Oropharyngeal squamous cell carcinoma treated with radiotherapy or radiochemotherapy: prognostic role of TP53 and HPV status.
OBJECTIVE
To study the prognostic value of the TP53 mutation and human papilloma virus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC).


METHODS
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.
Fallai
Carlo
C
Radiation Oncology Department, Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy. carlo.fallai@istitutotumori.mi.it
Perrone
Federica
F
Licitra
Lisa
L
Pilotti
Silvana
S
Locati
Laura
L
Bossi
Paolo
P
Orlandi
Ester
E
Palazzi
Mauro
M
Olmi
Patrizia
P
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000532:radiotherapy / Q000821:virology; D018389:Codon, Nonsense / Q000235:genetics; D003131:Combined Modality Therapy / Q000379:methods; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53 / Q000235:genetics*; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000532:radiotherapy / Q000821:virology; D011379:Prognosis; D016019:Survival Analysis
D018389:Codon, Nonsense; D004279:DNA, Viral