BACKGROUND: Accurate HPV detection and genotyping tests are useful for management of women with HPV infection and for monitoring HPV vaccine efficacy. OBJECTIVES: To evaluate the performance of the INNO-LiPA HPV Genotyping Extra assay (SPF10-LiPA) for the detection of carcinogenic HPV types in women referred for opportunistic cervical cancer screening by comparison with the Hybrid Capture 2 (HC2) assay. STUDY DESIGN: Cross-sectional analysis from baseline data of HC2 and SPF10-LiPA testing in cervical specimens collected from 1580 consecutive women and correlation with cervical cytology and histology data, when available. RESULTS: The two assays showed a good agreement for detection of carcinogenic HPV types and reported the same prevalence of carcinogenic HPV infections in different age groups. Stratification of study subjects by cervical cytology interpretation and histology results demonstrated that the two tests gave very similar results in the different cytology interpretation groups and in CIN2 and CIN3 samples, while in <CIN2 samples the SPF10-LiPA assay provided a significantly lower number of carcinogenic HPV-positive results than the HC2 test. A comparative analysis of the two assay for individual HPV types showed that HC2 identified as positive between 73% and 100% of specimens with carcinogenic HPV types detected by SPF10-LiPA and, in particular, approximately 90% and 80% of HPV16- and HPV18-positive samples, respectively. CONCLUSIONS: A good agreement was observed between HC2 and SPF10-LiPA for carcinogenic HPV type detection, that supports further evaluation of the clinical performance of the new version of SPF10-LiPA in cervical cancer screening protocols.