Human papillomavirus and mutated H-ras oncogene in cervical carcinomas and pathological negative pelvic lymph nodes: a retrospective follow-up

J Med Virol. 2008 Apr;80(4):694-701. doi: 10.1002/jmv.21076.

Abstract

The metastasis status of pelvic lymph nodes (PLNs) seems to be a predictive factor of survival. It was suggested that the presence of HPV DNA and other biological markers in PLN may indicate a sub clinical early metastasis. The aim was to describe the prevalence and distribution patterns of HPV DNA and H-ras mutations in intra operatively obtained cervical tumors and PLN. Thirty-seven cervical tumors and 61 lymph node biopsies from 37 patients with cervical cancer were selected. HPV typing and location were performed by PCR/dot blot and in situ hybridization (ISH) respectively. PCR/RFLP was used to scan for mutations in H-ras. Hundred percent of the cervical cancers and 85% of the PLN were HPV positive; co-infection with more than one type was 27%. HPV 16 was detected alone or co-infecting with other types in 84% of tumors and 46% of PLN; the second most frequent viral type was HPV 18 (tumor: 27%; PLN: 20%). In PLN, HPV was located in nuclei or/and cytoplasm of lymphocytes, macrophages, endothelial, and /or stromal cells. H-ras mutations were identified in 5/24 (21%) of patients with cervical tumors showing poor or moderated differentiation. HPV DNA in histological tumor-free PLN not necessary indicate metastasis, but it may be associated to an active immune reaction. Mutated H-ras is probably involved in cervical carcinogenesis and its detection in tumor and metastasis free PLN may be related to early metastasis or recurrence in at least a subset of poorly differentiated cervical tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cell Nucleus / virology
  • Cytoplasm / virology
  • DNA, Viral / genetics
  • Endothelial Cells / virology
  • Female
  • Follow-Up Studies
  • Genes, ras*
  • Human papillomavirus 16 / isolation & purification
  • Human papillomavirus 18 / isolation & purification
  • Humans
  • In Situ Hybridization
  • Lymph Nodes / virology*
  • Lymphocytes / virology
  • Macrophages / virology
  • Middle Aged
  • Mutation*
  • Papillomavirus Infections / virology*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Retrospective Studies
  • Stromal Cells / virology
  • Uterine Cervical Neoplasms / virology*

Substances

  • DNA, Viral