New Test Detects Hard-to-Find Cervical Cancers

Cervical cancer is the fourth most common cancer in women, especially in lower- and middle-income countries. A particular type of cervical cancer called cervical adenocarcinoma (ADC), which often goes undetected by Pap tests, accounts for up to a quarter of all cervical cancer cases. The Pap test, a method where pathologists examine tissue samples for abnormal cells, has successfully reduced the occurrence of cervical squamous cell cancer over the past sixty years. However, ADC remains a challenge to detect with this method, leading to higher mortality rates compared to the more common squamous cell cancer.

More recently, human papillomavirus (HPV) testing has become a standard cervical cancer screening tool alongside the Pap test. HPV is responsible for nearly all cases of cervical cancer. While there are over 100 types of HPV, three particular types—HPV 16, 18, and 45—account for more than 70% of all cervical cancer cases, with over 90% of ADC cases linked to them. Current HPV tests cover these three types, helping identify women at high risk of cervical cancer. Despite the effectiveness of vaccines like Gardasil-9, which protects against nine HPV types, many older women are ineligible for vaccination. Consequently, screening and treatment remain vital for cervical cancer prevention for generations to come.

Scientists at Montefiore Einstein Cancer Center (MECC, New York, NY, USA) have developed an innovative test for detecting ADC and its precursor lesions known as adenocarcinoma in situ (AIS), which often progress to ADC. This MECC-designed HPV test evaluates HPV 16, 18, and 45 using a unique approach focused on methylation levels. Methylation, the addition of methyl (CH3) groups to specific DNA regions, is a common process in DNA, both viral and human, and plays a crucial role in altering gene expression. To develop this test, the researchers examined methylation levels in cervical tissue samples from 1,400 women who had undergone cervical cancer screening before 2014, with known cervical cancer status. They analyzed the HPVs present in the cytological samples, calculating methylation percentages for 35 different viral-genome sites. Each sample received a final "methylation score" based on the average methylation percentage across these 35 sites. They found that women with methylation scores in the top 25% had a significantly higher likelihood of developing either ADC or AIS.

"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, M.D., 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 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."

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