The Sensitivity and Specificity of p16INK4a Cytology vs HPV Testing for Detecting High-Grade Cervical Disease in the Triage of ASC-US and LSIL Pap Cytology Results

Abstract

We analyzed the performance of p16(INK4a) immunocytochemistry on a series of 810 retrospectively collected atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) cases with available biopsy follow-up data, including 94 cases of cervical intraepithelial neoplasia (CIN) 2 and 128 cases of CIN 3. Human papillomavirus (HPV) testing was performed from the same residual liquid-based cytologic specimen, and results for both tests were correlated with histologic follow-up data. Sensitivity values for high-grade CIN (HGCIN) confirmed on biopsy within 6 months were 92.6% (ASC-US) and 92.2% (LSIL) for cytotechnologists' reviews of p16 cytology and 90.1% (ASC-US) and 95.7% (LSIL) for HPV testing. Sensitivity rates of initial pathologists' reviews were slightly lower, 76.4% to 80.1%, with levels comparable to cytotechnologists' results after adjudication. The specificity of p16 cytology for HGCIN detection was significantly higher than for HPV testing for cytotechnologists and pathologists: 63.2% to 71.1% (p16 cytology) vs 37.8% for HPV in ASC-US (P < .001) and 37.3% to 53.3% (p16 cytology) vs 18.5% for HPV in LSIL (P < .001). This evaluation of the diagnostic performance of p16 cytology confirms the potential of this stain for the efficient triage of ASC-US and LSIL cytologic results.

p16/ki‐67 dual‐stain cytology in the triage of ASCUS and LSIL Papanicolaou cytology

“…7,9,10,11 At the same time, specificity of p16 cytology-based testing was found to be substantially higher than the specificity of HPV testing in all studies. 7,8,9,10 This effect was even higher in women aged younger than 30 years because of the high prevalence rates of HPV infections in the younger age groups. 7,12 As both sensitivity and specificity are relevant metrics of the performance of tests used for the triage of equivocal or mildly abnormal Pap cytology results, it is important to implement triage algorithms that provide the highest level of specificity without sacrificing sensitivity.…”

“…7,8,9,10 This effect was even higher in women aged younger than 30 years because of the high prevalence rates of HPV infections in the younger age groups. 7,12 As both sensitivity and specificity are relevant metrics of the performance of tests used for the triage of equivocal or mildly abnormal Pap cytology results, it is important to implement triage algorithms that provide the highest level of specificity without sacrificing sensitivity. 13 The overexpression of p16 in cervical dysplasia has been shown to be associated with the transforming activity of the E7 oncoprotein of high-risk HPV types and can be regarded as a surrogate marker of the E7-mediated inactivation of the tumor-suppressor function of the retinoblastoma protein (pRb).…”

“…[1][2][3][4][5][6][7][8] In the majority of the studies, p16 cytology was found to provide sensitivity rates for the detection of underlying high-grade cervical intraepithelial neoplasia (CIN of grade 2 or higher, CIN2þ), which were similar or slightly lower compared with the sensitivity of testing for the presence of human papillomavirus (HPV) infections. 7,9,10,11 At the same time, specificity of p16 cytology-based testing was found to be substantially higher than the specificity of HPV testing in all studies. 7,8,9,10 This effect was even higher in women aged younger than 30 years because of the high prevalence rates of HPV infections in the younger age groups.…”

p16/Ki‐67 dual‐stain cytology in the triage of ASCUS and LSIL Papanicolaou cytology

“…The Ridder laboratory (and members of mtm) recently published an article by Denton et al 4 in the American Journal of Clinical Pathology that evaluated single p16 staining alone in 810 retrospectively identified cases of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) Pap smears. Their study confirmed the high sensitivity for high-grade dysplasia (approximately 92% for both dual staining and HPV testing) and an improved specificity when compared with HPV testing (62%-72% vs 37.8%).…”

“…Their study confirmed the high sensitivity for high-grade dysplasia (approximately 92% for both dual staining and HPV testing) and an improved specificity when compared with HPV testing (62%-72% vs 37.8%). 4 Schmidt et al 1 have expanded these studies to evaluate dual staining in a similar population: 776 women from the same ASCUS and LSIL cohort used for the p16 alone study. The sensitivity for detecting high-grade dysplasia was 92%-94%, and the specificity for CIN2þ jumped to 80% and 68% for ASCUS and LSIL, respectively.…”