Smear Test Detects Aggressive Ovarian Cancer Years before Clinical Diagnosis

Ovarian cancer, recognized as the deadliest gynecologic cancer, is particularly challenging due to its aggressive nature and poor prognosis. High-grade serous ovarian cancer (HGSOC) is the most common and deadly subtype. Tragically, over 70% of women diagnosed with HGSOC succumb to the disease within five years of their diagnosis. This high mortality rate is largely due to late detection, as the disease often lacks specific symptoms in its early stages. The survival rate for early-stage HGSOC (stage I) exceeds 90%, but drops to about 30% for those with advanced stages of the disease (stage III) and is even lower for stage IV, where distant metastases are present. The vast difference in survival rates between early and late stages underscores the critical importance of early detection in improving outcomes for HGSOC. However, efforts to develop effective early detection tests have historically been met with disappointment and skepticism. Now, a breakthrough has been achieved with a new test that assesses genomic instability from routine cervical smears, potentially identifying aggressive ovarian cancer up to nine years before clinical diagnosis.

This advancement was made possible by researchers at Humanitas University (Milan, Italy) who explored the possibility of using archival Papanicolaou (PAP) test smears which are commonly collected for cervical cancer screening, as a resource for early ovarian cancer detection. By conducting whole-genome sequencing on DNA from these PAP smears, they identified women who later developed HGSOC, characterized by a higher count of somatic copy number alterations (SCNAs) compared to those who remained cancer-free. This finding led to the development of the EVA (Early oVArian cancer) test, specifically designed for early HGSOC detection

In their retrospective study, the team analyzed PAP test smears collected during routine screenings, ranging from a month to 13.5 years before HGSOC diagnosis. The study included 113 women who were later diagnosed with HGSOC and 77 healthy controls. They assessed genome instability through shallow whole-genome sequencing of DNA from the PAP test samples, focusing on copy number profile abnormality (CPA). The results revealed significantly higher CPA levels in DNA from women who developed HGSOC compared to the healthy group. Integrating CPA scores into the EVA test yielded a sensitivity of 75%, a specificity of 96%, and an overall accuracy of 81%. Remarkably, the EVA test could detect HGSOC up to nine years before its clinical diagnosis.

“This finding confirms the continual shedding of tumor cells from fimbriae toward the endocervical canal, suggesting a new path for the early diagnosis of HGSOC,” noted the researchers.

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