Presence of High-Risk HPV MRNA in Relation to Future High-Grade Lesions Among High-Risk HPV DNA Positive Women with Minor Cytological Abnormalities

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Apr 21

PMID 25893988

Citations 12

Authors

Hanna Johansson

Kaj Bjelkenkrantz

Lotten Darlin

Joakim Dilllner

Ola Forslund

Affiliations

Soon will be listed here.

Abstract

Objective: Continuous expression of E6- and E7-oncogenes of high-risk human papillomavirus (HPV) types is necessary for the development and maintenance of the dysplastic phenotype. The aim of the study was to determine the sensitivity and specificity of the APTIMA HPV mRNA assay (Hologic) in predicting future development of high-grade cervical intraepithelial neoplasia (CIN) among high-risk HPV-DNA-positive women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous epithelial lesion (LSIL) cytology.

Methods: Archived SurePath cervical samples of women ≥ 35 years of age with high-risk HPV DNA-positive ASCUS (n = 211) or LSIL, (n = 131) were tested for the presence of high-risk HPV E6/E7 mRNA using the APTIMA HPV assay, and the women were monitored for development of histopathologically verified CIN2+.

Results: Twenty-nine percent (61/211) of the women in the ASCUS group, and 34.3% (45/131) in the LSIL group developed CIN2+ within 4.5 years of follow-up. The prevalence of HPV mRNA was 90.0% (95% CI 85.9-94.0) among women with ASCUS and 95.4% (95% CI 91.8-99.0) among women with LSIL. The presence of HPV E6/E7 mRNA was associated with future development of CIN2+ among women with ASCUS and LSIL (p=0.02). The mRNA assay demonstrated high sensitivity in predicting future CIN2+ and CIN3 for index ASCUS (96.7%; 95% CI 87.6-99.4 and 100%; 95% CI 82.2-100, respectively) and LSIL (97.8%, 95% CI 86.8-99.9 and 100%, 95% CI 79.9-100, respectively). The corresponding specificity was low, 12.7% (95% CI 7.9-19.3) and 5.8% (95% CI 2.2-13.6), for future CIN2+, respectively. The negative predictive value of the HPV mRNA assay for detecting future CIN3 was 100%, since no mRNA-negative woman developed CIN3 (0/27) as compared to 13.6% (43/315) of the mRNA-positive women (p = 0.03).

Conclusion: The APTIMA mRNA assay demonstrated high sensitivity but low specificity in predicting future CIN2+ among women with minor cytological abnormalities. The assay had high negative predictive value for future CIN3, indicating that HPV-mRNA-negative women are at low risk of progression to high grade CIN.

Citing Articles

Mathematical Modelling of Cervical Precancerous Lesion Grade Risk Scores: Linear Regression Analysis of Cellular Protein Biomarkers and Human Papillomavirus / RNA Staining Patterns.

Bumrungthai S, Ekalaksananan T, Kleebkaow P, Pongsawatkul K, Phatnithikul P, Jaikan J Diagnostics (Basel). 2023; 13(6).

PMID: 36980391 PMC: 10047622. DOI: 10.3390/diagnostics13061084.

E6/E7 mRNA Expression of the Most Prevalent High-Risk HPV Genotypes in Cervical Samples from Serbian Women.

Nikolic N, Basica B, Mandic A, Surla N, Gusman V, Medic D Diagnostics (Basel). 2023; 13(5).

PMID: 36900061 PMC: 10000477. DOI: 10.3390/diagnostics13050917.

Accuracy of high-risk HPV DNA PCR, p16 immunohistochemistry or the combination of both to diagnose HPV-driven oropharyngeal cancer.

Simoens C, Gheit T, Ridder R, Gorbaslieva I, Holzinger D, Lucas E BMC Infect Dis. 2022; 22(1):676.

PMID: 35933382 PMC: 9357318. DOI: 10.1186/s12879-022-07654-2.

Usefulness of E7 mRNA in HPV16-Positive Women to Predict the Risk of Progression to HSIL/CIN2.

Marti C, Marimon L, Glickman A, Henere C, Saco A, Rakislova N Diagnostics (Basel). 2021; 11(9).

PMID: 34573975 PMC: 8468571. DOI: 10.3390/diagnostics11091634.

14-type HPV mRNA test in triage of HPV DNA-positive postmenopausal women with normal cytology.

Asciutto K, Borgfeldt C, Forslund O BMC Cancer. 2020; 20(1):1025.

PMID: 33097006 PMC: 7583187. DOI: 10.1186/s12885-020-07498-6.

References

Waldstrom M, 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. 2011; 135(8):1052-6. DOI: 10.5858/2010-0411-OAR. View

Plummer M, Schiffman M, Castle P, Maucort-Boulch D, Wheeler C . A 2-year prospective study of human papillomavirus persistence among women with a cytological diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion. J Infect Dis. 2007; 195(11):1582-9. DOI: 10.1086/516784. View

Kirii Y, Matsukura T . Nucleotide sequence and phylogenetic classification of human papillomavirus type 67. Virus Genes. 1998; 17(2):117-21. DOI: 10.1023/a:1008002905588. View

Broccolo F, Fusetti L, Rosini S, Caraceni D, Zappacosta R, Ciccocioppo L . Comparison of oncogenic HPV type-specific viral DNA load and E6/E7 mRNA detection in cervical samples: results from a multicenter study. J Med Virol. 2013; 85(3):472-82. DOI: 10.1002/jmv.23487. View

Waldstrom M, Ornskov D . 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. 2011; 23(6):389-95. DOI: 10.1111/j.1365-2303.2011.00923.x. View

Safaeian M, Solomon D, Wacholder S, Schiffman M, Castle P . Risk of precancer and follow-up management strategies for women with human papillomavirus-negative atypical squamous cells of undetermined significance. Obstet Gynecol. 2007; 109(6):1325-31. DOI: 10.1097/01.AOG.0000263461.71732.40. View

Molden T, Kraus I, Skomedal H, Nordstrom T, Karlsen F . PreTect HPV-Proofer: real-time detection and typing of E6/E7 mRNA from carcinogenic human papillomaviruses. J Virol Methods. 2007; 142(1-2):204-12. DOI: 10.1016/j.jviromet.2007.01.036. View

Gage J, Schiffman M, Katki H, Castle P, Fetterman B, Wentzensen N . Reassurance against future risk of precancer and cancer conferred by a negative human papillomavirus test. J Natl Cancer Inst. 2014; 106(8). PMC: 4111283. DOI: 10.1093/jnci/dju153. View

Elfstrom K, Smelov V, Johansson A, Eklund C, Naucler P, Arnheim-Dahlstrom L . Long term duration of protective effect for HPV negative women: follow-up of primary HPV screening randomised controlled trial. BMJ. 2014; 348:g130. PMC: 3898575. DOI: 10.1136/bmj.g130. View

10.

Cuzick J, Arbyn M, Sankaranarayanan R, Tsu V, Ronco G, Mayrand M . Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries. Vaccine. 2008; 26 Suppl 10:K29-41. DOI: 10.1016/j.vaccine.2008.06.019. View

11.

Arbyn M, Martin-Hirsch P, Buntinx F, Van Ranst M, Paraskevaidis E, Dillner J . Triage of women with equivocal or low-grade cervical cytology results: a meta-analysis of the HPV test positivity rate. J Cell Mol Med. 2009; 13(4):648-59. PMC: 3822872. DOI: 10.1111/j.1582-4934.2008.00631.x. View

12.

Alanen K, Elit L, Molinaro P, McLachlin C . Assessment of cytologic follow-up as the recommended management for patients with atypical squamous cells of undetermined significance or low grade squamous intraepithelial lesions. Cancer. 1998; 84(1):5-10. View

13.

Schmitt M, Bravo I, Snijders P, Gissmann L, Pawlita M, Waterboer T . Bead-based multiplex genotyping of human papillomaviruses. J Clin Microbiol. 2006; 44(2):504-12. PMC: 1392679. DOI: 10.1128/JCM.44.2.504-512.2006. View

14.

Persson M, Elfstrom K, Brismar Wendel S, Weiderpass E, Andersson S . Triage of HR-HPV positive women with minor cytological abnormalities: a comparison of mRNA testing, HPV DNA testing, and repeat cytology using a 4-year follow-up of a population-based study. PLoS One. 2014; 9(2):e90023. PMC: 3936009. DOI: 10.1371/journal.pone.0090023. View

15.

Doorbar J . Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci (Lond). 2006; 110(5):525-41. DOI: 10.1042/CS20050369. View

16.

Munoz N, Bosch F, de Sanjose S, Herrero R, Castellsague X, Shah K . Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003; 348(6):518-27. DOI: 10.1056/NEJMoa021641. View

17.

Soderlund-Strand A, Carlson J, Dillner J . Modified general primer PCR system for sensitive detection of multiple types of oncogenic human papillomavirus. J Clin Microbiol. 2009; 47(3):541-6. PMC: 2650955. DOI: 10.1128/JCM.02007-08. View

18.

Cuschieri K, Wentzensen N . Human papillomavirus mRNA and p16 detection as biomarkers for the improved diagnosis of cervical neoplasia. Cancer Epidemiol Biomarkers Prev. 2008; 17(10):2536-45. PMC: 2900792. DOI: 10.1158/1055-9965.EPI-08-0306. View

19.

Arbyn M, Ronco G, Anttila A, Meijer C, Poljak M, Ogilvie G . Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine. 2012; 30 Suppl 5:F88-99. DOI: 10.1016/j.vaccine.2012.06.095. View

20.

Jeantet D, Schwarzmann F, Tromp J, Melchers W, van der Wurff A, Oosterlaken T . NucliSENS EasyQ HPV v1 test - Testing for oncogenic activity of human papillomaviruses. J Clin Virol. 2009; 45 Suppl 1:S29-37. DOI: 10.1016/S1386-6532(09)70006-X. View