Pap Smear Samples May Aid Early Diagnosis of Common Ovarian Cancer

Pap Smear Samples May Aid Early Diagnosis of Common Ovarian Cancer
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Genetic material collected in routine cervical cancer screenings could be used to screen for ovarian cancer several years before disease symptoms are evident, possible speeding diagnosis and treatment, a study suggests.

The study, “Detection of TP53 Clonal Variants in Papanicolaou Test Samples Collected up to 6 Years Prior to High-Grade Serous Epithelial Ovarian Cancer Diagnosis,” was published in JAMA Network Open.

One of the ongoing challenges regarding ovarian cancer treatment and research is that, often, the cancer is not diagnosed until it is at a fairly advanced stage. More advanced cancers are generally associated with poorer outcomes; as such, there is a need for tests that can diagnose ovarian cancer at earlier stages, when it is more amenable to treatment.

The Papanicolaou test — commonly referred to as a Pap smear — is a diagnostic tool that involves taking a sample of cells from the cervix to look at under a microscope. This test is routinely used to screen for cervical cancer, but recent studies have indicated that genetic material taken from the cervix may also be useful for diagnosing other gynecological cancers, including ovarian cancer.

Specifically, research has suggested that genetic material from cancers elsewhere in the reproductive tract might be detectable in Pap smear samples. This means that, in theory, these samples could be tested for cancer-specific mutations, which would raise a red flag for further diagnostic tests.

Such a test would require that there be common cancer-specific mutations for which to test. Given that every individual’s cancer is unique — and there is often genetic variance between cancer cells, even within the same tumor — this is not a sure thing.

However, high-grade serous epithelial ovarian cancer (HGS-EOC), the most common type of ovarian cancer, is notable because patients very often have mutations in the gene TP53; such mutations allow cells to divide and grow out of control. As many as 96% of HGS-EOC tumors are estimated to have TP53 mutations.

“The aim of this study was to explore the possibility of exploiting the Papanicolaou test conducted for cervical cancer screening years before diagnosis as a source of material to detect clonal variants in the TP53 gene as a basis to develop assays for the early diagnosis of HGS-EOC,” the investigators wrote.

Researchers in Italy analyzed medical records from San Gerardo Hospital. They identified 17 people with confirmed diagnoses of HGS-EOC who had undergone surgery between 2015 and 2019, and who had samples from Pap smears collected up to six years before their cancer diagnosis.

Their median age at diagnosis was 60, and the median time between Pap smear and cancer diagnosis was 14.9 months. Of the 17 people, a total of 22 previous Pap smear samples were available — three individuals had two previous tests, one had three, and the rest had one.

Genetic analysis of samples of the HGS-EOC tumors themselves revealed that all 17 were positive for TP53 mutations. Among the corresponding Pap smear samples, 11 (64%) were positive for the mutation.

“This cohort study found specific variants in multiple Papanicolaou tests from the same patients conducted up to 6 years before the diagnosis of HGS-EOC,” the researchers wrote. These results provide a proof-of-concept for this type of test as a feasible way to detect cancer-associated mutations in routinely collected cell samples.

Genetic tests were also conducted on Pap smear samples from 11 people without HGS-EOC diagnoses; none were positive for TP53 mutations.

“To our knowledge, this is the first investigation in which Papanicolaou tests from healthy women were used as controls to investigate the presence of TP53 variants in the same biological material analyzed in patients with HGS-EOC,” the researchers wrote. “The absence in the control samples of the TP53 variants identified in tumor DNA supports our hypothesis that the presence of these TP53 variants in patients’ archival Papanicolaou test samples represents an early sign of disease.”

Further studies will be needed to determine the most feasible way of implementing this approach in clinical practice, and to determine whether, once in place, it actually translates to measurable benefits in patient outcomes like survival, the team said.

“Our results hint at a promising prospect to significantly improve the future diagnosis of HGS-EOC, thus increasing its potential curability,” the researchers concluded.

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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