Top

Archives of Gynecology and Obstetrics

Published in:

01-02-2018 | Gynecologic Oncology

Diagnostic performance of HPV E6/E7 mRNA assay for detection of cervical high-grade intraepithelial neoplasia and cancer among women with ASCUS Papanicolaou smears

Authors: Chenchen Ren, Yuanhang Zhu, Li Yang, Xiaoan Zhang, Ling Liu, Chunying Ren

Published in: Archives of Gynecology and Obstetrics | Issue 2/2018

Abstract

Purpose

The aim of this study was to investigate the clinical performance of high risk (HR) HPV E6/E7 mRNA assay in detecting cervical high-grade intraepithelial neoplasia and cancer among women with atypical squamous cells of undetermined significance (ASCUS) Papanicolaou (Pap) smears.

Methods

A total of 160 patients with ASCUS who underwent HR-HPV DNA assay, HR-HPV E6/E7 mRNA assay and colposcopy biopsy at Third Affiliated Hospital of Zhengzhou University, China, from December 2015 to March 2017, were enrolled. Logistic regression analysis was used to evaluate the relationship between pathological results with clinical biologic factors.

Results

Univariate analysis showed that the qualitative results of HR-HPV DNA, qualitative results of HR-HPV E6/E7 mRNA and expression levels of HR-HPV E6/E7 mRNA were risk factors of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer (all P < 0.05). Multivariable analysis found that only the expression levels of HR-HPV E6/E7 mRNA was associated with high-grade CIN and cervical cancer (OR = 8.971, 95% CI = 2.572–31.289, P = 0.001). An optimal cut-off value of ≥ 558.26 copies/ml was determined using receiver operating characteristic curve, and specificity of cut-off value were higher than E6/E7 mRNA qualitative assay and DNA qualitative assay.

Conclusion

HPV E6/E7 mRNA quantitative assay may be a valuable tool in triage of ASCUS pap smears. A high specificity of E6/E7 mRNA quantitative assay as a triage test in women with ASCUS can be translated into a low referral for colposcopy.

Moyer VA (2012) Screening for cervical cancer: US preventive services task force recommendation statement. Ann Intern Med 156(12):880–891, W312. https://doi.org/10.7326/0003-4819-156-12-201206190-00424

Solomon D, Davey D, Kurman R et al (2002) The 2001 bethesda system: terminology for reporting results of cervical cytology. JAMA 287(16):2114–2119CrossRefPubMed

Catteau X, Simon P, Noël JC (2014) Evaluation of the oncogenic human papillomavirus DNA test with liquid-based cytology in primary cervical cancer screening and the importance of the ASC/SIL ratio: a Belgian study. ISRN Obstet Gynecol 2014:536495. https://doi.org/10.1155/2014/536495 CrossRefPubMedPubMedCentral

Arbyn M, Sasieni P, Meijer CJ, Clavel C, Koliopoulos G, Dillner J (2006) Chapter 9: Clinical applications of HPV testing: a summary of meta-analyses. Vaccine 24(Suppl 3):S3/78–89. https://doi.org/10.1016/j.vaccine.2006.05.117

Wright TC, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D (2007) 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 197(4):346–355. https://doi.org/10.1016/j.ajog.2007.07.047 CrossRefPubMed

Nobbenhuis MA, Helmerhorst TJ, van den Brule AJ, Rozendaal L, Voorhorst FJ, Bezemer PD, Verheijen RH, Meijer CJ (2001) Cytological regression and clearance of high-risk human papillomavirus in women with an abnormal cervical smear. Lancet 358(9295):1782–1783. https://doi.org/10.1016/S0140-6736(01)06809-X CrossRefPubMed

Discacciati MG, da SID, Villa LL, Reis L, Hayashi P, Costa MC, Rabelo-Santos SH, Zeferino LC (2014) Prognostic value of DNA and mRNA e6/e7 of human papillomavirus in the evolution of cervical intraepithelial neoplasia grade 2. Biomark Insights 9:15–22. https://doi.org/10.4137/BMI.S14296 CrossRefPubMedPubMedCentral

Liu TY, Xie R, Luo L, Reilly KH, He C, Lin YZ, Chen G, Zheng XW, Zhang LL, Wang HB (2014) Diagnostic validity of human papillomavirus E6/E7 mRNA test in cervical cytological samples. J Virol Methods 196:120–125. https://doi.org/10.1016/j.jviromet.2013.10.032 CrossRefPubMed

Mueller JL, Asma E, Lam CT et al (2017) International image concordance study to compare a point-of-care tampon colposcope with a standard-of-care colposcope. J Low Genit Tract Dis 21(2):112–119. https://doi.org/10.1097/LGT.0000000000000306 CrossRefPubMed

10.

Fakhreldin M, Elmasry K (2016) Improving the performance of reflex Human Papilloma Virus (HPV) testing in triaging women with atypical squamous cells of undetermined significance (ASCUS): a restrospective study in a tertiary hospital in United Arab Emirates (UAE). Vaccine 34(6):823–830. https://doi.org/10.1016/j.vaccine.2015.12.011 CrossRefPubMed

11.

Louvanto K, Rintala MA, Syrjänen KJ, Grénman SE, Syrjänen SM (2010) Genotype-specific persistence of genital human papillomavirus (HPV) infections in women followed for 6 years in the Finnish Family HPV Study. J Infect Dis 202(3):436–444. https://doi.org/10.1086/653826 CrossRefPubMed

12.

Muñoz N, Franceschi S, Bosetti C, Moreno V, Herrero R, Smith JS, Shah KV, Meijer CJ, Bosch FX (2002) Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case-control study. Lancet 359(9312):1093–1101. https://doi.org/10.1016/S0140-6736(02)08151-5 CrossRefPubMed

13.

Settheetham-Ishida W, Singto Y, Yuenyao P, Tassaneeyakul W, Kanjanavirojkul N, Ishida T (2004) Contribution of epigenetic risk factors but not p53 codon 72 polymorphism to the development of cervical cancer in Northeastern Thailand. Cancer Lett 210(2):205–211. https://doi.org/10.1016/j.canlet.2004.03.039 CrossRefPubMed

14.

Heng S, Sirichaisutdhikorn D (2016) Incidence of high grade squamous intraepithelial lesions in patients with atypical squamous cells of undetermined significance papanicolaou smears at Naresuan University Hospital. Asian Pac J Cancer Prev 17(5):2411–2414PubMed

15.

Rebolj M, Bonde J, Njor SH, Lynge E (2011) Human papillomavirus testing in primary cervical screening and the cut-off level for hybrid capture 2 tests: systematic review. BMJ 342:d2757CrossRefPubMedPubMedCentral

16.

Vince A, Kutela N, Iscic-Bes J, Harni V, Ivanisevic M, Sonicki Z, Culig Z, Poljak M (2002) Clinical utility of molecular detection of human papillomavirus in cervical samples by hybrid capture technology. J Clin Virol 25(Suppl 3):S109–S112CrossRefPubMed

17.

Lorincz AT, Castle PE, Sherman ME, Scott DR, Glass AG, Wacholder S, Rush BB, Gravitt PE, Schussler JE, Schiffman M (2002) Viral load of human papillomavirus and risk of CIN3 or cervical cancer. Lancet 360(9328):228–229. https://doi.org/10.1016/S0140-6736(02)09463-1 CrossRefPubMed

18.

Mills AM, Dirks DC, Poulter MD, Mills SE, Stoler MH (2017) HR-HPV E6/E7 mRNA in situ hybridization: validation Against PCR, DNA in situ hybridization, and p16 immunohistochemistry in 102 samples of cervical, vulvar, anal, and head and neck neoplasia. Am J Surg Pathol 41(5):607–615. https://doi.org/10.1097/PAS.0000000000000800 CrossRefPubMed

19.

Doorbar J (2006) Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci (Lond) 110(5):525–541. https://doi.org/10.1042/CS20050369 CrossRef

20.

Baron C, Henry M, Tamalet C, Villeret J, Richet H, Carcopino X (2015) Relationship between HPV 16, 18, 31, 33, 45 DNA detection and quantitation and E6/E7 mRNA detection among a series of cervical specimens with various degrees of histological lesions. J Med Virol 87(8):1389–1396. https://doi.org/10.1002/jmv.24157 CrossRefPubMed

21.

Johansson H, Bjelkenkrantz K, Darlin L, Dilllner J, Forslund O (2015) Presence of high-risk HPV mRNA in relation to future high-grade lesions among high-risk HPV DNA positive women with minor cytological abnormalities. PLoS One 10(4):e0124460. https://doi.org/10.1371/journal.pone.0124460 CrossRefPubMedPubMedCentral

22.

Arbyn M, Roelens J, Cuschieri K, Cuzick J, Szarewski A, Ratnam S, Reuschenbach M, Belinson S, Belinson JL, Monsonego J (2013) The APTIMA HPV assay versus the hybrid capture 2 test in triage of women with ASC-US or LSIL cervical cytology: a meta-analysis of the diagnostic accuracy. Int J Cancer 132(1):101–108. https://doi.org/10.1002/ijc.27636 CrossRefPubMed

23.

Yao YL, Tian QF, Cheng B, Cheng YF, Ye J, Lu WG (2017) Human papillomavirus (HPV) E6/E7 mRNA detection in cervical exfoliated cells: a potential triage for HPV-positive women. J Zhejiang Univ Sci B 18(3):256–262. https://doi.org/10.1631/jzus.B1600288 CrossRefPubMedPubMedCentral

24.

Origoni M, Carminati G, Sideri M, Clementi M, Rolla S, Candiani M (2012) “Low-grade positivity” of HPV viral load after atypical squamous cells of undetermined significance (ASC-US) cytology identifies women at low-risk for cervical intraepithelial neoplasia grade 2 and 3. Eur J Gynaecol Oncol 33(3):261–264PubMed

25.

Sørbye SW, Arbyn M, Fismen S, Gutteberg TJ, Mortensen ES (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. https://doi.org/10.1371/journal.pone.0026022 CrossRefPubMedPubMedCentral

26.

Gage JC, Katki HA, Schiffman M et al (2014) The low risk of precancer after a screening result of human papillomavirus-negative/atypical squamous cells of undetermined significance papanicolaou and implications for clinical management. Cancer Cytopathol 122(11):842–850. https://doi.org/10.1002/cncy.21463 CrossRefPubMed

Title: Diagnostic performance of HPV E6/E7 mRNA assay for detection of cervical high-grade intraepithelial neoplasia and cancer among women with ASCUS Papanicolaou smears
Authors: Chenchen Ren
Yuanhang Zhu
Li Yang
Xiaoan Zhang
Ling Liu
Chunying Ren
Publication date: 01-02-2018
Publisher: Springer Berlin Heidelberg
Published in: Archives of Gynecology and Obstetrics / Issue 2/2018
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-017-4588-1

At a glance: The STEP trials

Springer Medicine

Diagnostic performance of HPV E6/E7 mRNA assay for detection of cervical high-grade intraepithelial neoplasia and cancer among women with ASCUS Papanicolaou smears

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 2/2018

The morbidity of sexual dysfunction of 125 Chinese women following different types of radical hysterectomy for gynaecological malignancies

Clinical characteristics of acute pancreatitis in pregnancy: experience based on 121 cases

Successful treatment of acute promyelocytic leukemia in pregnancy with single-agent all-trans retinoic acid

Correlation between NM23 protein overexpression and prognostic value and clinicopathologic features of ovarian cancer: a meta-analysis

What is the net effect of introducing vitrification for cryopreservation of surplus 2PN oocytes in an IVF program?

Laparoscopic-assisted vaginal hysterectomy versus vaginal hysterectomy for benign uterine diseases: a prospective, randomized, multicenter, double-blind trial (LAVA)