Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Apr 22;6(4):e03745.
doi: 10.1016/j.heliyon.2020.e03745. eCollection 2020 Apr.

Detection of high-risk human papillomavirus RNA in urine for cervical cancer screening with HPV 16 & 18/45 genotyping

Radha Rani Padhy  1 , Adi Davidov  1 , Louise Madrigal  1 , Gina Alcide  1 , Almir Spahiu  1
Affiliations

Detection of high-risk human papillomavirus RNA in urine for cervical cancer screening with HPV 16 & 18/45 genotyping

Radha Rani Padhy et al. Heliyon. .

Abstract

Objective: To detect high-risk human papillomavirus (hrHPV) messenger-RNA (mRNA) in urine samples, compare their concordance with cervical samples including HPV 16 & 18/45 genotyping, and to determine the utility in detecting ≥ CIN 2 lesions.

Methods: A cohort of 189 non-pregnant patients (age ≥ 25) was recruited in three groups: Group 1 with abnormal pap-smears and hrHPV positivity, Group 2 with normal pap-smears and hrHPV positivity, and Group 3 with normal pap-smears and hrHPV negativity. Urine samples were tested for hrHPV-mRNA and subsequent hrHPV-mRNA genotype if positive. High-risk HPV detection and genotyping were performed using Aptima assays which are validated for cervical HPV testing. Colposcopy results from groups 1 & 2 were analyzed.

Results: The sensitivity of urine hrHPV-mRNA detection was 31.5% while the specificity and PPV were above 95% (96.9% & 95.1% respectively) (p < 0.001). The kappa agreement with cervical samples was fair (0.22, p = 0.04). The sensitivity and specificity of urine hrHPV-mRNA genotyping were 20.0% & 100% respectively (p < 0.001) with 100% genotype-specific concordance. The kappa agreement with cervical samples was fair (0.25, p = 0.16). For urine hrHPV-mRNA detection of ASC-H/HSIL when grouped by age ≥ 30, the sensitivity and specificity were 45.4% & 63.9% respectively (p = 0.009). For urine hrHPV-mRNA detection of ≥ CIN 2 for all ages, the sensitivity and specificity were 45.5% & 75.0% respectively (p = 0.03).

Conclusion: Using the Aptima Assay, urine hrHPV-mRNA detection is suboptimal for cervical cancer screening but given the high specificity, it has the potential to identify high-grade lesions (≥ CIN 2). Urine hrHPV-mRNA genotyping via this modality is not beneficial in triage settings of normal or abnormal cytology to determine the need for colposcopy.

Keywords: Cancer screening tests; Cervical intraepithelial neoplasia; Gynecology; HPV 16; HPV 18; HPV 45; Human papilloma virus; Messenger RNA; Oncology; Pap smear; Sensitivity; Specificity; Urine; Virology.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Study design and results. hrHPV: high-risk human papillomavirus, mRNA: messenger RNA, RNA: ribonucleic acid.
Figure 2
Figure 2
Proportion of urine hrHPV mRNA positive samples in Group 1 separated by cytology for age ≥30. hrHPV: high-risk human papillomavirus, HSIL: High-grade squamous intraepithelial lesion, ASC-H: Atypical squamous cells, cannot rule out HSIL, LSIL: Low-grade squamous intraepithelial lesion, ASCUS: Atypical squamous cells of undetermined significance.
Figure 3
Figure 3
Proportion of urine hrHPV mRNA positive samples in Groups 1 and 2 separated by histology. hrHPV: high-risk human papillomavirus, CIN: Cervical intraepithelial neoplasia.
See this image and copyright information in PMC

References

    1. Centers for Disease Control and Prevention Use of Pap-smears among women aged 18 and over, by selected characteristics: United States, selected years 1987-2015. https://www.cdc.gov/nchs/data/hus/2016/071.pdf
    1. Gakidou E., Nordhagen S., Obermeyer Z. Coverage of cervical cancer screening in 57 countries: low average levels and large inequalities. PLoS Med. 2008;5(6) - PMC - PubMed
    1. Asciutto K.C., Ernstson A., Forslund O. Self-sampling with HPV mRNA analyses from vagina and urine compared with cervical samples. J. Clin. Virol. 2018;101:69–73. - PubMed
    1. Cuschieri K., Cubie H., Graham C. Clinical performance of RNA and DNA based HPV testing in a colposcopy setting: influence of assay target, cut off and age. J. Clin. Virol. 2014;59(2):104–108. - PubMed
    1. Liu T.-Y., Xie R., Luo L. Diagnostic validity of human papillomavirus E6/E7 mRNA test in cervical cytological samples. J. Virol Methods. 2014;196:120–125. - PubMed