Risk of oral cancer associated with human papillomavirus infection, betel quid chewing, and cigarette smoking in Taiwan - an integrated molecular and epidemiological study of 58 cases

Background: The association between oral squamous cell carcinoma (OSCC) and human papillomavirus (HPV) 6, 11, 16 and 18 is uncertain. Past reports varied in the methodology and results. We conducted this study using in situ PCR in situ hybridization (ISH) assay which was considered as the most sensitive method for detection of viral DNA. We undertook an epidemiologic survey about the history of betel quid chewing and cigarette smoking, since these habits are common in Taiwan. Methods: In situ PCR ISH was performed on the tumor specimens from 29 patients with OSCC and the oral mucosal specimens from 29 patients without OSCC. Their betel quid chewing and cigarette smoking histories were also reviewed. Results: HPV16, HPV18, betel quid chewing and cigarette smoking were statistically significant risk factors in univariate analysis. HPV6 and 11 were not. Multivariate analysis showed that HPV16 infection (adjusted Odds ratio = 11.20) and betel quid chewing (adjusted Odds ratio = 17.06) remained to be independent factors for OSCC. Conclusions: Our results showed that HPV16 and betel quid chewing were two major risk factors for OSCC in Taiwan, indicating that they act through different mechanisms in the pathogenesis of OSCC.