Evaluation of p16INK4a as a diagnostic tool in the triage of pap smears demonstrating atypical squamous cells of undetermined significance

Lisa Duncan, Sanjivini Jacob, Elizabeth Hubbard

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

BACKGROUND. p16INK4a (p16) has emerged as a biomarker for the detection of high-risk human papillomavirus (HR-HPV) in Papanicolaou (Pap) smears. Many studies have confirmed a strong correlation between p16 immunohistochemical positivity and high-grade squamous intraepithelial lesions (HSIL) of the cervix. Because p16 is predictive of HR-HPV and HSIL, it seems plausible that p16 could be used as a diagnostic tool to triage atypical squamous cells of undetermined significance (ASCUS) Pap smears. In this way, Pap smears with no p16 staining could be recategorized as negative for intraepithelial lesion or malignancy (NILM) before final case disposition, thus preventing unnecessary and costly follow-up. METHODS. p16 immunostains were performed on 178 ThinPrep (Cytyc, Marlborough, Mass) Pap smears signed out as ASCUS among 5 cytopathologists. p16 stains were independently scored between 0 (no staining) and 4 (staining in cells with nuclear aberration) by either 2 or 3 pathologists. The p16 score was compared with both Hybrid Capture 2 (hc 2) (Digene, Gaithersburg, Md) and follow-up (Pap smear and tissue) results. RESULTS. The sensitivity and specificity of p16 immunohistochemistry compared with both hc2 and follow-up were not statistically significant, with both data subsets having P-values greater than .05. CONCLUSIONS. Statistical significance was not demonstrated in any of the data subsets, indicating that the p16 score alone cannot be used to recategorize Pap smears from ASCUS to NILM as a means to prevent unnecessary and expensive follow-up. Although not meeting criteria for statistical significance, the sensitivity and positive predictive value of p16 scores versus tissue follow-up only were more statistically favorable, suggesting that p16 has better correlation with tissue follow-up than results of hc2. In addition, p16 staining was identified consistently in atrophic Pap smears, including 23 of 25 additional NILM atrophic smears stained, indicating that p16 cannot be used as a marker to triage atypical atrophic smears.

Original languageEnglish (US)
Pages (from-to)34-48
Number of pages15
JournalCancer
Volume114
Issue number1
DOIs
StatePublished - Feb 25 2008

Fingerprint

Papanicolaou Test
Triage
Staining and Labeling
Neoplasms
Atypical Squamous Cells of the Cervix
Coloring Agents
Biomarkers
Immunohistochemistry
Sensitivity and Specificity

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Evaluation of p16INK4a as a diagnostic tool in the triage of pap smears demonstrating atypical squamous cells of undetermined significance. / Duncan, Lisa; Jacob, Sanjivini; Hubbard, Elizabeth.

In: Cancer, Vol. 114, No. 1, 25.02.2008, p. 34-48.

Research output: Contribution to journalArticle

@article{0239d1d2c1b644cf86cacb063c0bb0b0,
title = "Evaluation of p16INK4a as a diagnostic tool in the triage of pap smears demonstrating atypical squamous cells of undetermined significance",
abstract = "BACKGROUND. p16INK4a (p16) has emerged as a biomarker for the detection of high-risk human papillomavirus (HR-HPV) in Papanicolaou (Pap) smears. Many studies have confirmed a strong correlation between p16 immunohistochemical positivity and high-grade squamous intraepithelial lesions (HSIL) of the cervix. Because p16 is predictive of HR-HPV and HSIL, it seems plausible that p16 could be used as a diagnostic tool to triage atypical squamous cells of undetermined significance (ASCUS) Pap smears. In this way, Pap smears with no p16 staining could be recategorized as negative for intraepithelial lesion or malignancy (NILM) before final case disposition, thus preventing unnecessary and costly follow-up. METHODS. p16 immunostains were performed on 178 ThinPrep (Cytyc, Marlborough, Mass) Pap smears signed out as ASCUS among 5 cytopathologists. p16 stains were independently scored between 0 (no staining) and 4 (staining in cells with nuclear aberration) by either 2 or 3 pathologists. The p16 score was compared with both Hybrid Capture 2 (hc 2) (Digene, Gaithersburg, Md) and follow-up (Pap smear and tissue) results. RESULTS. The sensitivity and specificity of p16 immunohistochemistry compared with both hc2 and follow-up were not statistically significant, with both data subsets having P-values greater than .05. CONCLUSIONS. Statistical significance was not demonstrated in any of the data subsets, indicating that the p16 score alone cannot be used to recategorize Pap smears from ASCUS to NILM as a means to prevent unnecessary and expensive follow-up. Although not meeting criteria for statistical significance, the sensitivity and positive predictive value of p16 scores versus tissue follow-up only were more statistically favorable, suggesting that p16 has better correlation with tissue follow-up than results of hc2. In addition, p16 staining was identified consistently in atrophic Pap smears, including 23 of 25 additional NILM atrophic smears stained, indicating that p16 cannot be used as a marker to triage atypical atrophic smears.",
author = "Lisa Duncan and Sanjivini Jacob and Elizabeth Hubbard",
year = "2008",
month = "2",
day = "25",
doi = "10.1002/cncr.23255",
language = "English (US)",
volume = "114",
pages = "34--48",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "1",

}

TY - JOUR

T1 - Evaluation of p16INK4a as a diagnostic tool in the triage of pap smears demonstrating atypical squamous cells of undetermined significance

AU - Duncan, Lisa

AU - Jacob, Sanjivini

AU - Hubbard, Elizabeth

PY - 2008/2/25

Y1 - 2008/2/25

N2 - BACKGROUND. p16INK4a (p16) has emerged as a biomarker for the detection of high-risk human papillomavirus (HR-HPV) in Papanicolaou (Pap) smears. Many studies have confirmed a strong correlation between p16 immunohistochemical positivity and high-grade squamous intraepithelial lesions (HSIL) of the cervix. Because p16 is predictive of HR-HPV and HSIL, it seems plausible that p16 could be used as a diagnostic tool to triage atypical squamous cells of undetermined significance (ASCUS) Pap smears. In this way, Pap smears with no p16 staining could be recategorized as negative for intraepithelial lesion or malignancy (NILM) before final case disposition, thus preventing unnecessary and costly follow-up. METHODS. p16 immunostains were performed on 178 ThinPrep (Cytyc, Marlborough, Mass) Pap smears signed out as ASCUS among 5 cytopathologists. p16 stains were independently scored between 0 (no staining) and 4 (staining in cells with nuclear aberration) by either 2 or 3 pathologists. The p16 score was compared with both Hybrid Capture 2 (hc 2) (Digene, Gaithersburg, Md) and follow-up (Pap smear and tissue) results. RESULTS. The sensitivity and specificity of p16 immunohistochemistry compared with both hc2 and follow-up were not statistically significant, with both data subsets having P-values greater than .05. CONCLUSIONS. Statistical significance was not demonstrated in any of the data subsets, indicating that the p16 score alone cannot be used to recategorize Pap smears from ASCUS to NILM as a means to prevent unnecessary and expensive follow-up. Although not meeting criteria for statistical significance, the sensitivity and positive predictive value of p16 scores versus tissue follow-up only were more statistically favorable, suggesting that p16 has better correlation with tissue follow-up than results of hc2. In addition, p16 staining was identified consistently in atrophic Pap smears, including 23 of 25 additional NILM atrophic smears stained, indicating that p16 cannot be used as a marker to triage atypical atrophic smears.

AB - BACKGROUND. p16INK4a (p16) has emerged as a biomarker for the detection of high-risk human papillomavirus (HR-HPV) in Papanicolaou (Pap) smears. Many studies have confirmed a strong correlation between p16 immunohistochemical positivity and high-grade squamous intraepithelial lesions (HSIL) of the cervix. Because p16 is predictive of HR-HPV and HSIL, it seems plausible that p16 could be used as a diagnostic tool to triage atypical squamous cells of undetermined significance (ASCUS) Pap smears. In this way, Pap smears with no p16 staining could be recategorized as negative for intraepithelial lesion or malignancy (NILM) before final case disposition, thus preventing unnecessary and costly follow-up. METHODS. p16 immunostains were performed on 178 ThinPrep (Cytyc, Marlborough, Mass) Pap smears signed out as ASCUS among 5 cytopathologists. p16 stains were independently scored between 0 (no staining) and 4 (staining in cells with nuclear aberration) by either 2 or 3 pathologists. The p16 score was compared with both Hybrid Capture 2 (hc 2) (Digene, Gaithersburg, Md) and follow-up (Pap smear and tissue) results. RESULTS. The sensitivity and specificity of p16 immunohistochemistry compared with both hc2 and follow-up were not statistically significant, with both data subsets having P-values greater than .05. CONCLUSIONS. Statistical significance was not demonstrated in any of the data subsets, indicating that the p16 score alone cannot be used to recategorize Pap smears from ASCUS to NILM as a means to prevent unnecessary and expensive follow-up. Although not meeting criteria for statistical significance, the sensitivity and positive predictive value of p16 scores versus tissue follow-up only were more statistically favorable, suggesting that p16 has better correlation with tissue follow-up than results of hc2. In addition, p16 staining was identified consistently in atrophic Pap smears, including 23 of 25 additional NILM atrophic smears stained, indicating that p16 cannot be used as a marker to triage atypical atrophic smears.

UR - http://www.scopus.com/inward/record.url?scp=39749195507&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39749195507&partnerID=8YFLogxK

U2 - 10.1002/cncr.23255

DO - 10.1002/cncr.23255

M3 - Article

VL - 114

SP - 34

EP - 48

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 1

ER -