HiFi DNA Tech Urges FDA to Institute DNA Sequencing As Standard Validation for Human Papillomavirus (HPV) Genotyping

The U.S. Food and Drug Administration (FDA) should require DNA sequencing as the final method of validation in reviewing all in vitro HPV testing device applications for premarket clearance to prevent potential false positive results and wrong genotyping, said Sin Hang Lee, MD, on behalf of HiFi DNA Tech. He has asked the FDA to formally publish his letter http://www.fda.gov/OHRMS/DOCKETS/DOCKETS/07p0210/07p0210.htm concerning this matter, now listed on the FDA Dockets Management website under docket no. 2007P-0210, LET1.

“It is well known that a DNA probe designed for one HPV may react with other HPV types due to cross-hybridization despite the presence of base pair mismatches,” said Dr. Lee, a Connecticut pathologist.

He said that accurate genotyping is now recognized to be important in HPV DNA testing for follow-up of persistent infections which may lead to precancerous cell changes and cancer of the uterine cervix. Detection of a signature DNA sequence, confirmed by the national GenBank database, is the “gold standard” method for microbial and viral identification or genotyping in all DNA-based microbiological tests.

He said, “the false positive results generated by the currently available FDA-approved nucleic acid amplification tests for gonococcus and Chlamydia have caused a great deal of confusion among the pathologists who rely on these tests for the diagnosis of these two sexually transmitted infectious agents.” As a result, the Centers for Disease Control and Prevention has issued a guidance directing the clinical laboratories to routinely perform an additional test on every positive specimen to reduce the potential of adverse medical, social, and psychological impacts of false positive results on patients [MMWR 2002;51(RR15):1-27]. A requirement for genotyping by DNA sequencing will eliminate similar confusion with future in vitro diagnostic devices approved for HPV genotyping by the FDA, to ensure the highest degree of safety and effectiveness of the medical devices.

HiFi DNA Tech has developed the nation’s first PCR/DNA sequencing-based clinical HPV genotyping methodology which is published in www.infectagentscancer.com/content/2/1/11, and now used as a routine HPV test at Milford Medical Laboratory (see www.hpvtyping.com). HiFi DNA Tech has petitioned the FDA to down-classify all HPV DNA tests from class III cancer test devices to class II virology tests to allow small innovative companies to use the less burdensome 510k applications to introduce their new technologies for more accurate HPV testing on a competitive basis http://www.fda.gov/OHRMS/DOCKETS/DOCKETS/07p0210/07p0210.htm