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

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