Evaluation of the Efficacy of Human Papillomavirus Screening Compared With Cytology Screening in Pregnant Women - Protocol for a Prospective Multicenter Trial

Sep 23, 2026

Although cervical cancer incidence is declining globally, it is rising in regions with low HPV vaccination and screening uptake. Cervical screening during pregnancy may improve coverage as trials have excluded pregnant women, leaving HPV-testing performance poorly characterized. This prospective multicenter, nonrandomized single-arm trial evaluates whether an HPV protocol is noninferior to cytology for CIN2+ detection at early pregnancy and assesses postpartum persistence of negative results to inform optimal screening intervals.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Background

Objective

Methods

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Keywords

Introduction

JMIR RESEARCH PROTOCOLS Matsunaga et al Protocol Evaluation of the Efficacy of Human Papillomavirus Screening Compared With Cytology Screening in Pregnant Women: Protocol for a Prospective Multicenter Trial | Risa Matsunaga1, MD; Jun Tamura2, PhD; Kouji Yamamoto2, PhD; Kotaro PhD; Etsuko Miyagi1, MD, PhD; Taichi Mizushima 1, MD, PhD | Senuki3, MSc; Reo Tanoshima4, MD, | | --- | --- | | 1Department of Obstetrics and Gynecology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan 2Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan
3YCU Center for Novel and Exploratory Clinical Trials, Yokohama City University Hospital, Yokohama, Kanagawa, Japan
4Department of Health Data Science, Graduate School of Data Science, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan
Corresponding Author:
Taichi Mizushima, MD, PhD
Department of Obstetrics and Gynecology
Yokohama City University Graduate School of Medicine 3-9 Fukuura, Kanazawa-ku, Yokohama
Yokohama, Kanagawa, 236-0004 Japan
Phone: 81 0457872691
Fax: 81 0457013536
Email: [tmizushi@yokohama-cu.ac.jp](tmizushi@yokohama-cu.ac.jp)
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. Although HPV-based screening has been shown to be at least as effective as cytology screening for lesion detection in the general population, its performance during pregnancy remains poorly characterized due to the exclusion ofpregnant women in previous clinical trials. 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: This study is a multicenter, nonrandomized, single-arm comparative trial. In total, 5000 pregnant women aged 30 years and older in their first trimester will undergo both cervical cytology and HPV testing, with follow-up at 1 year. The primary end point is to assess the noninferiority of the HPV testing protocol compared with the cytology protocol for detecting cervical intraepithelial neoplasia grade 2 or higher, adenocarcinoma in situ, and invasive cervical cancer (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. The primary end point analysis will use a one-sided 10% noninferiority test using the method by Tango, and with 5000 cases, the study can achieve a statistical power of at least 80% . Secondary end points will include an evaluation of the persistence of negative results post partum to determine the optimal screening interval in this population. Results: The trial was funded in April 2024 and has already started. Data collection commenced in September 2024 and is scheduled to be completed by December 2026. As of March 2026, a total of 1906 participants have been recruited. Data analysis is currently planned to begin in December 2027, and the study findings are expected to be published in 2028. 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. International Registered Report Identifier (IRRID): DERR1-10.2196/86397 [https://www.researchprotocols.org/

FAQs

What is the trial’s main goal?

To evaluate the effectiveness of an HPV testing protocol versus a cervical cytology protocol for cervical cancer screening in pregnant women.

How does the study define the primary endpoint (CIN2+)?

In the cytology protocol, CIN2+ is defined by cytology-positive detection; in the HPV protocol, CIN2+ is defined by being HPV-positive and cytology-positive.

What timeline and study status are reported?

Funding started in April 2024, data collection began in September 2024, recruitment reached 1906 by March 2026, analysis is planned for December 2027, and results are expected in 2028.

Sep 23, 2026

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