25667975
OBJECTIVE	Triage of HPV screen-positive women is needed to identify those with underlying cervical intraepithelial neoplasia grade 2/3 or worse ( CIN2/3 + ) .
OBJECTIVE	Presently , cytology on a physician-taken cervical scrape is mostly accepted as triage test , but needs follow-up testing in order not to miss severe disease .
OBJECTIVE	Here , we evaluated the performance of combined cytology and bi-marker CADM1/MAL-methylation analysis as triage test on physician-taken cervical scrapes of HPV positive women .
METHODS	In this post-hoc analysis , we used 364 left-over HPV positive cytology triage samples of participants of a randomized controlled trial ( PROHTECT-3 : n = 46,001 ) performed in population-based cervical screening .
METHODS	Study endpoints were CIN2 + and CIN3 + detection .
METHODS	Cytology testing with and without methylation marker analysis was evaluated with regard to sensitivity , specificity , positive and negative predictive value , and referral rate .
RESULTS	Bi-marker CADM1/MAL-methylation positivity increased proportionally with severity of underlying lesions .
RESULTS	Overall , cytology and bi-marker CADM1/MAL-methylation analysis yielded similar performances with regard to CIN3 + detection , yet in combination a significantly higher sensitivity for CIN3 + ( 88.7 % ) was obtained at a specificity of 53.6 % and a colposcopy referral rate of 53.6 % .
RESULTS	The combined strategy detected all six cervical cancers , whereas triage by cytology alone failed to detect two of them .
CONCLUSIONS	Cytology and bi-marker CADM1/MAL-methylation analysis perform complementary for CIN2 + / CIN3 + detection when used as triage tool on cervical scrapes of HPV positive women .
CONCLUSIONS	This approach not only results in a higher CIN3 + sensitivity than cytology triage with an acceptable referral rate , but also seems to reduce the risk of missing cervical cancers and advanced high-grade lesions .

