Chiba Prefectural Health Prevention Foundation
Self-collected HPV tests have improved the rate of cervical cancer screening, but no difference has been observed in the detection of moderate or higher grade dysplasia, revealing issues
～Randomized controlled trial The ACCESS trial～
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Chief researcher Misuzu Fujita and research center director Akira Haneda of the Chiba Prefectural Health Prevention Foundation, in collaboration with Ichihara City, Keio University, Chiba University, and others, collected vaginal mucus themselves and detected human papillomavirus (Human Papillomavirus). We conducted a randomized controlled study (the ACCESS trial) to evaluate the effectiveness of a self-collected HPV test for HPV (human papillomavirus) infection. Study participants were randomly assigned to an intervention group (who could receive regular screening, starting with a self-collected HPV test or cytology) and a control group (who could receive regular screening). The rate of cervical cancer screening in the intervention group was significantly higher than in the control group, but no difference was observed in the detection of moderate or higher grade dysplasia. The main reason for this was thought to be low compliance with cytology triage testing when self-collected HPV tests were positive. When introducing self-collected HPV testing, ensuring compliance with cytology triage testing is an issue. The results of this research were published online in the academic journal
International Journal of Cancer on April 22, 2024.
Research background
In Japan, approximately 10,000 people are infected with cervical cancer and approximately 2,900 die each year. Cervical cancer is caused by HPV infection and can be prevented with HPV vaccination and cervical cancer screening. However, due to the suspension of active promotion of vaccination for about 9 years and the low screening participation rate, the incidence of cervical cancer has increased in recent years, especially among young women. Promoting preventive measures against cervical cancer is an urgent issue.
Cervical cancer screening in Japan has long been carried out using “cytology,” which observes changes in the cells of the cervix. In 2020, cervical cancer screening guidelines were updated, and for the first time, HPV testing was recommended in addition to cytology. HPV testing is different from cytology, and self-collection tests have been confirmed to be as accurate as physician collection. Previous studies in other countries have reported that the introduction of self-collected HPV tests has improved the rate of cervical cancer screening and increased the detection of moderate or higher grade dysplasia. However, as results have been found to vary between studies, it is recommended that the effectiveness and feasibility of self-collected HPV testing be verified in the country before introducing it.
This study is the first randomized controlled study in Japan to evaluate the effectiveness of self-collected HPV testing. The purpose of this study is to find out whether incorporating a self-collected HPV test into regular screening increases the screening participation rate and the detection of moderate or higher grade dysplasia. Research method
The subjects of the study are women aged 30-58 who are eligible for Ichihara City’s cervical cancer screening in 2021, and who have not undergone a city screening in three years or more. All subjects were informed of the research content by mail and consented by opting out Note 1). Those who did not refuse to participate in the study were randomly assigned to the “intervention group” and the “control group.” Women in the “intervention group” were able to undergo screening, starting with a self-collected HPV test, or regular screening (cytology) at their option. Women in the “control group” were able to undergo regular check-ups.
We accepted applications for self-collection HPV testing and sent self-collection kits (Evalin Brush) to applicants. After collecting the sample at home, the kit was returned to us. The test was conducted using a Cobas 8800, and the test results were mailed. At that time, regardless of the test results, we recommended that you undergo the city’s cervical cancer screening (cytology). In particular, if the HPV test was positive, we informed them of the risk of developing cervical cancer and encouraged them to undergo screening. Cytology and detailed tests based on the results were conducted at the city’s cervical cancer clinic, and the results were provided by the city for research. Research results
There were 20,555 women who met the criteria for study participation. Of these, 16,260 people were assigned to the intervention group (8,145 people) and control group (8,115 people), excluding those who declined to participate before allocation (4,283 people) and those whose address was unknown (12 people).
[Image 1: https://prtimes.jp/i/119713/12/resize/d119713-12-80dd6019399fad07af49-0.png&s3=119713-12-1dbfc4616152986db993bb45df602f9d-967×522.png ]
After excluding those who subsequently declined to participate (808 in the intervention group and 343 in the control group), the final number of participants was 7,337 in the intervention group and 7,772 in the control group. The mean age (standard deviation) of the intervention group and control group was 44.6 (8.3) years and 44.5 (8.3) years, with no difference observed between the two groups.
Of the intervention group, 1,196 people underwent self-collected HPV testing. Six of them had undergone cytology before sending their self-collected HPV test results, so we determined that they had undergone cytology as a primary screening. Ultimately, 1,468 people in the intervention group (1,190 with self-collected HPV tests and 278 with cytology) and 501 in the control group attended the primary screening. The screening participation rates in the intervention group and control group were 20.0% and 6.4%, respectively, resulting in a 3.10 times (95% confidence interval: 2.82-3.42) higher participation rate in the intervention group.
Of the 1,190 people who took self-collected tests, 72 were HPV positive, 1,103 were negative, and 15 were indeterminate. Of the 15 indeterminate patients, 11 underwent self-collected HPV testing again for retesting. Of these, 1 was positive, 7 were negative, and 3 were again indeterminate. Of the three, one was retested and the results were negative. The final results of self-collected HPV tests were 73 positive, 1,111 negative, and 6 indeterminate.
Of the 73 patients with positive cytology, 34 (46.8%) were women who underwent cytology. Among those with positive cytology, the percentage of women who underwent detailed testing was 76.9% (10/13) in the intervention group and 92.9% (13/14) in the control group, with a significant difference in both groups. No difference was observed. There were 5 patients in the intervention group and 4 patients in the control group who found moderate or higher grade dysplasia. The detection rate was 0.7 and 0.5 per 1000 people screened, with no significant difference between the two groups (relative risk: 1.32, 95% confidence interval: 0.36-4.93).
[Image 2: https://prtimes.jp/i/119713/12/resize/d119713-12-c536c7ccf49a7c02c3c8-1.png&s3=119713-12-8fc532485f396446ebe369a451be1cf7-1598×1118.png ]
comment
Previous studies have reported that self-collected HPV tests improve the rate of cervical cancer screening, but results vary. Additionally, the method of sending kits after receiving a test request (opt-in method) is known to be less effective in increasing the uptake rate than the method of sending kits directly to all eligible women (direct delivery method). A recent meta-analysis reported that the
participation rate was 1.45 times (95% confidence interval: 1.16-1.81) for the opt-in method and 2.50 times (95% confidence interval: 2.08-3.01) for the direct delivery method. This study adopted an opt-in method in which kits were sent after receiving applications, and the participation rate in the intervention group was 3.10 times (95% confidence interval: 2.82-3.42) compared to the control group. These results revealed that in Japan, even the opt-in method, which has great economic benefits, can sufficiently increase the screening participation rate.
In contrast to the effect of improving the screening participation rate, there was no significant difference in the detection rate of moderate or higher grade dysplasia between the two groups. Although all screening processes influence the detection of moderate dysplasia, the main reason why there was no significant difference was the low compliance rate for cytology triage testing among patients with a positive self-collected HPV test. It was thought that. Japan does not have a nationwide system for registering cytology results. Therefore, if the self-collected HPV test was positive, it is possible that the patient did not take advantage of the city’s screening program and underwent cytology. Such people are not registered in the city’s medical examination database, and the compliance rate for cytology triage tests may be underestimated. However, this number is a realistic value using the tracking method adopted in this study. When reporting the results of a positive self-collected HPV test, we explained to them that they were at risk for cervical cancer and encouraged them to take the city’s screening test. However, it became clear that this method could not ensure sufficient compliance with cytology triage testing. Efforts are needed to increase the compliance rate, such as contacting those who have not yet undergone a cytology triage test by multiple telephone calls, etc., and sending invitations for pre-booked cytology triage tests.
This study revealed that self-collected HPV testing improves the rate of cervical cancer screening. However, it did not contribute to an increase in the detection of moderate or higher grade dysplasia. The main reason for this appears to be the low compliance rate for cytology triage testing among HPV-positive patients. In order to maximize the detection of moderate or higher grade dysplasia using self-collected HPV testing, measures are needed to increase the rate of cytology triage testing.
Explanation of terms
Note 1) Consent by opting out: A method of obtaining consent by notifying or disclosing information such as the purpose of the research and guaranteeing the opportunity to refuse participation in the research. In this study, all individuals who met the study criteria were notified by mail and consented by opting out. In addition, written consent was obtained from the self-collected HPV test recipients. Before starting the research, we listened to the opinions of the Ichihara City Personal Information Protection Review Board and received approval from the Chiba Prefectural Health Prevention Foundation and other ethics review boards.
Paper information
Title: Effectiveness of self-sampling human papillomavirus test on pre-cancer detection and screening uptake in Japan: The ACCESS randomized controlled trial
Author: Misuzu Fujita1,2, Kengo Nagashima3,4, Minobu Shimazu5, Misae Suzuki6, Ichiro Tauchi6, Miwa Sakuma6, Setsuko Yamamoto6, Hideki Hanaoka5, Makio Shozu7, Nobuhide Tsuruoka8, Tokuzo Kasai1, Akira Hata1,9
1Chiba Prefectural Health Prevention Foundation, 2Chiba University Graduate School of Medicine, Department of Public Health, 3Keio University Hospital Clinical Research Promotion Center, Department of Biostatistics, 4Institute of Statistical Mathematics, Medical and Health Data Science Research Center, 5Chiba University Hospital Clinical Trials Department, 6 Ichihara City Health Center, 7 Department of Reproductive Medicine, Chiba University Graduate School of Medicine, 8 Ariakidai Clinic, 9 Chiba University Preventive Medicine Center
Magazine name: International Journal of Cancer
DOI: https://doi.org/10.1002/ijc.34970
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