Clinical significance of human papillomavirus infection in patients with oral squamocellular carcinoma
aInstitute for Medical Research, Crnotravska 17, Belgrade, bClinic of Maxillofacial Surgery, Military Medical Academy, Crnotravska 17, Belgrade
Background: Despite the improvements of treatment, oral cancer still has a high mortality rate. Infection with "high risk" HPVs (human papillomavirus) has been suggested to play a significant role in the development of various epithelial carcinomas and their response to therapy. Aim: The objective of this study was to determine the role of HPV in assotiation with other risik factors in oral squamous cell carcinomas (OSCC) and to find the correlation beetwen HPV infection with clinical parametars (stage of disease, hystological and nuclear grade, smoking and alcochol consumption) and clinical course of disease. Methods: We analysed 50 patients with stage II and III of hystologically confirmed OSCC of the tonguae or oral floor (hystological and nucler grade 1, 2 or 3). Patients were 45-72 years old, 97% were heavy smokers, 93% were alcochol consumers. Genomicic DNA was isolated according to standard procedure with phenol/chloroform/isoamilalcohol. Presence of HPV types 16, 18, 31 and 33 was detected by PCR/PAGE. Results: HPV infection was detected in 64% of patients. HPV16 was found in 10 pts (31.2%), HPV18 and HPV31 in 6 (18.7%) and none with HPV 33. Double positeve HPV infection HPV16+31 was detected in 3 patients (9.3%) and HPV18+31 in 7 patients (21%). Tumors in clinical stage III was more likely to contain HPV (58%). Moderately-differentiated OSCC with medium-nuclear grade were more likely to contain HPV (46.8%), well-differentiated to (40.6%) and poorly- differentiated in only (12.5%). Low-nuclear grade was detected in 28.1% and high-nuclear grade in 25% HPV positive tumors. Tobaco usage and alcochol consumption were an dependent predictor of HPV risk for OSCC. Disease-free interval (DFI) of patients ranged from 4 to 36 months. DFI and overall survival (OS) in pts with HPV infection compared to the pts without HPV infection was significantly shorter (log rank test). Conclusion: Infection with oncogenic HPV is frequent in oral cancers. Viral oncogene expression and viral integration suggest firm correlation between HPV infection and clinical course of disease in the examined grouop of patients.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 791 (Viral infections).