Oral Cancer News

Source: Journal of Clinical Oncology, Vol 27, No 36 (December 20), 2009: pp. 6213-6221
Authors: Wei Shi et al.

Purpose:
A significant proportion of oropharyngeal squamous cell carcinomas (OSCC) are associated with the human papilloma virus (HPV), particularly HPV16. The optimal method for HPV determination on archival materials however, remains unclear. We compared a quantitative real-time polymerase chain reaction (qRT-PCR) assay for HPV16 mRNA to a DNA in situ hybridization (ISH) method, and evaluated their significance for overall (OS) and disease-free (DFS) survival.

Patients and Methods:
Matched, archival biopsies from 111 patients with OSCC were evaluated for HPV16 using a qRT-PCR for E6 mRNA and ISH for DNA. Immunohistochemistry for p16, p53, and epidermal growth factor receptor were also performed.

Results:
HPV16 E6 mRNA was positive in 73 (66%) of 111 samples; ISH was positive in 62 of 106 samples (58%), with 86% concordance. P16 was overexpressed in 72 samples (65%), which was strongly associated with HPV16 status by either method. E6 mRNA presence or p16 overexpression were significantly associated with superior OS; E6 mRNA, HPV16 ISH, or p16 were all significantly associated with DFS. On multivariate analysis adjusted for age, stage, and treatment, positive E6 mRNA was the only independent predictor for superior OS; for DFS, p16 expression or HPV16 status determined by either method was significant.

Conclusion:
The prevalence of HPV16 in OSCC ranges from 58% to 66%, in a recently treated Canadian cohort. Classification of HPV-positivity by HPV16 E6 mRNA, HPV16 ISH or p16 immunohistochemistry (IHC) is associated with improved DFS. However, the latter two assays are technically easier to perform; hence, HPV16 ISH or p16 IHC should become standard evaluations for all patients with OSCC.

Authors:
Wei Shi, Hisayuki Kato, Bayardo Perez-Ordonez, Melania Pintilie, Shaohui Huang, Angela Hui, Brian O’Sullivan, John Waldron, Bernard Cummings, John Kim, Jolie Ringash, Laura A. Dawson, Patrick Gullane, Lillian Siu, Maura Gillison, Fei-Fei Liu

Authors’ affiliations:
From the Departments of Medical Biophysics and Radiation Oncology; Dalla Lana School of Public Health Sciences, University of Toronto; Division of Applied Molecular Oncology, and the Department of Pathology, Ontario Cancer Institute, University Health Network; Department of Radiation Oncology, and the Divisions of Biostatistics, Surgical Oncology, and Medical Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada; and Division of Medical Oncology, Ohio State University Medical Center, Columbus, OH.