Poor prognosis associated with human papillomavirus α7 genotypes in cervical carcinoma cannot be explained by intrinsic radiosensitivity

Int J Radiat Oncol Biol Phys. 2013 Apr 1;85(5):e223-9. doi: 10.1016/j.ijrobp.2012.11.030. Epub 2013 Jan 17.

Abstract

Purpose: To investigate the relationship between human papillomavirus (HPV) genotype and outcome after radiation therapy and intrinsic radiosensitivity.

Methods and materials: HPV genotyping was performed on cervix biopsies by polymerase chain reaction using SPF-10 broad-spectrum primers, followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse hybridization line probe assay (LiPA25) (version 1) (n=202). PapilloCheck and quantitative reverse transcription-polymerase chain reaction were used to genotype cervix cancer cell lines (n=16). Local progression-free survival after radiation therapy alone was assessed using log-rank and Cox proportionate hazard analyses. Intrinsic radiosensitivity was measured as surviving fraction at 2 Gy (SF2) using clonogenic assays.

Results: Of the 202 tumors, 107 (53.0%) were positive for HPV16, 29 (14.4%) for HPV18, 9 (4.5%) for HPV45, 23 (11.4%) for other HPV genotypes, and 22 (10.9%) were negative; 11 (5.5%) contained multiple genotypes, and 1 tumor was HPV X (0.5%). In 148 patients with outcome data, those with HPVα9-positive tumors had better local progression-free survival compared with α7 patients in univariate (P<.004) and multivariate (hazard ratio 1.54, 95% confidence interval 1.11-1.76, P=.021) analyses. There was no difference in the median SF2 of α9 and α7 cervical tumors (n=63). In the cell lines, 9 were α7 and 4 α9 positive and 3 negative. There was no difference in SF2 between α9 and α7 cell lines (n=14).

Conclusion: The reduced radioresponsiveness of α7 cervical tumors is not related to intrinsic radiosensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alphapapillomavirus / genetics*
  • Alphapapillomavirus / radiation effects
  • Biopsy
  • Cell Line, Tumor
  • Cervix Uteri / pathology
  • Cervix Uteri / virology
  • DNA Primers / genetics
  • Female
  • Genotype
  • Humans
  • Middle Aged
  • Papillomavirus Infections / mortality
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / radiotherapy
  • Papillomavirus Infections / virology*
  • Polymerase Chain Reaction / methods
  • Prognosis
  • Radiation Tolerance*
  • Retrospective Studies
  • Species Specificity
  • Time Factors
  • Tissue Preservation
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / radiotherapy*
  • Uterine Cervical Neoplasms / virology*
  • Young Adult

Substances

  • DNA Primers