High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma.
OBJECTIVE
Human papillomavirus (HPV) DNA tumors actively integrating the E6 and E7 oncogenes have a distinct biologic behavior resulting in a more favorable prognosis. To which extent the viral integration by itself, and/or the associated wild-type (wt) TP53 status, and/or a functional p16 contribute to prognosis is unclear.


METHODS
To clarify how the presence of high-risk (HR) -HPV, TP53, and p16INK4a status interact with clinical outcome, we considered a retrospective series of 90 consecutive oropharyngeal cancer patients treated primarily with surgery.


RESULTS
Seventeen (19%) patients showed integrated HPV 16 DNA (HPV positive), wt TP53 in all but two patients, normal p16INK4a in 15 assessable patients, and p16 expression in all 17 patients. Thirty-five patients (39%), two of whom were HPV positive, harbored TP53 mutations. p16INK4a deletion and p16 null immunophenotype occurred in 28 and 58 patients, respectively, and was similarly distributed in both patients with mutated TP53 (48% and 82%, respectively) and in patients with wt TP53 (46% and 77%, respectively). Statistical analysis showed that HPV-positive status significantly affects all investigated end points: overall survival (P = .0018), incidence of tumor relapse (P = .0371), and second tumor (P = .0152), whereas TP53 and p16INK4a status and p16 expression were not prognostic by themselves.


CONCLUSIONS
Our molecular and clinical results are in agreement with previous findings but provide additional information into the biologic mechanisms involved in HR-HPV oropharyngeal cancer in comparison to HPV-negative tumors. According to the reduced risk of relapse and second tumors associated with HR-HPV positivity of oropharyngeal cancer, the therapeutic strategy and follow-up procedures should be reviewed.
Licitra
Lisa
L
Head and Neck Cancer Medical Oncology Unit, Medical Statistics and Biometry, Department of Head and Neck Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. lisa.licitra@istitutotumori.mi.it
Perrone
Federica
F
Bossi
Paolo
P
Suardi
Simona
S
Mariani
Luigi
L
Artusi
Raffaella
R
Oggionni
Maria
M
Rossini
Chiara
C
Cantù
Giulio
G
Squadrelli
Massimo
M
Quattrone
Pasquale
P
Locati
Laura D
LD
Bergamini
Cristiana
C
Olmi
Patrizia
P
Pierotti
Marco A
MA
Pilotti
Silvana
S
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000601:surgery / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000235:genetics; D004252:DNA Mutational Analysis; D004279:DNA, Viral; D005260:Female; D005500:Follow-Up Studies; D019942:Genes, p16; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016609:Neoplasms, Second Primary; D009959:Oropharyngeal Neoplasms / Q000401:mortality* / Q000601:surgery / Q000821:virology*; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications*; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral