Comparison of Human Papillomavirus Detections in Urine, Vulvar, and Cervical Samples from Women Attending a Colposcopy Clinic

Abstract

e While urine-based sampling for human papillomavirus (HPV) is being explored as a simple and noninvasive approach for cervical cancer screening, data comparing HPV genotyping in urine and those in cellular sampling of the cervix and vulva, and their correlation with rigorously confirmed cervical disease status, are sparse. We performed HPV genotyping on voided-urine and clinician-collected vulvar and cervical samples from 72 women undergoing colposcopy. Although urine-based HPV carcinogenic HPV detection was lower (58.3%) than cervical (73.6%) and vulvar (72.1%) detection (P ‫؍‬ 0.05 and 0.07, respectively), the agreement of urine HPV with cervical and vulvar HPV was moderate (kappa ‫؍‬ 0.55) and substantial (kappa ‫؍‬ 0.62), respectively. Urine-based carcinogenic HPV detection had a clinical sensitivity of 80.8% (95% confidence interval [CI] ‫؍‬ 60.7 to 93.5) and a specificity of 53.3% (95% CI ‫؍‬ 37.9 to 68.3) for diagnosing cervical intraepithelial neoplasia grades 2/3 (CIN2/3) on histology; 90.0% of CIN3 was positive for urine HPV. The corresponding sensitivity and specificity values for vulvar sampling were 92% (95% CI ‫؍‬ 74 to 99) and 40.5% (95% CI ‫؍‬ 25.6 to 56.7), and those for cervical sampling were 96.2% (95% CI ‫؍‬ 80.4 to 99.9) and 40% (95% CI ‫؍‬ 25.7 to 55.7), respectively. HPV16 was the most common carcinogenic genotype detectable in 25% of urine, 33.8% of vulvar, and 31.9% of cervical samples overall, with prevalence increasing with cervical disease grade, regardless of the sampling method. Stronger cervical HPV PCR signal strengths were associated with increased frequency of urine HPV detection. In summary, the relatively lower detection rates but comparable clinical performance of urine-based HPV sampling underscore the need for larger studies to evaluate urine-based sampling for cervical cancer screening, epidemiologic studies, and postvaccination HPV disease surveillance. Human papillomavirus (HPV)-based primary screening or cotesting is being increasingly implemented as an alternative to cytology-based screening (1). Unlike cytology, HPV testing is amenable to simplified approaches for sample collection, including self-collected vaginal samples and urine-based sampling. These approaches may offer alternatives to clinic-based screening and improve access to care, particularly for hard-to-reach populations (2-11). While urine-based screening offers simplicity in sample collection, there are few studies of clinical performance of urine-based sampling and HPV genotypes detectable by this approach compared to that of cervical and external genital sampling in relation to rigorously confirmed cervical disease status. To expand the evidence in this area, we conducted a pilot study in a colposcopy referral population to evaluate HPV detection in voided urine samples, compare it to clinician-collected external genital (vulvar) and cervical sampling, and correlate results against histologically confirmed cervical disease ascertainment. MATERIALS AND METHODSThe study was nested within the National Ca...

Evaluation of clinical performance of a novel urine-based HPV detection assay among women attending a colposcopy clinic

“…The study, described previously 1, 4 , was nested within the National Cancer Institute (NCI) Biopsy Study, a population-based study of women referred to colposcopy for abnormal cervical cancer screening results, conducted at the University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK. Eligible and consenting participants provided first-void urine samples, prior to undergoing pelvic examination.…”

“…A study clinician collected each cervical sample using a Wallach broom, which was placed in a ThinPrep® vial (Hologic, Inc., Marlborough, MA) for liquid cytology and HPV genotyping. Each patient then underwent colposcopy and biopsy, as previously described 1, 4 .…”

“…Urine-based testing for human papillomavirus (HPV) has been explored as an alternative approach for cervical cancer screening 1, 2 . Yet, existing approaches for urine HPV testing have less than optimal analytical and clinical sensitivity, likely due to factors such as low levels of HPV DNA in urine, inappropriate extraction or amplification protocols, and the presence of contaminants or inhibitors 3 .…”

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

“…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.…”