Oral lichen planus (OLP) can undergo malignant transformation and become squamous cell carcinoma (SCC). Oral infection with human papillomavirus (HPV) is associated with a significant risk of developing oral cancer. Although HPV DNA is detected more often in OLP tissue than in normal oral mucosa, there is as yet no firm evidence that HPV is a causative factor of malignant transformation in OLP. The objective of the present investigation was to assess HPV-genotype distribution in OLPs of Japanese patients and additionally to clarify the relationship between malignant transformation in OLP and HPV infection using PCR, in situ hybridization, and immunohistochemistry. DNA of 200 formalin-fixed, paraffin-embedded biopsy and surgical specimens of OLP was extracted. HPV infection was first detected by PCR using consensus HPV primers. Positive PCR samples were then further analyzed by PCR using HPV type-specific primers (HPV-6, -11, -16, -18 and -33). Eighty-three samples (41.5 %) out of the total 200 OLP specimens analyzed were HPV positive. In the HPV type-specific PCR assay, the most frequent type of HPV was HPV-16 (25.5 %), which is a high-risk type of HPV that is associated with malignant disorders and is often detected in SCC. The highest HPV-16 positive rate was obtained for the erosive type of OLP (28.3 %). Positive staining for HPV DNA by in situ hybridization was observed in the nuclei of cells in all layers of the epithelium in all HPV PCR positive samples. Immunohistochemically, nuclei of cells in the upper layer of the epithelium in all HPV PCR positive samples stained positive for the anti-HPV antibody. These results indicated that HPV-16 was often present in OLP of Japanese patients, especially in the erosive type of OLP, and suggested that HPV infection is a risk factor for malignant transformation in OLP lesions.
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