Urine HPV Test as Alternative to Cervical Smear

Roxanne Nelson

September 16, 2014

A simple urine test for human papillomavirus (HPV) may be a more acceptable alternative to conventional screening methods that require a cervical smear, and could increase uptake in hard-to-reach subgroups.

Detecting HPV in urine could also potentially be used for post-vaccination HPV surveillance programs, where pelvic examination is not practical.

These suggestions come from a group of authors who report meta-analysis of published studies showing that DNA detected in urine had good accuracy for the presence of cervical HPV. The study was published online on September 16 in BMJ.

However, a related editorial suggests that although the idea of a urine HPV test is appealing, especially in underresourced countries, there is still a lot of work to be done, and the urine test needs to be validated alongside vaginal self-sampling.

Increased Accuracy at First Void

Led by Neha Pathak, of the Women’s Health Research Unit, Barts and the London School of Medicine and Dentistry, United Kingdom, the authors found a total of 16 articles reporting on 14 studies (n = 1443 women) that met their inclusion criteria and were eligible for the meta-analysis.

Most of these studies used commercial polymerase chain reaction methods on first-void urine samples.

The majority of the studies were using the urine HPV test for cervical cancer screening, but some used the test for HPV surveillance or follow-up of neoplasia.

The team found that sensitivity was moderate for detecting any HPV, as well as high-risk HPV strains. The specificity was especially high for any HPV and HPV 16 and 18, which are the most oncogenic strains, they comment.

The team reports that any HPV detected in urine samples had a pooled sensitivity of 87% (95% confidence interval [CI], 78% - 92%) and specificity of 94% (95% CI, 82% - 98%).

For high-risk HPV, the pooled sensitivity was 77% (68% - 84%) and specificity was 88% (58% - 97%). Urine detection of the highly oncogenic strains of HPV 16 and 18 had a pooled sensitivity of 73% (56% - 86%) and specificity of 98% (91% - 100%).

Upon metaregression, the authors observed a 22-fold increase in overall accuracy when urine samples were collected as first void, as compared with random or midstream urine samples (relative diagnostic odds ratio, 21.7). However, they point out that the difference in accuracy is based exclusively on a significant increase in sensitivity of first-void urine (relative sensitivity, 1.2; P = .004).

Conversely, specificity was not affected by the urine sampling method (P = .46). In addition, the purpose for testing, mean age of participants, HIV status, cytology and biopsy results, detection methods, use of commercial methods, or risk for bias as a result of patient selection did not explain any heterogeneity between indices for study accuracy.

Prospective Data and CIN Endpoint Needed

Although this meta-analysis shows that urine testing is a potentially useful self-sampling screening tool for HPV infection, there is more work to be done, according to an editorial in the same issue of BMJ.

Henry C Kitchener, MD, and Gemma L Owens, MB, BCh, BAO, BSc (Hons), both from the University of Manchester, United Kingdom, write that unlike vaginal self samples, urine self sampling has yet to evaluated for "the outcome that matters most," which is detecting cervical intraepithelial neoplasia (CIN).

"The success of screening for CIN depends on both the reliability of the test used and the coverage achieved, particularly if screening is aimed at previous non-attenders," they point out. "Several studies of vaginal self sampling have specifically targeted this vulnerable group."

If serious consideration is to be given to this method of HPV screening, further evaluation is essential, and this would include an "adequately powered, high quality prospective study comparing urine testing with vaginal self sampling and reporting the detection of high grade CIN as the primary endpoint," say the editorialists.

In addition, even though self sampling is generally regarded as a screening option for women who have "previously defaulted," there is no doubt that this method would appeal to other women as well, they further note.

"In well resourced health systems, self sampling could be used for women who are reluctant to attend for regular cervical screening," they conclude. "In lower income countries that lack infrastructure, self sampling might even be beneficial and cost effective for all women who are eligible for screening. More research is now required to identify the true clinical performance and acceptability of urine testing for HPV in both settings."

This study did not receive any funding. The authors have disclosed no relevant financial relationships.

BMJ. Published online September 16, 2014. Full text, Editorial


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