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• Posted September 7, 2023

New Test Could Spot a Tough-to-Detect Cervical Cancer

A new test detects a type of cervical cancer often missed by a standard Pap test, providing an important advance in detection.

The test was developed by scientists at Montefiore Einstein Cancer Center in New York City.

“Our novel test appears sensitive for detecting cervical adenocarcinoma [ADC] — which now accounts for up to 25% of cervical cancer cases — as well as its precursor lesions, adenocarcinoma in situ [AIS], that often develop into ADCs,” said researcher Dr. Howard Strickler of the cancer center.

“Because ADCs are often missed by current screening methods, they have higher [death] rates than the more common cervical squamous cell cancer,” Strickler added in a cancer center news release. “Our goal is to catch the disease early, before it develops into cancer.”

While widespread use of the Pap test has significantly reduced cervical squamous cell cancer over the past 60 years, cases of ADC have not decreased, likely because the Pap test is less effective at detecting it.

Testing for human papillomaviruses (HPVs) has joined the Pap test in recent years as a standard screening tool for cervical cancer. HPVs cause virtually all cases of cervical cancer.

More than 100 types of HPV exist, but three of them — HPV 16, 18, and 45 — account for more than 70% of all cervical cancer cases and more than 90% of ADC cases.

Current HPV tests can help infected women know they face a high risk for cervical cancer.

Vaccines for preventing cervical cancer now exist for younger women, but several generations are already above the age for receiving the vaccine. One of those vaccines, Gardasil-9, protects against nine HPV types when administered to adolescents and younger women.

The fact that many age groups aren't eligible for these vaccines means that screening and treatment for prevention of cervical cancer will continue to be critical for several more decades.

The new test assesses HPV 16, 18 and 45 in a different way, looking specifically at what are called methylation levels.

Methylation involves modifications in DNA, both viral and human. It has an important role in altering gene expression.

For the study, the researchers examined methylation levels in cervical tissue samples from 1,400 women who had received cervical cancer screening at Kaiser Permanente Northern California before 2014.

“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 study co-lead Dr. Robert Burk, a professor of women's health at Einstein.

In samples, the researchers tallied the methylation percentages for 35 viral-genome sites and gave each an average score.

Women with methylation scores in the upper 25% had very high odds for having developed either ADC or AIS.

“Our findings, if confirmed by clinical trials, suggest that women with a high methylation score may benefit from colposcopy and specialized 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,” Burk said.

The test uses equipment that could be simplified, Strickler said, which has the potential to expand testing in countries with fewer resources.

Lower- and middle-income countries have a high burden of cervical cancer. In sub-Saharan Africa, HIV-HPV coinfections are common.

The United States is not immune to the disparities. Cervical cancer rates in the Bronx, for example, are 50% higher than in Manhattan. Both are boroughs in New York City.

More frequent and effective screening could help address this health disparity, according to the study authors.

“Ideally, the new HPV methylation test would only need to be done once every three to five years,” Strickler said. “We are hopeful that this test will be able to increase cervical cancer screening equity in the U.S. as well.”

The study findings were published online Sept. 7 in the Journal of the National Cancer Institute.

More information

The World Health Organization has more on cervical cancer.

SOURCE: Montefiore Einstein Cancer Center, news release, Sept. 7, 2023