A comparison of a prototype PCR assay and Hybrid Capture 2 for detection of carcinogenic human papillomavirus DNA in women with equivocal or mildly abnormal Papanicolaou smears

Mark Schiffman, Cosette M. Wheeler, Abhijit Dasgupta, Diane Solomon, Philip E. Castle

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

We evaluated Hybrid Capture 2 (HC2) and polymerase chain reaction (PCR) results for paired specimens collected at 19,187 visits from 5,026 of 5,060 women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS). We examined the test agreement between HC2 and PCR detection for any of 13 carcinogenic human papillomavirus types targeted by HC2 and compared clinical performance of the 2 tests for detecting concurrent and follow-up cervical intraepithelial neoplasia (CIN) 3 or cancer. The κ value for the 2 assays was 0.65 (95% confidence interval, 0.64-0.66), with 82.7% crude agreement. HC2 was more sensitive (93.6% vs 89.3%; P < .0005) but less specific (41.2% vs 48.5%; P < .0005) than PCR for detecting 2-year cumulative CIN 3 or cancer (n = 503). The presence of multiple types as detected by PCR and/or cytologic abnormality increased the likelihood of an HC2+ result. Increased sensitivity of HC2 compared with PCR was surprising, given the theoretical advantages of PCR-based methods for analytic sensitivity. Smaller amounts of material used in PCR could have limited its sensitivity, but our results demonstrate the importance of optimization and standardization of PCR-based assays for clinical applications.

Original languageEnglish (US)
Pages (from-to)722-732
Number of pages11
JournalAmerican Journal of Clinical Pathology
Volume124
Issue number5
DOIs
StatePublished - Nov 2005
Externally publishedYes

Fingerprint

Papanicolaou Test
Polymerase Chain Reaction
DNA
Cervical Intraepithelial Neoplasia
Triage
Neoplasms
Confidence Intervals

Keywords

  • Cervical intraepithelial neoplasia
  • HPV
  • Human papillomavirus
  • Hybrid Capture
  • PCR
  • Polymerase chain reaction
  • Triage

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

A comparison of a prototype PCR assay and Hybrid Capture 2 for detection of carcinogenic human papillomavirus DNA in women with equivocal or mildly abnormal Papanicolaou smears. / Schiffman, Mark; Wheeler, Cosette M.; Dasgupta, Abhijit; Solomon, Diane; Castle, Philip E.

In: American Journal of Clinical Pathology, Vol. 124, No. 5, 11.2005, p. 722-732.

Research output: Contribution to journalArticle

@article{afbdbaeb4e1045308e7636e5aa13489e,
title = "A comparison of a prototype PCR assay and Hybrid Capture 2 for detection of carcinogenic human papillomavirus DNA in women with equivocal or mildly abnormal Papanicolaou smears",
abstract = "We evaluated Hybrid Capture 2 (HC2) and polymerase chain reaction (PCR) results for paired specimens collected at 19,187 visits from 5,026 of 5,060 women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS). We examined the test agreement between HC2 and PCR detection for any of 13 carcinogenic human papillomavirus types targeted by HC2 and compared clinical performance of the 2 tests for detecting concurrent and follow-up cervical intraepithelial neoplasia (CIN) 3 or cancer. The κ value for the 2 assays was 0.65 (95{\%} confidence interval, 0.64-0.66), with 82.7{\%} crude agreement. HC2 was more sensitive (93.6{\%} vs 89.3{\%}; P < .0005) but less specific (41.2{\%} vs 48.5{\%}; P < .0005) than PCR for detecting 2-year cumulative CIN 3 or cancer (n = 503). The presence of multiple types as detected by PCR and/or cytologic abnormality increased the likelihood of an HC2+ result. Increased sensitivity of HC2 compared with PCR was surprising, given the theoretical advantages of PCR-based methods for analytic sensitivity. Smaller amounts of material used in PCR could have limited its sensitivity, but our results demonstrate the importance of optimization and standardization of PCR-based assays for clinical applications.",
keywords = "Cervical intraepithelial neoplasia, HPV, Human papillomavirus, Hybrid Capture, PCR, Polymerase chain reaction, Triage",
author = "Mark Schiffman and Wheeler, {Cosette M.} and Abhijit Dasgupta and Diane Solomon and Castle, {Philip E.}",
year = "2005",
month = "11",
doi = "10.1309/E067-X0L1-U3CY-37NW",
language = "English (US)",
volume = "124",
pages = "722--732",
journal = "American Journal of Clinical Pathology",
issn = "0002-9173",
publisher = "American Society of Clinical Pathologists",
number = "5",

}

TY - JOUR

T1 - A comparison of a prototype PCR assay and Hybrid Capture 2 for detection of carcinogenic human papillomavirus DNA in women with equivocal or mildly abnormal Papanicolaou smears

AU - Schiffman, Mark

AU - Wheeler, Cosette M.

AU - Dasgupta, Abhijit

AU - Solomon, Diane

AU - Castle, Philip E.

PY - 2005/11

Y1 - 2005/11

N2 - We evaluated Hybrid Capture 2 (HC2) and polymerase chain reaction (PCR) results for paired specimens collected at 19,187 visits from 5,026 of 5,060 women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS). We examined the test agreement between HC2 and PCR detection for any of 13 carcinogenic human papillomavirus types targeted by HC2 and compared clinical performance of the 2 tests for detecting concurrent and follow-up cervical intraepithelial neoplasia (CIN) 3 or cancer. The κ value for the 2 assays was 0.65 (95% confidence interval, 0.64-0.66), with 82.7% crude agreement. HC2 was more sensitive (93.6% vs 89.3%; P < .0005) but less specific (41.2% vs 48.5%; P < .0005) than PCR for detecting 2-year cumulative CIN 3 or cancer (n = 503). The presence of multiple types as detected by PCR and/or cytologic abnormality increased the likelihood of an HC2+ result. Increased sensitivity of HC2 compared with PCR was surprising, given the theoretical advantages of PCR-based methods for analytic sensitivity. Smaller amounts of material used in PCR could have limited its sensitivity, but our results demonstrate the importance of optimization and standardization of PCR-based assays for clinical applications.

AB - We evaluated Hybrid Capture 2 (HC2) and polymerase chain reaction (PCR) results for paired specimens collected at 19,187 visits from 5,026 of 5,060 women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS). We examined the test agreement between HC2 and PCR detection for any of 13 carcinogenic human papillomavirus types targeted by HC2 and compared clinical performance of the 2 tests for detecting concurrent and follow-up cervical intraepithelial neoplasia (CIN) 3 or cancer. The κ value for the 2 assays was 0.65 (95% confidence interval, 0.64-0.66), with 82.7% crude agreement. HC2 was more sensitive (93.6% vs 89.3%; P < .0005) but less specific (41.2% vs 48.5%; P < .0005) than PCR for detecting 2-year cumulative CIN 3 or cancer (n = 503). The presence of multiple types as detected by PCR and/or cytologic abnormality increased the likelihood of an HC2+ result. Increased sensitivity of HC2 compared with PCR was surprising, given the theoretical advantages of PCR-based methods for analytic sensitivity. Smaller amounts of material used in PCR could have limited its sensitivity, but our results demonstrate the importance of optimization and standardization of PCR-based assays for clinical applications.

KW - Cervical intraepithelial neoplasia

KW - HPV

KW - Human papillomavirus

KW - Hybrid Capture

KW - PCR

KW - Polymerase chain reaction

KW - Triage

UR - http://www.scopus.com/inward/record.url?scp=24144497484&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=24144497484&partnerID=8YFLogxK

U2 - 10.1309/E067-X0L1-U3CY-37NW

DO - 10.1309/E067-X0L1-U3CY-37NW

M3 - Article

C2 - 16203281

AN - SCOPUS:24144497484

VL - 124

SP - 722

EP - 732

JO - American Journal of Clinical Pathology

JF - American Journal of Clinical Pathology

SN - 0002-9173

IS - 5

ER -