Chromosomal gains measured in cytology samples from women with abnormal cervical cancer screening results

Patricia Luhn, Jane Houldsworth, Lynnette Cahill, Mark Schiffman, Philip E. Castle, Rosemary E. Zuna, S. Terence Dunn, Michael A. Gold, Joan Walker, Nicolas Wentzensen

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Objective Chromosomal gains at 3q26, 5p15 and 20q13 have been described in cervical precancer and cancer. We evaluated a novel fluorescence in situ hybridization (FISH) assay that detects gains at these three loci simultaneously as a possible biomarker for detecting cervical precancer. Methods Chromosomal copy numbers at 3q26, 5p15, 20q13 and the centromere of chromosome7 (cen7) in liquid-based cytology specimens from 168 women enrolled in the Biopsy Study were determined by FISH. The number of cells with ≥ 3 or ≥ 4 signals for a genomic locus was enumerated and diagnostic test performance measures were calculated using receiver operating characteristic (ROC) analyses. Sensitivity and specificity values were determined for the detection of CIN2 + and/or HSIL. Results The median number of cells with ≥ 3 signals increased with the severity of cervical lesion for each genomic locus (p-trend < 0.02 for each locus). ROC analysis for the number of cells with ≥ 3 signals resulted in area under the curve values of 0.70 (95% CI: 0.54-0.86), 0.67 (0.52-0.83), 0.67 (0.51-0.83) and 0.78 (0.64-0.92) for 3q26, 5p15, 20q13 and cen7, respectively, for the detection of CIN2 + and/or HSIL. Positivity for gains at multiple loci resulted in only slightly better test performance measures than those for the individual probes for four distinct combinations of probes. Conclusions Chromosomal gains at 3q26, 5p15, 20q13 and cen7 are associated with severity of cervical lesions. Further studies are required to quantify risk stratification of FISH assays for cervical cancer screening.

Original languageEnglish (US)
Pages (from-to)595-600
Number of pages6
JournalGynecologic Oncology
Volume130
Issue number3
DOIs
StatePublished - Sep 2013

Fingerprint

Fluorescence In Situ Hybridization
Early Detection of Cancer
Uterine Cervical Neoplasms
Cell Biology
Cell Count
ROC Curve
Centromere
Routine Diagnostic Tests
Area Under Curve
Biomarkers
Biopsy
Sensitivity and Specificity

Keywords

  • 3q26
  • Cervical cancer
  • FISH
  • Genomic gains
  • HPV

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Chromosomal gains measured in cytology samples from women with abnormal cervical cancer screening results. / Luhn, Patricia; Houldsworth, Jane; Cahill, Lynnette; Schiffman, Mark; Castle, Philip E.; Zuna, Rosemary E.; Dunn, S. Terence; Gold, Michael A.; Walker, Joan; Wentzensen, Nicolas.

In: Gynecologic Oncology, Vol. 130, No. 3, 09.2013, p. 595-600.

Research output: Contribution to journalArticle

Luhn, P, Houldsworth, J, Cahill, L, Schiffman, M, Castle, PE, Zuna, RE, Dunn, ST, Gold, MA, Walker, J & Wentzensen, N 2013, 'Chromosomal gains measured in cytology samples from women with abnormal cervical cancer screening results', Gynecologic Oncology, vol. 130, no. 3, pp. 595-600. https://doi.org/10.1016/j.ygyno.2013.06.005
Luhn, Patricia ; Houldsworth, Jane ; Cahill, Lynnette ; Schiffman, Mark ; Castle, Philip E. ; Zuna, Rosemary E. ; Dunn, S. Terence ; Gold, Michael A. ; Walker, Joan ; Wentzensen, Nicolas. / Chromosomal gains measured in cytology samples from women with abnormal cervical cancer screening results. In: Gynecologic Oncology. 2013 ; Vol. 130, No. 3. pp. 595-600.
@article{458600d81014467cb7995892d0c12574,
title = "Chromosomal gains measured in cytology samples from women with abnormal cervical cancer screening results",
abstract = "Objective Chromosomal gains at 3q26, 5p15 and 20q13 have been described in cervical precancer and cancer. We evaluated a novel fluorescence in situ hybridization (FISH) assay that detects gains at these three loci simultaneously as a possible biomarker for detecting cervical precancer. Methods Chromosomal copy numbers at 3q26, 5p15, 20q13 and the centromere of chromosome7 (cen7) in liquid-based cytology specimens from 168 women enrolled in the Biopsy Study were determined by FISH. The number of cells with ≥ 3 or ≥ 4 signals for a genomic locus was enumerated and diagnostic test performance measures were calculated using receiver operating characteristic (ROC) analyses. Sensitivity and specificity values were determined for the detection of CIN2 + and/or HSIL. Results The median number of cells with ≥ 3 signals increased with the severity of cervical lesion for each genomic locus (p-trend < 0.02 for each locus). ROC analysis for the number of cells with ≥ 3 signals resulted in area under the curve values of 0.70 (95{\%} CI: 0.54-0.86), 0.67 (0.52-0.83), 0.67 (0.51-0.83) and 0.78 (0.64-0.92) for 3q26, 5p15, 20q13 and cen7, respectively, for the detection of CIN2 + and/or HSIL. Positivity for gains at multiple loci resulted in only slightly better test performance measures than those for the individual probes for four distinct combinations of probes. Conclusions Chromosomal gains at 3q26, 5p15, 20q13 and cen7 are associated with severity of cervical lesions. Further studies are required to quantify risk stratification of FISH assays for cervical cancer screening.",
keywords = "3q26, Cervical cancer, FISH, Genomic gains, HPV",
author = "Patricia Luhn and Jane Houldsworth and Lynnette Cahill and Mark Schiffman and Castle, {Philip E.} and Zuna, {Rosemary E.} and Dunn, {S. Terence} and Gold, {Michael A.} and Joan Walker and Nicolas Wentzensen",
year = "2013",
month = "9",
doi = "10.1016/j.ygyno.2013.06.005",
language = "English (US)",
volume = "130",
pages = "595--600",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Chromosomal gains measured in cytology samples from women with abnormal cervical cancer screening results

AU - Luhn, Patricia

AU - Houldsworth, Jane

AU - Cahill, Lynnette

AU - Schiffman, Mark

AU - Castle, Philip E.

AU - Zuna, Rosemary E.

AU - Dunn, S. Terence

AU - Gold, Michael A.

AU - Walker, Joan

AU - Wentzensen, Nicolas

PY - 2013/9

Y1 - 2013/9

N2 - Objective Chromosomal gains at 3q26, 5p15 and 20q13 have been described in cervical precancer and cancer. We evaluated a novel fluorescence in situ hybridization (FISH) assay that detects gains at these three loci simultaneously as a possible biomarker for detecting cervical precancer. Methods Chromosomal copy numbers at 3q26, 5p15, 20q13 and the centromere of chromosome7 (cen7) in liquid-based cytology specimens from 168 women enrolled in the Biopsy Study were determined by FISH. The number of cells with ≥ 3 or ≥ 4 signals for a genomic locus was enumerated and diagnostic test performance measures were calculated using receiver operating characteristic (ROC) analyses. Sensitivity and specificity values were determined for the detection of CIN2 + and/or HSIL. Results The median number of cells with ≥ 3 signals increased with the severity of cervical lesion for each genomic locus (p-trend < 0.02 for each locus). ROC analysis for the number of cells with ≥ 3 signals resulted in area under the curve values of 0.70 (95% CI: 0.54-0.86), 0.67 (0.52-0.83), 0.67 (0.51-0.83) and 0.78 (0.64-0.92) for 3q26, 5p15, 20q13 and cen7, respectively, for the detection of CIN2 + and/or HSIL. Positivity for gains at multiple loci resulted in only slightly better test performance measures than those for the individual probes for four distinct combinations of probes. Conclusions Chromosomal gains at 3q26, 5p15, 20q13 and cen7 are associated with severity of cervical lesions. Further studies are required to quantify risk stratification of FISH assays for cervical cancer screening.

AB - Objective Chromosomal gains at 3q26, 5p15 and 20q13 have been described in cervical precancer and cancer. We evaluated a novel fluorescence in situ hybridization (FISH) assay that detects gains at these three loci simultaneously as a possible biomarker for detecting cervical precancer. Methods Chromosomal copy numbers at 3q26, 5p15, 20q13 and the centromere of chromosome7 (cen7) in liquid-based cytology specimens from 168 women enrolled in the Biopsy Study were determined by FISH. The number of cells with ≥ 3 or ≥ 4 signals for a genomic locus was enumerated and diagnostic test performance measures were calculated using receiver operating characteristic (ROC) analyses. Sensitivity and specificity values were determined for the detection of CIN2 + and/or HSIL. Results The median number of cells with ≥ 3 signals increased with the severity of cervical lesion for each genomic locus (p-trend < 0.02 for each locus). ROC analysis for the number of cells with ≥ 3 signals resulted in area under the curve values of 0.70 (95% CI: 0.54-0.86), 0.67 (0.52-0.83), 0.67 (0.51-0.83) and 0.78 (0.64-0.92) for 3q26, 5p15, 20q13 and cen7, respectively, for the detection of CIN2 + and/or HSIL. Positivity for gains at multiple loci resulted in only slightly better test performance measures than those for the individual probes for four distinct combinations of probes. Conclusions Chromosomal gains at 3q26, 5p15, 20q13 and cen7 are associated with severity of cervical lesions. Further studies are required to quantify risk stratification of FISH assays for cervical cancer screening.

KW - 3q26

KW - Cervical cancer

KW - FISH

KW - Genomic gains

KW - HPV

UR - http://www.scopus.com/inward/record.url?scp=84882451588&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84882451588&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2013.06.005

DO - 10.1016/j.ygyno.2013.06.005

M3 - Article

C2 - 23769811

AN - SCOPUS:84882451588

VL - 130

SP - 595

EP - 600

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 3

ER -