Molecular analyses of unselected head and neck cancer cases demonstrates that human papillomavirus transcriptional activity is positively associated with survival and prognosis.
Human papillomavirus DNA detection in head and neck squamous cell carcinoma has been linked to improved patient prognosis. The main aims of the study was to test the hypotheses that HPV16 E6/E7 oncogene and p53 function within tumours were associated with the widely reported improved patient survival and prognosis in head and neck cancer.



HPV16 DNA, mRNA and p53 mRNA presence were analysed in a prospective study of 42 unselected HNSCC patients; correlating the data with patient age, tumour staging/grade, treatment response, disease recurrence and survival.



HPV16 DNA and HPV16 mRNA were present in 45.2 % and 21.4 % of patients, respectively. There was a significant positive association between the detection of HPV16 E6/E7 mRNA and p53 mRNA (p = 0.032), but this was not replicated for HPV16 DNA. Five-year disease free survival for the whole cohort was 63 % (CI 52.5-73.5 %). Multivariable analysis revealed only HPV16 E6/E7 mRNA expression to have significant prognostic influence (p = 0.04).



Our study suggests that HPV16 oncogenic transcriptional activity within HNSCC tumours is associated with improved patient survival and better prognosis in a German population. Simple HPV DNA detection alone did not demonstrate this association. The significant association of full-length (wild-type) p53 with HPV16 E6/E7 mRNA is further evidence for a functional relationship, which could contribute to the widely reported improved survival and prognosis. Larger studies are required to validate the frequency of HPV16 mRNA expression in HNSCC.
Department of Pathology, University of Cambridge, Cambridge, UK.|Department of Otorhinolaryngology, Cambridge University Hospitals NHS Trust, Cambridge, UK.
Liam
L
Masterson
Department of Pathology, University of Cambridge, Cambridge, UK.
David M
DM
Winder
Department of Pathology, University of Cambridge, Cambridge, UK.
Siolian L R
SL
Ball
Department of Pathology, University of Cambridge, Cambridge, UK.
Katie
K
Vaughan
Department of Otorhinolaryngology, Bielefeld Academic Teaching Hospital, Bielefeld, Germany.
Martin
M
Lehmann
Department of Otorhinolaryngology, Bielefeld Academic Teaching Hospital, Bielefeld, Germany.
Lars-Uwe
LU
Scholtz
Department of Pathology, University of Cambridge, Cambridge, UK.
Jane C
JC
Sterling
Department of Otorhinolaryngology, Bielefeld Academic Teaching Hospital, Bielefeld, Germany.
Holger H
HH
Sudhoff
Department of Pathology, University of Cambridge, Cambridge, UK. peter.goon@nhs.net.
Peter K C
PK
Goon
D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality / Q000821:virology*; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality / Q000821:virology*; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality / Q000821:virology*; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D012097:Repressor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C059731:oncogene protein E7, Human papillomavirus type 16
HNSCC; Human papillomavirus; Molecular diagnosis and prognosis; p53