HUMAN PAPILLOMA VIRUS E6/E7 MESSENGER RNA AS A BIOMARKER FOR DETECTING THE RISK EVALUATION OF CERVICAL CANCER PROGRESSION: OVERVIEW OF RECENT CLINICAL TRIALS
DOI:
https://doi.org/10.11113/jt.v75.3746Keywords:
Cervical cancer detection, HPV mRNA, biomarkerAbstract
Cervical cancer is one of the major women health problems, which is considered to be responsible for significant percentage of cancer related deaths in low and middle income countries. While Human Papilloma virus (HPV) DNA testing has an established role in cervical cancer prevention, there is a need to use other biomarkers with higher specificity and prognostic value to recognize patients at risk of progressive illness. There are evidences suggest that, direct detection of HPV messenger RNA transcripts may establish a more specific method for defining clinically important infection than viral DNA detection. Our objective was to provide an overview of the literature on specificity of HPV mRNA testing compared to DNA testing for detecting the risk evaluation of cervical intraepithelial neoplasia and invasive cervical cancer. We focused on recent clinical studies that support the application of HPV E6/E7 mRNA as a marker in advanced cervical cancer screening program. We provide overview of sample size, recruitment setting, age, HPV mRNA and HPV DNA assays for researches included in our review. The pooled review of clinical studies provided evidence that HPV mRNA might be a relevant diagnostic biomarker but additional studies need to be developed in order to make strong conclusion.
References
2013. Comprehensive Cervical Cancer Prevention and Control : a Healthier Future for Girls and Women. WHO Guidance NOTE.
Paavonen, J. 2007. Human Papillomavirus Infection and the Development of Cervical Cancer and Related Genital Neoplasias. International Journal of Infectious Diseases. 11(2): 3–9.
Khorasanizadeh, F., Hassanloo, J., Khaksar, N., Taheri, S. M., Marzaban, M., Rashidi, B. H., Akbari Sari, A and Zendehdel, K. 2013. Epidemiology of Cervical Cancer and Human Papilloma Virus Infection Among Iranian women-Analyses of National Data and Systematic Review of the Literature. Gynecologic Oncology. 128(2): 277-281.
Martin, C.N, and O’Leary, J. J. 2011. Histology of Cervical Intraepithelial Neoplasia and the Role of Biomarkers. Best Practice and Research Clinical Obstetrics and Gynaecology. 25(5): 605-615.
Muñoz, N., Hernandez-Suarez, G., Méndez, F., Molano, M., Posso, H., Moreno, V., Murillo, R., Ronderos, M., Meijer, C and Muñoz, A. 2009. Persistence of HPV Infection and Risk of High-Grade Cervical Intraepithelial Neoplasia in a Cohort of Colombian Women. British Journal of Cancer. 100(7): 1184-1190.
Brink, A. A. P., Snijders, P. J. F., Meijer, C. J. L. M, Berkhof, J and Verheijen, R. H. M. 2006. HPV Testing in Cervical Screening. Best Practice and Research Clinical Obstetrics and Gynaecology. 20(2): 253-266.
Castle, P. E, and Cremer, M. 2013. Human Papillomavirus Testing in Cervical Cancer Screening. Obstetrics and gynecology clinics of North America. 40(2): 377-390.
Kotaniemi-Talonen, L., Anttila, A., Malila, N., Tarkkanen, J., Laurila, P., Hakama, M and Nieminen, P. 2008. Screening with a Primary Human Papillomavirus Test Does Not Increase Detection of Cervical cancer and Intraepithelial Neoplasia 3. European Journal of Cancer. 44(4): 565-571.
McCredie, M. R. E., Sharples, K. J., Paul, C., Baranyai, J., Medley, G., Jones, R. W and Skegg, D. C. G. 2008. Natural History of Cervical Neoplasia and Risk of Invasive Cancer in Women with Cervical Intraepithelial Neoplasia 3: a Retrospective Cohort Study. Lancet Oncology. 9(5): 425-434.
Bhatla, N, and Moda, N. 2009. The Clinical Utility of HPV DNA Testing in Cervical Cancer Screening Strategies. Indian Journal of Medical Research. 130(3): 261-265.
Ratnam, S., Coutlee, F., Fontaine, D., Bentley, J., Escott, N., Ghatage, P., Gadag, V., Holloway, G., Bartellas, E., Kum, N., Giede, C and Lear, A. 2011. Aptima HPV E6/E7 mRNA Test is as Sensitive as Hybrid Capture 2 Assay but More Specific at Detecting Cervical Precancer and Cancer. Journal of Clinical Microbiology. 49(2): 557-564.
Coquillard, G., Palao, B and Patterson, B. K. 2011. Quantification of Intracellular HPV E6/E7 mRNA Expression Increases the Specificity and Positive Predictive Value of Cervical Cancer Screening Compared to HPV DNA. Gynecologic Oncology. 120(1): 89-93.
Boulet, G. A. V., Horvath, C. A. J., Berghmans, S. and Bogers, J. 2008. Human Papillomavirus in Cervical Cancer Screening: Important Role as Biomarker. Cancer Epidemiology, Biomarkers and Prevention. 17(4): 810-817.
Abreu, A. L. P., Souza, R. P., Gimenes, F, and Consolaro, M. E. L. 2012. a Review of Methods for Detect Human Papillomavirus infection. Virology Journal. 9(1): 262.
Arney, A, and Bennett, K. M. 2010. Molecular Diagnostics of Human Papillomavirus. Lab Med. 41(9): 523-530.
Kulasingam, S. L., Hughes, J. P., Kiviat, N. B., Mao, C., Weiss, N. S., Kuypers, J. M, and Koutsky, L. A. 2002. Evaluation of Human Papillomavirus Testing in Primary Screening for Cervical Abnormalities. Jama. 288(14): 1749.
Arbyn, M., Sasieni, P., Meijer, C. J. L, M., Clavel, C., Koliopoulos, G and Dillner, J. 2006. Chapter 9: Clinical Applications of HPV Testing: a Summary of Meta-Analyses. Vaccine. 24(3): 78-89.
Cubie, H. A, and Cuschieri, K. 2013. Understanding HPV Tests and their Appropriate Applications. Cytopathology. 24(5): 289-308.
Hoste, G., Vossaert, K and Poppe, W. A. J. 2013. The Clinical Role of HPV Testing in Primary and Secondary Cervical Cancer Screening. Obstetrics and Gynecology International. 2013(2013).
Bowring, J., Albrow, R., Fisher, A., Downey, G., Cullimore, J., Patnick, J., Walker, P. G and Kitchener, H. C. 2013. A Prospective Study of Human Papillomavirus (HPV) Testing to Resolve Uncertainty in Colposcopy. Cytopathology. 24(5):309-13.
Moyer, V. A. 2012. Screening for Cervical Cancer: U.S. Preventive Services Task Force Recommendation Statement. Annals of Internal Medicine. 156(12): 880-891.
2012. ACOG Practice Bulletin Number 131: Screening for Cervical Cancer. Obstetrics and gynecology. 120(5): 1222-1238.
Verdoodt, F., Szarewski, A., Halfon, P., Cuschieri, K and Arbyn, M. 2012. Triage of Women with Minor Abnormal Cervical Cytology. Cancer Cytopathology. 121(12): 675-687.
Nieves, L., Enerson, C., Belinson, S., Brainard, J., Chiesa-Vottero, A., Nagore, N., Booth, C., Pérez, A., Chávez-Avilés, M and Belinson, J. 2013. Primary Cervical Cancer Screening and Triage Using an mRNA Human Papillomavirus Assay and Visual Inspection. International Journal of Gynecological Cancer. 23(3): 513-518.
Zielinski, G., Bais, A., Helmerhorst, T., Verheijen, R., De Schipper, F., Snijders, P., Voorhorst, F., Van Kemenade, F., Rozendaal, L and Meijer, C. 2004. HPV Testing and Monitoring of Women after Treatment of CIN 3. Obstetrical & Gynecological Survey. 59(7): 543-553.
Sørbye, S. W., Arbyn, M., Fismen, S., Gutteberg, T.J and Mortensen, E. S. 2011. HPV E6/E7 mRNA Testing is More Specific than Cytology in Post-Colposcopy Follow-up of Women with Negative Cervical Biopsy. PLoS One. 6(10):e26022.
Persson, M., Brismar Wendel, S., Ljungblad, L., Johansson, B., Weiderpass, Eand Andersson, S. 2012. High-Risk Human Papillomavirus E6/E7 mRNA and L1 DNA as Markers of Residual/Recurrent Cervical Intraepithelial Neoplasia. Oncology Reports. 28(1): 346-52.
Cattani, P., Siddu, A., D’Onghia, S., Marchetti, S., Santangelo, R., Vellone, V. G., Zannoni, G. F, and Fadda, G. 2009. RNA (E6 and E7) Assays Versus DNA (E6 and E7) Assays for Risk Evaluation for Women Infected with Human Papillomavirus. Journal of Clinical Microbiology. 47(7): 2136-2141.
Rijkaart, D. C., Heideman, D. A. M., Coupe, V. M. H., Brink, A. A. T. P., Verheijen, R. H. M., Skomedal, H., Karlsen, F., Morland, E., Snijders, P. J. F, and Meijer, C. J. L. M. 2012. High-Risk Human Papillomavirus (hrHPV) E6/E7 mRNA Testing by PreTect HPV-Proofer for Detection of Cervical High-Grade Intraepithelial Neoplasia and Cancer among hrHPV DNA-Positive Women with Normal Cytology. Journal of Clinical Microbiology. 50(7): 2390-2396.
Reuschenbach, M., Clad, A., Von Knebel, C., Wentzensen, N., Rahmsdorf, J., Schaffrath, F., Griesser, H., Freudenberg, N and Von Knebel, M. 2010. Performance of p16 INK4a -Cytology, HPV mRNA, and HPV DNA Testing to Identify High Grade Cervical Dysplasia in Women with Abnormal Screening Results. Gynecologic Oncology. 119(1): 98-105.
Salimovi, I., Tomi´c-ˇCiˇca, A., Smailji, A and Hukic, M. 2013. Comparision of Detection of HPV-16,18,31,33 and 45 by Type-Specific DNA- andE6/E7 mRNA Based Assays of HPV DNA Positive Women with Abnormal Pap smears. Journal of Virological Methods. 194(1-2):222-228.
Cattani, P., Zannoni, G. F., Ricci, C., D’Onghia, S., Trivellizzi, I. N., Di Franco, A., Vellone, V. G., Durante, M., Fadda, G., Scambia, G., Capelli, G, and De Vincenzo, R. 2009. Clinical Performance of Human Papillomavirus E6 and E7 mRNA Testing for High-Grade Lesions of the Cervix. Journal of Clinical Microbiology. 47(12): 3895-3901.
Varnai, A. D., Bollmann, M., Bankfalvi, A., Speich, N., Schmitt, C., Griefingholt, H., Kovács. K., Klozoris, C and Bollmann, R. 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. Oncology Reports. 19(2): 457-65.
Lie, A. K., Risberg, B., Borge, B., Sandstad, B., Delabie, J., Rimala, R., Onsrud, M and Thoresen, S. 2005. DNA- Versus RNA-Based Methods for Human Papillomavirus Detection in Cervical Neoplasia. Gynecologic Oncology. 97(3): 908-915.
Molden, T., Kraus, I and Karlsen, F. 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 Comparison of Human Papillomavirus Messenger RNA and DNA. Cancer Epidemiology, Biomarkers and Prevention. 14(2): 367-372.
Liverani, C., Ciavattini, A., Monti, E., Puglia, D., Mangano, M., Giuseppe, J. D. I., Zizzi, A., Goteri, G and Bolis, G. 2012. High Risk HPV DNA Subtypes and E6/E7 mRNA Expression in a Cohort of Colposcopy Patients from Northern Italy with High-Grade Histologically Verified Cervical Lesions. American Journal of Translational Research. 4(4): 452-457.
Sotlar, K., Stubner, A., Diemer. D., Menton, S., Menton, M., Dietz, K., Wallwiener, D., Kandolf, R and Bültmann, B. 2004. Detection of High-Risk Human Papillomavirus E6 and E7 Oncogene Transcripts in Cervical Scrapes by Nested RT-Polymerase Chain Reaction. Journal of Medical Virology. 74(1): 107-116.
Sotlar, K., Diemer, D., and Stubner, A. 2005. Detection of High-Risk Human Papillomavirus (HPV) E6 and E7 Oncogene Transcripts Increases the Specificity of the Detection of a Cervical Intraepithelial Neoplasia (CIN). Verhandlungen der Deutschen Gesellschaft für Pathologie. 2005(89): 195-200.
Woodman, C. B., Collins, S., Winter, H., Bailey, A., Ellis, J., Prior, P., Yates, M., Rollason, T. P. and Young, L. S. 2001. Natural History of Cervical Human Papillomavirus Infection in Young Women: a Longitudinal Cohort Study. Lancet. 357(9271): 1831-1836.
Pierry, D., Weiss, G., Lack, B., Chen, V and Fusco, J. 2012. Intracellular human Papillomavirus E6, E7 mRNA Quantification Predicts CIN 2+ in Cervical Biopsies Better than Papanicolaou Screening for Women Regardless of Age. Archives of Pathology & Laboratory Medicine. 136(8): 956-960.
Kösel, S., Burggraf, S., Engelhardt, W and Olgemöller, B. 2007. Increased Levels of HPV16 E6*I Transcripts in High-Grade Cervical Cytology and Histology (CIN II+) Detected by Rapid Real-Time RT-PCR Amplification. Cytopathology. 18(5): 290-299.
Liu, T.Y., Xie, R., Luo, L., Reilly, K. H., He, C., Lin, Y.Z., Chen, G., Zheng, X.W., Zhang, L.L, and Wang, H.B. 2014. Diagnostic Validity of Human Papillomavirus E6/E7 mRNA Test in Cervical Cytological Samples. Journal of Virological Methods 196: 120-125.
Castle, P. E., Dockter, J., Giachetti, C., Garcia, F. A. R., McCormick M. K., Mitchell, A. L., Holladay, E. B and Kolk, D. P. 2007. A Cross-Sectional Study of a Prototype Carcinogenic Human Papillomavirus E6/E7 Messenger RNA Assay for Detection of Cervical Precancer and Cancer. Clinical Cancer Research. 13(9): 2599-2605.
Waldstrom, M, and Ornskov, D. 2011. Comparison of the Clinical Performance of an HPV mRNA Test and an HPV DNA Test in Triage of Atypical Squamous Cells of Undetermined Significance (ASC-US). Cytopathology. 23(6): 389-395.
Kottaridi, C., Tsiodras, S., Spathis, A., Chranioti, A and Pappas, A. 2011. Clinical Performance of Human Papillomavirus E6, E7 mRNA Flow Cytometric Assay Compared to Human Papillomavirus DNA Typing. Analytical and Quantitative Cytology and Histology. 33(6): 305-310.
Molden, T., Nygård, J. F., Kraus, I., Karlsen, F., Nygård, M., Skare, G. B., Skomedal, H., Thoresen, S. O, and Hagmar, B. 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. International Journal of Cancer. 114(6): 973-976.
Cuschieri, K. S., Whitley, M. J and Cubie, H. A. 2004. Human Papillomavirus Type Specific DNA and RNA Persistence Implications for Cervical Disease Progression and Monitoring. Journal of Medical Virology. 73(1): 65-70.
Castle, P. E., Solomon, D., Hildesheim, A., Herrero, R., Concepcion Bratti, M., Sherman, M. E., Cecilia Rodriguez, A., Alfaro, M., Hutchinson, M. L., Terence Dunn, S., Kuypers, J and Schiffman, M. 2003. Stability of Archived Liquid-Based Cervical Cytologic Specimens. Cancer. 99(2): 89-96.
Waldstrøm, M and Ørnskov, D. 2011. Clinical Performance of a Human Papillomavirus Messenger RNA Test (Aptima HPV Assay) on Residual Material from Archived 3-Year-Old PreservCyt Samples. Archives of Pathology & Laboratory Medicine. 135(8): 1052-1056.
Cuschieri, K. S., Beattie, G., Hassan, S., Robertson, K and Cubie, H. 2005. Assessment of Human Papillomavirus mRNA Detection Over Time in Cervical Specimens Collected in Liquid Based Cytology Medium. Journal of Virological Methods. 124(1-2): 211-215.
Tarkowski, T. A., Rajeevan, M. S., Lee, D. R and Unger, E. R. 2001. Improved Detection of Viral RNA Isolated from Liquid-Based Cytology Samples. Molecular diagnosis. 6(2): 125-130.
Habis, A. H., Vernon, S.D., Lee, D. R., Verma, M and Unger, E. R. 2004. Molecular Quality of Exfoliated Cervical Cells : Implications for Molecular Epidemiology and Biomarker Discovery. Cancer Epidemiology, Biomarkers & Prevention. 13(3): 492-496.
Evans, M. F., Peng, Z., Clark, K. M., Adamson, C. S.C., Ma, X.J., Wu, X., Wang, H., Luo, Y., and Cooper, K. 2014. HPV E6/E7 RNA In Situ Hybridization Signal Patterns as Biomarkers of Three-Tier Cervical Intraepithelial Neoplasia Grade. PLoS One. 9(3): e91142.
Wentzensen, N, and von Knebel Doeberitz, M. 2007. Biomarkers in Cervical Cancer Screening. Disease Markers. 23(4): 315-330.
Origoni, M. 2012. New Biomarkers Improving Cervical Cancer Screening Efficacy. Journal of Women's Health, Issues & Care. 1(1): 9-10.
Litjens, R. J., Hopman, A. H., van de Vijver, K. K., Ramaekers, F. C., Kruitwagen, R. F. and Kruse, A. J. 2013. Molecular Biomarkers in Cervical Cancer Diagnosis: a Critical Appraisal. Expert Opinion on Medical Diagnostics. 7(4): 365-377.
an Bogaert, L. J. 2014. Cervical Preneoplasia Biomarkers: a Conundrum for the Community Based Gynecologic Surgical Pathologist. Journal of Gynecologic Oncology. 25(1):3–5.
Hwang, S. J, and Shroyer, K. R. 2012. Biomarkers of Cervical Dysplasia and Carcinoma. Journal of Oncology. 2012(2012.
Downloads
Published
Issue
Section
License
Copyright of articles that appear in Jurnal Teknologi belongs exclusively to Penerbit Universiti Teknologi Malaysia (Penerbit UTM Press). This copyright covers the rights to reproduce the article, including reprints, electronic reproductions, or any other reproductions of similar nature.
