Urine-based human papillomavirus DNA testing as a screening tool for cervical cancer in high-risk women

Abstract

Objective To test the hypothesis that self-collected urine could be used to detect high-risk human papillomavirus (HPV) DNA with sensitivity and specificity comparable to those of standard cervical testing. Methods Women attending a gynecology clinic for evaluation of abnormal cytology were recruited. Fifty-two participants (21–60 years of age) collected urine samples, and clinicians collected cervical brush samples. When appropriate, cervical biopsies were obtained during colposcopy. HPV detection and typing were performed on DNA extracts from each sample, using commercial reagents for L1 consensus polymerase chain reaction (PCR) and type-specific hybridization. HPV 16 viral load was determined by quantitative PCR in HPV 16-positive samples. A diagnostic test analysis was conducted for urine samples. Results Fifty paired samples were analyzed, with 76% agreement between samples. The 12 discrepant pairs were all urine negative/cervix positive. The most common HPV types detected were 16, 51, 53, and 62. The urine test correctly identified 100% of the uninfected and 65% of the infected patients. Conclusion The results indicate that HPV DNA detection using urine is less sensitive than cervical sampling in a population with abnormal cytology. Further exploration is warranted to determine clinical utility when other options are unavailable.

Detection of Genital HPV Infection Using Urine Samples: a Population Based Study in India

“…Urine is an adequate alternative specimen to monitor HPV prevalence among women when there are cultural and religious hardships in obtaining genital samples (Vorsters et al, 2012) (Enerly et al, 2013) (Mendez et al, 2014). Eventhough urine samples are less sensitive compared to cervical samples, it is inexpensive and more socially acceptable for large epidemiological surveys in developing countries.…”

Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes

“…To examine the hrHPV genome in urine ccfDNA, we developed custom dualsequence capture baits to enrich samples for hrHPV DNA from 12 high-risk types (HPV16, 18,31,33,35,39,45,51,52,56,58, and 59). We used liquid-based sequence capture baits to measure the hrHPV genome in urine ccfDNA from women with and without cervical premalignant lesions.…”

“…We compared samples from women with no intraepithelial lesions or malignancy (NILM) and CIN1 lesions with samples from women with CIN2 þ lesions and found that ZNF516 has 91.7% sensitivity, We then tested this panel of 3 classifiers in liquid-based cytology samples (n ¼ 67) from women in Puerto Rico, a subset of which had been previously tested for concordance of hrHPV genotype between cervical cytology and urine DNA (31). We compared samples from women with NILM and CIN1 lesions with samples from women with CIN2 þ lesions and found that ZNF516 has 72.7% sensitivity, 48.1% specificity, and an AUC of 0.63; FKBP6 has 63.6% sensitivity, 34.6% specificity, and an AUC of 0.50; INTS1 has 91% sensitivity, 35% specificity, and an AUC of 0.66.…”

“…Yet, there are no agreed upon clinical tests of progression (15,30). Recent reports have explored the use of urine-based hrHPV testing, as a complementary approach to liquid cytology for cervical cancer screening, in an attempt to identify less invasive screening technologies (31,32). Most of the studies have failed to attain clinical usefulness, as they are limited by poor sensitivity; inappropriate protocols for DNA extraction from circulating cellfree DNA (ccfDNA) in urine; and the limit of detection of the HPV assays utilized (33)(34)(35).…”

Reducing unnecessary Pap smears in a community clinic: Is the U.S. still over-screening for cervical cancer?

“…[5] Studies are beginning to explore the possibility of using urine testing as a non-invasive screening method to detect dangerous strains of HPV in women. [6,7] Using the current scientific knowledge, not screening women who are under the age of 21 years is now justified and recommended. [3,5] To prevent one true case of invasive cervical cancer in 20-24 year old women, the clinician would have to perform between 12,500 to 40,000 additional screening tests; a strong indication that cervical cancer is rare in this age group.…”