HPV status in patients with head and neck of carcinoma of unknown primary site: HPV, tobacco smoking, and outcome.
OBJECTIVE
Infection with human papillomavirus (HPV) is linked to oropharyngeal cancer. This analysis investigated possible associations between HPV status, smoking history and survival outcome in patients with neck metastasis and carcinoma of unknown primary (CUP).


METHODS
Registries at the Universities of Hamburg and Kiel were searched for patients with CUP diagnosed from 2002 to 2011 who had formalin-fixed and paraffin-embedded metastatic lymph node samples available. All patients underwent routine diagnostic procedures to establish the primary site and received radiotherapy (60Gy using conventional fractionation) with or without concurrent cisplatin-based chemotherapy depending on disease extent. Genotyping was performed using polymerase chain reaction; p16([INK4a]) expression was assessed using immunohistochemistry.


RESULTS
Sixty-three patients were included; 23 (37%) had HPV DNA/p16+ samples and 40 (63%) were negative for either/both markers. A high proportion of patients had a history of tobacco smoking; significantly fewer patients with HPV+/p16+ samples were smokers than those who were negative for either/both markers (61% vs. 90%, respectively; p = 0.0067). There were no statistically significant differences between overall or recurrence-free survival in HPV+/p16+ patients vs. those negative for either/both markers. Overall survival appeared to be superior in patients with <10 pack-years smoking history and HPV+/p16+ disease.


CONCLUSIONS
This study, the largest to date investigating HPV status in head and neck CUP, identified HPV and p16 overexpression in over one-third of patients. Tobacco smoking history appeared to affect survival in HPV+/p16+ patients. Smoking status should be considered as a prognostic factor in patients with CUP, along with HPV DNA status.
Department of Radiation Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. tribius@uke.uni-hamburg.de
Silke
S
Tribius
Anna S
AS
Hoffmann
Sophie
S
Bastrop
Tibor
T
Görögh
Jochen
J
Haag
Christoph
C
Röcken
Till
T
Clauditz
Tobias
T
Grob
Waldemar
W
Wilczak
Pierre
P
Tennstedt
Aileen
A
Borcherding
Cordula
C
Petersen
Markus
M
Hoffmann
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000556:secondary / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000556:secondary / Q000821:virology*; D061809:Human Papillomavirus DNA Tests; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D006801:Humans; D008198:Lymph Nodes; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009333:Neck; D009382:Neoplasms, Unknown Primary / Q000401:mortality*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology*; D015996:Survival Rate; D013997:Time Factors
D019941:Cyclin-Dependent Kinase Inhibitor p16