TABLE 5.

Summary of molecular diagnostic tests FDA-approved in the United States (FDA-approved) and clinically validated in Europe for HPV detection and genotyping^a

Assay type	FDA approval, yr	Meets Meijer criteria (125)	Test	Manufacturer	Chemistry	Instrumentation	Target	Internal control	Test medium	Analytical sensitivity
DNA-based assays	1999 (replaced HC1, which was approved in 1995); in 2003 expanded use to include cotesting indication	Standard comparator test	Digene Hybrid Capture 2 high-risk HPV DNA test	Qiagen, Redwood City, CA	DNA-probe hybridization with chemiluminescent signal amplification in a microtiter plate	Manual or semiautomated Rapid Capture system	Multigene probes; 13 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) as a pooled result	None	PreservCyt or Qiagen specimen transport Medium	1,000–5,000 copies/reaction
	No	Standard comparator test	GP5+/6+-EIA	NAb	Target amplification with detection of digoxigenin-labeled PCR products with solution hybridization to specific HPV group- and type-specific probes using the PCR ELISA Dig Detection kit (Boehringer Mannheim, Germany) biotin-labeled probes	Standard thermocycler and colorimetric microplate reader	L1; 14 high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68)	None	Cytobrush in phosphate-buffered saline	50 copies/reaction of HPV16
	2009	Partially validated	Cervista HPV HR and Genfind DNA extraction kit	Hologic Gen-Probe, Inc., San Diego, CA, USA	Invader signal amplification	Manual or semiautomated on the Cervista high-throughput automation system	L1, E6, E7 genes; 14 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) as a pooled result	Intrinsic control, human histone 2 gene	PreservCyt	1,250–2,500 copies/reaction for types 16, 18, 31, 45, 52, and 56; 2,500–5,000 copies/reaction for types 33, 39, 51, 58, 59, 66, and 68; 5,000–7,500 copies/reaction for type 35
	2011	Yes	cobas HPV test	Roche Molecular Systems, Inc., Pleasanton, CA, USA	Multiplex real-time PCR and nucleic acid hybridization	Automated on the cobas 4800 system	L1 gene; 14 high-risk HPV types; identifies HPV16 and HPV18 and concurrently detects high-risk types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 as a pooled result	Intrinsic control, β-globin	Cobas PCR collection medium or PreservCyt	150 copies/ml for type 45; 300 copies/ml for types 31, 33, 39, 51, and 59; 600 copies/ml for types 16, 18, 35, and 58; 1,200 copies/ml for types 55, 66, and 65; 2,400 copies/ml for type 52
	No	Yes	PapilloCheck HPV	Greiner Bio-One GmbH, Frickenhausen, Germany	Low-density microarray-PCR amplification of the E1 gene by a group of new E1-specific primers, followed by hybridization to a DNA chip with immobilized HPV oligoprobes	Different manual or automated extraction methods; thermocycler; hybridized signals are visualized on the CheckScanner with CheckReport software	E1 ORF; separate identification of 18 high-risk/probable-risk and 6 low-risk HPV types (6, 11, 16, 18, 31, 33, 35, 39, 40, 42, 43, 44/55, 45, 51, 52, 53, 56, 58, 59, 66, 68, 70, 73, and 82)	Intrinsic control, ADAT1 (tRNA-specific adenosine desaminase 1)	PreservCyt (Hologic, Bedford, MA USA), Surepath, (BD, Franklin Lakes, NJ, USA), STM (Qiagen, Gaithersburg, MD, USA), biopsy tissues	30–750 copies/reaction
	No	Yes	Abbott real-time high-risk HPV test	Abbott Molecular GmbH & Co. KG, Wiesbaden, Germany	Multiplex real-time PCR with 14 type-specific probes	Automation with m2000 System (extraction, m2000sp, m24; amplification and detection: m2000rt)	Separately identifies HPV16 and HPV18 while concurrently detecting the 12 remaining high-risk types as a pooled result (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68)	Intrinsic control, β-globin	PreservCyt solution (Hologic, Inc.). SurePath preservative fluid (TriPath Imaging), Abbott Cervi-Collect specimen collection kit	Types 16, 18, 35, 39, 45, 51, 59, 66, and 68 can be detected at 500 copies/assay, types 31, 33, 52, and 56 at 2,000 copies/assay, and type 58 at 5,000 copies/assay
	No	Yes	BD Onclarity	Becton, Dickinson and Company, Sparks, MD, USA	Real-time PCR and fluorescently labeled detector probes	BD Viper LT system	E6/E7 DNA; six discrete high-pressure liquid chromatography-risk HPV genotypes (16, 18, 31, 45, 51, and 52) with the remaining eight high-risk genotypes reported in three small groups (33 and 58, 35, 39, and 68, and 56, 59, and 66)	Intrinsic control, β-globin	BD Onclarity HPV cervical brush collection kit, BD SurePath preservative fluid, and PreservCyt solution	Type 16 can be detected at 137 copies/ml (Onclarity cervical brush diluent), 1,584 copies/ml (SurePath preservative fluid), and 1.835 copies/ml (PreservCyt); type 18 can be detected at 51copies/ml (Onclarity cervical brush diluent), 915 copies/ml (SurePath preservative fluid), and 1,786 copies/ml (PreservCyt); limits of detection for other HPV types can be found in the package insert
	No	Yes	HPV-Risk	Self-Screen BV, Amsterdam, The Netherlands	Multiplex real-time PCR with detection by hydrolysis probes	Different automated DNA extraction procedures and real-time PCR platforms (e.g., Life Technologies and Bio-Rad)	E7 DNA; 15 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51,52, 56, 58, 59, 66, 67, and 68); individual results for HPV16 and HPV18 and a pooled result for non-HPV16/HPV18 high-risk HPV types	Intrinsic control, β-globin	Physician-collected cervical scrapings in SurePath preservative fluid; self-collected vaginal brush (VibaBrush (Rovers Medical Devices, Oss, The Netherlands), and cervicovaginal lavage specimens (Delphi Screener; Delphi Biosciences, Scherpenzeel, The Netherlands); formalin-fixed, paraffin-embedded tissue samples	460 copies/reaction for types 16,18, and 56; 4,600 copies/reaction for types 31, 33, 35, 39, 45, 51, 59, and 68; 46,000 copies/reaction for types 52, 58, 66, and 67
E6/E7 mRNA-based assay	2012	Yes	Aptima HPV assay	Hologic Gen-Probe, Inc., San Diego, CA	Target capture; transcription-mediated amplification; hybridization protection assay	Fully automated on the Tigris DTS system or Panther system	E6/E7 viral mRNA; 14 high-risk HPV types (16,18,31,33,35,39,45,51,52,56,58,59,66, and 68) as a pooled result	Extrinsic control; noninfectious RNA transcript	Aptima cervical specimen collection or Preserv Cyt	24–488 copies/reaction
HPV genotyping assays	2011	NA	cobas HPV test	Roche Molecular Systems, Inc., Pleasanton, CA	See entry above	See entry above	See entry above	See entry above	See entry above	See entry above
	2009	NA	Cervista HPV16/18	Hologic Gen-Probe, Inc., San Diego, CA	Invader signal amplification	Manual or semiautomated on the Cervista high-throughput automation system	Detects and differentiates HPV16 and HPV18	Intrinsic control, human histone 2 gene	PreservCyt or Qiagen specimen transport Medium	625–1,250 copies/reaction
	2012 (Tigris instrument); 2013 (Panther instrument)	NA	Aptima HPV 16 18/45 genotype assay	Hologic Gen-Probe, Inc., San Diego, CA	Target capture; transcription-mediated amplification; hybridization protection assay	Fully automated Tigris DTS System or Panther System	E6/E7 viral mRNA of HPV16, -18, and -45; differentiates HPV16 from HPV18 and HPV45 but does not differentiate between HPV18 and HPV45	Extrinsic control, noninfectious RNA transcript	Aptima cervical specimen collection or Preserv Cyt	57.3 copies/reaction for HPV16; 84.8 copies/reaction for HPV18; 60 copies/reaction for HPV45

^aAdapted from reference 105 with permission from Elsevier.

^bNA, not applicable.