Pap tests could one day tell women if they have breast or ovarian cancer

Experts have identified changes in a woman’s cervix that can help detect tumors elsewhere in the body. These tests involve scraping cells from the cervix to detect any abnormalities that could cause cervical cancer. But researchers from Innsbruck University and gynecological cancer research charity The Eve Appeal found the cells from this test can also give clues and alerts for other types of cancers. With development, they state that the method used could one day predict the risk of developing ovarian, breast, womb, and cervical cancers from a straightforward smear pap test.

They developed their system using a process known as DNA methylation — epigenetic modifications to DNA that don’t alter the genetic sequence but do determine whether a gene expresses or stifles its function: in this case, forming or preventing cancer in the body. These modifications leave ‘methylation markers or signatures’ on genomic regions that scientists can read to determine what has occurred within a person’s body throughout their lifetime. Akin to the rings of a tree, this method can provide chronological clues as to what has happened in our biological life.

Researchers created the test, dubbed WID (Women’s Risk Identification), to analyze markers left by cancerous activity in the DNA of cervical cells. By calculating a woman’s WID, they hope to identify those with a high risk of developing ovarian, breast, womb, or cervical cancers: providing an early-warning system for medical teams to increase treatment outcomes.

The team was able to spot these modifications because they matched DNA markers found in diseased cervical, breast, ovarian, and womb biopsy tissue (a highly invasive procedure) to those found in the easier to access cells of the cervix — whose similar biological structures undergo the same hormonal changes as the tissues these cancers flourish in.

Finding cancer through the cervix

The first study examined cervical cell samples collected from 242 women with ovarian cancer and 869 healthy controls. To develop the WID risk scale, the scientists measured 14,000 epigenetic changes to identify ovarian cancer’s unique DNA signature to spot the presence of the disease in epithelial tissue scraped from the cervix.

They then validated the signature in an additional cohort of 47 women who had ovarian cancer and 227 healthy subjects. Results identified 71% of women under 50 and roughly 55% of the volunteers older than 50 who had previously tested positive for the disease — giving the tests an overall specificity of 75%. A test’s specificity is its ability to correctly identify people without the disease.

Professor Martin Widschwendter of the University of Innsbruck and UCL, heading up the research, said the findings suggest their WID index is picking up cancer predisposition, adding that the results were similar to a study on women with cancer of the womb. He is adamant their test cannot predict ovarian, with more studies needed.

A possible screening method for an undetectable cancer 

In the second study, the same team analyzed epigenetic changes in cervical cell samples provided by 329 women with breast cancer against those from the same 869 healthy volunteers in the first study. Using the WID index, they were able to identify women with breast cancer based on a unique epigenetic signature. The group once again confirmed these markers in a smaller consort of 113 breast cancer patients and 225 women without this condition.

The researchers also used the patterns to predict whether patients had breast cancer-but they didn’t say exactly how accurate the tests were. Instead, they stressed that further trials are needed-with the hope that clinicians could use their WID as a regular test for women in the future-specifically for those under fifty years of age who do not have access to screening for this disease.

“This research is incredibly exciting,” said Liz O’Riordan, a breast cancer surgeon who was also diagnosed with this disease. “At the moment, there is no screening test for breast cancer in women under the age of 50. If this test can help pick up women with a high risk of developing breast, ovarian, cervical, and uterine cancer at a younger age, it could be a game-changer.”

The team adds that these findings are also crucial for ovarian cancer, whose symptoms can be as benign as a bloated abdomen. The biggest killer of women out of gynecological-based tumors, this disease is diagnosed late by clinicians in an alarming 3 out of four cases.

But for now, Widschwendter says, the findings suggest that the molecular signatures in cervical cells may detect the predisposition to other women-specific cancers rather than providing a solid prediction of the disease.

Because of the pandemic, women have stopped taking pap tests

A pap smear test detects abnormal cells on the cervix, which is the entrance to the uterus from the vagina. Removing these cells can prevent cervical cancer, which most commonly affects sexually-active women aged between 30 and 45. In most cases, the human papillomavirus causes this cancer after being acquired through unprotected sex or skin-to-skin contact. To summarise, the whole point of these tests is to detect women at risk of developing cancer and encourage them to carry further health check-ups, not to find those displaying cancer symptoms.

Around the world, the number of women taking smear tests has dropped substantially during the pandemic. In England, for instance, one of the countries with the highest testing rates, just 7 out of 10 eligible women got a cervical check-up — and conditions are expected to worsen due to a new policy brought in by the UK government at the start of 2022, which saw all eligible women in Wales have their wait times increased from three to five years in between tests. The government expects to roll out the policy in England this year after the pandemic caused the delay of its initial release. Experts insisted the move was safe, but campaigners hit back at the plans, arguing it would cause preventable deaths by delaying the detection of cancer or pre-cancerous issues.

In a statement to the Guardian, the UK’s Secretary for Patient Safety and Primary Care says it’s “great to see how this new research could help alert women who are at higher risk to help prevent breast, ovarian, womb, and cervical cancer before it starts.” Until this time, cancer screening remained vital and urged all women aged 25 and above to attend their appointments when invited. The secretary did not remark on the new government policy.

An ovarian cancer specialist urged caution in interpreting the data: They show a “moderate association” between the methylation signature and ovarian cancer, said Dr. Rebecca Stone, the Kelly Gynecologic Oncology Service director at Johns Hopkins Hospital. “They are not showing that it’s predictive or diagnostic,” Stone stressed. Clarifying that to see whether the cervical cell signature predicts cancer, a study would have to observe a large group of women over a long period.

Filling the gap in screening options for women

In contrast, Athena Lamnisos, CEO of the Eve Appeal, emphasizes the importance of a new screening tool:

“Creating a new screening tool for the four most prevalent cancers that affect women and people with gynae organs, particularly the ones which are currently most difficult to detect at an early stage, from a single test could be revolutionary.”

The Eve Appeal goes on that women could get separate risk scores for each of the four cancers in the future where medical teams could offer those with high scores more active monitoring, regular mammograms, risk-reducing surgery, or therapeutics.

Ultimately, it’s better to prevent than to treat, and this method could offer women worldwide access to proper screening services that could save lives through the application of early intervention and preventative medicine.

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