A methylation score, composed of the average methylation percentage across 35 CpG sites in the L2/L1 open reading frames of human papillomavirus (HPV)16, 18, and 45, and two human loci, can identify the risk for cervical adenocarcinoma (ADC) and adenocarcinoma in situ (AIS), according to a study published online July 19 in the Journal of the National Cancer Institute.
Anna Gradissimo, Ph.D., from the Albert Einstein College of Medicine in Bronx, New York, and colleagues measured methylation levels at CpG sites in HPV16, HPV18, and HPV45, as well as human loci DCC and HS3ST2, to develop a DNA methylation score for AIS and ADC screening. Exfoliated cervicovaginal cells were obtained from women who were positive for either HPV16, 18, or 45: 176 with AIS/ADC and 353 with cervical intraepithelial neoplasia-3 (CIN3) or cervical squamous cell cancer (SCC). Controls who cleared (579 HPV clearers) or had persistent HPV16, 18, or 45 infection (292 HPV persisters) were also included.
The researchers found that relative to either control group, patients with AIS/ADC and with CIN3/SCC had higher methylation percentages at each individual CpG site in exfoliated cervicovaginal cells. For AIS/ADC, the methylation score had a sensitivity and specificity of 74 and 89 percent, respectively. Using HPV clearers as controls, the multivariate odds ratio between the fourth and first quartile of the methylation score for AIS/ADC was 49.01; similar albeit weaker, associations were seen for CIN3/SCC.
“If confirmed, our findings suggest that HPV16/18/45-positive women with a high Methylation Score may warrant enhanced screening with careful histologic evaluation of the cervical transition zone,” the authors write.
Two authors disclosed ties to the pharmaceutical industry.