1.      Are the submitted studies acceptable for establishing high-risk HPV DNA testing performance when used with the normal Pap smear for detecting CIN 3/cervical cancer?  Considering that;

a.  the non-U.S. populations studied showed marked differences in cervical cancer prevalence and screening practices when compared to the US population,

b.  three sites used HPV DNA collection devices with unestablished performance and one of these an unvalidated matrix, and

c.  there were potential flaws in identification of positive disease in one US site in which positive pathologies were defined using any positive result up to 3 years after HPV testing.

2.      Is Digene s criteria of decreasing false negative rate more than 25% and not decreasing specificity (true negative rate) by more than 10% acceptable to measure the benefit of adding high-risk HPV testing to the normal Pap smear?

3.      Given the disparate populations and conditions used to derive data and the non-poolable nature of the data, how might the device be labeled and what recommendations made for its use?