title: Urine testing to monitor the impact of HPV vaccination in Bhutan and Rwanda.
abstract: Bhutan (2010) and Rwanda (2011) were the first countries in Asia and Africa to introduce national, primarily school-based, human papillomavirus (HPV) vaccination programmes. These target 12 year-old girls and initially included catch-up campaigns (13-18 year-olds in Bhutan and ninth school grade in Rwanda). In 2013, to obtain the earliest indicators of vaccine effectiveness, we performed two school-based HPV urine surveys; 973 female students (median age: 19 years, 5th-95th percentile: 18-22) were recruited in Bhutan and 912 (19 years, 17-20) in Rwanda. Participants self-collected a first-void urine sample using a validated protocol. HPV prevalence was obtained using two PCR assays that differ in sensitivity and type spectrum, namely GP5+/GP6+ and E7-MPG. 92% students in Bhutan and 43% in Rwanda reported to have been vaccinated (median vaccination age = 16, 5th-95th: 14-18). HPV positivity in urine was significantly associated with sexual activity measures. In Rwanda, HPV6/11/16/18 prevalence was lower in vaccinated than in unvaccinated students (prevalence ratio, PR = 0.12, 95% confidence interval, CI: 0.03-0.51 by GP5+/GP6+, and 0.45, CI: 0.23-0.90 by E7-MPG). For E7-MPG, cross-protection against 10 high-risk types phylogenetically related to HPV16 or 18 was of borderline significance (PR = 0.68; 95% CI: 0.45-1.01). In Bhutan, HPV6/11/16/18 prevalence by GP5+/GP6+ was lower in vaccinated than in unvaccinated students but CIs were broad. In conclusion, our study supports the feasibility of urine surveys to monitor HPV vaccination and quantifies the effectiveness of the quadrivalent vaccine in women vaccinated after pre-adolescence. Future similar surveys should detect increases in vaccine effectiveness if vaccination of 12 year-olds continues.
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: Ministry of Health of Rwanda, Kigali, Rwanda.
authors.forename: M
authors.initials: M
authors.lastname: Chantal Umulisa
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: 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: 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 Laboratory Services, Jigme Dorji Wangchuck National Referral Hospital, Thimphu, Bhutan.
authors.forename: Tshokey
authors.initials: T
authors.lastname: Tshokey
authors.affiliation: Ministry of Health of Rwanda, Kigali, Rwanda.
authors.forename: Maurice
authors.initials: M
authors.lastname: Gatera
authors.affiliation: Ministry of Health of Rwanda, Kigali, Rwanda.
authors.forename: Fidele
authors.initials: F
authors.lastname: Ngabo
authors.affiliation: Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Van Damme
authors.affiliation: Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 Amsterdam, HV, 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: Massimo
authors.initials: M
authors.lastname: Tommasino
authors.affiliation: Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of 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.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Clifford
mesh_terms: D000293:Adolescent; D052685:Alphapapillomavirus / Q000145:classification / Q000235:genetics; D001631:Bhutan / Q000453:epidemiology; D015415:Biomarkers; D002648:Child; D005260:Female; D006801:Humans; D017063:Outcome Assessment, Health Care; D030361:Papillomavirus Infections / Q000517:prevention & control* / Q000652:urine* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011159:Population Surveillance; D015995:Prevalence; D012307:Risk Factors; D012432:Rwanda / Q000453:epidemiology; D016482:Urinalysis; D014611:Vaccination; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053918:Papillomavirus Vaccines
keywords: Bhutan; HPV; HPV vaccination; Rwanda; effectiveness; urine