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Ovarian cancer, towards early diagnosis thanks to the Pap test

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Ovarian cancer, towards early diagnosis thanks to the Pap test

Today the discovery of ovarian cancer in the early stage is mostly accidental and rare, accounting for just 10% of cases. Yet a test could turn the situation around, detecting the signs of the disease very early, thanks to Pap test swabs. This is the intuition of the test created by a team of Italian researchers presented today on the pages of Science Translational Medicinewhich manages to reveal traces of the disease several years before it appears.

Ovarian cancer, often late diagnosis

“Identifying ovarian cancer in the early stages means recovery, unlike late diagnoses, which are often lethal,” she says Maurizio D’Incalciprofessor of pharmacology at Humanitas University and coordinator of the study together with his colleague from the Translational Genomics Unit Sergio Marchini. In fact, it is estimated that 5-year survival from diagnosis for high-grade serous carcinomas, the most common form of ovarian tumors, in the advanced stage is around 30%, compared to 90% in the early stages. And it is precisely to identify the disease early – a tumor which has around 5,200 diagnoses per year in Italy – that various research groups are working to develop early diagnosis tests. There are those who hunt for signals attributable to the presence of cancer by analyzing the DNA circulating in the blood, and those who, like the Humanitas team, exploit samples taken from women who underwent Pap tests years earlier. Parallel paths that could also be combined together in the future, D’Incalci does not rule out. But let’s go in order.

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What are the tumor clues to look for in the Pap test

“Previous studies have shown that the majority of ovarian tumors begin development in the tubes, and then migrate towards the ovary – explains D’Incalci – but these cells, just as they move towards the ovary, perhaps can also move towards the ovary early on. ‘uterus”. Hence the researchers’ idea to go and look for these traces there, combining medicine, molecular biology, biostatistics and computer science skills.

For now they have done it backwards, that is, through a retrospective study that analyzed the Pap test swabs of women who subsequently developed ovarian tumors and women who did not develop the disease (113 and 77 respectively, coming from different Italian hospitals ). In this way, explains D’Incalci, the researchers already knew to a large extent what to look for in the Pap test samples, because they already knew the molecular characteristics of the tumors, in particular high-grade serous carcinomas, the ones on which they concentrated.

“In the first analysis we tried to look for specific mutations of p53, a tumor suppressor gene often mutated in tumors. We observed that the same p53 mutations in the tumors were actually also found in Pap test samples from years earlier. But this marker is not specific enough, because mutations of this gene are found in normal tissues, as a product of aging,” explains the expert. But not only that, as we read in the study: it is necessary to first know what to look for in the samples, that is, to know the specific mutation of the gene. And this is not always an advantage. Here then, continues D’Incalci, the idea was to direct attention to other molecular signatures of tumors, such as their genomic instability, appreciable with alterations in the chromosomes and highly specific: “We observed that this characteristic is already present in the early stages of the disease, even up to 9 years before diagnosis”. The test – tested for now in the retrospective study and to date considered only for research purposes, the scholars point out – has an accuracy of 81%.

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What is needed to validate the test for ovarian cancer

For now, therefore, these are only preliminary studies, but it is worth continuing along this line of research. Pap test swabs, they explain, are relatively easy to find and very widespread thanks to screening initiatives. “There already exists a network that carries out Pap tests – continues D’Incalci – and by using it we could imagine offering our test to a large group of women, so as to be able to validate it”. With a prospective study, the researcher imagines, involving thousands of women. At the same time, collaborations could be set up with centers that deal with salpingectomy and oophorectomy (i.e. the removal of tubes and ovaries) following positivity to BRCA genes, which increase the risk of various tumors, first those in the breast and ovary.

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“By carrying out a Pap test before surgery we could possibly verify, if the disease was present in the initial stages, the concordance with our test”, concludes D’Incalci. Not all women with mutations in these genes develop ovarian tumors, and a test – validated on large numbers – could perhaps allow us to delay this type of surgery, even considering the possibility of having children.

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