Tsiodras et al. BMC Cancer 2010, 10:53 http://www.biomedcentral.com/1471-2407/10/53 negative likelihood ratios for cytological and molecular HPV testing and histological diagnosis of CIN2+ or CIN3+ are provided in Table 4. Positive likelihood ratios (PLR) of 9.4, 3.8 and 3.4 were noted for ≥ LSIL, positive HC2 or positive HPV testing respectively and CIN2+ histology (Table 4). For CIN2+ histological lesion the best positive likelihood ratios (PLR) were observed with Thin prep testing exhibiting ≥ LSIL (PLR = 9.4), or ≥ HSIL (PLR = infinite), and for high risk type of virus detection either by HC2 (PLR = 5.5), or PCR (PLR = 11.4). Similar figures were observed for CIN3 (Table 4). Negative likelihood ratios of 0.13, 0.21, and 0 were noted for cytology ≥ LSIL, positive HC2 or positive HPV testing respectively and CIN2+ histology (Table 4). Discussion This study depicts the successful use of both HC2 and PCR in liquid based ThinPrep samples. Use of the same samples for both DNA tests was done to avoid bias. The HC2 kit assesses the presence of 18 low risk (i.e. Page 5 of 8 6,11,42,43 and 44) and high risk (i.e. 16, 18, 31, 33, 35, 39, 45, 51, 51, 56, 58, 59 and 68) HPV types [15,16]. On the other hand, using the L1 consensus primers GP5 +/GP6+ by PCR, we were able to screen for 22 HPV types. The concordance rate between the PCR and HC2 test results was high in our series. Both molecular tests exhibited high reproducibility measured by Cohen’s kappa value of 0.691, similar to previous reported results [17,18]. Although not all studies use the same PCR pro- tocol, the concordance between HC2 and PCR testing across various studies is generally high, usually exceed- ing 80% [17-20]. It appears that after a certain DNA concentration cutoff point, HC2 sensitivity increases, carrying a certain risk for false positive results[17]. Newer generation kits decrease rates of false positive testing[21]. Certain cutoff levels for relative light units compared to the ones generated by the positive control samples to increase the specificity of the assay without compromising sensitivity may be used[18]. One explana- tion for some of the discordant results between HC2 PLR ≥ CIN 2 NLR ≥ CIN2 11.4 PLR ≥ CIN 3 5.8 9.4 ∞ 3.8 5.5 3.4 5.6 9.3 3.7 5.3 3.2 13.4 166.6 0 0.13 0.19 0.21 0.31 0.21 0 0 0 0 NLR ≥ CIN 3 0.07 0.067 0.33 0.31 ThinPrep Pap ≥ ASCUS ThinPrep Pap ≥ LSIL ThinPrep Pap ≥ HSIL HC2 (+) ALL HC2 (+) HR only HPV PCR (+) HPV PCR (+) 16/18/31/33 ThinPrep Pap ≥ ASCUS ThinPrep Pap ≥ LSIL ThinPrep Pap ≥ HSIL HC2 (+) ALL HC2 (+) HR only HPV PCR (+) HPV PCR (+) 16/18/31/33 No. positive 241/1270 18.9% 260/1270 20.4% 140/1270 11% 21/1270 1.7% 185/1270 14.6% 397/1270 31.3% 109/1270 8.6% No. positive 241/1270 18.9% 260/1270 20.4% 140/1270 11% 21/1270 1.7% 185/1270 14.6% 397/1270 31.3% 109/1270 8.6% Sens ≥ CIN2 26/26 100% 23/26 88.5% 21/26 80.8% 19/26 73.1% 19/26 73.1% 26/26 100% 21/26 80.8% 15/15 100% 14/15 93.3% 14/15 93.3% 11/15 73.3% 11/15 73.3% 15/15 100% 15/15 100% Sens ≥ CIN3 Spec ≥ CIN2 1029/1244 82.7% 1127/1244 90.6% 1244/1244 100% 1003/1244 80.6% 1078/1244 86.7% 873/1244 70.2% 1156/1244 92.9% Spec ≥ CIN 3 1029/1255 82% 1129/1255 90% 1248/1255 99.44 1006/1255 80.2% 1081/1255 86.1% 873/1255 69.6% 1161/1255 92.5% PPV ≥ CIN 2 26/241 10.8% 23/140 16.4% 21/21 100% 19/260 7.3% 19/185 10.3% 26/397 6.5% 21/109 19.3% PPV ≥ CIN 3 15/241 6.2% 14/140 10% 14/21 66.7 11/260 4.2% 11/185 5.9% 15/397 3.8% 15/109 13.8% 1244/1249 99.6% NPV ≥ CIN 2 1029/1029 100% 1127/1130 99.7% 1003/1010 99.3% 1078/1085 99.4% 873/873 100% 1156/1161 99.6% NPV ≥ CIN 3 1029/1029 100% 1129/1130 99.9% 1248/1249 99.9% 1006/1010 99.6% 1081/1085 99.6% 873/873 100% 1161/1161 100% Table 4 Sensitivity, specificity, positive and negative predictive values and likelihood ratios of the various methods HSIL: High-grade squamous intraepithelial lesion, Sens: sensitivity, Spec: specificity, PPV: Positive predictive value, NPV: Negative predictive value, PLR: positive likelihood ratio, NLR: negative likelihood ratio