title: Mechanisms of carcinogenesis in human skin against the background of papillomavirus infection.
abstract: The cells in the skin tumor developing under conditions of persisting papillomavirus infection are morphologically identical to blast cells in a blood smear from a leukemia patient. The cells filling the lesion focus are morphologically and immunohistochemically related to blood stem cells. A mechanism of epithelial layer modification under conditions of papillomavirus infection leading to carcinogenesis is proposed. The dynamics of structural changes in the skin is characterized by disturbed interactions between the epithelium and adjacent connective tissue, destruction of the basal membrane, disorders in the cambial keratinocyte differentiation, and absence of the spinous and granular layers. We conclude that detection of blast leukocytes in the human skin lesion can be explained by disorders in the cell-cell interactions in the epithelium-mesenchymal tissue system. High proliferative activity followed by death of cambial keratinocytes, migration of effector antigen-presenting CD68 cells to the adjacent connective tissue are the factors inducing migration of blast leukocytic forms to the focus. Not only keratinocyte restitution capacity, but also epithelium-dependent differentiation of young leukocytes disappeared. Undifferentiated cells are migrated from the blood to the epithelium alteration zone, but not in the reverse direction. The insufficiency or the absence of blood blast cell differentiation of the in the focus of epidermal injury and adjacent tissue triggers carcinogenesis. The authors suggest their model of carcinogenesis. The conclusions offer a new concept of cancer pathogenesis and suggest a new strategy in the search for methods for early diagnosis of carcinogenesis.
authors.affiliation: School of Biomedicine, Far-Eastern Federal University, Vladivostok, Russia.
authors.forename: I V
authors.initials: IV
authors.lastname: Reva
authors.forename: G V
authors.initials: GV
authors.lastname: Reva
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: V E
authors.initials: VE
authors.lastname: Tolmachyov
mesh_terms: D000368:Aged; D052685:Alphapapillomavirus / Q000302:isolation & purification* / Q000472:pathogenicity; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D006801:Humans; D008875:Middle Aged; D012878:Skin Neoplasms / Q000821:virology*