High-risk HPV DNA status and p16 (INK4a) expression as prognostic markers in patients with squamous cell cancer of oral cavity and oropharynx.

AIM OF THE STUDY: To determine and compare the influence of the HPV DNA status and p16(INK4a) expression on the outcome of postoperative radiotherapy for squamous cell cancer of the oral cavity or oropharynx. MATERIAL AND METHODS: 59 patients with high-risk squamous cell cancer of the oral cavity or oropharynx were enrolled. They underwent major surgery and postoperative radiotherapy. The HPV DNA status and p16(INK4a) expression were assessed with QPCR and immunohistochemistry and correlated with loco-regional control and overall survival. RESULTS: 15.3% of tissue samples were HPV positive. All positive patients were identified with HPV16 subtype infection, and no other subtypes of high-risk HPV were detected. 5-year LRC in HPV(+) patients was 100%, compared to 50% in the HPV(-) group. 17.9% of all samples had evident p16(INK4a) expression. Among HPV(+) cases, 55.6% showed p16(INK4a) expression. 5-year LRC in patients with p16(INK4a) expression was 89%, compared to 51% in the p16(INK4a) negative group but this tendency was not significant (p = 0.055). CONCLUSION: These data show that the HPV status is a good predictor of loco-regional control and overall survival in patients treated with radical surgery and adjuvant radiotherapy. The study shows a strong correlation between high-risk HPV infection and p16(INK4a) expression, but detection of viral DNA with QPCR has stronger prognostic potential.

PTEN as a prognostic and predictive marker in postoperative radiotherapy for squamous cell cancer of the head and neck.

BACKGROUND: Tumor suppressor PTEN is known to control a variety of processes related to cell survival, proliferation, and growth. PTEN expression is considered as a prognostic factor in some human neoplasms like breast, prostate, and thyroid cancer. METHODOLOGY/PRINCIPAL FINDINGS: In this study we analyzed the influence of PTEN expression on the outcome of a randomized clinical trial of conventional versus 7-days-a-week postoperative radiotherapy for squamous cell cancer of the head and neck. The patients with cancer of the oral cavity, oropharynx, and larynx were randomized to receive 63 Gy in fractions of 1.8 Gy given 5 days a week (CF) or 7 days a week (p-CAIR). Out of 279 patients enrolled in the study, 147 paraffin blocks were available for an immunohistochemical assessment of PTEN. To evaluate the prognostic value of PTEN expression and the effect of fractionation relative to PTEN, the data on the outcome of a randomized clinical trial were analyzed. Tumors with a high intensity of PTEN staining had significant gain in the loco-regional control (LRC) from p-CAIR (5-year LRC 92.7% vs. 70.8%, for p-CAIR vs. CF, p = 0.016, RR = 0.26). By contrast, tumors with low intensity of PTEN did not gain from p-CAIR (5-year LRC 56.2% vs. 47.2%, p = 0.49, RR = 0.94). The intensity of PTEN highly affected the LRC in a whole group of 147 patients (5-year LRC 80.9% vs. 52.3% for high vs. low PTEN, p = 0.0007, RR = 0.32). In multivariate Cox analysis, including neck node involvement, EGFR, nm23, Ki-67, p53, cyclin D1, tumor site and margins, PTEN remained an independent predictor of LRC (RR = 2.8 p = 0.004). CONCLUSIONS/SIGNIFICANCE: These results suggest that PTEN may serve as a potent prognostic and predictive marker in postoperative radiotherapy for high-risk squamous cell cancer of the head and neck.