Human papillomavirus integration perspective in small cell cervical carcinoma

Nat Commun. 2022 Oct 10;13(1):5968. doi: 10.1038/s41467-022-33359-w.


Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, we report human papillomavirus features and genomic landscape in SCCC via high-throughput HPV captured sequencing, whole-genome sequencing, whole-transcriptome sequencing, and OncoScan microarrays. HPV18 infections and integrations are commonly detected. Besides MYC family genes (37.9%), we identify SOX (8.4%), NR4A (6.3%), ANKRD (7.4%), and CEA (3.2%) family genes as HPV-integrated hotspots. We construct the genomic local haplotype around HPV-integrated sites, and find tandem duplications and amplified HPV long control regions (LCR). We propose three prominent HPV integration patterns: duplicating oncogenes (MYCN, MYC, and NR4A2), forming fusions (FGFR3-TACC3 and ANKRD12-NDUFV2), and activating genes (MYC) via the cis-regulations of viral LCRs. Moreover, focal CNA amplification peaks harbor canonical cancer genes including the HPV-integrated hotspots within MYC family, SOX2, and others. Our findings may provide potential molecular criteria for the accurate diagnosis and efficacious therapies for this lethal disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphapapillomavirus*
  • Carcinoma, Small Cell*
  • Female
  • Humans
  • Microtubule-Associated Proteins / genetics
  • N-Myc Proto-Oncogene Protein / genetics
  • Nuclear Proteins / genetics
  • Papillomaviridae / genetics
  • Papillomavirus Infections*
  • Uterine Cervical Neoplasms* / pathology
  • Virus Integration / genetics


  • ANKRD12 protein, human
  • Microtubule-Associated Proteins
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • TACC3 protein, human