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March 2024 | George M. Pikler, M.D., Ph.D., FACP, Lead Oncology Advocate N1X10

Analyzing DNA From Pap Smears Could Help Diagnose Ovarian Cancer Early

High-grade serous ovarian cancer (HGSOC) is the gynecological cancer with the highest mortality rate, with this trend driven by late diagnosis due to non-specific symptoms in early stages and a lack of early screening methods. Studies have shown that most HGSOC cases start as tumors at the end of the fallopian tubes, shedding cancerous cells from the tubes towards the uterus. Additionally, HGSOC cells accumulate or lose genomic material, a phenomenon called aneuploidy. Instead of having two copies of each gene, HGSOC cancer cells can have one copy (genomic material loss) or more than two copies (genomic material gain).

Findings from a recent study suggest DNA taken from Papanicolaou (Pap) smears used for the screening of cervical cancer could potentially help detect these tumors early. The study provides proof of principle for an early ovarian cancer test, named EVA based on the analysis of the genomic instabilities in the DNA of Pap tests.

The investigators used a retrospective, multicentric selection of 250 archival routine Pap smear samples from 113 women who were not symptomatic at the time of collection but were later diagnosed with HGSOC, as well as samples from 77 healthy women. Samples were from between 1 month and 13.5 years before diagnosis with HGSOC. Low-pass whole-genome sequencing (WGS) of DNA from the Pap samples was used to detect genome instability 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. The study 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.

Sci. Transl. Med. 2023; 15 (725)
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Erica

Erica Cross, PA

PA

Erica is a board certified Physician Assistant. She obtained her Master’s degree in Physician Assistant studies from Our Lady of the Lake College in Baton Rouge, LA. She began practicing in 2011 and has worked clinically in Orthopedics and Dermatology. The majority of her career has been spent in a Dermatology practice where she assisted in Mohs surgery, treating various types of skin cancer. She also teaches in the medical simulation department at the University of South Alabama and enjoys every aspect of medical education.