AccScience Publishing / JCTR / Online First / DOI: 10.36922/jctr.24.00080
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ORIGINAL ARTICLE

Non-invasive early detection of cervical carcinogenesis through the olfactory response of Caenorhabditis elegans

Hideyuki Hatakeyama1 ,  Aya Hasan Alshammari1 ,  Masayo Morishita1 ,  Umbhorn Ungkulpasvich1 ,  Junichi Yamaguchi1 ,  Takaaki Hirotsu1 ,  Eric di Luccio1*
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1 Hirotsu Bio Science Inc., R&D Department, 22F The New Otani Garden Court, Chiyoda-ku, Tokyo, Japan
JCTR, 00080 https://doi.org/10.36922/jctr.24.00080
Received: 27 November 2024 | Revised: 21 February 2025 | Accepted: 17 April 2025 | Published online: 30 April 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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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. Early detection of progressive cervical carcinogenesis is crucial for improving outcomes. By targeting CIN, a pre-cancerous stage, therapeutic interventions are most effective and least invasive, offering the potential to reduce the incidence of invasive cervical cancer drastically. Early cervical carcinogenesis detection is hindered by inadequate screening coverage due to barriers, inaccurate screening methods, and patient compliance issues. Optimizing the timing, frequency, and technology availability of screening in resource-limited settings also poses significant challenges. Aim: This study evaluates the efficacy of Nematode-NOSE (N-NOSE), a novel Caenorhabditis elegans-based olfactory cancer screening tool, in detecting early cervical carcinogenesis. Methods: Urine specimens from 74 patients with cervical cancer and 245 patients with CIN were analyzed, with institutional review board approval from the National Hospital Organization Shikoku Cancer Center Hospital, Ehime, Japan. Results: We discovered that urine samples from CIN patients were successfully predicted to be positive using the N-NOSE test, with a sensitivity of 73% (180/245 patients) and 100% (9/9 patients) for CIN and pre-cancerous CIN3, respectively. Conclusion: N-NOSE demonstrates high sensitivity in detecting both early-stage CIN and invasive cervical cancer, suggesting its potential as a non-invasive, urine-based screening tool for early detection. This advancement also holds the promise of significantly improving preventive healthcare by enabling timely identification and intervention, leading to more efficient treatment modalities that effectively halt the progression of cervical carcinogenesis. Relevance for patients: The N-NOSE test offers a non-invasive, urine-based method for early detection of cervical cancer and pre-cancerous changes, enabling timely intervention and potentially enhancing patient outcomes.

Keywords
Caenorhabditis elegans
Cervical carcinogenesis
N-NOSE
Olfactory response
Funding
None.
Conflict of interest
The authors are employees of HIROTSU BIO SCIENCE Inc., which developed and commercialized the N-NOSE technology described in this paper. T.H. is the CEO and Founder.
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Journal of Clinical and Translational Research, Electronic ISSN: 2424-810X Print ISSN: 2382-6533, Published by AccScience Publishing
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