Simultaneous detection of human papillomavirus integration and c-MYC gene amplification in cervical lesions: an emerging marker for the risk to progression

Arch Gynecol Obstet. 2016 Apr;293(4):857-63. doi: 10.1007/s00404-015-3870-3. Epub 2015 Aug 28.


Purpose: The persistence of high-risk oncogenic human papillomavirus (HR-HPV) infection and its integration into the host genome are key steps in the induction of malignant alterations. c-MYC chromosome region is a frequent localization for HPV insertion that has been observed in chromosome band 8q24 by fluorescence in situ hybridization (FISH). We report the HPV viral integration and amplification patterns of the c-MYC gene in cytological smears with FISH as a potential biomarker for the progression of squamous intraepithelial lesions (SIL).

Methods: HPV detection and genotyping by polymerase chain reaction (PCR) and FISH analysis by "Vysis Cervical FISH Probe" kit (ABBOTT Molecular Inc.) were performed in 37 cervical samples including 8 NILM, 7 ASC-US, 7 LSIL, 3 ASC-H, 7 HSIL and 5 SCC.

Results: The results show concordance between FISH and PCR techniques for HPV detection. The majority of the samples contained HR-HPV, the majority being -16 and -18 genotypes. HPV integration as determined by FISH was most frequent in high-risk lesions. The c-MYC gene amplification was found only in HPV-positive samples and was detected primarily in high-risk lesions and in cells with an integrated form of HPV.

Conclusions: HPV integration and c-MYC gene amplification detected by FISH could be an important biomarker for use in clinical practice to determine SIL with a risk of progression.

Keywords: Biomarkers; Cervical cancer; Human papillomavirus; Integration; c-MYC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Disease Progression
  • Female
  • Gene Amplification*
  • Genes, myc / genetics*
  • Genotype
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 18 / genetics
  • Humans
  • In Situ Hybridization, Fluorescence / methods*
  • Middle Aged
  • Papillomaviridae / genetics*
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / virology
  • Polymerase Chain Reaction / methods
  • Squamous Intraepithelial Lesions of the Cervix / diagnosis
  • Squamous Intraepithelial Lesions of the Cervix / genetics*
  • Squamous Intraepithelial Lesions of the Cervix / virology
  • Uterine Cervical Dysplasia / diagnosis
  • Uterine Cervical Dysplasia / genetics
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / virology