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Test shows promise in detecting ‘hard-to-find’ cervical cancers

Cervical cancer is the fourth most common cancer in women, with the burden significantly higher in lower- and middle-income countries

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Scientists at the Montefiore Einstein Cancer Center (MECC) have developed a test for detecting a “hard-to-find” type of cervical cancer.

The novel test appears sensitive for detecting cervical adenocarcinoma [ADC], which accounts for up to 25 per cent of cervical cancer cases, as well as some lesions, called adenocarcinoma in situ [AIS], that often develop into ADCs.

Because ADCs are often missed by current screening methods, they have higher mortality rates than the more common cervical squamous cell cancer. Researchers at MECC are hoping to catch the disease early, before it develops into cancer.

The widespread use of the smear test, in which a doctor examines tissue samples for abnormal cells, has significantly reduced the incidence of cervical squamous cell cancer over the past six decades. However, the incidence of ADC has not decreased.

In recent years, testing for human papillomaviruses (HPVs), responsible for 99.7 per cent of cervical cancer cases, joined the smear test as a standard screening tool for cervical cancer.

Although there are more than 100 types of HPV, three types, HPV 16, 18, and 45, account for more than 70 per cent of all cervical cancer cases and more than 90 per cent of ADC cases.

The current HPV tests cover all three types and can alert infected women that they face a high risk for developing cervical cancer.

But while vaccines for preventing cervical cancer are safe and effective, researchers say several generations of women are above the age for receiving the vaccine.

The MECC-developed HPV test assessed HPV 16, 18, and 45 in a novel way by specifically looking at methylation levels. Methylation is a chemical modification of DNA and other molecules that may be retained as cells divide to make more cells.

“The advent of next-generation genetic testing has opened up opportunities for us to more accurately detect oncogenic HPV strains and patterns in the genomes that correspond with the development of AIS and ADC,” said Robert D. Burk, professor of pediatrics, of microbiology and immunology, of epidemiology and population health, and of obstetrics and gynaecology and women’s health at Einstein and MECC member, who co-led the study.

“Our findings, if confirmed by clinical trials, suggest that women with a high methylation score may benefit from colposcopy and specialised tissue evaluation, beyond just a Pap test, which could lead to early diagnosis and treatment for ADC or the removal of AIS lesions before they develop into ADC.”

He added: “Given that our test uses equipment that could be simplified, it has the potential to expand testing in lower-resourced countries.”

Cervical cancer remains the fourth most common cancer in women worldwide, with the burden significantly higher in lower- and middle-income countries, including those in Sub-Saharan Africa, where HIV-HPV co-infections are common.

There are also significant disparities within the United States. For example, in New York City, rates of cervical cancer in the Bronx, which is home to the poorest urban congressional district in the country, are 50 per cent higher than in Manhattan.

More frequent and effective screening could help address this health disparity, scientists believe.

“Ideally, the new HPV methylation test would only need to be done once every three to five years,” explained Howard Strickler, co-senior and corresponding author of the Journal of the National Cancer Institute (JNCI) and a member of MECC.

“We are hopeful that this test will be able to increase cervical cancer screening equity in the US.”

Menopause

High street bakery chain Gail’s reveals menopause plan

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Gail’s has unveiled a menopause action plan offering new workplace support to thousands of staff ahead of legal reforms due in 2027.

The high street bakery chain will offer new benefits including 24/7 digital GP access and a new employee assistance programme, according to The Times.

It will also explore new online training for staff, including specific training for management.

Gail’s people director Miranda Burgum told The Times: “All we’re trying to do is talk freely and for it not to be a forbidden subject. It’s helping our managers and teams understand that this isn’t a taboo.”

“We’re going to develop the education with our managers, so it will be threaded through all our policies

“It will look at induction training, it will look at the types of people we need to make sure that we make reasonable adjustments for.

“And if somebody needs some sort of risk assessment, we’re going to be looking at [that].”

The move comes ahead of reforms due to be introduced in spring 2027 under the Employment Rights Act.

UK employers with 250 or more employees will be legally required to publish and update official menopause action plans.

The plans are intended to support employers to take effective action to improve workplace gender equality and support employees experiencing menopause.

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Fertility

Paracetamol use may impact future fertility, studies suggest

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Paracetamol use in pregnancy was not linked to autism or ADHD, while separate research found reproductive differences in girls exposed before birth.

One study analysed health records from more than 120,000 children and found no increased risk of autism following prenatal paracetamol exposure.

A separate analysis of nearly 100,000 children also found no increased risk of ADHD among those born to mothers who used the painkiller during pregnancy.

Researchers from the Hong Kong Hospital Authority examined electronic health records covering pregnancies between January 2001 and December 2023.

The autism analysis included 124,333 children, who were nine years old on average and split almost evenly between males and females. There were 3,445 autism diagnoses, representing 2.8 per cent of the group.

The ADHD analysis involved 97,285 children, who were seven years old on average and also split evenly between males and females. There were 5,168 ADHD diagnoses, representing 5.3 per cent.

Women prescribed paracetamol during pregnancy were more likely to be older and have pre-existing conditions including psychiatric disorders, as well as reasons for taking the drug such as infection, fever or chronic pain.

No association was found between prenatal paracetamol exposure and either autism or ADHD.

The findings did not differ according to the trimester in which paracetamol was taken or whether use was intermittent or daily. Advanced maternal age, defined as pregnancy in women over 35, did not alter the findings.

The researchers wrote: “Paracetamol remains a safe and essential analgesic [pain reliever] and antipyretic [fever reducer] during pregnancy, whereas alternatives, such as NSAIDs and opioids carry well-documented risks.

“Unwarranted reluctance to use paracetamol could lead to undertreatment of pain and fever, or the use of more harmful alternatives, both posing risks to the pregnancy and developing fetus.”

The authors said women should assess paracetamol use with guidance from their doctor.

A separate study involving 685 pregnant women without pre-existing conditions and 302 infant daughters found associations between prenatal paracetamol exposure and differences in reproductive organs and hormone levels.

Researchers from Copenhagen University Hospital enrolled the women during their first trimester and assessed them during the first trimester, third trimester and again when their babies were three months old.

At around three months, infants experience a temporary rise in reproductive hormones sometimes called mini-puberty.

Pregnant participants completed questionnaires every two weeks about their use of pain medicines including paracetamol. Infant girls underwent ultrasound scans of their reproductive organs and blood tests to measure hormone levels.

Researchers also examined a separate group of 1,210 girls followed from infancy to adolescence whose mothers reported paracetamol use during the third trimester.

Three-month-old girls exposed to paracetamol before birth had an average 40 per cent smaller ovarian volume, 13 per cent smaller uterine volume and 23 per cent fewer ovarian follicles.

Girls exposed during the first trimester also had lower levels of Anti-Müllerian hormone, a marker of ovarian function.

Among the older girls, those exposed before birth were more likely to have smaller uteruses at puberty and smaller ovaries during their teenage years.

Dr Margit Bistrup Fischer, lead study author and postdoctoral researcher in the Department of Growth and Reproduction at Rigshospitalet hospital in Denmark, said: “Animal studies have demonstrated that impaired formation of ovarian follicles can lead to reduced fertility and earlier reproductive aging.

“Whether the differences observed in our study have implications for fertility and age at menopause in humans remains unknown and will require long-term follow-up of the girls in our cohort.”

She cautioned that women who had used paracetamol during pregnancy “should not be alarmed by our findings”, as the study found associations rather than direct causation and outcomes for individual women and children are unclear.

“Importantly, our study does not evaluate whether [acetaminophen] causes reproductive problems, nor does it provide evidence that prenatal exposure affects future fertility or age at menopause,” she said.

“Although we observed similar associations in an independent cohort, long-term follow-up is needed to determine whether these early-life differences have any clinical significance later in life.”

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Insight

Research uncovers potential new target for breast cancer therapy

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Targeting CD1d altered immune cells slowed tumour growth and improved immunotherapy responses in mouse models of breast cancer, researchers found.

The findings suggest blocking the molecule could make the environment around breast tumours more favourable to anti-cancer immune responses.

Further work is needed to understand how these immune changes occur and how the approach could be safely used in patients.

Researchers from King’s College London, the Francis Crick Institute and University College London investigated how immune cells inside breast tumours influence cancer growth.

They focused on myeloid cells, a group of immune cells found in large numbers within tumours that can either support an immune attack against cancer or contribute to tumour growth and immune evasion.

The team examined CD1d, a molecule found on the surface of myeloid and other immune and tissue cells that helps regulate immune responses.

When CD1d was genetically removed from cells in a mouse model of breast cancer, the mice were more resistant to tumour growth. Researchers also saw changes in myeloid cell populations, including increased activity among cells that can help attack cancer.

The team then blocked CD1d using an antibody and again observed changes in myeloid cells and slower tumour growth. Blocking CD1d also improved responses to immunotherapy in the mouse model.

Researchers used single-cell RNA sequencing, a technique that examines gene activity in individual cells, to investigate the immune changes in more detail.

They identified a population of myeloid cells called monocytes that expressed genes associated with inflammation, an important part of the immune response. These cells were particularly important in restricting tumour growth in the mouse models.

A similar pattern of gene activity was identified in data from human breast cancer tumours. Its presence in myeloid cells was associated with positive responses to immunotherapy in breast cancer patients.

However, the findings in people were based on gene expression data and did not test CD1d-targeting treatment in patients.

Professor Patricia Barral, professor of immunobiology at King’s College London and senior author of the study, said: “Many breast cancers do not respond well to current immunotherapies.

“Our findings reveal a previously unrecognised mechanism by which immune cells within tumours are regulated.

“While CD1d is best known for helping immune cells recognise lipid molecules, we found that it also plays a role in shaping the behaviour of myeloid cells within tumours.

“These findings suggest that targeting the immune cells that surround and support tumours could boost anti-cancer immunity and potentially improve treatment responses in the future.”

Researchers now plan to investigate how the immune changes occur and how they can be safely harnessed in patients.

They also want to examine whether targeting CD1d could enhance existing treatments and influence treatment responses in different cancer types.

The work was supported by UKRI BBSRC, Breast Cancer Now and the Cancer Research UK City of London Centre.

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