Limitations of widely used high-risk human papillomavirus laboratory-developed testing in cervical cancer screening

Abstract

Objective: To increase awareness of the limitations of high-risk human papillomavirus (hrHPV) laboratory-developed testing (LDT) widely used in US cervical cancer screening. Methods and results: A young woman in her 30s was diagnosed and treated for stage 1B1 cervical squamous cell carcinoma in which HPV 16 DNA was detected using polymerase chain reaction testing. Both 1 month before and 42 months before cervical cancer diagnosis, the patient had highly abnormal cytology fndings; however, residual SurePath™ (Becton, Dickson and Company, Franklin Lakes, NJ) vial fuid yielded negative Hybrid Capture 2 (HC2; Qiagen N V, Hilden, Germany) hrHPV LDT results from each of the two specimens. This prompted questions to be asked concerning the performance characteristics of hrHPV LDT. A review of the available data indicates that (1) purifcation of DNA from SurePath specimens requires complex sample preparation due to formaldehyde crosslinking of proteins and nucleic acids, (2) HC2-SurePath hrHPV testing had not been Food and Drug Administration-approved after multiple premarket approval submissions, (3) detectible hrHPV DNA in the SurePath vial decreases over time, and (4) US laboratories performing HC2-SurePath hrHPV LDT testing are not using a standardized manufacturer-endorsed procedure. Conclusion: Recently updated cervical screening guidelines in the US recommend against the use of hrHPV LDT in cervical screening, including widely used HC2 testing from the SurePath vial. The manufacturer recently issued a technical bulletin specifcally warning that use of SurePath samples with the HC2 hrHPV test may provide false negative results and potentially compromise patient safety. Co-collection using a Food and Drug Administration-approved hrHPV test medium is recommended for HPV testing of patients undergoing cervical screening using SurePath samples. © 2012 Naryshkin and Austin, publisher and licensee Dove Medical Press Ltd.