AbstractAlmost all cases of cervical cancer (CC) can be attributed to high‐risk human papillomavirus (HPVs) infections in keratinocytes. However, it is unknown whether HPV invades immune cells such as macrophages and T cells. We analyzed the single‐cell transcriptome of the CC and its adjacent tissues and found that HPV16 genes, including E1, E6, and E7, expressed in the macrophages and CD8⁺ T cells in addition to the malignant cells. HPV16⁺ macrophages highly expressed the genes that promote cell adhesion and the favorable genes such as WAS, IQCB1, MYO1F, and PDZD11 in CC prognosis. The transcription factor KLF5 potentially accounted for the induction of these protective genes and thus facilitated the infiltration of the immune cells in tumor tissues. Our single‐cell transcriptome analysis suggests the potential value of the HPV16⁺ macrophage in CC prognosis. However, extensive experimental studies investigating the characteristics and functions of the HPV⁺ immune cells are still required.