MYCN and infection: It has been suggested that infection by the human papillomavirus, which is more prevalent in LMICs, is associated with the development of nonhereditary retinoblastoma, and it is possible that this could be associated with more aggressive disease behavior.35 Another possible explanation relates to the genetic landscape of retinoblastoma and especially to cases with no RB1 mutation but a high level of amplification of the oncogene MYCN. 36 These cases are unilateral, develop at an early age, and show aggressive features.