Recently approved HPV test may prompt unecessary surgical biopsies on women: HiFi DNA Seeks Transparency of “Results” from the FDA and scientific data on newly approved human papillomavirus (HPV) tests

March 30, 2009 - TRUMBULL, Conn. - Trumbull-based HiFi DNA Tech issued a call to the US Food and Drug Administration (FDA) that its recent approval of an HPV test may improperly influence American physicians to order more unnecessary colposcopic biopsy cancer tests. HiFi DNA wants the FDA to publish the positive predictive value (PPV) and scientific basis for approving the Cervista HPV HR test to determine the need for referral to colposcopy and the Cervista 16/18 genotyping test.

“In this era of transparency, the scientific data should be made public to ensure that decisions made by the FDA do not lead to unnecessary surgical procedures, and also lead to increased national healthcare costs,” said Sin Hang Lee, MD, of HiFi DNA.

In the letter to The Honorable Daniel R. Levinson, the Inspector General, Dr. Lee wrote: “HPV test kit manufacturers tend to perform their clinical trials in a population with extremely high cervical cancer prevalence rate and market the developed test kits with FDA approval to influence doctors’ referrals of patients to colposcopic biopsy cancer work-up in the suburban/rural American female population with a very low prevalence rate of cervical cancer. The result leads to excessive unnecesary biopsy procedures on American women at great cost to society because the PPV of such test drops dramatically when it is transplanted to the US from a high disease prevalence population to a low prevalence population.” 

Dr. Lee reminded the acting director of the Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD), that “Pursuant to 21CFR 814.9(e), the FDA will make available to the public a detailed summary of information submitted to FDA respecting the safety and effectiveness of the device that is the subject of the PMA (pre-marketing approval) and that is the basis for the order.” Dr. Lee also sent a copy of the letter he sent to OIVD acting director Don St. Pierre, to the Inspector General of the Dept. of Health and Human Services in an attempt to force the FDA to comply with the law, 

 “More than 95% of referrals to colposcopic biopsy for diagnostic workup in the U.S. are performed needlessly on healthy women or women who have mostly reversible cervical cellular change. Screening with combined cytologic and HPV testing leads to the highest number of excessive colposcopic referrals,” quoted Dr. Lee from a publication by the Department of Health Policy and Management, Harvard School of Public Health in his previous letter sent to the FDA Commissioner. Dr. Lee requested immediate FDA action to reverse this trend by withdrawing the approval order of March 31, 2003. The letter has been totally ignored by the FDA.

Dr. Lee, a cancer pathologist and the president of HiFi DNA Tech, and his colleagues at Milford Hospital have analyzed the HPV test results on 2633 women who live in a suburban population consisting of 93.6% non-Hispanic whites and who are under the care of board-certified gynecologists in private practice, using the most sensitive polymerase chain reaction (PCR) and the most specific DNA sequencing for HPV testing. The study shows that in a population with a cervical cancer prevalence rate of 6.8 or less per 100,000 women, such as that in suburban and rural Connecticut, a one-occasion HPV test result is useless “to screen patients with atypical squamous cells of undetermined significance (ASC-US) cervical cytology results to determine the need for referral to colposcopy.” It will only lead to unnecessary biopsies. The report, the first of its type, is published in the International Journal of Gynecology and Obstetrics.   

Dr. Lee also questions the scientific basis for approval of the HPV-16 and HPV-18 genotyping based on hybridization probes because in a previous ruling by Dr. Steven Gutman, the former director of OIVD stated “Probe design is a critical process for HPV DNA testing because of the large number of closely related HPV genotypes. Complex probe cocktails may crossreact and /or compete with one another.” It is well known that there are many variants of HPV-16. Some of them are very closely related to other HPV genotypes in DNA sequences. 

HiFi DNA Tech filed a lawsuit at the District Court against the FDA on January 11, 2008 for its denial to a petition for down-classifying the HPV test from a Class III cancer test to a Class II virology test to reduce the burden on small innovative manufacturers to introduce their new HPV test devices into clinical practice to improve patient care and to reduce the health care cost. The case is waiting for the judge to set a court date for the open hearing. 

Contact: Ken Warren at 203-891-9001