FDG PET metabolic indices between SCC and NSCC. The Kaplan-Meier estimates of 2-year PFS and OS rates were 60% and 70% for SCC and 40% and 76% for NSCC, respectively. Multivariate analyses showed that MTV and TLG were the independent prognostic factors for PFS and OS in SCC; in contrast, SUVmax was the independent prognostic factor for PFS and OS in NSCC. Metabolic burden (MTV and TLG) could be beneficial for the prognostic prediction of cervical SCC patients; in contrast, metabolic intensity (SUVmax) could be beneficial for the prognostic prediction of NSCC patients. The different prognostic implications might be based on the differences of tissue integrity and histological heterogeneity between SCC and NSCC.

Metabolic tumor burden predicts prognosis of ovarian cancer patients who receive platinum-based adjuvant chemotherapy.

Volumetric parameters of positron emission tomography-computed tomography using 18F-fludeoxyglucose ((18) F-FDG PET/CT) that comprehensively reflect both metabolic activity and tumor burden are capable of predicting survival in several cancers. The aim of this study was to investigate the predictive performance of metabolic tumor burden measured by (18) F-FDG PET/CT in ovarian cancer patients who received platinum-based adjuvant chemotherapy after cytoreductive surgery. Included in this study were 37 epithelial ovarian cancer patients. Metabolic tumor burden in terms of metabolic tumor volume (MTV) and total lesion glycolysis (TLG), clinical stage, histological type, residual tumor after primary cytoreductive surgery, baseline serum carbohydrate antigen 125 (CA125) level, and the maximum standardized uptake value (SUVmax ) were determined, and compared for their performance in predicting progression-free survival (PFS). Metabolic tumor volume correlated with CA125 (r = 0.547, P < 0.001), and TLG correlated with SUVmax and CA125 (SUVmax , r = 0.437, P = 0.007; CA125, r = 0.593, P < 0.001). Kaplan-Meier analysis showed a significant difference in PFS between the groups categorized by TLG (P = 0.043; log-rank test). Univariate analysis indicated that TLG was a statistically significant risk factor for poor PFS. Multivariate analysis adjusted according to the clinicopathological features was carried out for MTV, TLG, SUVmax , tumor size, and CA125. Only TLG showed a significant difference (P = 0.038), and a 3.915-fold increase in the hazard ratio of PFS. Both MTV and TLG (especially TLG) could serve as potential surrogate biomarkers for recurrence in patients who undergo primary cytoreductive surgery followed by platinum-based chemotherapy, and could identify patients at high risk of recurrence who need more aggressive treatment.

Relation between outcomes and expression of estrogen receptor-α phosphorylated at Ser(167) in endometrioid endometrial cancer.

Both ligand-dependent and ligand-independent activation of estrogen receptor (ER)α is modulated by receptor phosphorylation and results in activation of the ERα-dependent pathways that are involved in endometrioid endometrial cancer (EEC) pathogenesis. It is also known that the mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) and MAPK/p90 ribosomal S6 kinase (RSK) signaling pathways coordinately regulate phosphorylated-ERα at Ser(167) (p-Ser(167) -ERα). However, the expression of p-Ser(167) -ERα in EEC and its prognostic role in ECC is largely unexplored. The purpose of the present study was to investigate the expression of p-Ser(167) -ERα in ECC and its relationship with prognosis. Immunohistochemical staining of primary EEC surgical specimens (n = 103) was carried out using antibodies specific for p-Ser(167) -ERα and for p-mTOR/p-S6K1 and p-MAPK/p-RSK. The correlation of p-Ser(167) -ERα expression with clinicopathological features and survival of ECC was studied. Patients that were positive for nuclear p-Ser(167) -ERα had significantly shorter relapse-free survival, and although the result was not significant, levels of nuclear p-Ser(167) -ERα tended to be higher in advanced-stage ECC patients. Nuclear p-Ser(167) -ERα was significantly positively correlated with p-MAPK and p-S6K1, and with significantly shorter relapse-free survival in EEC.