Tshomo Ugyen, Franceschi Silvia, Tshokey Tshokey, Tobgay Tashi, Baussano Iacopo, Tenet Vanessa, Snijders Peter J F, Gheit Tarik, Tommasino Massimo, Vorsters Alex, Clifford Gary M
Department of Obstetrics & Gynaecology, Jigme Dorji Wangchuck National Referral Hospital, Thimphu, Bhutan.
International Agency for Research on Cancer, 150 cours Albert Thomas, 69372, Lyon cedex 08, France.
Virol J. 2017 Apr 8;14(1):74. doi: 10.1186/s12985-017-0744-2.
Urine sampling may offer a less invasive solution than cervical sampling to test for human papillomavirus (HPV) for HPV vaccine impact monitoring.
Paired samples of urine and exfoliated cervical cells were obtained for 89 women with history of high-risk (HR) HPV-positive normal cytology in Bhutan. Urine sampling protocol included self-collection of first-void urine immediately into a conservation medium and procedures to optimize DNA yield. Colposcopical abnormalities were biopsied. Two HPV assays were used: a multiplex type-specific PCR (E7-MPG) and a less analytically sensitive GP5+/6+ PCR followed by reverse line blot.
HPV positivity for 21 types common to both assays was similar in urine and cells by E7-MPG (62.9% and 57.3%, respectively, p = 0.32) but lower in urine by GP5+/6+ (30.3% and 40.4%, p = 0.05). HPV6/11/16/18 positivity did not significantly differ between urine and cells by either assay. Sensitivity of urine (using cells as gold standard) to detect 21 HPV types was 80% and 58% for E7-MPG and GP5+/6+, respectively, with specificity 61% and 89%. HPV type distribution in urine and cells was similar, regardless of assay. The 5 detected CIN3+ were HR-HPV positive in cells by both assays, compared to 4 and 3 by E7-MPG and GP5+/6+, respectively, in urine samples.
For the monitoring of vaccine impact, we demonstrate validity of a urine sampling protocol to obtain HPV prevalence data that are broadly comparable to that from cervical cells. However, detection of HPV in urine varies according to assay sensitivity, presumably because low level infections are frequent.
对于人乳头瘤病毒（HPV）疫苗影响监测而言，尿液采样可能比宫颈采样提供一种侵入性较小的检测解决方案。
在不丹，为89名有高危（HR）HPV阳性且细胞学正常病史的女性采集配对的尿液和宫颈脱落细胞样本。尿液采样方案包括将首次晨尿立即自行采集到保存介质中以及优化DNA产量的程序。对阴道镜检查异常进行活检。使用了两种HPV检测方法：多重型特异性PCR（E7-MPG）和分析灵敏度较低的GP5+/6+ PCR，随后进行反向线印迹分析。
两种检测方法共有的21种HPV类型的阳性率在尿液和细胞中，通过E7-MPG检测时相似（分别为62.9%和57.3%，p = 0.32），但通过GP5+/6+检测时尿液中的阳性率较低（30.3%和40.4%，p = 0.05）。通过任何一种检测方法，尿液和细胞中HPV6/11/16/18的阳性率均无显著差异。以细胞作为金标准，尿液检测21种HPV类型的灵敏度，E7-MPG为80%，GP5+/6+为58%，特异性分别为61%和89%。无论采用哪种检测方法，尿液和细胞中的HPV型别分布相似。检测到的5例CIN3+病例在细胞中两种检测方法均为HR-HPV阳性，而在尿液样本中，E7-MPG检测到4例，GP5+/6+检测到3例。
对于疫苗影响监测，我们证明了一种尿液采样方案的有效性，该方案可获得与宫颈细胞广泛可比的HPV流行率数据。然而，尿液中HPV的检测因检测方法的灵敏度而异，推测是因为低水平感染很常见。
