We utilized a system that resembles the natural infection with HPV as closely as possible, comprising of primary KCs that stably maintain the hrHPV genome as episomes and were shown to undergo the entire differentiation-dependent HPV life cycle in organotypic raft cultures, non-infected primary KC cultures, and primary KCs newly infected with authentic HPV16 virions (13), to show that hrHPV presence renders KCs more resistant to both necroptosis and the antiproliferative effects instigated by IFNγ and TNFα and reveal the biological mechanisms responsible. Here, IFNG is linked to infection.