Many high-income countries have established HPV vaccination programs from 2006 to 2008 and have already reported effectiveness versus individual HPV types, cervical lesions, and genital warts1. Bhutan (2010) and Rwanda (2011) were the first low-income countries to introduce national vaccination programme. These targeted 12 year-old girls (>90% coverage) and initially included catch-up campaigns (13–18 year-olds in Bhutan and ninth school grade in Rwanda). The two countries can therefore provide the earliest evaluation of such programs.
In 2013, IARC, in collaboration with the Ministries of Health, performed two school-based HPV urine surveys2. 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). In Bhutan, HPV6/11/16/18 prevalence by GP5+/GP6+ was lower in vaccinated than in unvaccinated students but CIs were broad.
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. In the future, as vaccinated cohorts of women will predominantly represent those vaccinated in pre-adolescence in Bhutan and Rwanda, similar repeat urine assays can be expected to detect greater increases in HPV vaccine effectiveness than in our present study. Medium/long-term monitoring in low-income countries would benefit from the introduction of HPV-based screening and the strengthening of cancer registries and mortality data. For the moment, if resources for surveillance of viral or clinical endpoint are lacking, priorities in LMICs should be monitoring coverage and side effects.
1. Brotherton JM, Jit M, Gravitt PE, Brisson M, Kreimer AR, Pai SI, Fakhry C, Monsonego J, Franceschi S. Eurogin Roadmap 2015: How has HPV knowledge changed our practice: Vaccines. Int J Cancer 2016;139: 510-7.
2. Franceschi S, Chantal Umulisa M, Tshomo U, Gheit T, Baussano I, Tenet V, Tshokey T, Gatera M, Ngabo F, Van Damme P, Snijders PJ, Tommasino M, et al. Urine testing to monitor the impact of HPV vaccination in Bhutan and Rwanda. Int J Cancer 2016;139: 518-26.