New Test Detects Cervical Cancer Often Missed by Pap Test

Scientists at Montefiore Einstein Cancer Center (MECC) have developed a new test for detecting a type of cervical cancer that is often missed by traditional Pap tests. This breakthrough could have significant implications for cervical cancer screening. The findings of their research are published in the Journal of the National Cancer Institute.

“Because (cervical adenocarcinomas) are often missed by current screening methods, they have higher mortality rates than the more common cervical squamous cell cancer,” said co-senior author Howard Strickler, MD, of MECC. “Our goal is to catch the disease early before it develops into cancer. 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.”

The Pap test, which involves examining tissue samples for abnormal cells, has been instrumental in reducing the incidence of cervical squamous cell cancer for more than 50 years, but is less effective at detecting ADC. In recent years, HPV testing has been introduced as a standard screening tool alongside the Pap test. HPV is responsible for nearly all cases of cervical cancer, with three specific types (HPV 16, 18, and 45) accounting for 70% of all cervical cancer cases and 90% of ADC cases. HPV tests can identify women at high risk of developing cervical cancer who should receive the HPV vaccine, but some women are above the age limit for receiving it, making effective screening essential for those women.

The HPV test developed by MECC researchers takes a novel approach by assessing HPV 16, 18, and 45 by examining methylation levels.

Methylation involves adding methyl groups (CH3) to a region DNA and is routine occurrence in both viral and human DNA, plying a critical role in altering gene expression. The recent study, conducted in collaboration with the National Cancer Institute (NCI) assessed methylation levels in cervical tissue samples from 1,400 women who had undergone cervical cancer screening at Kaiser Permanente Northern California before 2014 and whose cervical cancer status was known.

Assessing the HPVs in the cytological samples, the team recorded the the methylation percentages for each of 35 different viral-genome sites, with each sample receiving a final “methylation score” equal to the average methylation percentage across all 35 sites. Women with methylation scores in the top 25% had significantly higher 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,” said co-leader of the study Robert D. Burk, MD, professor of pediatrics, of microbiology & immunology, of epidemiology and population health, and of obstetrics & gynecology and women’s health at Einstein and MECC.

“Given that our test uses equipment that could be simplified, it has the potential to expand testing in lower-resourced countries,” added Strickler. “Ideally, the new HPV methylation test would only need to be done once every three to five years. We are hopeful that this test will be able to increase cervical cancer screening equity in the U.S. as well.”

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