Abstract: Background: In 2000, cervical acid phosphatase (CAP) has been
recently described as a biomarker labeling abnormal squamous cells on Pap
smears (USPTO #6,143,512). The enzyme activity is presented as a red, granular
deposit on a modified Papanicolaou background. This unique property was
utilized for development of MarkPap® technology intended for cervical
cancer screening. Material/patients & methods: We conduct a multicenter, random
assignment, assessor blinded, 2-group (test and control), split-sample designed
clinical trial on 1,500 subject/specimens to assess safety and efficacy of the
new test, in comparison with the control, for cervical cancer screening in
standard Pap test environment. Safety is measured with frequency, severity and
relation of adverse events. Efficacy is measured with primary endpoints
(portion of positive/abnormal specimens detected, and the false negative rate).
At the end of the follow-up period (two years) when the study will be
completed, other efficacy endpoints such as accuracy (sensitivity/specificity)
and predictive values will be added to the method evaluation. Here we present
in interim analysis. Results: In April 2003, the recruitment was completed and the first
twelve hundred cases have been evaluated. There was no serious or related
adverse event in both groups. Minor, unrelated adverse events were rare and
insignificantly distributed in both groups. Primary endpoints: A: Portion of positive/abnormal specimens
detected: Pe (new test) = 0.166, Ps (Pap control): 0.082; Ps' (ACS reported
value for US in year 2000): 0.07. Pe ⩾ Ps + δ, for δ = 0.5Ps.
B. False negative rate: Pe = 0.05, Ps' = 0.10. Confidence intervals: 95% CI:
Test [0.148–0.193], Pap control [0.068–0.098]. OR = 2.26.
χ^2 = 40.69101 is greater than the critical value of
3.841 (P < 0.01). Conclusion: We concluded that CAP had added to visibility of Pap
test and has enabled cytoscreeners to significantly improve the detection of
positive/abnormal specimens and reduce false negative rate. We discuss this
unique property of CAP with emphasis on using it as a surrogate endpoint for
colposcopy and eventual removal of a cervical lesion that, if untreated, could
progress into cancer.
Keywords: biomarker, acid phosphatase, Pap test, cervical cancer, cancer prevention, in vitro diagnostics, medical device, surrogate endpoint
Journal: Disease Markers, vol. 19, no. 6, pp. 279-286, 2003,2004
