Langerhans' cells, papillomaviruses and oesophageal carcinoma. A hypothesis

A hypothesis linking the concept of mucosal immune surveillance (Langerhans' cells and intra-epithelial lymphocytes) with recent evidence of human papillomavirus (HPV) infection of the oesophagus in a sequence of events which leads to squamous dysplasia and invasive carcinoma is presented. It is believed that the essential pathway to squamous carcinoma involves an aberration of the Langerhans' cell/lymphocyte network and its symbiotic relationship with squamous cells as a result of persistent HPV infection in the epithelium. Neoplastic transformation may occur when this 'at-risk' mucosa is exposed to one or several co-carcinogenic factors present in the environment. This hypothesis is supported by morphological changes present in acanthotic lesions of the oesophagus and by immunocytochemical evidence of HPV infection of the mucosa. In addition, this viewpoint offers a possible explanation for the regional variation of oesophageal carcinoma, the rising incidence of the disease, and the association with multifocal squamous carcinomas of the upper aerodigestive tract.