Original Article

Assessment of Cervical Cancer Molecular-Based Screening Tools; HPV-DNA Detection versus E6/E7 mRNA Testing; First Report of a Prospective Cohort Study among Iranian Women


Background: Human papillomavirus (HPV) has been found as the most considerable causes of cervical cancer. Recently, several molecular methods have been introduced to increase the accuracy of the screening programs and decrease the mortality rate. Among these methods, mRNA-based methods have more advantages as they assess the expression level of HPV E6 and E7 oncogenic mRNAs. This study aimed to evaluate the results of HPV RNA- and DNA-based methods among Iranian women population with normal cytology results.

Methods: Overall, 4640 women were enrolled referred to the Gynecology Oncology Ward of Vali-e-Asr Hospital, private and academic clinics, Tehran, Iran from Jan 2016 to Apr 2018. To assess the HPV-DNA infection INNO-LiPA® HPV Genotyping Extra-II kit was used. For HPV-RNA assessment, Aptima HPV Assay and in house HPV-RNA genotyping methods were applied.

Results: The positivity rates of HPV infection according to DNA- and RNA-based methods were 18.0% and 11.2%, respectively (P<0.001). The positive predictive value, negative predictive value, specificity and sensitivity of DNA-based method in contrast with RNA-based method were 59.2% (56.6-61.6), 99.4% (99.0-99.6), 91.7% (90.8-92.6) and 95.2% (93.0-96.9) respectively.

Conclusion: At the present study for prognosis of cervical cancer, RNA-based method seemed to be more specific in contrast to DNA-based method. Patient follow up and further studies will be conducted in order to clarify the clinical sensitivity and specificity of the two methods.

Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12-9.

Einstein MH, Schiller JT, Viscidi RP, Strickler HD, Coursaget P, Tan T, et al. Clinician's guide to human papillomavirus immunology: knowns and unknowns. Lancet Infect Dis. 2009;9(6):347-56.

zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2002;2(5):342-50.

Humans IWGotEoCRt. Biological agents. Volume 100 B. A review of human carcinogens. IARC Monogr Eval Carcinog Risks Hum. 2012;100(Pt B):1-441.

Bzhalava D, Guan P, Franceschi S, Dillner J, Clifford G. A systematic review of the prevalence of mucosal and cutaneous human papillomavirus types. Virology. 2013;445(1-2):224-31.

Huh WK. Human papillomavirus infection: a concise review of natural history. Obstet Gynecol. 2009;114(1):139-43.

Moscicki AB, Schiffman M, Burchell A, Albero G, Giuliano AR, Goodman MT, et al. Updating the natural history of human papillomavirus and anogenital cancers. Vaccine. 2012;30 Suppl 5:F24-33.

Smith JS, Lindsay L, Hoots B, Keys J, Franceschi S, Winer R, et al. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer. 2007;121(3):621-32.

Cuschieri KS, Whitley MJ, Cubie HA. Human papillomavirus type specific DNA and RNA persistence--implications for cervical disease progression and monitoring. J Med Virol. 2004;73(1):65-70.

Boulet GA, Horvath CA, Berghmans S, Bogers J. Human papillomavirus in cervical cancer screening: important role as biomarker. Cancer Epidemiol Biomarkers Prev. 2008;17(4):810-7.

Katki HA, Kinney WK, Fetterman B, Lorey T, Poitras NE, Cheung L, et al. Cervical cancer risk for women undergoing concurrent testing for human papillomavirus and cervical cytology: a population-based study in routine clinical practice. Lancet Oncol. 2011;12(7):663-72.

Huh WK, Ault KA, Chelmow D, Davey DD, Goulart RA, Garcia FA, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Gynecol Oncol. 2015;136(2):178-82.

Stoler MH, Wright TC, Jr., Cuzick J, Dockter J, Reid JL, Getman D, et al. APTIMA HPV assay performance in women with atypical squamous cells of undetermined significance cytology results. Am J Obstet Gynecol. 2013;208(2):144 e1-8.

Monsonego J, Hudgens MG, Zerat L, Zerat JC, Syrjanen K, Halfon P, et al. Evaluation of oncogenic human papillomavirus RNA and DNA tests with liquid-based cytology in primary cervical cancer screening: the FASE study. Int J Cancer. 2011;129(3):691-701.

Monsonego J, Hudgens MG, Zerat L, Zerat JC, Syrjanen K, Smith JS. Risk assessment and clinical impact of liquid-based cytology, oncogenic human papillomavirus (HPV) DNA and mRNA testing in primary cervical cancer screening (the FASE study). Gynecol Oncol. 2012;125(1):175-80.

Cuzick J, Cadman L, Mesher D, Austin J, Ashdown-Barr L, Ho L, et al. Comparing the performance of six human papillomavirus tests in a screening population. Br J Cancer. 2013;108(4):908-13.

Nieves L, Enerson CL, Belinson S, Brainard J, Chiesa-Vottero A, Nagore N, et al. Primary cervical cancer screening and triage using an mRNA human papillomavirus assay and visual inspection. Int J Gynecol Cancer. 2013;23(3):513-8.

Heideman DA, Hesselink AT, van Kemenade FJ, Iftner T, Berkhof J, Topal F, et al. The Aptima HPV assay fulfills the cross-sectional clinical and reproducibility criteria of international guidelines for human papillomavirus test requirements for cervical screening. J Clin Microbiol. 2013;51(11):3653-7.

Reid JL, Wright TC, Jr., Stoler MH, Cuzick J, Castle PE, Dockter J, et al. Human papillomavirus oncogenic mRNA testing for cervical cancer screening: baseline and longitudinal results from the CLEAR study. Am J Clin Pathol. 2015;144(3):473-83.

Iftner T, Becker S, Neis KJ, Castanon A, Iftner A, Holz B, et al. Head-to-Head Comparison of the RNA-Based Aptima Human Papillomavirus (HPV) Assay and the DNA-Based Hybrid Capture 2 HPV Test in a Routine Screening Population of Women Aged 30 to 60 Years in Germany. J Clin Microbiol. 2015;53(8):2509-16.

Pouryasin M, Sharafi H, Mousavi AS, Khodadad S, Marjani M, Jamshidi F, et al. Distribution of Human Papillomavirus Genotypes in Liquid-based Samples; Abundance of HPV-53 in Tehran, Iran. Iran J Public Health. 2014;43(8):1159-60.

Lindh M, Gorander S, Andersson E, Horal P, Mattsby-Balzer I, Ryd W. Real-time Taqman PCR targeting 14 human papilloma virus types. J Clin Virol. 2007;40(4):321-4.

Szklo M, Nieto FJ, Reilly T, Parker K. Epidemiology : beyond the basics. 2014.

Cid Arregui A, Gariglio P, Kanda T, Doorbar J. ONCOGENIC HUMAN PAPILLOMAVIRUSES: High-Risk Human Papillomaviruses: Towards a Better Understanding of the Mechanisms of Viral Transformation, Latency and Immune-Escape. Open Virol J. 2012;6:160-2.

Doorbar J, Quint W, Banks L, Bravo IG, Stoler M, Broker TR, et al. The biology and life-cycle of human papillomaviruses. Vaccine. 2012;30 Suppl 5:F55-70.

de Sanjose S, Brotons M, Pavon MA. The natural history of human papillomavirus infection. Best Pract Res Clin Obstet Gynaecol. 2017.

Abreu AL, Souza RP, Gimenes F, Consolaro ME. A review of methods for detect human Papillomavirus infection. Virol J.


Haedicke J, Iftner T. A review of the clinical performance of the Aptima HPV assay. J Clin Virol. 2016;76 Suppl 1:S40-S8.

Choi YJ, Park JS. Clinical significance of human papillomavirus genotyping. J Gynecol Oncol. 2016;27(2):e21.

Guan P, Howell-Jones R, Li N, Bruni L, de Sanjose S, Franceschi S, et al. Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer. 2012;131(10):2349-59.

Tjalma WA, Fiander A, Reich O, Powell N, Nowakowski AM, Kirschner B, et al. Differences in human papillomavirus type distribution in high-grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe. Int J Cancer. 2013;132(4):854-67.

IssueVol 49 No 9 (2020) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v49i9.4093
Cervical cancer; Human Papillomavirus (HPV) Intraepithelial lesion Malignancy

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
MOUSAVI A-S, POURYASIN A, YARANDI F, PIRZADEH L, ALIPOUR A, KHODADAD S, POURYASIN M. Assessment of Cervical Cancer Molecular-Based Screening Tools; HPV-DNA Detection versus E6/E7 mRNA Testing; First Report of a Prospective Cohort Study among Iranian Women. Iran J Public Health. 49(9):1734-1742.