Single‐cell RNA‐sequencing dissects cellular heterogeneity and identifies two tumor‐suppressing immune cell subclusters in HPV‐related cervical adenosquamous carcinoma

The intratumor heterogeneity of human papillomavirus (HPV)-related cervical cancer remains poorly defined. We performed single-cell RNA sequencing on 18 046 individual cells derived from two HPV-related cervical adenosquamous carcinoma samples to analyze the transcriptional heterogeneity of both epithelial and immune constituents, identifying seven epithelial (Epi1-7) and 11 immune subclusters. Based on expression of known cervical cancer markers, Epi1-2 primarily displayed features of adenocarcinoma, whereas Epi3-6 were instead characterized by features of squamous carcinoma. Our analyses also revealed that hypoxia and Kirsten rat sarcoma viral oncogene signaling were highly represented within Epi1; metabolic pathways mediating glycolysis and oxidative phosphorylation were enriched in Epi2-4; while Epi5 was enriched in p53 pathway components and features of epithelial-mesenchymal transition. Moreover, CD8