Ovarian cancer can be predicted years in advance, even up to a decade, thanks to genetic analysis of Pap test data. The hope of early diagnosis for ovarian cancer is now a step closer to reality, declared the Milanese IRCCS, revealing the results of a study published in ‘Science Translational Medicine,’ thanks to Humanitas’ Italian research. The findings pave the way for a DNA test that can “detect the presence of molecular abnormalities specific to ovarian cancer” long before the disease reveals itself, using swabs from the routine cervical cancer screening test.
According to Humanitas experts, more than 5,000 new cases of ovarian cancer are detected in Italy each year, adding to the approximately 30,000 women already receiving treatment for the disease. High-grade serous ovarian carcinoma (Hgsoc) is the most frequent variety, accounting for 70% of all diagnoses and being the most aggressive and fatal type, typically resistant to chemotherapy medicines since it is detected in advanced stages. Ovarian cancer symptoms might be difficult to recognise, but early detection can be the difference between life and death: the 5-year survival rate rises from 30% for tumours diagnosed in the third stage to over 90% for those diagnosed in the first stage.
According to Maurizio D’Incalci, Professor of Pharmacology at Humanitas University and head of the Antitumor Pharmacology Laboratory at the Humanitas Clinical Institute, and Sergio Marchini, head of Humanitas’ Translational Genomics Unit, changing the ability to make early diagnoses means changing the treatment options. They planned and organised the study, saying that this is what they think is possible with a new method that can be used on a big scale and doesn’t involve any harm—in other words, using Pap test swabs and genomic analysis methods that can find a key genetic feature of this tumour: its genomic instability.
Many research teams from around the world have been trying, unsuccessfully, to create an early detection method for ovarian cancer in the past few decades. One of these techniques, similar to the one that the Humanitas scientists have now suggested and that the IRCCS in Rozzano has emphasised was predicated on examining Pap test swabs. But in that instance, their hunt for a genetic mutation was insufficiently particular. Marchini highlights examining another biological trait of cancer cells—their genetic instability—which makes the difference this time. Today, we know that the DNA of future neoplastic cells is marked by fundamental aberrations in its structure and organisation during the early phases of the cancer transformation process. Therefore, genomic instability is a fundamental feature unique to sick cells and provides a great basis for developing an early diagnostic test.
The current study was conducted retrospectively using Pap test swabs from 113 women with ovarian cancer collected years before diagnosis. The samples were collected and analysed in collaboration with numerous centres across Italy, including Irccs Ospedale San Gerardo di Monza, Irccs Policlinico Gemelli di Roma, Irccs Istituto Nazionale Tumori di Milano, Irccs Ospedale San Raffaele di Milano, Centro di Riferimento Oncologico – CRO di Aviano, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Istituto Mario Negri di Milano, and Università degli Studi di Padova.
The researchers used a DNA sequencing approach to detect minuscule amounts of cancer DNA and measure its genomic instability. The results were then compared to Pap test results from 77 women who did not receive a cancer diagnosis in the years that followed.
The data is actually promising for the first time in ovarian cancer diagnosis research, according to the study’s original authors, Lara Paracchini and Laura Mannarino, who conducted the laboratory trials and did the data’s bioinformatic analysis. They show that the technology can detect the presence of cancer DNA in swabs for years, even nine years before the disease develops. The number of false positives in the control group is quite low, as is the amount of false negatives in cancer swabs.
As the Institute underlines, the Humanitas researchers’ work is a critical first step towards showing the feasibility and usefulness of an early diagnosis tool for this condition.
D’Incalci emphasises that diagnostic tests are particularly difficult to validate since they must be examined in the real world, with huge numbers of patients, and in a prospective manner. Only by detecting these residues of highly unstable DNA will it be possible to demonstrate that we can actually foresee the disease and establish a monitoring strategy that can save lives, says the researcher. The newly published data paved the way for scientists to launch a big and comprehensive prospective study to validate the data and make the dream of early ovarian cancer detection a tangible reality.
According to the release, the research was made possible by the help of Fondazione Alessandra Bono, Fondazione Airc per la Ricerca sul Cancro, and Alleanza contro il Cancro. Rinascente will contribute to the studies through the Fondazione Humanitas per la Ricerca.
