Validation of an HPV DNA cervical screening test that provides expanded HPV typing

Background/Purpose
As cervical cancer screening shifts from cytology to human papillomavirus (HPV) testing, a major question is the clinical value of identifying individual HPV types. We aimed to validate Onclarity™ (Becton Dickinson Diagnostics, Sparks MD), a nine-channel HPV test recently approved by FDA, by assessing: 1) the association of Onclarity type/channels with precancer/cancer; 2) HPV type/channel agreement between Onclarity and cobas™ (Roche Molecular Systems, Pleasanton CA), another FDA-approved test; and 3) Onclarity typing for all types/channels compared to typing results from a research assay (Linear Array™, LA, Roche).Methods.We compared Onclarity to histopathology, cobas, and LA. We tested a stratified random sample (n=9,701) of discarded routine clinical specimens that had tested positive by Hybrid Capture 2 (HC2, Qiagen, Germantown MD). A subset had already been tested by cobas and LA (n=1,965). Cervical histopathology was ascertained from electronic health records.Results.Hierarchical Onclarity channels showed a significant linear association with histologic severity. Onclarity and cobas had excellent agreement on partial typing of HPV16, HPV18, and the other twelve types as a pool (sample-weighted kappa: 0.83); cobas was slightly more sensitive for HPV18 and slightly less sensitive for the pooled high-risk types. Typing by Onclarity showed excellent agreement with types and group of types identified by LA (kappas from 0.80 for HPV39/68/35 to 0.97 for HPV16).DiscussionOnclarity typing results corresponded well to histopathology and to an already-validated HPV DNA test, and could provide additional clinical typing if such discrimination is determined to be clinically desirable.

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