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Editorials

Urine testing for HPV

BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g5542 (Published 16 September 2014) Cite this as: BMJ 2014;349:g5542
  1. Henry C Kitchener, professor and chair of gynaecological oncology,
  2. Gemma L Owens, academic clinical fellow in obstetrics and gynaecology
  1. 1Institute of Cancer Sciences, University of Manchester, St Mary’s Hospital, Manchester M13 9WL, UK
  1. Correspondence to: H C Kitchener henry.kitchener{at}manchester.ac.uk

A promising screening option that deserves further evaluation

Cervical screening has traditionally relied on samples of cervical cells, taken under direct vision by a doctor, using either a conventional cervical smear test or, more recently, liquid based cytology. The causal role of high risk types of human papillomavirus (HPV) in cervical carcinogenesis has led to the rigorous evaluation of HPV DNA testing of cervical samples in primary screening. A pooled analysis1 of four European randomised trials2 3 4 5 comparing cytology with cytology plus HPV testing over at least two screening rounds, reported that the combination increased protection by 60-70% compared with cytology alone. HPV testing is now set to replace cytology in several national screening programmes. HPV testing can be performed on self collected samples, including urine. In a linked paper (doi:10.1136/bmj.g5264) Pathak and colleagues report on the accuracy of HPV testing on urine samples compared with cervical samples obtained by a doctor.6

In recent years, coverage in cervical screening in the United Kingdom has fallen below 80%,7 particularly among women aged 25-30. Aside from possible increasing indifference to prevention among young women, documented barriers to cervical screening include practical problems such as difficulty arranging a convenient appointment, as well as emotional factors such as embarrassment or fear of a speculum examination.7

One means of overcoming some of these difficulties is self sampling, allowing women to obtain their own samples at a time of their choosing and in a more personal setting. To date, self sampling for cervical screening has been most extensively explored using vaginal swabs, which on meta-analysis have been shown to have a pooled sensitivity, when compared with cervical sampling, of 76% for cervical intraepithelial neoplasia (CIN) grade 2 or worse and 84% for grade 3 or worse.8

Given the added sensitivity of HPV testing alone over cytology alone9 and the potential to increase uptake of screening, the reduced sensitivity associated with self sampling could be considered acceptable.

The rigorous review by Pathak and colleagues is therefore timely, and reports that, compared with cervical samples, urine HPV testing has a pooled sensitivity of 77% and a specificity of 94% to detect the high risk types of HPV required for cervical screening.6 The studies in the review did not use a uniform approach and there were clear variations in timing of collection of the urine sample (random, first void, or midstream), volume analysed, storage temperature, and method used to detect HPV. Additionally, the meta-analysis pooled studies conducted in a range of clinical settings on cohorts of different ages, although in some respects this might increase the reliability and generalisability of the findings. Urine testing emerges as a potentially useful self sampling screening test for HPV infection.

But there is more work to do. Unlike vaginal self samples, urine samples have not been evaluated for the outcome that matters most—the detection of 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. Several studies of vaginal self sampling have specifically targeted this vulnerable group. Response rates were highest in the Netherlands10 and Sweden11 where uptake was increased by 30%, but lower in London.12 Women who test positive for HPV by whatever method require immediate cytology on a subsequent cervical sample to determine ongoing management, but compliance with follow-up among women testing HPV positive has been as high as 90%.13

If serious consideration is to be given to using urine HPV testing in cervical screening programmes, then further evaluation is essential, including 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. Participants could do both tests without the quality of one sample being reduced by the other. The study could be performed in women attending for routine screening, with urine and vaginal samples collected before the “gold standard” cervical sample. Ideally, samples would be obtained using standardised protocols and tested using a single validated HPV test.

Although self sampling is usually regarded as a screening option for women who have previously defaulted, no doubt many other eligible women would also prefer self testing. Although a degree of reduced sensitivity may be acceptable for non-attenders, more widespread use in screening programmes would require urine HPV testing to be as sensitive as cervical sampling, otherwise the extra diagnostic performance associated with HPV testing would be lost. Using an under-performing HPV test would prevent programmes from extending their screening intervals from three years to five or six years—one of the principal benefits afforded by primary HPV screening.

In conclusion, HPV testing of self collected samples whether by urine or by vaginal swabs seems to provide a feasible alternative to HPV testing of cervical samples collected by health professionals under direct visualisation.

In well resourced health systems, self sampling could be used for women who are reluctant to attend for regular cervical screening. 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.

Notes

Cite this as: BMJ 2014;349:g5542

Footnotes

  • Research, doi:10.1136/bmj.g5264
  • Competing interest: We have read and understood the BMJ policy on declarations of interests and declare the following interests: HCK is chair of the Advisory Committee for Cervical Screening (Public Health England), but the views expressed in this article are those of the author and in no way reflect those of Public Health England.

  • Provenance and peer review: Commissioned; not externally peer reviewed.

References

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