Top

Published in:

01-06-2011 | Original paper

Diagnostic and prognostic validity of the human papillomavirus E6/E7 mRNA test in cervical cytological samples of HC2-positive patients

Authors: Maria Benevolo, Irene Terrenato, Marcella Mottolese, Ferdinando Marandino, Mariantonia Carosi, Francesca Rollo, Livia Ronchetti, Paola Muti, Luciano Mariani, Stefano Sindico, Giuseppe Vocaturo, Amina Vocaturo

Published in: Cancer Causes & Control | Issue 6/2011

Abstract

The study aimed to assess the clinical utility in identifying CIN2 or worse (CIN2+), of the Pretect HPV-Proofer test for E6/E7 mRNA detection in Hybrid Capture 2 (HC2)-positive patients, who underwent colposcopy. In particular, the study analyzed the mRNA test performance as the third test in a subgroup of HC2+ patients with less severe than high-grade squamous intraepithelial lesions (HSIL−). We analyzed 464 cervico-vaginal samples by liquid-based cytology (LBC) and PreTect HPV-Proofer. Moreover 231 patients also had a biopsy at baseline and 75, with HSIL−, were followed up within 2 years by LBC, colposcopy, and histology when indicated. The highest sensitivity for CIN2+ belonged to the mRNA compared to LBC, at the HSIL+ threshold (72% vs. 58%), whereas the LBC showed the highest specificity and positive predictive value (PPV) (99 and 93% vs. 73 and 39%, respectively). Focusing on the 408 HSIL− patients, the mRNA positivity was significantly more associated with CIN2+ than CIN2− lesions (p < 0.0001). Moreover, among the 75 HSIL− followed up patients, the mRNA displayed high longitudinal Specificity (89%), even if the sensitivity and the PPV were low (50 and 20%, respectively). The present data suggest that the mRNA test may have a diagnostic and a potentially prognostic role in HC2+/HSIL− patients.

Walboomers JM, Jacobs MV, Manos MM et al (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:12–19PubMedCrossRef

Solomon D, Schiffman M, Tarone R (2001) Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst 93:293–299PubMedCrossRef

Saslow D, Runowicz CD, Solomon D et al (2002) American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin 52:342–362PubMedCrossRef

Cuzick J, Szarewski A, Cubie H et al (2003) Management of women who test positive for high-risk types of human papillomavirus: the HART study. Lancet 362:1871–1876PubMedCrossRef

Ronco G, Giorgi-Rossi P, Carozzi F et al (2006) New Technologies for Cervical Cancer screening Working Group. Human papillomavirus testing and liquid-based cytology in primary screening of women younger than 35 years: results at recruitment for a randomised controlled trial. Lancet Oncol 7:547–555PubMedCrossRef

Sellors JW, Karwalajtys TL, Kaczorowski J et al (2003) Incidence, clearance and predictors of human papillomavirus infection in women. CMAJ 168:421–425PubMed

Nobbenhuis MA, Helmerhorst TJ, van den Brule AJ et al (2001) Cytological regression and clearance of high-risk human papillomavirus in women with an abnormal cervical smear. Lancet 358:1782–1783PubMedCrossRef

Kjaer SK, van den Brule AJ, Paull G et al. (2002) Type specific persistence of high risk human papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study. BMJ 325:572

Cuzick J, Clavel C, Petry KU et al (2006) Overview of the European and North American studies on HPV testing in primary cervical cancer screening. Int J Cancer 119:1095–1101PubMedCrossRef

10.

von Knebel Doeberitz M (2002) New markers for cervical dysplasia to visualise the genomic chaos created by aberrant oncogenic papillomavirus infections. Eur J Cancer 38:2229–2242CrossRef

11.

Lie AK, Kristensen G (2008) Human papillomavirus E6/E7 mRNA testing as a predictive marker for cervical carcinoma. Expert Rev Mol Diagn 8:405–415PubMedCrossRef

12.

Castle PE, Dockter J, Giachetti C et al (2007) A cross-sectional study of a prototype carcinogenic human papillomavirus E6/E7 messenger RNA assay for detection of cervical precancer and cancer. Clin Cancer Res 13:2599–2605PubMedCrossRef

13.

Cuschieri K, Wentzensen N (2008) Human papillomavirus mRNA and p16 detection as biomarkers for the improved diagnosis of cervical neoplasia. Cancer Epidemiol Biomarkers Prev 17:2536–2545PubMedCrossRef

14.

Ho CM, Lee BH, Chang SF et al (2010) Type-specific human papillomavirus oncogene messenger RNA levels correlate with the severity of cervical neoplasia. Int J Cancer 127:622–632PubMedCrossRef

15.

de Boer MA, Jordanova ES, Kenter GG et al (2007) High human papillomavirus oncogene mRNA expression and not viral DNA load is associated with poor prognosis in cervical cancer patients. Clin Cancer Res 13:132–138PubMedCrossRef

16.

Szarewski A, Ambroisine L, Cadman L et al (2008) Comparison of predictors for high-grade cervical intraepithelial neoplasia in women with abnormal smears. Cancer Epidemiol Biomarkers Prev 17:3033–3042PubMedCrossRef

17.

Solomon D, Davey D, Kurman R et al (2002) The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 287:2114–2119PubMedCrossRef

18.

Rosini S, Zappacosta R, Di Bonaventura G et al (2007) Management and triage of women with human papillomavirus infection in follow-up for low-grade cervical disease: association of HPV-DNA and RNA-based methods. Int J Immunopathol Pharmacol 20:341–347PubMed

19.

Cattani P, Zannoni GF, Ricci C et al (2009) Clinical performance of human papillomavirus E6 and E7 mRNA testing for high-grade lesions of the cervix. J Clin Microbiol 47:3895–3901PubMedCrossRef

20.

Varnai AD, Bollmann M, Bankfalvi A et al (2008) Predictive testing of early cervical pre-cancer by detecting human papillomavirus E6/E7 mRNA in cervical cytologies up to high-grade squamous intraepithelial lesions: diagnostic and prognostic implications. Oncol Rep 19:457–465PubMed

21.

Cuschieri KS, Whitley MJ, Cubie HA (2004) Human papillomavirus type specific DNA and RNA persistence implications for cervical disease progression and monitoring. J Med Virol 73:65–70PubMedCrossRef

22.

Molden T, Kraus I, Karlsen F, Skomedal H, Nygard JF, Hagmar B (2005) Comparison of human papillomavirus messenger RNA and DNA detection: a cross-sectional study of 4, 136 women &;30 years of age with a 2-year follow-up of high-grade squamous intraepithelial lesion. Cancer Epidemiol Biomarkers Prev 14:367–372PubMedCrossRef

23.

Lie AK, Risberg B, Borge B et al (2005) DNA- versus RNA-based methods for human papillomavirus detection in cervical neoplasia. Gynecol Oncol 97:908–915PubMedCrossRef

24.

Halfon P, Benmoura D, Agostini A et al (2010) Relevance of HPV mRNA detection in a population of ASCUS plus women using the NucliSENS EasyQ HPV assay. J Clin Virol 47:177–181PubMedCrossRef

25.

Ronco G, Segnan N, Giorgi-Rossi P et al (2006) Human papillomavirus testing and liquid-based cytology: results at recruitment from the new technologies for cervical cancer randomized controlled trial. J Natl Cancer Inst 98:765–774PubMedCrossRef

26.

Ronco G, Giorgi-Rossi P, Carozzi F et al (2008) Results at recruitment from a randomized controlled trial comparing human papillomavirus testing alone with conventional cytology as the primary cervical cancer screening test. J Natl Cancer Inst 100:492–501PubMedCrossRef

27.

Pretorius RG, Bao YP, Belinson JL et al (2007) Inappropriate gold standard bias in cervical cancer screening studies. Int J Cancer 12:2218–2224CrossRef

28.

Cuzick J, Arbyn M, Sankaranarayanan R et al (2008) Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries. Vaccine 26(Suppl 10):K29–K41PubMedCrossRef

29.

Molden T, Nygard JF, Kraus I et al (2005) Predicting CIN2+ when detecting HPV mRNA and DNA by PreTect HPV-proofer and consensus PCR: a 2-year follow-up of women with ASCUS or LSIL Pap smear. Int J Cancer 114:973–976PubMedCrossRef

Title: Diagnostic and prognostic validity of the human papillomavirus E6/E7 mRNA test in cervical cytological samples of HC2-positive patients
Authors: Maria Benevolo
Irene Terrenato
Marcella Mottolese
Ferdinando Marandino
Mariantonia Carosi
Francesca Rollo
Livia Ronchetti
Paola Muti
Luciano Mariani
Stefano Sindico
Giuseppe Vocaturo
Amina Vocaturo
Publication date: 01-06-2011
Publisher: Springer Netherlands
Published in: Cancer Causes & Control / Issue 6/2011
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI: https://doi.org/10.1007/s10552-011-9757-0

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2011

Physical activity and cancer prevention: a systematic review of clinical trials

Cigarette smoking and the risk of incident and fatal melanoma in a large prospective cohort study

Erratum to: Assessing environmental and occupational risk factors for lung cancer in Mexican–Americans

Association of tobacco habits, including bidi smoking, with overall and site-specific cancer incidence: results from the Mumbai cohort study

Association of plasma vitamin B6 with risk of colorectal adenoma in a multiethnic case–control study

Association study of type 2 diabetes genetic susceptibility variants and risk of pancreatic cancer: an analysis of PanScan-I data

Keynote webinar | Spotlight on antibody–drug conjugates in cancer