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

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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.

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References

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

    Article  PubMed  CAS  Google Scholar 

  2. 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 93:293–299

    Article  PubMed  CAS  Google Scholar 

  3. 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 52:342–362

    Article  PubMed  Google Scholar 

  4. 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 362:1871–1876

    Article  PubMed  CAS  Google Scholar 

  5. 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 7:547–555

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  7. 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 358:1782–1783

    Article  PubMed  CAS  Google Scholar 

  8. 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

    Google Scholar 

  9. 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 119:1095–1101

    Article  PubMed  CAS  Google Scholar 

  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 38:2229–2242

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  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 13:2599–2605

    Article  PubMed  CAS  Google Scholar 

  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 17:2536–2545

    Article  PubMed  CAS  Google Scholar 

  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 127:622–632

    Article  PubMed  CAS  Google Scholar 

  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 13:132–138

    Article  PubMed  Google Scholar 

  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 17:3033–3042

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  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 20:341–347

    PubMed  CAS  Google Scholar 

  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 47:3895–3901

    Article  PubMed  Google Scholar 

  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 19:457–465

    PubMed  Google Scholar 

  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 73:65–70

    Article  PubMed  CAS  Google Scholar 

  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 14:367–372

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  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 47:177–181

    Article  PubMed  CAS  Google Scholar 

  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 98:765–774

    Article  PubMed  Google Scholar 

  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 100:492–501

    Article  PubMed  Google Scholar 

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

    Article  Google Scholar 

  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–K41

    Article  PubMed  Google Scholar 

  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 114:973–976

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Michael Kenyon for his formal revision of the manuscript and Maria Assunta Fonsi for her secretarial assistance. This study was supported by the New Idea Award Group in Gynecological Oncology of the Regina Elena Cancer Institute, by the Italian Ministry of Health and by Lega Italiana per la Lotta contro i Tumori.

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Authors and Affiliations

  1. Pathology Department, Regina Elena Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy

    Maria Benevolo, Marcella Mottolese, Ferdinando Marandino, Mariantonia Carosi, Francesca Rollo, Livia Ronchetti & Amina Vocaturo

  2. Epidemiology Department, Regina Elena Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy

    Irene Terrenato

  3. Oncologic Gynecology Department, Regina Elena Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy

    Luciano Mariani, Stefano Sindico & Giuseppe Vocaturo

  4. Scientific Direction, Regina Elena Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy

    Paola Muti

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  1. Maria Benevolo
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  2. Irene Terrenato
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  3. Marcella Mottolese
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  12. Amina Vocaturo
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Correspondence to Amina Vocaturo.

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Benevolo, M., Terrenato, I., Mottolese, M. et al. Diagnostic and prognostic validity of the human papillomavirus E6/E7 mRNA test in cervical cytological samples of HC2-positive patients. Cancer Causes Control 22, 869–875 (2011). https://doi.org/10.1007/s10552-011-9757-0

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  • DOI: https://doi.org/10.1007/s10552-011-9757-0

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