Effectiveness of self-sampling human papillomavirus test on precancer detection and screening uptake in Japan: The ACCESS randomized controlled trial.

Japan is lagging in cervical cancer prevention. The effectiveness of a self-sampling human papillomavirus (HPV) test, a possible measure to overcome this situation, has not yet been evaluated. A randomized controlled trial was performed to evaluate the effectiveness of a self-sampling HPV test on detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and screening uptake. Women between 30 and 58 years old who did not participate in the cervical cancer screening program for ≥3 years were eligible and assigned to the intervention group (cytology or self-sampling HPV test) or control group (cytology). Participants assigned to the intervention group were sent a self-sampling kit according to their ordering (opt-in strategy). A total of 7337 and 7772 women were assigned to the intervention and control groups, respectively. Screening uptake in the intervention group was significantly higher than that in the control group (20.0% vs. 6.4%; risk ratio: 3.10; 95% confidence interval [CI]: 2.82, 3.42). The compliance rate with cytology triage for HPV-positive women was 46.8% (95% CI: 35.5%, 58.4%). CIN2+ was detected in five and four participants in the intervention and control groups, respectively; there was no difference for intention-to-screen analysis (risk ratio: 1.32; 95% CI: 0.36, 4.93). Self-sampling of HPV test increased screening uptake; however, no difference was observed in the detection of CIN2+, probably due to the low compliance rate for cytology triage in HPV-positive women. Efforts to increase cytology triage are essential to maximize precancer detections.

Impact of the COVID-19 pandemic on gastric surgery in Japan: A nationwide study using interrupted time-series analyses.

BACKGROUND AND AIM: Changes in the number of surgeries for gastric cancer during the coronavirus disease 2019 (COVID-19) pandemic have been reported, but data are insufficient to understand the impact at the national level. This study aimed to determine the impact of the COVID-19 pandemic on gastric surgery in Japan. METHODS: Insurance claims data registered from January 2015 to January 2021 were used. Changes in the number of endoscopic resections and gastrectomies for gastric cancer were estimated using an interrupted time-series analysis. RESULTS: The number of endoscopic resections significantly decreased in July 2020 (-1565; 95% confidence interval [CI]: -2022, -1108) and January 2021 (-539; 95% CI: -970, -109), and the number of laparoscopic surgeries significantly decreased in July 2020 (-795; 95% CI: -1097, -492), October 2020 (-313; 95% CI: -606, -19), and January 2021 (-507; 95% CI: -935, -78). Meanwhile, the number of open gastrectomies remained unchanged, and the number of robot-assisted gastrectomies steadily increased since their coverage by public health insurance in April 2018. CONCLUSIONS: The decreased number of endoscopic resections and laparoscopic surgeries in Japan suggests a decline in early-stage gastric cancer diagnosis, likely due to the suspension of gastric cancer screening and diagnostic testing during the pandemic. Meanwhile, the number of open and robot-assisted gastrectomies remained unchanged and increased, respectively, indicating that these applications were not affected by the pandemic-related medical crisis. These findings highlight that procedures for cancer diagnosis, including screening, should still be provided during pandemics.

Impact of the coronavirus disease 2019 pandemic on primary and metastatic lung cancer treatments in Japan: A nationwide study using an interrupted time series analysis.

BACKGROUND: The coronavirus disease 2019 pandemic prompted healthcare providers to use different approaches from the current standards of care. We aimed to identify the changes in the number of treatments for primary non-small cell lung cancer (NSCLC) and metastatic lung cancer during the pandemic. METHODS: We used nationwide insurance claims data from January 2015 to January 2021, and estimated changes in the number of treatments using an interrupted time series analysis. RESULTS: The number of surgical resections for primary NSCLC significantly decreased in April 2020 (-888; 95% confidence interval [CI]: -1530 to -246) and July 2020 (-1314; 95% CI: -1935 to -694), while the number of stereotactic body radiotherapies (SBRTs) increased in April 2020 (95; 95% CI: 8-182) and July 2020 (111; 95% CI: 24-198). The total number of treatments for primary NSCLC remained unchanged; however, non-significant decreases were observed in 2020. The number of surgical resections for metastatic lung cancer significantly decreased in April 2020 (-201; 95% CI: -337 to -65), but it eventually increased in July 2020 (170; 95% CI: 32-308). Additionally, the number of SBRTs significantly increased in April 2020 (37; 95% CI: 3-71) and October 2020 (57; 95% CI: 23-91). The total number of treatments for metastatic lung cancer was maintained, with an initial decrease in April 2020 followed by a subsequent increase in July and October 2020. CONCLUSION: In Japan, surgical triage for primary and metastatic lung cancer are likely to have been implemented during the pandemic. Despite these proactive measures, patients with primary NSCLC may have been untreated, likely owing to their undiagnosed disease, potentially leading to a deterioration in prognosis. By contrast, patients diagnosed with cancer prior to the pandemic are presumed to have received standard management throughout the course of the pandemic.

Acceptability of self-sampling human papillomavirus test for cervical cancer screening in Japan: A questionnaire survey in the ACCESS trial.

PURPOSE: In terms of medical policy for cervical cancer prevention, Japan lags far behind other industrialized countries. We initiated a randomized controlled trial to evaluate the self-sampling human papillomavirus (HPV) test as a tool to raise screening uptake and detection of pre-cancer. This study was conducted to explore the acceptability and preference of self-sampling using a subset of the data from this trial. METHODS: A pre-invitation letter was sent to eligible women, aged 30-59 years who had not undergone cervical cancer screening for three or more years. After excluding those who declined to participate in this trial, the remaining women were assigned to the self-sampling and control groups. A second invitation letter was sent to the former group, and those wanting to undergo the self-sampling test ordered the kit. A self-sampling HPV kit, consent form, and a self-administered questionnaire were sent to participants who ordered the test. RESULTS: Of the 7,340 participants in the self-sampling group, 1,196 (16.3%) administered the test, and 1,192 (99.7%) answered the questionnaire. Acceptability of the test was favorable; 75.3-81.3% of participants agreed with positive impressions (easy, convenient, and clarity of instruction), and 65.1-77.8% disagreed with negative impressions (painful, uncomfortable, and embarrassing). However, only 21.2% were confident in their sampling procedure. Willingness to undergo screening with a self-collected sample was significantly higher than that with a doctor-collected sample (89.3% vs. 49.1%; p<0.001). Willingness to undergo screening with a doctor-collected sample was inversely associated with age and duration without screening (both p<0.001), but that with a self-collected sample was not associated. CONCLUSIONS: Among women who used the self-sampling HPV test, high acceptability was confirmed, while concerns about self-sampling procedures remained. Screening with a self-collected sample was preferred over a doctor-collected sample and the former might alleviate disparities in screening rates.

Changes in colorectal cancer treatment during the COVID-19 pandemic in Japan: Interrupted time-series analysis using the National Database of Japan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic forced us to accept changes in our usual diagnostic procedures and treatments for colorectal cancer. This study aimed to determine the impact of the pandemic on colorectal cancer treatment in Japan. METHODS: The number of colorectal surgeries, stoma constructions, stent placements or long tube insertions, and neoadjuvant chemoradiotherapies were determined each month using sampling datasets from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. The observation periods before and during the pandemic were January 2015 to January 2020 and April 2020 to January 2021, respectively. An interrupted time-series analysis was used to estimate the changes in the number of procedures during the pandemic. RESULTS: The number of endoscopic surgeries for colon cancer significantly decreased in April and July 2020 and for rectal cancer in April 2020. Additionally, the number of laparoscopic and open surgeries for colon cancer significantly decreased in July 2020 and October 2020, respectively. The number of stoma constructions and stent placements or long tube insertions did not increase during the observation period. Neoadjuvant chemoradiotherapy for rectal cancer significantly increased in April 2020 but levels returned shortly thereafter. These results suggest that the recommendations to overcome the pandemic proposed by expert committees, including the replacement of laparoscopic surgery with open surgery, stoma construction to avoid anastomotic leak, and replacement of surgery on the ileus with stent placement, were not widely implemented in Japan. However, as an exception, neoadjuvant chemoradiotherapy for rectal cancer was performed as an alternative treatment to delay surgery in small quantities. CONCLUSION: A declining number of surgeries raises concerns about cancer stage progression; however, we found no evidence to suggest cancer progression from the trajectory of the number of stoma constructions and stent placements. In Japan, even during the pandemic, conventional treatments were performed.

Impact of coronavirus disease 2019 pandemic on breast cancer surgery using the National Database of Japan.

Various countries have reported a decrease in breast cancer surgeries during the coronavirus disease 2019 (COVID-19) pandemic; however, inconsistent results have been reported in Japan. This study revealed changes in the number of surgeries during the pandemic using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) from January 2015 to January 2021, where insurance claims data from Japan as a whole are comprehensively accumulated. The number of breast-conserving surgeries (BCS) without axillary lymph node dissection (ALND) significantly decreased in July (- 846; 95% confidence interval (CI) - 1190 to - 502) and October 2020 (- 540; 95% CI - 861 to - 218). No decrease was observed for other types of surgery, BCS with ALND, and mastectomy with or without ALND. In the age-specific subgroup analysis, significant and transient reduction in BCS without ALND was observed in all age groups (0-49, 50-69, and ≥ 70 years). The number of BCS without ALND significantly decreased for a relatively short period in the early pandemic stages, suggesting reduced surgery for patients with a relatively low stage of cancer. Some patients with breast cancer might have been left untreated during the pandemic, and an unfavorable prognosis would be a concern.

Changes in the number of cancer diagnosis practices due to the COVID-19 pandemic: interrupted time-series analysis using the National Database of Japan.

PURPOSE: This study aimed to reveal the impact of coronavirus disease 2019 on the number of practices commonly used for cancer diagnosis in Japan. METHODS: The sampling dataset of the National Database of Japan from January 2015 to January 2021 was used to generate 25-point time-series data for the number of practices (21 points before and 4 points during the pandemic outbreak). The decreased number was estimated by interrupted time-series analysis using a seasonal autoregressive integrated moving average model. Using the pre-pandemic data, expected counterfactual numbers during the pandemic were predicted, and decreased rate was calculated. RESULTS: In most practices, the number dramatically decreased in the early stage of the pandemic and recovered rapidly thereafter. As of April 2020, gastric endoscopy decreased at the top of the practices (- 42.1%, with 95% confidence intervals of - 50.5% and - 33.7%), followed by gastric biopsy (- 38.6%, with 95% confidence intervals of - 46.7% and - 30.6%). The period of declined practices for lung cancer was relatively prolonged. The number of sentinel lymph node biopsies for breast cancer and colposcopies and biopsies for cervical cancer did not decrease in April 2020, but significantly decreased later in July 2020, which is assumed to be the time lapse after the primary testing before surgical treatment or intense scrutiny. CONCLUSION: In general, the number of practices for cancer diagnosis in Japan showed only a temporary decline, which was concordant with reports from several other countries.

Implementation of a self-sampling HPV test for non-responders to cervical cancer screening in Japan: secondary analysis of the ACCESS trial.

A self-sampling human papillomavirus (HPV) test could improve the morbidity and mortality of cervical cancer in Japan. However, its effectiveness and feasibility have not been demonstrated sufficiently. Hence, we launched a randomized controlled trial, which is ongoing, and report the results of a secondary analysis. To ensure autonomous participation with a minimum selection bias, opt-out consent was obtained from women who met the inclusion criteria, and written consent was obtained from those who underwent a self-sampling test. The number of women who met the inclusion criteria was 20,555; 4283 and 1138 opted out before and after the assignment, respectively. Of the 7340 women in the self-sampling arm, 1372 (18.7%) ordered and 1196 (16.3%) underwent the test. Younger women in their 30 s and 40 s tended to undertake the test more frequently than older women in their 50 s (P for trend < 0.001). Invalid HPV test results were rare (1.3%), and neither adverse events nor serious complaints were reported. Despite adopting the opt-out procedure, more women than expected declined to participate, suggesting the need for a waiver of consent or assignment before consent to reduce selection bias. A self-sampling HPV test can be implemented in Japan and would be more accessible to young women, the predominant group affected by cervical cancer.

Study protocol of the ACCESS trial: a randomised trial to evaluate the effectiveness of human papillomavirus testing by self-sampling in cervical cancer screening uptake and precancer detection.

INTRODUCTION: Recently, the incidence of cervical cancer has increased in Japan, probably because of an interruption in human papillomavirus (HPV) vaccination and a low cervical cancer screening rate. There is a lack of evidence for self-sampling HPV testing as a cervical cancer screening tool in Japan. The Accelerating Cervical Cancer Elimination by Self-Sampling test trial aims to compare the effectiveness of screening using the self-sampling HPV test with that of routine screening concerning screening uptake and precancer detection. METHODS AND ANALYSIS: This trial has a single-municipality, open-label, parallel, superiority and randomised design. Approximately 20 000 women who have not undergone cervical cancer screening for at least 3 years will be assigned randomly to the self-sampling arm and the control arm using a 1:1 ratio. Participants assigned to the control arm will undergo routine cervical cancer screening (cytology test) provided by Ichihara City, while those assigned to the self-sampling arm will choose the routine screening or self-sampling HPV test. HPV tests will be performed using the cobas 8800 system (Roche Diagnostics, Rotkreuz, Switzerland). Participants who will undergo the self-sampling HPV testing will be recommended to undergo routine screening. The results of the cytology test and further tests, such as colposcopy and biopsy, will be collected and used for this trial. The risk ratio and risk difference in the proportion of participants with cervical intraepithelial neoplasia two or worse between the two arms will be calculated. The test for the null hypothesis (the detection rates are equal between the two arms) will be performed using Pearson's χ2 test. ETHICS AND DISSEMINATION: This trial was approved by the Research Ethics Committees of the Chiba Foundation for Health Promotion and Disease Prevention and the collaborating research institutes. The results will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: jRCT1030200276. Pre-results.

Is cytology/HPV co-testing for cervical cancer screening useful in Japan?

OBJECTIVE: In Japan, no region has introduced primary HPV testing for cervical cancer screening. We assessed the diagnostic value and possible harm of HPV testing in Japan. METHODS: This cross-sectional study with historical controls used cytology-based screening and co-testing data in Japan. As surrogate indicators of possible harm, colposcopy referral rate and cervical intraepithelial neoplasm (CIN) 1 detection rates were calculated. As surrogate indicators with diagnostic values, the detection rates of CIN2 or greater (CIN2+) and CIN3+ were calculated. RESULTS: The data of 297 970 women (182 697 for cytology-based, 115 273 for co-testing) were examined. The detection rates of CIN1, CIN2+, and CIN3+ were significantly higher in the co-testing group than in the cytology-based group (P < 0.001, P < 0.0001, P < 0.01, respectively). Between ages 25-49, CIN2+ detection rates were significantly higher in the co-testing group than in the cytology-based group (P < 0.05 for each 5-year age group). Between ages 30-49, CIN3+ detection rates were significantly higher in the co-testing group than in the cytology-based group (P < 0.05 for each 5-year age group). CONCLUSION: Limiting the target age group may minimize the possible harm of screening. Cytology/HPV co-testing may be useful in Japanese populations if balance is maintained between benefit and harm.

Effectiveness of human papillomavirus vaccination in young Japanese women: a retrospective multi-municipality study.

In Japan, government support for human papillomavirus (HPV) vaccination began in November 2010. However, the mass media repeatedly reported on severe adverse events. The Japanese Ministry of Health, Labor and Welfare suspended proactive recommendations for HPV vaccines in June 2013. Japan's HPV vaccination rate dropped from 70% to less than 1% in 2017.We examined cervical cancer screening results in terms of abnormal cytology, histology, and HPV vaccination status among 11,903 women aged 20 to 25 y in the fiscal year 2015. The overall rate of HPV vaccination was 26.1% (3,112/11,903). Regarding cytology, the rate of atypical squamous cells of undetermined significance (ASC-US) or worse was 3.3% (103/3,112) in women who received HPV vaccination (vaccine (+) women) and 5.6% (496/8,791) in women who did not (vaccine (-) women). The rate of high-grade squamous intraepithelial lesion (HSIL) or worse was 0.26% (8/3,112) in vaccine (+) women and 0.81% (72/8,791) in vaccine (-) women. Regarding histology, the rate of cervical intraepithelial neoplasia 1 or worse (CIN1+) was 1.4% (42/3,112) in vaccine (+) women and 2.1% (178/8,791) in vaccine (-) women. The rates of CIN2+ and CIN3+ were similar regardless of vaccination. We found a significantly lower incidence of CIN in vaccine (+) women. These results suggest that the resumption of recommending HPV vaccination as primary prevention for cervical cancer is needed in Japan.

Implementation of primary HPV testing in Japan.

Cervical cancer screening has been shifting from primary cytology to primary HPV testing worldwide as primary HPV testing is more sensitive than primary cytology. To the best of our knowledge, the current study is the first in Japan to examine the feasibility of primary HPV testing. One of the disadvantages of this shift is that hrHPV-/≥LSIL/CIN2+ (high-risk HPV negative cancers or pre-cancerous lesions with abnormal cytology results) can be missed. The objectives of the present study are to clarify in detail CIN2+ missed by this shift and to evaluate the feasibility of primary HPV testing in Japan. Data from 115,273 women who underwent co-testing with cytology and HPV testing in cancer screening were used in the current study. The cases with hrHPV-/≥LSIL ('hrHPV-/≥L-SIL' include CIN2-, in contrast, 'hrHPV-/≥L-SIL/CIN2+' doesn't include CIN2-) were analysed in detail. Women with hrHPV-/≥LSIL comprised 0.3% of the total. The prevalence of CIN2, CIN3, SCC or cervical adenocarcinomas in the lesions with HPV-/≥LSIL was 0.03% in the cancer screening group. Only one case of 14 cervical adenocarcinomas in ≥LSIL was hrHPV-. The prevalence of cancer missed by the shift in patients >50 years of age was significantly higher compared with patients younger than 49 years. In conclusion, the prevalence of CIN2+, which might be missed by the shift from primary cytology to primary HPV testing, was remarkably low in this Japanese cancer screening. The data indicated that primary HPV testing, which was more sensitive for CIN2+ than primary cytology, was a feasible method that can be used in Japan. In particular, primary HPV testing should be introduced for women <50 years old.

Liquid-based endometrial cytology using SurePath™ is not inferior to suction endometrial tissue biopsy for detecting endometrial malignancies: Midterm report of a multicentre study advocated by Japan Association of Obstetricians and Gynecologists.

OBJECTIVE: We conducted a prospective, multicentre study to compare the clinical performance of liquid-based endometrial cytology (LBEC) using SurePath™ with that of suction endometrial tissue biopsy (SETB). This study is officially advocated and reported by the Japan Association of Obstetricians and Gynecologists. By publishing our midterm data, we intend to disseminate the benefits of LBEC system, using the descriptive reporting format and algorithmic interpretational approach. METHODS: From April 2014 to December 2015, we consecutively assessed 1116 LBEC specimens and 1044 SETB specimens in our five outpatient clinics. RESULTS: The sensitivity of suction tissue biopsies was 85.2%, whereas the sensitivity of LBEC was 92.2%. The specificity of suction tissue biopsies was 98.9% and that of LBEC was 98.5%. The negative predictive value of LBEC (99.1%) was higher than that of SETB (98.1%), although the difference between these values was not significant. CONCLUSIONS: The clinical performance of LBEC for detecting endometrial malignancies was almost identical to the performance of SETB. This indicates that LBEC was not inferior to SETB for the detection of endometrial cancer. The LBEC is appropriate for various clinical situations as the first-step detecting tool. In addition, it could be used for cancer surveillance for women with signs highly suggestive of endometrial malignancies and in Lynch syndrome patients, on a larger scale.