title: Evaluation of the performance of Human Papillomavirus testing in paired urine and clinician-collected cervical samples among women aged over 30 years in Bhutan.
abstract: 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.
authors.affiliation: Department of Obstetrics & Gynaecology, Jigme Dorji Wangchuck National Referral Hospital, Thimphu, Bhutan.
authors.forename: Ugyen
authors.initials: U
authors.lastname: Tshomo
authors.affiliation: International Agency for Research on Cancer, 150 cours Albert Thomas, 69372, Lyon cedex 08, France.
authors.forename: Silvia
authors.initials: S
authors.lastname: Franceschi
authors.affiliation: Department of Pathology & Laboratory Medicine, Jigme Dorji Wangchuck National Referral Hospital, Thimphu, Bhutan.
authors.forename: Tshokey
authors.initials: T
authors.lastname: Tshokey
authors.affiliation: Department of Pathology & Laboratory Medicine, Jigme Dorji Wangchuck National Referral Hospital, Thimphu, Bhutan.
authors.forename: Tashi
authors.initials: T
authors.lastname: Tobgay
authors.affiliation: International Agency for Research on Cancer, 150 cours Albert Thomas, 69372, Lyon cedex 08, France.
authors.forename: Iacopo
authors.initials: I
authors.lastname: Baussano
authors.affiliation: International Agency for Research on Cancer, 150 cours Albert Thomas, 69372, Lyon cedex 08, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Tenet
authors.affiliation: Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
authors.affiliation: International Agency for Research on Cancer, 150 cours Albert Thomas, 69372, Lyon cedex 08, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Gheit
authors.affiliation: International Agency for Research on Cancer, 150 cours Albert Thomas, 69372, Lyon cedex 08, France.
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
authors.affiliation: Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
authors.forename: Alex
authors.initials: A
authors.lastname: Vorsters
authors.affiliation: International Agency for Research on Cancer, 150 cours Albert Thomas, 69372, Lyon cedex 08, France. clifford@iarc.fr.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Clifford
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001631:Bhutan; D001706:Biopsy; D002584:Cervix Uteri / Q000821:virology*; D003127:Colposcopy; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D013048:Specimen Handling / Q000379:methods*; D014556:Urine / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*; D055815:Young Adult
keywords: Bhutan; Cervical cancer; Human papillomavirus; Urine