Page 67 - JCTR-11-3

Journal of Clinical and

Translational Research

ORIGINAL ARTICLE
Non-invasive early detection of cervical

carcinogenesis through the olfactory response
of Caenorhabditis elegans

Hideyuki Hatakeyama, Aya Hasan Alshammari , Masayo Morishita ,
Umbhorn Ungkulpasvich , Junichi Yamaguchi , Takaaki Hirotsu , and
Eric di Luccio*
Hirotsu Bio Science Inc., R&D Department, 22F The New Otani Garden Court, Chiyoda-ku, Tokyo,
Japan

Abstract

Background: Human papillomavirus (HPV) is the primary cause of cervical cancer,
often through the development of cervical intraepithelial neoplasia (CIN). Persistent
infection with high-risk HPV types can lead to severe dysplasia and invasive cancer.
*Corresponding author: Early detection of progressive cervical carcinogenesis is crucial for improving
Eric di Luccio outcomes. By targeting CIN, a pre-cancerous stage, therapeutic interventions are
(e.diluccio@hbio.jp) most effective and least invasive, offering the potential to reduce the incidence
Citation: Hatakeyama H, of invasive cervical cancer drastically. Early cervical carcinogenesis detection is
Alshammari AH, Morishita M, hindered by inadequate screening coverage due to barriers, inaccurate screening
et al. Non-invasive early detection methods, and patient compliance issues. Optimizing the timing, frequency,
of cervical carcinogenesis
through the olfactory response of and technology availability of screening in resource-limited settings also poses
Caenorhabditis elegans. J Clin significant challenges. Aim: This study evaluates the efficacy of Nematode-
Transl Res. 2025;11(3):61-70. NOSE (N-NOSE), a novel Caenorhabditis elegans-based olfactory cancer screening
doi: 10.36922/jctr.24.00080
tool, in detecting early cervical carcinogenesis. Methods: Urine specimens from
Received: November 27, 2024 74 patients with cervical cancer and 245 patients with CIN were analyzed, with
1st revised: January 27, 2025 institutional review board approval from the National Hospital Organization
Shikoku Cancer Center Hospital, Ehime, Japan. Results: We discovered that urine
2nd revised: February 21, 2025
samples from CIN patients were successfully predicted to be positive using the
Accepted: April 17, 2025 N-NOSE test, with a sensitivity of 73% (180/245 patients) and 100% (9/9 patients)
Published online: April 30, 2025 for CIN and pre-cancerous CIN3, respectively. Conclusion: N-NOSE demonstrates
high sensitivity in detecting both early-stage CIN and invasive cervical cancer,
Copyright: © 2025 Author(s).
This is an Open-Access article suggesting its potential as a non-invasive, urine-based screening tool for early
distributed under the terms of the detection. This advancement also holds the promise of significantly improving
Creative Commons AttributionNon- preventive healthcare by enabling timely identification and intervention, leading
Commercial 4.0 International (CC
BY-NC 4.0), which permits all to more efficient treatment modalities that effectively halt the progression of
non-commercial use, distribution, cervical carcinogenesis. Relevance for patients: The N-NOSE test offers a non-
and reproduction in any medium, invasive, urine-based method for early detection of cervical cancer and pre-
provided the original work is
properly cited. cancerous changes, enabling timely intervention and potentially enhancing
patient outcomes.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in
published maps and institutional Keywords: Caenorhabditis elegans; Cervical carcinogenesis; N-NOSE; Olfactory response
affiliations.

Volume 11 Issue 3 (2025) 61 doi: 10.36922/jctr.24.00080