According to the International Agency for Research on Cancer (IARC), cervical cancer (CC) ranks fourth among the most frequently diagnosed cancers worldwide. Women with negative or atypical cytology (ASCUS) and high-risk human papillomavirus (HR-HPV) infection represent a special group that establishes a management challenge. Recently, epigenetic mechanisms such as DNA methylation have gained importance as early diagnostic biomarkers for neoplastic lesions. Methylation of the FAM19A4 and miR124-2 genes has emerged as a potential biomarker for improved risk stratification in this population. This is a retrospective case-control study; we included women aged 25 to 70 yr with HR-HPV positivity and negative cytology or ASCUS. FAM19A4 and miR124-2 methylation were analyzed using the Qiasure methylation test. Cases (n=25) were defined as patients progressing to histologically confirmed high-grade squamous intraepithelial lesion (HSIL) within 1 to 3 yr. Controls (n=66) had no progression. Associations between methylation status, HPV genotype, and lesion progression were assessed. FAM19A4 and/or miR124-2 methylation were observed in 44% of cases and 37.9% of controls ( P =0.71). Methylation of miR124-2 alone showed a non-significant progress toward association with progression ( P =0.07). Infection with HPV16/18 ( P =0.014) and multiple HPV genotype infections ( P =0.018) were significantly associated with progression to HSIL. Methylation of FAM19A4 and miR124-2 did not significantly predict short-term progression to HSIL in this cohort. However, HPV genotype, particularly HPV16/18 infection, remains a strong predictor. Further studies are necessary to clarify the prognostic value of methylation testing in HPV-positive women with low-grade or negative cytology.
Salazar-Huayna et al. (Thu,) studied this question.