HPV DNA and survivin expression in epithelial oral carcinogenesis: a relationship?

Abstract 

HPV has been thought to be involved in the development of several oral diseases, such as premalignant mucosal lesions and oral carcinoma. Survivin is a recently characterized IAP protein, which is abundantly expressed in most solid and haematological malignancies, but undetectable in normal adult tissues. Aim of this study was to investigate survivin expression and HPV presence in oral premalignant lesions and oral carcinoma. 47 samples of oral tissue including 11 squamous cell carcinomas (OSCC), 16 oral leukoplakias (OL) and 20 normal oral mucosa specimens, after investigation of HPV presence by nested PCR (consensus MY/GP primers) and viral genotype identification by direct sequencing were investigated by immunohistochemistry to detect survivin expression. Survivin expression was evident in 4/7 (57.1%) HPV+ and 4/4 (100%) HPV− OSCC, 6/7 (85.7%) HPV+ and 5/9 (55.5%) HPV− OL and in 0/20 (0%) control samples. Data showed high levels of survivin expression in HPV-positive SCCs, even if mean values were lower than HPV-negative ones, which in particular showed survivin expression in 100% of cases. Conversely, survivin expression was greater in HPV+ precancerous lesions than in HPV− ones. Our findings suggest that survivin may be involved in HPV- mediated deregulation during maturation of squamous epithelium through modulation of the apoptotic processes and, conversely, HPV may have a direct or indirect effect on the regulation of the survivin expression level. In particular, the results of this study suggest distinguishing between cancerous and precancerous oral lesions with respect to survivin expression when HPV infection is present. The most unfavourable behaviour is likely to be for the HPV− OSCC.

Keywords:  Survivin, HPV, Oral squamous cell carcinoma, Oral precancerous lesion, Epithelial carcinogenesis