探索病毒对坦桑尼亚北部视网膜母细胞瘤易感性的影响：ENVISION-Tanzania研究

Background Retinoblastoma (RB) is the most common intraocular malignancy in children, with survival rates exceeding 90% in high-income countries but remaining unacceptably low in many low- and middle-income settings. While RB arises primarily from bi-allelic inactivation of the RB1 tumour suppressor gene, emerging evidence suggests that viral oncogenesis particularly from high-risk human papillomavirus (HR-HPV) may also contribute to tumour initiation and progression. The E6 and E7 oncoproteins of HR-HPV disrupt the p53 and pRb pathways, molecular mechanisms central to both HPV-driven malignancies and RB pathogenesis. However, the potential role of HR-HPV in RB remains poorly explored, especially in African populations where both HR-HPV prevalence and RB incidence are high. Generating region specific evidence could reshape understanding of RB biology and inform new preventive strategies Objective To investigate the association between maternal and tumour HR-HPV infection and the development of retinoblastoma in children in Northern Tanzania Methods This cross-sectional, hospital-based study will be conducted at Kilimanjaro Christian Medical Centre (KCMC), the principal paediatric oncology referral centre in Northern Tanzania. We aim to recruit 215 children diagnosed with RB and their 215 biological mothers. Enucleated tumour specimens will be processed into formalin-fixed, paraffin-embedded (FFPE) blocks for DNA extraction and HPV genotyping using PCR-based assays. Maternal cervical swabs will be collected and analysed for HR-HPV detection and genotyping. Quantitative RT-PCR will be used to assess E6 and E7 oncogene expression, while immunohistochemistry will localize viral proteins and evaluate the expression of key tumour suppressor proteins (pRb, p53, p16). Logistic regression models, adjusted for clinical and demographic variables, will be used to estimate the association between maternal HR-HPV infection and RB occurrence in offspring. Status The study is currently in the preparatory phase. Ethical approvals have been obtained, and logistical arrangements for molecular analysis are underway at KCMC's pathology and molecular oncology units. Expected Impact The ENVISION Tanzania study will generate the first molecular data examining viral contributions to RB in Sub-Saharan Africa. Identifying HR-HPV as a potential co-factor in RB pathogenesis could fundamentally shift paradigms in paediatric oncology by linking viral prevention strategies to childhood cancer control. Beyond its scientific contribution, the project aims to strengthen local molecular oncology capacity, foster North South research collaborations, and build a sustainable platform for infection-related cancer research in Tanzania.