Source: Clinical Cancer Research 15, 1779, March 1, 200
Author: Jens P. Klussmann et al.

Purpose:
Patients with human papillomavirus (HPV)-containing oropharyngeal squamous cell carcinomas (OSCC) have a better prognosis than patients with HPV-negative OSCC. This may be attributed to different genetic pathways promoting cancer.

Experimental Design:
We used comparative genomic hybridization to identify critical genetic changes in 60 selected OSCC, 28 of which were associated with HPV-16 as determined by HPV-specific PCR and fluorescence in situ hybridization analysis and positive p16INK4A immunostaining. The results were correlated with HPV status and clinical data from patients.

Results:
Two thirds of OSCC harbored gain at 3q26.3-qter irrespective of HPV status. In HPV-negative tumors this alteration was associated with advanced tumor stage (P = 0.013). In comparison with HPV-related OSCC, the HPV-negative tumors harbored: (a) a higher number of chromosomal alterations and amplifications (P = 0.03 and 0.039, respectively); (b) significantly more losses at 3p, 5q, 9p, 15q, and 18q, and gains/amplifications at 11q13 (P = 0.002, 0.03; <0.001, 0.02, 0.004, and 0.001, respectively); and (c) less often 16q losses and Xp gains (P = 0.02 and 0.03). Survival analysis revealed a significantly better disease-free survival for HPV-related OSCC (P = 0.02), whereas chromosome amplification was an unfavorable prognostic indicator for disease-free and overall survival (P = 0.01 and 0.05, respectively). Interestingly, 16q loss, predominantly identified in HPV-related OSCC, was a strong indicator of favorable outcome (overall survival, P = 0.008; disease-free survival, P = 0.01) and none of these patients had a tumor recurrence.

Conclusions:
Genetic signatures of HPV-related and HPV-unrelated OSCC are different and most likely underlie differences in tumor development and progression. In addition, distinct chromosomal alterations have prognostic significance.

Authors:
Jens P. Klussmann1, Jeroen J. Mooren5,6, Martin Lehnen1, Sandra M.H. Claessen5, Markus Stenner1, Christian U. Huebbers1,3, Soenke J. Weissenborn5, Inga Wedemeyer2, Simon F. Preuss1, Jos M.J.A.A. Straetmans6, Johannes J. Manni6, Anton H.N. Hopman5 and Ernst-Jan M. Speel5

Authors’ affiliations:
Departments of 1 Oto-Rhino-Laryngology, Head and Neck Surgery, and 2 Pathology, 3 Jean-Uhrmacher Institute, 4 Institute of Virology, University of Cologne, Cologne, Germany; and Departments of 5 Molecular Cell Biology and 6 Otorhinolaryngology, Head and Neck Surgery, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands