PURPOSE: To evaluate carcinogenic human papillomavirus (HPV) mRNA for E6 and E7 mRNA detection on clinical specimens to identify women with cervical precancer and cancer. EXPERIMENTAL DESIGN: We evaluated a prototype assay that collectively detects oncogenes E6/E7 mRNA for 14 carcinogenic HPV genotypes on a sample of liquid cytology specimens (n=531), masked to clinical data and to the presence of HPV genotypes detected by PGMY09/11 L1 consensus primer PCR assay. RESULTS: We found an increasing likelihood of testing positive for carcinogenic HPV E6/E7 mRNA with increasing severity of cytology (P(Trend) < 0.0001) and histology (P(Trend) < 0.0001), with 94% of cervical intraepithelial neoplasia grade 3 (CIN3) histology cases (46 of 49) and all five cancer cases testing positive for carcinogenic HPV E6/E7 mRNA. Overall, fewer specimens tested positive for carcinogenic HPV E6/E7 mRNA than for carcinogenic HPV DNA (P<0.0001, McNemar's chi(2) test), especially in women with <CIN1 (P<0.0001). We also found that using a higher positive cutpoint for detection of carcinogenic HPV E6/E7 mRNA improved the association of positive test results with cervical precancer and cancer by reducing the number of test positives in women without precancer without reducing clinical sensitivity for cervical precancer and cancer compared with detection of carcinogenic HPV E6/E7 mRNA using a lower positive cutpoint by the same assay and with detection of carcinogenic HPV DNA. CONCLUSIONS: We found that carcinogenic HPV E6/E7 mRNA is a potentially useful biomarker for detection of cervical precancer and cancer and warrants further evaluation.
PURPOSE: To evaluate carcinogenic human papillomavirus (HPV) mRNA for E6 and E7 mRNA detection on clinical specimens to identify women with cervical precancer and cancer. EXPERIMENTAL DESIGN: We evaluated a prototype assay that collectively detects oncogenes E6/E7 mRNA for 14 carcinogenic HPV genotypes on a sample of liquid cytology specimens (n=531), masked to clinical data and to the presence of HPV genotypes detected by PGMY09/11 L1 consensus primer PCR assay. RESULTS: We found an increasing likelihood of testing positive for carcinogenic HPV E6/E7 mRNA with increasing severity of cytology (P(Trend) < 0.0001) and histology (P(Trend) < 0.0001), with 94% of cervical intraepithelial neoplasia grade 3 (CIN3) histology cases (46 of 49) and all five cancer cases testing positive for carcinogenic HPV E6/E7 mRNA. Overall, fewer specimens tested positive for carcinogenic HPV E6/E7 mRNA than for carcinogenic HPV DNA (P<0.0001, McNemar's chi(2) test), especially in women with <CIN1 (P<0.0001). We also found that using a higher positive cutpoint for detection of carcinogenic HPV E6/E7 mRNA improved the association of positive test results with cervical precancer and cancer by reducing the number of test positives in women without precancer without reducing clinical sensitivity for cervical precancer and cancer compared with detection of carcinogenic HPV E6/E7 mRNA using a lower positive cutpoint by the same assay and with detection of carcinogenic HPV DNA. CONCLUSIONS: We found that carcinogenic HPV E6/E7 mRNA is a potentially useful biomarker for detection of cervical precancer and cancer and warrants further evaluation.
Authors: G Gross; N Becker; N H Brockmeyer; S Esser; U Freitag; M Gebhardt; L Gissmann; P Hillemanns; H Grundhewer; H Ikenberg; H Jessen; A Kaufmann; S Klug; J P Klußmann; A Nast; D Pathirana; K U Petry; H Pfister; U Röllinghof; P Schneede; A Schneider; E Selka; S Singer; S Smola; B Sporbeck; M von Knebel Doeberitz; P Wutzler Journal: Geburtshilfe Frauenheilkd Date: 2014-03 Impact factor: 2.915
Authors: Philip E Castle; Stephen Follansbee; Sylvia Borgonovo; Diane Tokugawa; Lauren M Schwartz; Thomas S Lorey; Brandon LaMere; Julia C Gage; Barbara Fetterman; Teresa M Darragh; Ana Cecilia Rodriguez; Nicolas Wentzensen Journal: Cancer Epidemiol Biomarkers Prev Date: 2012-11-15 Impact factor: 4.254