Evaluating human papillomavirus vaccine introduction inTanzania and other low-resource settings.

Abstract

Evaluation of the success and impact of human papillomavirus (HPV) vaccine introduction and collation of key lessons learnt in low and middle-income countries (LAMICs) is now possible given the number of recent HPV vaccine pilots, or ‘demonstration projects’, and national programmes. Results may be useful for countries that have not yet commenced implementation of the HPV vaccine and may also be generalizable to future introductions of other pre-adolescent and adolescent vaccines. This PhD addresses four aspects of HPV vaccine introduction: 1) barriers to adherence to multi-dose vaccine schedules, 2) the potential impact of the HPV vaccine on human immunodeficiency virus (HIV) acquisition, 3) the potential impact of HPV vaccine introduction on other health services, and 4) lessons learnt and recommendations for HPV vaccine implementation in LAMICs. A systematic review of the published literature on factors influencing multi-dose vaccine adherence in adolescents was conducted. The paucity of published data from LAMICs meant that no geographical restriction was set in the search terms. The majority of research included in the synthesis originated in the United States of America (USA), where race, insurance status and parental healthcare seeking behaviour were found to be predictors of vaccine schedule completion. As vaccination programmes in older children become more established in LAMICs, more research is needed on factors influencing adherence in these settings. The association between HPV infection and subsequent HIV acquisition was assessed in a nested case-control study using stored cervical samples from previous study cohorts of Tanzanian and Ugandan women. In contrast to previous observational studies that have found an association between HPV infection and HIV acquisition in men and women, we found no evidence of an association between HPV infection, clearance or persistence, and subsequent HIV acquisition. This precluded the calculation of an estimate of the potential population attributable fraction for the effect of HPV infection (and vaccination) on HIV incidence. Data from health facility register books and interviews with health workers in two regions of Tanzania were analysed to examine the potential impact of HPV vaccination introduction through a demonstration project in Northern Tanzania in 2014 on the provision of routine primary health services. A controlled before-after analysis was carried out on count data of consultations at facilities involved in HPV vaccine delivery in Kilimanjaro Region, and control facilities in a neighbouring region. Interviews with health workers provided important contextual information. There was no evidence that the number of consultations at the health facilities fell during campaign weeks in intervention facilities compared to control facilities. Utilisation of the health facilities was highly variable. Interviews indicated that the quality of care provided at the facility during vaccination campaigns might be affected by staff absence. Lessons learnt from 37 LAMICs with at least one year of experience in HPV vaccine delivery were collated from 41 published articles, 124 pieces of unpublished literature, and 27 key informant interviews. Recommendations were formulated in 7 key themes: preparation, communication, delivery, coverage achievements, sustainability, value of demonstration projects and common pitfalls. Lessons were consistent across world regions and included the importance of collaboration during planning between the ministries of health and education, strategies to respond to rumours and challenges encountered during delivery. Key findings were disseminated widely and stimulated on-going supplemental research. There is now a large evidence base to support the rationale for HPV vaccine introduction and its successful delivery in LAMICs, which currently suffer the heaviest burden of cervical cancer disease in the world. To date, HPV vaccine delivery in low resource settings has achieved high coverage and experienced fewer barriers than expected. It is clear that if funding is available, LAMICs can effectively introduce the HPV vaccine nationally and prevent a high burden of a major and serious disease in women.