Human Papillomavirus in Proliferative Verrucous Leukoplakia

Introduction: Proliferative verrucous leukoplakia (PVL) is an aggressive form of oral leukoplakia that progresses to oral squamous cell carcinoma in a high proportion of cases. Human papillomavirus (HPV) DNA has been found in PVL lesions, but with varying frequencies, ranging from 0-89%.

Objectives: 1) Determine the presence of HPV in PVL by polymerase chain reaction (PCR) through the dot-blot method. 2) Determine the strain variants of HPV 16 and other major oncogenic types in HPV-positive samples through sequencing of the E6 region.

Methods: Samples included 20 PVL and 23 non-PVL benign and malignant oral lesions as controls. The investigators were blinded to the histologic diagnosis of the tissues. Forty-three paraffin-embedded samples from 25 patients (12 males and 13 females) were amplified by PCR along with positive and negative controls for beta-globin and HPV. PCR products were probed for HPV using dot-blot. If positive for the HPV consensus, samples were further probed for over 40 different types of HPV, including HPV 16. Samples positive for HPV consensus but negative for the HPV types probed were considered to contain an unknown HPV type. Samples negative for beta-globin were excluded from the analysis.

Results: All samples were positive for beta-globin. Six of 43 samples (14%) were found to have HPV DNA: one of 20 (5%) PVL, three of 10 (30%) hyperkeratosis with mild epithelial dysplasia, one of 4 (25%) severe epithelial dysplasia, and one of one (100%) lichen planus. None were positive for HPV 16 and other major oncogenic types. Thus, none were sequenced for strain variants.

Conclusion: HPV was not found frequently in our PVL samples. A larger sample size is needed to better characterize the relationship between HPV and PVL and fresh-frozen samples will be studied to determine if specimen preservation method will affect the frequency of HPV detection.