Diagnostic value of HPV E6/E7 mRNA in screening for cervical intraepithelial neoplasia grade 2 or worse: A systematic review and meta‑analysis

Xu,Fengsheng; Ran,Tianfu; Wei,Qiangang; Pan,Rirun; Chen,Shangzhong; Luo,Jing

doi:10.3892/ol.2024.14364

Diagnostic value of HPV E6/E7 mRNA in screening for cervical intraepithelial neoplasia grade 2 or worse: A systematic review and meta‑analysis

Authors:
- Fengsheng Xu
- Tianfu Ran
- Qiangang Wei
- Rirun Pan
- Shangzhong Chen
- Jing Luo
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Affiliations: College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350100, P.R. China, Intensive Care Unit, People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China, Department of Andrology, People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China, Department of Neurology, People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
Published online on: March 26, 2024 https://doi.org/10.3892/ol.2024.14364
Article Number: 231
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Histology is considered the gold standard for diagnosing the pathological progress of cervical cancer development, while cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) is the cutoff for intervention in clinical practice. The diagnostic value of human papillomavirus (HPV) E6/E7 mRNA in screening for CIN2+ has not been systematically summarized. A meta‑analysis was conducted as part of the present study conducted to explore the diagnostic value of HPV E6/E7 mRNA in screening for CIN2+, aiming to provide a new marker for earlier clinical diagnosis of cervical cancer. The PubMed, Embase and Cochrane Library databases were searched from inception to May 2023. Studies reporting the true positive, false positive, true negative and false negative values in differentiating between CIN2+ and CIN2‑ were included, while duplicate publications, studies without full text, incomplete information or inability to conduct data extraction, animal experiments, reviews and systematic reviews were excluded. STATA software was used to analyze the data. A total of 2,224 patients were included of whom there were 1,274 patients with CIN2+ and 950 patients with CIN2‑. The pooled sensitivity and specificity of the studies overall were 0.89 (95% CI, 0.84‑0.92) and 0.59 (95% CI, 0.46‑0.71), respectively; the positive likelihood ratio (LR) and the negative LR of the studies overall were 2.31 (95% CI, 1.61‑3.32) and 0.21 (95% CI, 0.14‑0.30), respectively. The pooled diagnostic odds ratio of the studies overall was 11.53 (95% CI, 6.85‑19.36). Additionally, the area under the curve was 0.88. The analysis indicated that HPV E6/E7 mRNA has high diagnostic efficacy for CIN2+. HPV E6/E7 mRNA is highly sensitive in the diagnosis of CIN2+, which helps to reduce the rate of missed diagnoses. However, lower specificity may lead to a higher number of misdiagnoses in healthy patients.

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1	Nadile M, Kornel A, Sze NSK and Tsiani E: A comprehensive review of Genistein's effects in preclinical models of cervical cancer. Cancers (Basel). 16:352023. View Article : Google Scholar : PubMed/NCBI
2	Cervical Cancer Treatment, . Patient version. PDQ Cancer Information Summaries. National Cancer Institute; Bethesda, MD: 2002
3	Ikeda S, Ueda Y, Hara M, Yagi A, Kitamura T, Kitamura Y, Konishi H, Kakizoe T, Sekine M, Enomoto T and Sobue T: Human papillomavirus vaccine to prevent cervical intraepithelial neoplasia in Japan: A nationwide case-control study. Cancer Sci. 112:839–846. 2021. View Article : Google Scholar : PubMed/NCBI
4	Marth C, Landoni F, Mahner S, McCormack M, Gonzalez-Martin A, Colombo N and Committee EG: Cervical cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 28 (Suppl 4):iv72–iv83. 2017. View Article : Google Scholar : PubMed/NCBI
5	Meijer CJLM, Berkhof J, Castle PE, Hesselink AT, Franco EL, Ronco G, Arbyn M, Bosch FX, Cuzick J, Dillner J, et al: Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older. Int J Cancer. 124:516–520. 2009. View Article : Google Scholar : PubMed/NCBI
6	Wolf JL, Billingsley CC, Kendler A and Jackson AL: Cervical stratified mucin-producing intraepithelial lesion: A systematic review of diagnosis and management. J Low Genit Tract Dis. 24:259–264. 2020. View Article : Google Scholar : PubMed/NCBI
7	Fischer M, Uxa S, Stanko C, Magin TM and Engeland K: Human papilloma virus E7 oncoprotein abrogates the p53-p21-DREAM pathway. Sci Rep. 7:26032017. View Article : Google Scholar : PubMed/NCBI
8	Rebolj M, Rimmer J, Denton K, Tidy J, Mathews C, Ellis K, Smith J, Evans C, Giles T, Frew V, et al: Primary cervical screening with high risk human papillomavirus testing: observational study. BMJ. 364:l2402019. View Article : Google Scholar : PubMed/NCBI
9	Argyri E, Tsimplaki E, Daskalopoulou D, Stravopodis DJ, Kouikoglou O, Terzakis E and Panotopoulou E: E6/E7 mRNA expression of high-risk HPV types in 849 Greek women. Anticancer Res. 33:4007–4011. 2013.PubMed/NCBI
10	Hoppe-Seyler K, Bossler F, Braun JA, Herrmann AL and Hoppe-Seyler F: The HPV E6/E7 oncogenes: Key factors for viral carcinogenesis and therapeutic targets. Trends Microbiol. 26:158–168. 2018. View Article : Google Scholar : PubMed/NCBI
11	Wang R, Pan W, Jin L, Huang W, Li Y, Wu D, Gao C, Ma D and Liao S: Human papillomavirus vaccine against cervical cancer: Opportunity and challenge. Cancer Lett. 471:88–102. 2020. View Article : Google Scholar : PubMed/NCBI
12	Derbie A, Mekonnen D, Woldeamanuel Y, Van Ostade X and Abebe T: HPV E6/E7 mRNA test for the detection of high grade cervical intraepithelial neoplasia (CIN2+): A systematic review. Infect Agent Cancer. 15:92020. View Article : Google Scholar : PubMed/NCBI
13	Ryan D and Giele H: The scratch collapse test: A QUADAS-2 assessment of a systematic review. J Plast Reconstr Aesthet Surg. 72:1418–1833. 2019. View Article : Google Scholar : PubMed/NCBI
14	Andersson E, Kärrberg C, Rådberg T, Blomqvist L, Zetterqvist BM, Ryd W, Lindh M and Horal P: Type-specific human papillomavirus E6/E7 mRNA detection by real-time PCR improves identification of cervical neoplasia. J Clin Microbiol. 49:3794–3799. 2011. View Article : Google Scholar : PubMed/NCBI
15	Waldstrom M and Ornskov D: Clinical performance of a human papillomavirus messenger RNA test (Aptima HPV Assay) on residual material from archived 3-year-old PreservCyt samples with low-grade squamous intraepithelial lesion. Arch Pathol Lab Med. 135:1052–1056. 2011. View Article : Google Scholar : PubMed/NCBI
16	Liu TY, Xie R, Luo L, Reilly KH, He C, Lin YZ, Chen G, Zheng XW, Zhang LL and Wang HB: Diagnostic validity of human papillomavirus E6/E7 mRNA test in cervical cytological samples. J Virol Methods. 196:120–125. 2014. View Article : Google Scholar : PubMed/NCBI
17	Shi WJ, Liu H, Wu D, Tang ZH, Shen YC and Guo L: E6/E7 proteins are potential markers for the screening and diagnosis of cervical pre-cancerous lesions and cervical cancer in a Chinese population. Oncol Lett. 14:6251–6258. 2017.PubMed/NCBI
18	Camus C, Vitale S, Loubatier C, Pénaranda G, Khiri H, Plauzolles A, Carcopino X, Halfon P and Giordanengo V: Quantification of HPV16 E6/E7 mRNA spliced isoforms viral load as a novel diagnostic tool for improving cervical cancer screening. J Clin Med. 7:5302018. View Article : Google Scholar : PubMed/NCBI
19	Fan Y and Shen Z: The clinical value of HPV E6/E7 and STAT3 mRNA detection in cervical cancer screening. Pathol Res Pract. 214:767–775. 2018. View Article : Google Scholar : PubMed/NCBI
20	Han L, Husaiyin S, Zhao F, Rezhake R and Niyazi M: Clinical value of human papillomavirus E6/E7 mRNA detection in screening for cervical cancer in women positive for human papillomavirus DNA or. Clin Lab. 64:1363–1371. 2018. View Article : Google Scholar : PubMed/NCBI
21	Pan D, Zhang CQ, Liang QL and Hong XC: An efficient method that combines the ThinPrep cytologic test with E6/E7 mRNA testing for cervical cancer screening. Cancer Manag Res. 11:4773–4780. 2019. View Article : Google Scholar : PubMed/NCBI
22	Zhang SK, Guo Z, Wang P, Kang LN, Jia MM, Wu ZN, Chen Q, Cao XQ, Zhao DM, Guo PP, et al: The potential benefits of HPV E6/E7 mRNA test in cervical cancer screening in China. Front Oncol. 10:5332532020. View Article : Google Scholar : PubMed/NCBI
23	Sun J, Yue Y, Li R, Sun Q, Hu C, Ge X and Guan Q: Detection of HPV E6/E7 mRNA in the diagnosis of cervical cancer and precancerous lesions after kidney transplantation. Am J Transl Res. 13:7312–7317. 2021.PubMed/NCBI
24	Qian S, Zhang S, Lu M, Chen S, Liu L, Liu S, Jiang F and Zhang J: The accuracy of screening tools for sarcopenia in older Chinese adults: A systematic review and meta-analysis. Front Public Health. 12:13103832024. View Article : Google Scholar : PubMed/NCBI
25	Molden T, Kraus I, Skomedal H, Nordstrom T and Karlsen F: PreTect HPV-proofer: Real-time detection and typing of E6/E7 mRNA from carcinogenic human papillomaviruses. J Virol Methods. 142:204–212. 2007. View Article : Google Scholar : PubMed/NCBI
26	Basu P, Banerjee D, Mittal S, Dutta S, Ghosh I, Chowdhury N, Abraham P, Chandna P and Ratnam S: Sensitivity of APTIMA HPV E6/E7 mRNA test in comparison with hybrid capture 2 HPV DNA test for detection of high risk oncogenic human papillomavirus in 396 biopsy confirmed cervical cancers. J Med Virol. 88:1271–1278. 2016. View Article : Google Scholar : PubMed/NCBI
27	Song Y, Zhang M, Zhang C, Du S and Zhai F: HPV E6/E7 mRNA combined with thin-prep cytology test for the diagnosis of residual/recurrence after loop electrosurgical excision procedure in patients with cervical intraepithelial neoplasia. Diagn Microbiol Infect Dis. 108:1161192024. View Article : Google Scholar : PubMed/NCBI
28	Duvlis S, Popovska-Jankovic K, Arsova ZS, Memeti S, Popeska Z and Plaseska-Karanfilska D: HPV E6/E7 mRNA versus HPV DNA biomarker in cervical cancer screening of a group of Macedonian women. J Med Virol. 87:1578–1586. 2015. View Article : Google Scholar : PubMed/NCBI
29	Zhang Y, Wang J, Zhang R, Lei F and Lai S: Application value of detection of high-risk HPV infection in early cervical cancer patients in disease diagnosis and prognosis evaluation. Clin Lab. 66:2020. View Article : Google Scholar