DOI QR코드

DOI QR Code

Diagnostic Performance of HPV E6/E7 mRNA and HPV DNA Assays for the Detection and Screening of Oncogenic Human Papillomavirus Infection among Woman with Cervical Lesions in China

  • Wang, Hye-young ;
  • Lee, Dongsup ;
  • Park, Sunyoung ;
  • Kim, Geehyuk ;
  • Kim, Sunghyun ;
  • Han, Lin ;
  • Yubo, Ren ;
  • Li, Yingxue ;
  • Park, Kwang Hwa ;
  • Lee, Hyeyoung
  • Published : 2015.12.03

Abstract

Background: Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and it is responsible for most cases of cervical uterine cancer. Although HPV infections of the cervix do not always progress to cancer, 90% of cervical cancer cases have been found to be associated with high risk HPV (HR-HPV) infection. HPV DNA testing is widely used, along with Papanicolaou (Pap) testing, to screen for cervical abnormalities. However, there are no data on the prevalence of genotype-specific HPV infections assessed by measuring HPV E6/E7 mRNA in women representative of the Chinese population across a broad age range. Materials and Methods: In the present study, we compared the results with the CervicGen HPV RT-qDx assay, which detects 16 HR-HPV genotypes (Alpha-9: HPV 16, 31, 33, 35, 52, and 58; Alpha-7: HPV 18, 39, 45, 51, 59, and 68; and Alpha-5, 6: HPV 53, 56, 66, and 69), and the REBA HPV-ID assay, which detects 32 HPV genotypes based on the reverse blot hybridization assay (REBA) for the detection of oncogenic HPV infection according to cytological diagnosis. We also investigated the prevalence and genotype distribution of HPV infection with a total of 324 liquid-based cytology samples collected in western Shandong province, East China. Results: The overall HPV prevalences determined by HPV DNA and HPV E6/E7 mRNA assays in this study were 79.9% (259/324) and 55.6% (180/324), respectively. Although the positivity of HPV E6/E7 mRNA expression was significantly lower than HPV DNA positivity, the HPV E6/E7 mRNA assay showed greater specificity than the HPV DNA assay (88.6% vs. 48.1%) in normal cytology samples. The prevalence of Alpha-9 (HPV 16, 31, 33, 35, 52, and 58) HPV infection among these women accounted for up to 80.3% and 76.1% of the high-grade lesions detected in the HPV mRNA and DNA tests, respectively. The HR-HPV genotype distribution, based on HPV DNA and E6/E7 mRNA expression by age group in patients with cytologically confirmed lesions, was highest in women aged 40 to 49 years (35.9% for cytologically confirmed cases, Pearson correlation r value=0.993, p<0.001) for high-grade lesions. Among the oncogenic HR-HPV genotypes for all age groups, there was little difference in the distribution of HPV genotypes between the HPV DNA (HPV -16, 53, 18, 58, and 33) and HPV E6/E7 mRNA (HPV -16, 53, 33, 58, and 18) assays. HPV 16 was the most common HPV genotype among women with high-grade lesions. Conclusions: Our results suggest that the HPV E6/E7 mRNA assay can be a sensitive and specific tool for the screening and investigation of cervical cancer. Furthermore, it may provide useful information regarding the necessity for early cervical cancer screenings and the development of additional effective HPV vaccines, such as one for HPV 53 and 58. Additionally, gaining knowledge of HPV distribution may also inform us about ecological changes in HPV after the vaccination.

Keywords

Cervical cancer;HPV;E6/E7 mRNA;REBA;prevalence;molecular diagnosis

References

  1. Agarossi A, Ferrazzi E, Parazzini F, et al (2009). Prevalence and type distribution of high-risk human papillomavirus infection in women undergoing voluntary cervical cancer screening in Italy. J Med Virol, 81, 529-35. https://doi.org/10.1002/jmv.21347
  2. Andersson E, Karrberg C, Radberg T, et al (2011). Type-specific human papillomavirus E6/E7 mRNA detection by real-time PCR improves identification of cervical neoplasia. J Clin Microbiol, 49, 3794-99. https://doi.org/10.1128/JCM.00549-11
  3. Ault KA (2007). Human papillomavirus vaccines and the potential for cross-protection between related HPV types. Gynecol Oncol, 107, 31-33. https://doi.org/10.1016/j.ygyno.2007.08.059
  4. Bruni L, Diaz M, Castellsague X, et al (2010). Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis, 202, 1789-99. https://doi.org/10.1086/657321
  5. Clifford GM, Gallus S, Herrero R, et al (2005). Worldwide distribution of human papillomavirus types in cytologically normal women in the international agency for research on cancer HPV prevalence surveys: a pooled analysis. Lancet, 366, 991-8. https://doi.org/10.1016/S0140-6736(05)67069-9
  6. Coquillard G, Palao B, Patterson BK (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 Oncol, 120, 89-93. https://doi.org/10.1016/j.ygyno.2010.09.013
  7. Cox, JT (2009). History of the use ofHPV testing in cervical screening and in the management of abnormal cervical screening results. J Clin Virol, 45, 3-12. https://doi.org/10.1016/S1386-6532(09)70002-2
  8. de Sanjose S, Serrano B, Castellsague X, et al (2012). Human papillomavirus (HPV) and related cancers in the global alliance for vaccines and immunization (GAVI) countries. A WHO/ICO HPV information centre report. Vaccine, 30, 1-83.
  9. Ding X, Liu Z, Su J, et al (2014). Human papillomavirus typespecific prevalence in women referred for colposcopic examination in Beijing. J Med Virol, 86, 1937-43. https://doi.org/10.1002/jmv.24044
  10. Doorbar J (2006). Molecular biology of human papillomavirus infection and cervical cancer. Clinical science, 110, 525-41. https://doi.org/10.1042/CS20050369
  11. Ergunay K, Misirlioglu M, Pinar F, et al (2007). Human papilloma virus DNA in cervical samples with cytological abnormalities and typing of the virus. Mikrobiyol Bul, 41, 219-26.
  12. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  13. Kim S, Lee D, Park S, et al (2012). REBA HPV-$ID^{(R)}$ for efficient genotyping of human papillomavirus in clinical samples from Korean patients. J Med Virol, 84, 1248-53. https://doi.org/10.1002/jmv.23334
  14. Kjaer SK, Breugelmans G, Munk C, et al (2008). Populationbased prevalence, type- and age-specific distribution of HPV in women before introduction of an HPV-vaccination program in Denmark. Int J Cancer, 123, 1864-70. https://doi.org/10.1002/ijc.23712
  15. Laudadio, J (2013). Human papillomavirus detection: testing methodologies and their clinical utility in cervical cancer screening. Adv Anat Pathol, 20, 158-67. https://doi.org/10.1097/PAP.0b013e31828d1893
  16. Lee, D, Kim S, Park S, et al (2011). Human papillomavirus prevalence in gangwon province using reverse blot hybridization assay. Korean J Pathol, 45, 348-53. https://doi.org/10.4132/KoreanJPathol.2011.45.4.348
  17. Li N, Franceschi S, Howell-Jones R, et al (2011). Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type and year of publication. Int J Cancer, 128, 927-35. https://doi.org/10.1002/ijc.25396
  18. Liu XX, Fan XL, Yu YP, et al (2014). Human papillomavirus prevalence and type-distribution among women in Zhejiang province, southeast china: across-sectional study. BMC Infect Dis, 14, 708-14. https://doi.org/10.1186/s12879-014-0708-8
  19. Mayrand MH, Duarte-Franco E, Rodrigues I, et al (2007). Human papillomavirus DNA versus papanicolaou screening tests for cervical cancer. N Engl J Med, 357, 1579-88. https://doi.org/10.1056/NEJMoa071430
  20. Molden T, Kraus I, Karlsen F, et al (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, 367-72. https://doi.org/10.1158/1055-9965.EPI-04-0410
  21. Munger K, Baldwin A, Edwards KM, et al (2004). Mechanisms of human papillomavirus-induced oncogenesis. J Virol, 78, 11451-60. https://doi.org/10.1128/JVI.78.21.11451-11460.2004
  22. Okadome M, Saito T, Tanaka H, et al (2014). Potential impact of combined high- and low-risk human papillomavirus infection on the progression of cervical intraepithelial neoplasia 2. J Obstet Gynaecol Res, 40, 561-69. https://doi.org/10.1111/jog.12202
  23. Poljak M, Seme K, Maver PJ, et al (2013). Human papillomavirus prevalence and type-distribution, cervical cancer screening practices and current status of vaccination implementation in Central and Eastern Europe. Vaccine, 7, 59-70.
  24. Ronco G, Giorgi-Rossi P, Carozzi F, et al (2008). New technologies for cervical cancer screening working group. 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. https://doi.org/10.1093/jnci/djn065
  25. Sotlar K, Stubner A, Diemer D, et al (2004). Detection of highrisk human papillomavirus E6 and E7 oncogene transcripts in cervical scrapes by nested RT-polymerase chain reaction. J Med Virol, 74, 107-16. https://doi.org/10.1002/jmv.20153
  26. Sun B, He J, Chen X, et al (2014). Prevalence and genotype distribution of human papillomavirus infection in harbin, Northeast China. Arch Virol, 159, 1027-32. https://doi.org/10.1007/s00705-013-1886-1
  27. Sorbye SW, Fismen S, Gutteberg T, et al (2010). Triage of women with minor cervical lesions: data suggesting a ''test and treat'' approach for HPV E6/E7 mRNA testing. PLoS One, 5, 12724-29. https://doi.org/10.1371/journal.pone.0012724
  28. Vizcaino AP, Moreno V, Bosch FX, et al (1998). International trends in the incidence of cervical cancer: I. Adenocarcinoma and adenosquamous cell carcinomas. Int J Cancer, 75, 536-45. https://doi.org/10.1002/(SICI)1097-0215(19980209)75:4<536::AID-IJC8>3.0.CO;2-U
  29. 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. https://doi.org/10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F
  30. zur Hausen, H (2009). Papillomaviruses in the causation of human cancers - a brief historical account. Virology, 384, 260-65. https://doi.org/10.1016/j.virol.2008.11.046

Cited by

  1. Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection vol.39, pp.4, 2017, https://doi.org/10.1177/1010428317697547
  2. Prevalence of human papilloma virus and their high-risk genotypes in Sri Lankan women vol.29, pp.1, 2018, https://doi.org/10.1007/s13337-018-0419-7
  3. Development and validation of a multiplex reverse transcript real-time PCR for E6/E7 mRNA detection of high-risk human papillomavirus vol.67, pp.10, 2018, https://doi.org/10.1099/jmm.0.000824
  4. Diagnostic Utility of HPV16 E6 mRNA or E7 mRNA Quantitative Expression for Cervical Cells of Patients with Dysplasia and Carcinoma vol.27, pp.9, 2018, https://doi.org/10.1177/0963689718788521

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)