Abstract
Introduction
HSIL or CIN2/3 lesions in HPV-positive women <30 years have high spontaneous regression rates. To reduce overtreatment, biomarkers are needed to delineate advanced CIN lesions that require treatment. We analysed the
FAM19A4/miR124-2 methylation test and HPV16/18 genotyping in HPV-positive women <30 years aiming to identify CIN2/3 lesions in need of treatment.
Methods
A European multicentre retrospective study was designed evaluating the
FAM19A4/miR124-2 methylation test and HPV16/18 genotyping in cervical scrapes of 1,061 HPV-positive women aged 15-29 years (690 ≤CIN1, 166 CIN2 and 205 CIN3+). A subset of 62 CIN2 and 103 CIN3 were immunohistochemically characterized by HPV E4 expression, a marker for a productive HPV infection and p16
ink4a and Ki-67, markers indicative for a transforming infection. CIN2/3 lesions with low HPV E4 expression and high p16
ink4a/Ki-67 expression were considered as non-productive, transforming CIN, compatible with advanced CIN2/3 lesions in need of treatment.
Results
FAM19A4/miR124-2 methylation positivity increased significantly with CIN grade and age groups (<25, 25-29 and ≥30 years), while HPV16/18 positivity was comparable across age groups.
FAM19A4/miR124-2 methylation positivity was HPV type independent. Methylation-positive CIN2/3 lesions had higher p16
ink4a/Ki-67-immunoscores (
p = 0.003) and expressed less HPV E4 (
p = 0.033) compared with methylation-negative CIN2/3 lesions. These differences in HPV E4 and p16
ink4a/Ki-67 expression were not found between HPV16/18-positive and non-16/18 HPV-positive lesions.
Conclusions
Compared with HPV16/1 8 genotyping, the
FAM19A4/miR124-2 methylation test detects non-productive, transforming CIN2/3 lesions with high specificity in women <30 years, providing clinicians supportive information about the need for treatment of CIN2/3 in young HPV-positive women.
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