Currently submitted to: JMIR Research Protocols
Date Submitted: Dec 22, 2025
Date Accepted: May 12, 2026
Warning: This is an author submission that is not peer-reviewed or edited. Preprints - unless they show as "accepted" - should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.
Protocol for a prospective multicenter trial to evaluate the efficacy of human papillomavirus screening compared with cytology screening in pregnant women (HOPER trial; Human papillomavirus testing for pregnant women: Pregnant women health initiative)
ABSTRACT
Background:
Although the overall number of cervical cancer cases is declining worldwide, the incidence of this type of cancer is increasing in regions with low human papillomavirus (HPV) vaccination and cancer screening rates. In such regions, screening pregnant women can help improve the overall screening rate. Worldwide, cervical cancer screening is shifting from cervical cytology to HPV testing, which reduces the incidence of cervical cancer and, when negative, allows for longer screening intervals.
Objective:
The aim of this trial is to evaluate the effectiveness of an HPV testing protocol compared with that of a cervical cytology protocol for cervical cancer screening in pregnant women.
Methods:
In this study, 5000 pregnant women in their first trimester will undergo both cervical cytology and HPV testing, with follow-up for 1 year. The primary endpoint is to assess the non-inferiority of the HPV testing protocol compared with the cytology protocol for detecting cervical intraepithelial neoplasia (CIN2+) in early pregnancy. In the cytology protocol, CIN2+ cases will be defined as those detected in cytology-positive participants. In the HPV protocol, CIN2+ cases will be defined as those detected in HPV-positive and cytology-positive participants. Secondary endpoints will include an evaluation of the persistence of negative results postpartum to determine the optimal screening interval in this population.
Results:
The trial was funded in April 2024 and it has already started. As of October 2025, 1147 participants have been recruited. Data analysis will be performed after data collection is completed, and the results will be published after this time.
Conclusions:
The results of this trial will clarify whether the HPV testing protocol should be adopted as the primary cervical cancer screening method for pregnant women or whether cervical cytology should remain the standard of care. Clinical Trial: The trial is registered as jRCT 1030240280; https://jrct.mhlw.go.jp/latest-detail/jRCT1030240280.
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