Utility of methylation markers in cervical cancer early detection: appraisal of the state-of-the-science.
OBJECTIVE
We wanted to identify the most promising methylation marker candidates for cervical cancer early detection.


METHODS
A systematic literature review was performed in Medline and weighted average frequencies for methylated genes stratified by tissue source and methods used were computed.


RESULTS
51 studies were identified analyzing 68 different genes for methylation in 4376 specimens across all stages of cervical carcinogenesis. 15 genes, DAPK1, RASSF1, CDH1, CDKN2A, MGMT, RARB, APC, FHIT, MLH1, TIMP3, GSTP1, CADM1, CDH13, HIC1, and TERT have been analyzed in 5 or more studies. The published data on these genes is highly heterogeneous; 7 genes (CDH1, FHIT, TERT, CDH13, MGMT, TIMP3, and HIC1) had a reported range of methylation frequencies in cervical cancers of greater than 60% between studies. Stratification by analysis method did not resolve the heterogeneity. Three markers, DAPK1, CADM1, and RARB, showed elevated methylation in cervical cancers consistently across studies.


CONCLUSIONS
There is currently no methylation marker that can be readily translated for use in cervical cancer screening or triage settings. Large, well-conducted methylation profiling studies of cervical carcinogenesis could yield new candidates that are more specific for HPV-related carcinogenesis. New candidate markers need to be thoroughly validated in highly standardized assays.
Wentzensen
Nicolas
N
Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Room 5012, Rockville, MD 20854-7234, USA. wentzenn@mail.nih.gov
Sherman
Mark E
ME
Schiffman
Mark
M
Wang
Sophia S
SS
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000821:virology; D019175:DNA Methylation; D055088:Early Detection of Cancer; D005260:Female; D005819:Genetic Markers; D006801:Humans; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000235:genetics*
D005819:Genetic Markers