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

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 of pregnant 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.