High-risk human papillomavirus in patients with oral leukoplakia and oral squamous cell carcinoma - A multi-centre study in Sweden, Brazil and Romania.

Objectives Although causal associations between oral leukoplakia (OL), oral squamous cell carcinoma (OSCC), and high-risk human papillomavirus (HR-HPV) have been speculated upon in several reports, conclusive evidence has not been presented. This study investigates whether the number of cases of HR-HPV in OL has increased over time and whether the prevalence of HR-HPV-positive OL differs in various parts of the world. Patients and methods A total of 432 patients with OL from Sweden, Brazil and Romania was analysed. Patients were divided into historical (1992-2002) and contemporary (2011-2017) cohorts from the respective countries. Seventeen patients with OL developed oral squamous cell carcinoma (OSCC). A Real-Time PCR assay, targeting HPV sub-types 6,11,16,18,31,33,35,39,45,52,56,58, and 59, was performed to detect HR-HPV in patients with OL. Results In the Swedish and Romanian cohorts none of the investigated HPV sub-types were detected. In the Brazilian cohorts, five patients with OL (3%) were positive for HR-HPV, including four patients from the contemporary cohort (HPV 16, 31, 33) and one from the historical cohort (HPV 11). All the cases of OL that transformed into OSCC were HR-HPV-negative, as were the corresponding tumours. Conclusions In summary, the prevalence of HR-HPV in OL is low in all the tested countries, and the incidence has not changed over time. HR-HPV in OL does not seem to be a driver of oncogenesis.