Johns Hopkins Medicine specialists report they have developed a urine test for the likely emergence of cervical cancer that is highly accurate compared to other tests based on genetic markers derived directly from cervical tissue.
The new urine test, they say, is different because it analyzes not only multiple sources of human cellular DNA altered by precancerous changes, but also DNA from HPV that is sexually transmitted and causes virtually all cases of the disease.
In a proof-of-concept study, described online in Cancer Prevention Research on November 8, the investigators say their genetic markers test showed a "sensitivity" or accuracy rate of 90.9 percent in identifying so-called CIN2 lesions -- cervical lesions with abnormal cells likely to not only develop into cancer, but also to develop into cancers likely to spread. Additionally, they demonstrated that the DNA for all three human genes and one viral gene could be successfully extracted from urine, and they could identify such lesions with 75 percent sensitivity.
Two commercial tests based on markers of DNA chemical changes called methylation, released in Europe last summer, require Pap smears or swabs of cervical tissue, and show 64 percent sensitivity in identifying similar lesions, according to senior investigator Rafael Guerrero-Preston, Dr.P.H., M.P.H., assistant professor of otolaryngology-head and neck surgery at the Johns Hopkins University School of Medicine and member of the Johns Hopkins Kimmel Cancer Center.
"If further studies confirm these findings, we see a significant use of urine screening as a way to quickly and inexpensively determine if a biopsy is warranted, or if physicians can use a ’watch and wait’ approach before intervening," says Guerrero-Preston. Typically, he says, a woman who tests positive for HPV and has an abnormal Pap smear undergoes a biopsy to rule out cervical cancer using cells taken directly from cervical tissue. But previous studies suggest more than 50 percent of these biopsies are unnecessary and can result in pain, worry, infertility and higher health care costs.
"Our urine test would serve as a molecular triage," he says, "at times supplementing Pap test information. In developing countries that don’t have the money, medical infrastructure or cultural approval for Pap test, our test could be used instead."
The new study builds on the Johns Hopkins team’s previously published work, in which investigators identified three genes associated with cervical cancer or abnormal-looking cells known to become cancerous: FKBP6, INTS1 and ZNF516. As abnormalities progress, these genes were more likely to have a chemical methyl group attached to their DNA in certain spots.
The researchers tested the value of these genes as markers using 214 cervical cell samples collected from women undergoing Pap smears at Hospital Dr. Hernan Henriquez Aravena in Chile. The women ranged in age from 18 to 86. Among the test samples, 34 showed no abnormalities in their cervix; 87 showed one of three types of precancerous, abnormal tissue; and 90 showed clear evidence of cervical cancer.
Next, Guerrero-Preston’s team isolated DNA from each cervical tissue sample and used advanced genetic sequencing methods to spell out the DNA makeup of cells in the cervical tissue samples. The researchers then compared the number of methyl groups attached to each gene in samples from the 34 healthy women to 53 samples with a specific subset of precancerous markers.
