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CLIA 88 regulations specify that at least 10% of negative for intraepithelial lesion or malignancy (NILM) Paps be rescreened as a means of quality control (QC). With the incorporation of HPV DNA testing into American Society for Colposcopy and Cervical Pathology guidelines for women ≥30 years of age, a population of NILM patients with positive HPV results exists. Slides from this cohort were rescreened to judge the value of focused QC. Three hundred and eighty-six consecutive, NILM, HCII+, Paps (SurePath and ThinPrep, September 2009 to December 2009) from women aged ≥30 were retrieved from the CellNetix files. These slides were rescreened by cytotechnologists. Slides rescreened as atypical squamous cells (ASC) or higher by cytotechnologists were viewed by cytopathologists (CDS/RJT) who assigned a final interpretation. Of the 386 rescreened cases, 50 (12.9%) were placed in categories of ASC or higher, and 11 (2.9%) were interpreted as LSIL or above. By comparison, routine QC (including random, FocalPoint enriched, and historically high risk cases) was performed on a total of 20,580 Paps (21% of 99,501 annual cases). Concomitant routine QC revealed that 2.1% (427/20,580) were upgraded to ASC or higher and 0.3% (52/20,580) were upgraded to LSIL or higher. Focused rescreening of NILM cases with positive HPV DNA resulted in the detection of approximately ten times more SIL cases than did routine QC Pap slide review at CellNetix. Focused rescreening of this patient set may enhance QC in cytopathology laboratories performing liquid-based Paps. An inherent potential bias in study design is recognized, as results of DNA testing were by definition known at the time of rescreen.