Cervical cancer screening: efficacy of PAX1 and JAM3 methylation assay in the triage of atypical squamous cell of undetermined significance (ASC-US)

• Published in: BMC cancer 2024-11, Vol.24 (1), p.1385-10, Article 1385
• Main Authors: Chen, Xiaoyan, Jiang, Haimin, Xu, Hubin, Wang, Linhai, Liu, Pei, Ma, Dongxue, Wang, Hui, Shou, Huafeng, Fang, Xuqian
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis; ASC-US; Atypical Squamous Cells of the Cervix - pathology; Atypical Squamous Cells of the Cervix - virology; Biological markers; Biomarkers; Biomarkers, Tumor - genetics; Biopsy; Cancer; Cancer screening; Cell Adhesion Molecules; Cellular biology; Cervical cancer; Colposcopy; Consent; Cytology; Development and progression; Diagnosis; DNA Methylation; DNA, Viral - genetics; Early Detection of Cancer - methods; Female; Genetic aspects; Genetic screening; Genetic testing; Health aspects; Human papillomavirus; Humans; JAM3; Kinases; Lesions; Medical colleges; Medical screening; Methylation; Middle Aged; Mortality; Paired Box Transcription Factors - genetics; Papillomavirus Infections - diagnosis; Papillomavirus Infections - virology; Pathology; PAX1; Resource utilization; Risk factors; Sensitivity analysis; Sensitivity and Specificity; Squamous cells; Transcription factors; Triage (Medicine); Triage - methods; Tumors; Uterine Cervical Dysplasia - diagnosis; Uterine Cervical Dysplasia - genetics; Uterine Cervical Dysplasia - pathology; Uterine Cervical Dysplasia - virology; Uterine Cervical Neoplasms - diagnosis; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology; Vaginal Smears; Womens health
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-024-13082-z

Atypical squamous cells of undetermined significance (ASC-US) often present diagnostic challenges with cytology-based results, leading to potential underdiagnosis or overdiagnosis. An effective triage method is essential for managing these cases to reduce unnecessary referrals and treatment. A total of 322 women diagnosed with ASC-US were tested for HPV-DNA and the PAX1 and JAM3 methylation (PAX1 /JAM3 ) test in the study. Methylation levels of PAX1 and JAM3 were significantly elevated in cervical lesions classified as CIN2 or more severe lesions (CIN2+). The methylation assay demonstrated a sensitivity of 83.8% and a specificity of 95.8%, outperforming HPV-DNA testing in differentiating high-grade cervical lesions among women with ASC-US. Moreover, PAX1 /JAM3 testing significantly reduced the colposcopy referral rate for further diagnostic procedures in high-risk HPV-positive women by 79.5%. PAX1 /JAM3 testing shows promise as a reliable supplemental method to HPV-DNA testing for the triage of women with cytologic ASC-US. In addition, the molecular triage based on the CISCER assay or single PAX1 or JAM3 methylation, had better effects in the women with non-HPV16/18 group. This approach could potentially minimize overtreatment and unnecessary referrals in clinical practice, enhancing patient management and resource utilization.