Ovarian Cancer
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A test that measures overall genomic instability in routine cervical smears can detect aggressive ovarian cancer up to nine years before its clinical diagnosis, research suggests.

Whole-genome sequencing of DNA purified from Pap smears, which are routinely collected during cervical cancer screening, highlighted women who had gone on to develop high-grade serous ovarian cancer (HGSOC).

These women had a greater number of somatic copy number alterations (SCNAs) than those who remained cancer free. The researchers have incorporated the results into a test that they have named EVA (Early oVArian cancer), which can be used for the early diagnosis of HGSOC.

Reporting in the journal Science Translational Medicine, the team suggests that cervical cell swabs offer the potential for population-wide screening.

“They can be easily incorporated into routine gynecological examinations, rendering them accessible to many women,” maintain Lara Paracchini, PhD, from Humanitas University in Milan, and colleagues.

“This accessibility could lead to increased early detection rates and ultimately improve survival rates for ovarian cancer.”

Paracchini et al. add that the EVA test “is cheap and easily integratable in already ongoing mass screening programs for the early detection of cervical cancer.”

More than 70 percent of patients with HGSOC die within five years of diagnosis, mostly due to a lack of specific symptoms early on.

While 90 percent of women with stage 1 of this cancer survive for five years, this drops by two thirds or more for those with advanced disease.

In an attempt to improve on its detection, the team conducted a retrospective study of Papanicolaou (Pap) test smears collected during routine gynecological screening. Samples taken from between a month and 13.5 years prior to diagnosis were assessed for 113 presymptomatic women who were subsequently diagnosed with HGSOC and 77 healthy women.

Genome instability was assessed through shallow whole-genome sequencing of the DNA from Pap test samples in terms of copy number profile abnormality (CPA). Results showed that CPA in DNA from Pap test samples among women who went on to develop HGSOC were substantially higher than in those from healthy women.

Paracchini and co-workers integrated the CPA score into the EVA test, resulting in a sensitivity of 75% and specificity of 96%, with accuracy of 81%.

The assay was able to detect the presence of HGSOC up to nine years before 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,” the researchers note.

They add: “The results presented here are consistent with recent evidence from large-scale pan-cancer studies suggesting that in many cancer types, genomic alterations are present before the disease is detectable and may possibly contribute to disease development.”

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