Focused rescreening of NILM Pap slides from women ≥30 years of age with positive high risk HPV DNA: An enhanced quality control measure

Abstract

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.

Knowledge of the HPV status biases cytotechnologists' interpretation of Pap tests originally diagnosed as negative for intraepithelial lesion or malignancy

“…Interestingly, in both cases, a subset of cytotechnologists identified the rare HSIL cells in both phases of the study when the HPV status was provided and withheld. This suggests that a second review may have resulted in increased sensitivity in these cases, and this would support other literature that has recommended performing quality‐control reviews on all HPV‐positive NILM cases before sign‐out . However, even with knowledge of an HPV‐positive status, occasional HSIL cases may be missed; there were 3 instances in this study in which a cytotechnologist interpreted an HSIL case with a known HPV‐positive status as NILM (see Tables and ).…”

“…This suggests that a second review may have resulted in increased sensitivity in these cases, and this would support other literature that has recommended performing quality-control reviews on all HPV-positive NILM cases before sign-out. 11,12 However, even with knowledge of an HPV-positive status, occasional HSIL cases may be missed; there were 3 instances in this study in which a cytotechnologist interpreted an HSIL case with a known HPV-positive status as NILM (see Tables 2 and 3). At the time of this study, our institution did not use the HPV status for sending cases to quality assurance.…”

Negative Pap tests in women with high‐grade cervical lesions on follow‐up biopsies: Contributing factors and role of human papillomavirus genotyping

“…Our results along with those of previous studies raise questions regarding the effectiveness of mandatory routine 10% rescreening. In an effort to reduce the false‐negative rate of the Pep test, several investigators have proposed focused rescreening . In a study performed by Sturgis et al, 386 NILM Pap tests with positive hrHPV results were rescreened and 50 (13%) were upgraded to ASC‐US or higher, which resulted in detecting ten times more SIL lesions than routine 10% Pap slide review.…”

Novel cytomorphologic characteristics suggesting human papillomavirus infection in patients diagnosed as negative for intraepithelial lesion or malignancy and a comparison of diagnostic performance of three human papillomavirus tests

“…There have been a few attempts to identify novel cytomorphologic features that can predict HPV infection in samples that were initially diagnosed with NILM or ASCUS based on the diagnostic criteria presented by the Bethesda system . Bollmann et al tested a PCR‐based HPV assay that could detect 16 HPV genotypes and suggested a predictive model combined with 4 cytomorphologic alterations (namely, subtle nuclear changes, disordered keratinization, abortive koilocytes and measles cells, and degenerative changes), which are mainly focused on high‐power fields observed using the ThinPrep‐based preparation.…”

“…[19][20][21] There have been a few attempts to identify novel cytomorphologic features that can predict HPV infection in samples that were initially diagnosed with NILM or ASCUS based on the diagnostic criteria presented by the Bethesda system. 6,[22][23][24] Bollmann et al 6 4 Accordingly, false-negative results for these 2 HPV types may lead to critical outcomes in patients.…”