A new epigenetic test for cervical cancer demonstrated 100% accuracy, predicting development of the disease as many as 5 years in advance, according to a blinded case-control study published in International Journal of Cancer.
“I wanted to evaluate the clinical performance of an epigenetic biomarker signature that I had developed earlier in clinical studies from the U.K.,” Attila Lorincz, PhD, director of the molecular epidemiology laboratory at the Wolfson Institute of Preventive Medicine and professor at Queen Mary University, told HemOnc Today. “The large screening study from Canada allowed me to validate my signature in a globally relevant manner to show that it can prevent cervical cancer.”
Liquid-based cytology alone can detect only about half of cervical precancers. Testing for HPV —the primary cause of cervical cancer — does not identify actual risks for cancer, which are quite low even when the test result is positive, according to a press release.
Lorincz and colleagues evaluated the performance of the new S5 DNA methylation classifier within the randomized HPV FOCAL trial, which compared HPV testing with liquid-based cytology for primary cervical cancer screening. The study included 257 women aged 25 to 65 years with confirmed HPV cytology results and pathology outcomes.
Researchers randomly assigned women to one of three groups:
- Group 1: HPV-positive with abnormal cytology (n = 104; cervical intraepithelial neoplasia grades 2-3, n = 54);
- Group 2: HPV positive, persistent at 12 months, with normal cytology (n = 103; CIN grades 2-3, n = 53 ); and
- Group 3: HPV positive with normal cytology and clearance of HPV at 12 months (n = 50; all assumed CIN less than grade 2).
For the combined groups, researchers compared relative sensitivity, specificity and positive predictive value of the new S5 methylation classifier with that of other triage approaches, including Pap smear and HPV testing.
Results showed that for CIN grade 3, baseline S5 testing had relative sensitivity of 93.2% (95% CI, 81.4-98) vs. 86.4% (95% CI, 75-95.7) for combined abnormal cytology/HPV16/18 positivity.
For specificity, the rates were 41.8% (95% CI, 35.2-48.8) vs. 49.8% (95% CI, 43.1-56.6).
Researchers calculated adjusted positive predictive values of 18.2% (95% CI, 16.2-20.4) with S5 and 19.3% (95% CI, 16.6-22.2) with the combined triage.
S5 testing also was positive in baseline specimens from eight cancers detected during or after the trial.
“All cancers were predicted by the epigenetic signature up to 5 years before diagnosis,” Lorincz said. “In addition, 93% of precancers were detected in the study. The new test method had significantly better performance than any other test used in the trial.”
Lorincz called the new test an “enormous development,” adding that it is likely to significantly improve diagnosis of cervical cancer.
HemOnc Today. “The new approach is more accurate and less expensive than anything that is being used today. Thousands of women can be saved from cancer every year.” – by Jennifer Byrne
For more information:
Attila Lorincz, PhD, can be reached at Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ; email:firstname.lastname@example.org
Disclosures : Lorincz reports no relevant disclosures. Please see the study for all other authors’ relevant disclosures.