Background: A significant portion of oropharyngeal squamous cell carcinomas (OSCC) has emerged to be associated with human papillomavirus (HPV) infection. HPV-DNA detection may have prognostic significance for OSCC however this has not been studied in relation to other predictive markers. Material and Methods: We analyzed 106 newly diagnosed OSCC treated between 1997 and 2002. Tumors were tested for HPV-DNA by multiple PCR assays. expression of p16 and epidermal growth factor receptor (EGFR) were determined by automat based immunohistochemistry. Predictive significance for disease-free and overall survival for these and additional clinical markers were examined using Kaplan-Meier method, log rank test and COX regression hazard model. Results: Of the tested carcinomas 28% contained oncogenic HPV and 30% were positive for p16. P16 expression was highly correlated with the presence of HPV-DNA (p<0.001). EGFR and p16 expression tended to be inversely correlated (p=0.083) with 65.5% of the p16 positive carcinomas being EGFR negative. Survival analysis revealed significant better outcome for p16 positive tumors for 5-year disease-free (84% vs. 49%, p=0.009), and overall survival (73% vs. 49%, p=0.07). There was a trend for better prognosis for EGFR negative tumors for disease-free (74% vs. 47%, p=0.08) and overall survival (70% vs. 45%, n.s.). Remarkable highly significant was the inverse combination of p16 and EGFR leading to 5-year disease-free survival estimates of 93% for p16+/ EGFR- tumors vs. 39% for p16-/ EGFR+ cases (p=0.005) and overall survival (79% vs. 38%, p=0.02). In multivariate analysis p16 remained to be a significant marker (p=0.059 overall-survival, p=0.03 disease-free survival) with p16 negative patients having a 4-fold risk for relapse. Conclusion: Our data indicate that p16 is a surrogate marker for most HPV positive OSCC and his prognostic impact is superior to all other tested predictors. Using p16 and EGFR in combination leads to highest prediction still applicable for routine histology.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]