Growing molecular and clinical evidence indicates that human papillomavirus (HPV) is involved in the aetiology of oral squamous cell carcinomas (SCCs). HPV(+) tumours appear to be clinically distinct from HPV(−) tumours, conferring improved survival outcomes for patients in oropharyngeal cancer but limited knowledge exist on oral cancer. Determination of the HPV status of tumours may assist in patient risk-stratification and ultimately guide optimum treatment. The primary aim of this study was to examine the distribution of HPV in oral SCCs as assessed in vitro amplification assays and correlated with clinical and demographic data. The secondary aim was to correlate the positivity of HPV tumours with clinical outcome in the largest series of oral cancer published with a long follow-up (up to 20 years).

Materials and Methods One hundred thirty-one invasive oral SCCs were tested for HPV using laboratory-developed PCR assays for HPV16. P53 expression, tumour angiogenesis (CD-31 staining) and proliferation (MIB-1) were also assessed by immunohistochemistry in parafine embedded tissue. Patients mean age was 58.09±10.41, median 59 (116 men and 15 women). Clinical Stage distribution was: st I:17 cases; II: 56,III:32.IV:26. Most tumours were histological grade I (39) and II (74). Patients with pathological stage I-II were refereed to surgery (65 cases) and patients with Stage III-IVA were referred to surgery and postoperative radiation therapy (66 cases). Mean radiotherapy given doses were 62.13±7.74, median 65 Gy in 1.8-2 Gy fractions. No chemotherapy was used in any case.

Results 41 cases (31.3%) were HPV 16(+). No relation was found with age, gender, or tumour characteristics. In fact no relation was found to p53 expression, tumour proliferation or angiogenesis. 15-year DFS was 62.20% in HPV(+) patients was, compared to 37.3% in the HPV(-) group (p<0.076). In stage III-IV cases (treated by surgery and radiation therapy) this differences reached statistical signification (15 y DFS 72.4% vs 36.0% p<0.020). Similar results were found for Cause Especific Survival (15 y DFS 68.4% vs 26.2% p<0.054).

Conclusion These data show that the HPV status is a good predictor of DFS and survival in patients treated with radical surgery and adjuvant radiotherapy in oral carcinomas. This prognostic advantage seem to be independent of tumour proliferation, p53 status or angiogenesis. Other molecular processes could be implicated in the different response to radiotherapy.