Oropharyngeal squamous cell carcinoma treated with radiotherapy or radiochemotherapy: prognostic role of TP53 and HPV status

Int J Radiat Oncol Biol Phys. 2009 Nov 15;75(4):1053-9. doi: 10.1016/j.ijrobp.2008.12.088. Epub 2009 Jul 4.

Abstract

Purpose: To study the prognostic value of the TP53 mutation and human papilloma virus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC).

Methods and materials: The TP53 mutation and HPV status were analyzed in 78 cases of locoregionally advanced OPSCC. The possible correlation of these factors with locoregiownal control, relapse-free survival, disease-specific survival, and overall survival (OS) was also investigated.

Results: Of these 78 cases, 22 had disruptive and 22 had non-disruptive (silent) TP53 mutations; the remaining 34 cases had wild-type (WT) TP53. HPV 16 DNA was found in 9 cases (11%), but all HPV-positive (HPV+) cases carried a functional p53 protein, except for 1 case that had a silent mutation. HPV+ patients fared better than HPV-negative (HPV-) patients in terms of all survival parameters, with highly statistically significant differences between the groups. Specifically, no distant metastases were observed in the HPV+ patients, whereas they occurred in 17% of the HPV- patients. However, no difference was observed between the WT TP53 and mutation group, even when this was analyzed in terms of disruptive and non-disruptive mutations. Regardless, treatment with chemotherapy nearly doubled the 5-year OS rates, both in the mutation (42% vs. 22%) and WT (30 vs. 16%) group, but only the mutation group showed improvement in all survival parameters. In addition, the second tumor-free 5-year survival rate was 72% in HPV- cases, but no second tumors were observed in HPV+ and WT p53 cases.

Conclusions: Patients with HPV+ OPSCC have an excellent prognosis after radiochemotherapy, but cisplatin-based chemotherapy may not confer a satisfactory outcome, especially in WT cases, thereby justifying the additional or alternative use of taxanes and epidermal growth factor receptors inhibitors. Uncommon distant metastases and second tumors in the HPV+ group may be cause for clinicians to review the follow-up policies in these patients.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / mortality
  • Carcinoma, Squamous Cell* / radiotherapy
  • Carcinoma, Squamous Cell* / virology
  • Codon, Nonsense / genetics
  • Combined Modality Therapy / methods
  • DNA, Viral / isolation & purification
  • Female
  • Gene Deletion
  • Genes, p53 / genetics*
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / isolation & purification*
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Mutation, Missense / genetics
  • Oropharyngeal Neoplasms* / drug therapy
  • Oropharyngeal Neoplasms* / genetics
  • Oropharyngeal Neoplasms* / mortality
  • Oropharyngeal Neoplasms* / radiotherapy
  • Oropharyngeal Neoplasms* / virology
  • Prognosis
  • Survival Analysis

Substances

  • Codon, Nonsense
  • DNA, Viral