In cervical cancer screening, HPV test detects DNA of 12 high risk (hr) HPV types (16/18/31/33/35/39/45/51/52/56/58/59) and, depending on test, HPV with probable (68) or possible (66) risk. Among clinically validated tests, Hybrid Capture®2 (HC2®, QIAGEN®) detects 13 HPV types (hr and 68) by in solution hybridization, while Cobas®4800 (ROCHE®) detects 14 types (also 66) in Real-Time PCR. In the Florentine area, from May 2016, HC2® test has been replaced by Cobas® test.
The objective of the study is to evaluate the impact of the transition from HC2® to Cobas® on the HPV primary screening of the Florentine Area, comparing: HPV positivity, cytology triage abnormalities and histological results to immediate colposcopy.
We considered samples from women participating to HPV primary screening program of the Florentine area (34-64 years), collected in ThinPrep®(HOLOGIC®) from June 2015 to March 2017. Until May 2016, samples were analysed by HC2® on automatic instrumentation (QIASymphony®/RCS®, QIAGEN®). From June 2016, samples were analysed by Cobas®.
The samples collected in ThinPrep® during the considered period were 37775, of which 17137 (45.4%) tested on HC2® and 20638 (54.6%) on Cobas®. The average age of women is similar (46.5 vs 46.1).
HPV positivity was 9.8% (1677/17137) for HC2® samples and 7.4% (1529/20368) for Cobas® samples (p<0.0001).
480 HC2® positive women (28.6%) had abnormal cytology triage and 17 (1%) inadequate; 418 Cobas® positive women (27.3%) had abnormal cytology triage and 21 (1.37%) inadequate.
Adhesion to colposcopy was 90.3% (449/497) in HC2® group and 77.4% (340/439, of which 14 are waiting for histology) in Cobas® group until now, as several women are waiting to perform colposcopy.
For the 449 women of HC2® group, compared to the 326 women of Cobas® group, at the immediate colposcopy we found: 108 vs 118 CIN2+(PPV: 24.1% vs 36.2%, p<0.0002), 145 (32.3%) vs 88 (27%) CIN1, 195 (43.4%) vs 118 (36.2%) normal colposcopies/histologies (p<0.05) and 1 (0.2%) vs 2 (0.6%) inadequate histologies.
The use of HC2® as primary screening test, compared to Cobas®, has registered: greater HPV positivity, lower CIN2+ PPV at the immediate colposcopy and higher frequency of normal colposcopies/histologies (all statistically significant differences). These results could be explained by the well known HC2® cross-hybridization with non-hrHPV types, unlike Cobas®, which has a higher analytical specificity. Non-hrHPV types detected by HC2® but not by Cobas® likely increase HPV positivity and abnormal cytologies,but decrease PPV at the immediate colposcopy, since they are mostly associated with no lesions or low grade lesions (CIN1), as resulted by our data.