Detection of human papillomavirus 16, 18, and 45 in women with ASC-US cytology and the risk of cervical precancer: Results from the CLEAR HPV study

Philip E. Castle, Jack Cuzick, Mark H. Stoler, Thomas C. Wright, Jennifer L. Reid, Janel Dockter, Cristina Giachetti, Damon Getman

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objectives: The Aptima human papillomavirus (HPV) 16 18/45 Genotype (GT) assay (AHPV-GT) is a qualitative E6/E7 oncogene messenger RNA test that detects HPV 16 and a pool of HPV 18 and 45. The CLEAR (Clinical Evaluation of APTIMA mRNA) study was the pivotal, prospective, multicenter US clinical study to validate the Aptima HPV (AHPV) assays. Methods: In this analysis, we evaluated the clinical performance of AHPV and AHPV-GT assays for detection of cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and grade 3 (CIN3) or adenocarcinoma in situ in 912 women with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou result. The AHPV-GT assay was performed on high-risk HPV (hrHPV) positives as determined by the AHPV assay. Results: Overall, the percent positive for hrHPV was 38.8% (354/912), of which 34.2% (121/354) were GT positive. Among hrHPV-positive women, the risks of CIN2+ were 37.0% for HPV 16 positives, 15.9% for HPV 18/45 positives, 14.3% for other hrHPV positives, and 2.2% for AHPV negatives. The risks of CIN3+ were 20.5% for HPV 16 positives, 9.1% for HPV 18/45 positives, 4.3% for other hrHPV positives, and 0.7% for HPV negatives. Conclusions: We demonstrated that AHPV-GT is a reliable and effective test for cervical cancer risk stratification in women with an ASC-US cytology diagnosis.

Original languageEnglish (US)
Pages (from-to)160-167
Number of pages8
JournalAmerican Journal of Clinical Pathology
Volume143
Issue number2
DOIs
StatePublished - Feb 1 2015

Fingerprint

Human papillomavirus 18
Human papillomavirus 16
Cell Biology
Messenger RNA
Genotype
Atypical Squamous Cells of the Cervix
Cervical Intraepithelial Neoplasia
Oncogenes
Uterine Cervical Neoplasms

Keywords

  • Aptima
  • ASC-US
  • Cervical cancer
  • Cervical intraepithelial neoplasia
  • E6/E7 mRNA
  • Genotyping
  • HPV

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Detection of human papillomavirus 16, 18, and 45 in women with ASC-US cytology and the risk of cervical precancer : Results from the CLEAR HPV study. / Castle, Philip E.; Cuzick, Jack; Stoler, Mark H.; Wright, Thomas C.; Reid, Jennifer L.; Dockter, Janel; Giachetti, Cristina; Getman, Damon.

In: American Journal of Clinical Pathology, Vol. 143, No. 2, 01.02.2015, p. 160-167.

Research output: Contribution to journalArticle

Castle, Philip E. ; Cuzick, Jack ; Stoler, Mark H. ; Wright, Thomas C. ; Reid, Jennifer L. ; Dockter, Janel ; Giachetti, Cristina ; Getman, Damon. / Detection of human papillomavirus 16, 18, and 45 in women with ASC-US cytology and the risk of cervical precancer : Results from the CLEAR HPV study. In: American Journal of Clinical Pathology. 2015 ; Vol. 143, No. 2. pp. 160-167.
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abstract = "Objectives: The Aptima human papillomavirus (HPV) 16 18/45 Genotype (GT) assay (AHPV-GT) is a qualitative E6/E7 oncogene messenger RNA test that detects HPV 16 and a pool of HPV 18 and 45. The CLEAR (Clinical Evaluation of APTIMA mRNA) study was the pivotal, prospective, multicenter US clinical study to validate the Aptima HPV (AHPV) assays. Methods: In this analysis, we evaluated the clinical performance of AHPV and AHPV-GT assays for detection of cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and grade 3 (CIN3) or adenocarcinoma in situ in 912 women with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou result. The AHPV-GT assay was performed on high-risk HPV (hrHPV) positives as determined by the AHPV assay. Results: Overall, the percent positive for hrHPV was 38.8{\%} (354/912), of which 34.2{\%} (121/354) were GT positive. Among hrHPV-positive women, the risks of CIN2+ were 37.0{\%} for HPV 16 positives, 15.9{\%} for HPV 18/45 positives, 14.3{\%} for other hrHPV positives, and 2.2{\%} for AHPV negatives. The risks of CIN3+ were 20.5{\%} for HPV 16 positives, 9.1{\%} for HPV 18/45 positives, 4.3{\%} for other hrHPV positives, and 0.7{\%} for HPV negatives. Conclusions: We demonstrated that AHPV-GT is a reliable and effective test for cervical cancer risk stratification in women with an ASC-US cytology diagnosis.",
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T1 - Detection of human papillomavirus 16, 18, and 45 in women with ASC-US cytology and the risk of cervical precancer

T2 - Results from the CLEAR HPV study

AU - Castle, Philip E.

AU - Cuzick, Jack

AU - Stoler, Mark H.

AU - Wright, Thomas C.

AU - Reid, Jennifer L.

AU - Dockter, Janel

AU - Giachetti, Cristina

AU - Getman, Damon

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KW - Cervical cancer

KW - Cervical intraepithelial neoplasia

KW - E6/E7 mRNA

KW - Genotyping

KW - HPV

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