Elsevier

Gynecologic Oncology

Volume 123, Issue 2, November 2011, Pages 278-283
Gynecologic Oncology

Comparison of different commercial methods for HPV detection in follow-up cytology after ASCUS/LSIL, prediction of CIN2–3 in follow up biopsies and spontaneous regression of CIN2–3

https://doi.org/10.1016/j.ygyno.2011.07.024Get rights and content

Abstract

Objective

Different Human Papilloma Virus (HPV) tests are currently used. An integrated comparison of the Amplicor, Cobas4800, PreTect HPV-Proofer and APTIMA HPV tests has not been done.

Methods

We compared the high-risk HPV detection power of these HPV tests in 528 consecutive population-based follow-up Liquid-Based Cytology samples (LBC) after ASCUS/LSIL index cytology. Their sensitivity and specificity to detect HPV in LBC, their predictive values of histopathologic CIN2–3 in follow-up punch biopsies and CIN2–3 regression in the subsequent cones was assessed. The HPV subtypes detected by the Linear Array genotyping-test (LA), PreTect HPV-Proofer and Cobas4800 were also compared. The follow-up histopathology was consensus expert-reviewed and Ki67/p16-supported. The predictive values of the HPV results in LBC by the different tests for presence of CIN2–3 in follow-up biopsies, and regression in subsequent cones, was assessed.

Results

Amplicor, Cobas4800 and APTIMA show good agreement for HPV-positivity/negativity. PreTect HPV-Proofer has many discrepancies versus any of the other methods. The sensitivities for Amplicor, Cobas4800 and APTIMA to detect CIN2–3 were very high (96–100%), but rather low for PreTect HPV-Proofer (53%). Specificity in case of CIN1 or less in follow-up biopsies of Amplicor and Cobas4800 is lower than APTIMA and highest for PreTect HPV-Proofer. HPV subtyping by LA agreed in 90% with Cobas4800 but 70% with PreTect HPV-Proofer.

Conclusions

The Amplicor, Cobas4800 and APTIMA give comparable results but PreTect HPV-Proofer differs from the other tests, with low sensitivity but higher specificity. None of the methods predicted regression of CIN2–3.

Highlights

► Amplicor and Cobas4800 detect HPV-DNA, PreTect HPV-Proofer and APTIMA HPV-mRNA. ► Amplicor, Cobas4800 and APTIMA are comparable, PreTect HPV-Proofer less sensitive. ► Spontaneous regression of CIN2–3 was not predicted by either method.

Section snippets

Background

Cytology screening is useful to detect cervical intraepithelial neoplasia (CIN) and cancer [1]. Interpretive variability and low sensitivity are problematic for atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) [2], [3], [4], [5], [6]. Human Papilloma Virus (HPV) testing is widely performed [7], [8], [9], [10], as persistent carcinogenic HPV infection is necessary for cervical neoplasia [11], [12]. Much attention is paid to use

Ethics

The study has been approved by the Regional Medical Ethics Committee of Health West, Norway (2010/2550).

Patient material

Originally, 550 cases with a referral = index cytology diagnosis of ASCUS (n = 371), LSIL (n = 157), high-grade intraepithelial lesion (HSIL, n = 10), atypical cells suspect for high-grade lesion (ASCH, n = 5), atypical glandular cells of uncertain significance (AGUS, n = 2) and cases with no referral cytology (n = 5) were diagnosed in the Norwegian population-based Cervical Cancer Screening Program (

Results

Eighty percent of the women were > 30 years, the median age was 37, mean 40, Range: (25–69) years.

Discussion

The detection of hrHPV and the sensitivity to predict CIN2–3 by the Amplicor, Cobas4800 and APTIMA show almost perfect agreement, while Proofer differs significantly from the other tests, with considerably fewer HPV positives and lower sensitivity. The partial genotyping results of the PreTect HPV Proofer showed many discrepancies with the LA Genotyping test, while the Cobas4800 had good agreement with the LA.

A number of the samples which were HPV positive by the DNA tests were negative by the

Conflict of interest statement

We hereby declare that none of the authors or the study sponsors has conflicts of interest regarding the study design, collection of data, analyzing and interpretation of data, writing the report or in the decision to submit the report for publication. None of the authors has any financial interest in publishing these data, nor any financial or advisory relationship with a company producing the equipment or chemicals described in this article.

References (49)

  • R. Herrero et al.

    New approaches to cervical cancer screening in Latin America and the Caribbean

    Vaccine

    (2008)
  • R. Murillo et al.

    Cervical cancer screening programs in Latin America and the Caribbean

    Vaccine

    (2008)
  • J. Ferlay et al.

    Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008

    Int J Cancer

    (2008)
  • D. Solomon et al.

    Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial

    J Natl Cancer Inst

    (2001)
  • J. Cuzick et al.

    Overview of the European and North American studies on HPV testing in primary cervical cancer screening

    Int J Cancer

    (2006)
  • A. Anttila et al.

    Rate of cervical cancer, severe intraepithelial neoplasia, and adenocarcinoma in situ in primary HPV DNA screening with cytology triage: randomised study within organised screening programme

    BMJ

    (2010)
  • P. Naucler et al.

    Efficacy of HPV DNA testing with cytology triage and/or repeat HPV DNA testing in primary cervical cancer screening

    J Natl Cancer Inst

    (2009)
  • M.H. Stoler et al.

    Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study

    JAMA

    (2001)
  • D.C. Rijkaart et al.

    Comparison of HPV and cytology triage algorithms for women with borderline or mild dyskaryosis in population-based cervical screening (VUSA-screen study)

    Int J Cancer

    (2009)
  • A.C. Rodriguez et al.

    The natural history of human papillomavirus infection and cervical intraepithelial neoplasia among young women in the Guanacaste cohort shortly after initiation of sexual life

    Sex Transm Dis

    (2007)
  • J. Dillner et al.

    Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study

    BMJ

    (2008)
  • P.E. Castle et al.

    An analysis of high-risk human papillomavirus DNA-negative cervical precancers in the ASCUS-LSIL Triage Study (ALTS)

    Obstet Gynecol

    (2008)
  • J.M. Walboomers et al.

    Human papillomavirus is a necessary cause of invasive cervical cancer worldwide

    J Pathol

    (1999)
  • M. Arbyn et al.

    How to evaluate emerging technologies in cervical cancer screening?

    Int J Cancer

    (2009)
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