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.
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.
Authors: Pontus Naucler; Walter Ryd; Sven Törnberg; Anders Strand; Göran Wadell; Kristina Elfgren; Thomas Rådberg; Björn Strander; Bo Johansson; Ola Forslund; Bengt-Göran Hansson; Eva Rylander; Joakim Dillner Journal: N Engl J Med Date: 2007-10-18 Impact factor: 91.245
Authors: Marie-Hélène Mayrand; Eliane Duarte-Franco; Isabel Rodrigues; Stephen D Walter; James Hanley; Alex Ferenczy; Sam Ratnam; François Coutlée; Eduardo L Franco Journal: N Engl J Med Date: 2007-10-18 Impact factor: 91.245
Authors: Qinghua Feng; Stephen E Hawes; Joshua E Stern; Amadou Dem; Papa Salif Sow; Birama Dembele; Papa Toure; Pavel Sova; Peter W Laird; Nancy B Kiviat Journal: Cancer Epidemiol Biomarkers Prev Date: 2007-06 Impact factor: 4.254
Authors: F E Henken; S M Wilting; R M Overmeer; J G I van Rietschoten; A O H Nygren; A Errami; J P Schouten; C J L M Meijer; P J F Snijders; R D M Steenbergen Journal: Br J Cancer Date: 2007-10-30 Impact factor: 7.640
Authors: Divya A Patel; Laura S Rozek; Justin A Colacino; Adrienne Van Zomeren-Dohm; Mack T Ruffin; Elizabeth R Unger; Dana C Dolinoy; David C Swan; Juanita Onyekwuluje; Cecilia R DeGraffinreid; Electra D Paskett Journal: J Virol Methods Date: 2012-06-01 Impact factor: 2.014
Authors: Megan A Clarke; Nicolas Wentzensen; Lisa Mirabello; Arpita Ghosh; Sholom Wacholder; Ariana Harari; Attila Lorincz; Mark Schiffman; Robert D Burk Journal: Cancer Epidemiol Biomarkers Prev Date: 2012-10-03 Impact factor: 4.254
Authors: Nicolas Wentzensen; Chang Sun; Arpita Ghosh; Walter Kinney; Lisa Mirabello; Sholom Wacholder; Ruth Shaber; Brandon LaMere; Megan Clarke; Attila T Lorincz; Philip E Castle; Mark Schiffman; Robert D Burk Journal: J Natl Cancer Inst Date: 2012-10-23 Impact factor: 13.506