Smear Test Flags Ovarian Cancer

Mij · Dec 7, 2023

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).

https://www.insideprecisionmedicine.com/topics/precision-medicine/smear-test-flags-ovarian-cancer/

Mij · Dec 7, 2023

Editor’s summary
Ovarian cancer is often diagnosed at a late stage, which leads to increased patient mortality in part because of lack of early detection tests. Here, Paracchini et al. evaluated the use of archival Papanicolaou test smears as a source of tissue for early detection of ovarian cancer. The authors obtained DNA from these samples from which they performed shallow whole-genome sequencing and identified high copy number profile abnormality (CPA) correlated to ovarian cancer development. They created an early ovarian cancer test (EVA), providing a proof of principle for using Pap smears and CPA for early diagnosis of ovarian cancer. —Dorothy Hallberg
Abstract
Late diagnosis and the lack of screening methods for early detection define high-grade serous ovarian cancer (HGSOC) as the gynecological malignancy with the highest mortality rate. In the work presented here, we investigated a retrospective and multicentric cohort of 250 archival Papanicolaou (Pap) test smears collected during routine gynecological screening. Samples were taken at different time points (from 1 month to 13.5 years before diagnosis) from 113 presymptomatic women who were subsequently diagnosed with HGSOC (pre-HGSOC) and from 77 healthy women. Genome instability was detected through low-pass whole-genome sequencing of DNA derived from Pap test samples in terms of copy number profile abnormality (CPA). CPA values of DNA extracted from Pap test samples from pre-HGSOC women were substantially higher than those in samples from healthy women. Consistently with the longitudinal analysis of clonal pathogenic TP53 mutations, this assay could detect HGSOC presence up to 9 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. We integrated the CPA score into the EVA (early ovarian cancer) test, the sensitivity of which was 75% (95% CI, 64.97 to 85.79), the specificity 96% (95% CI, 88.35 to 100.00), and the accuracy 81%. This proof-of-principle study indicates that the early diagnosis of HGSOC is feasible through the analysis of genomic alterations in DNA from endocervical smears.
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https://www.science.org/doi/10.1126/scitranslmed.adi2556

Mij · Dec 7, 2023

Women aren't aware they have ovarian cancer until Stage 4. No symptoms except possible lower back pain and bloating.

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Smear Test Flags Ovarian Cancer

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