Page 238 - Textbook of Pathology, 6th Edition

222 the characteristic tumour being malignant mesothelioma of iii) Vertical transmission, when the infection is genetically
the pleura. Other examples of physical agents in transmitted from infected parents to offsprings.
carcinogenesis are the implants of inert materials such as Based on their nucleic acid content, oncogenic viruses fall
plastic, glass etc in prostheses or otherwise, and foreign into 2 broad groups:
bodies observed to cause tumour development in 1. Those containing deoxyribonucleic acid are called DNA
experimental animals. However, tumorigenesis by these oncogenic viruses.
materials in humans is rare. 2. Those containing ribonucleic acid are termed RNA
oncogenic viruse or retroviruses.
D. BIOLOGIC CARCINOGENESIS Both types of oncogenic viruses usually have 3 genes and
SECTION I
are abbreviated according to the coding pattern by each gene:
The epidemiological studies on different types of cancers i) gag gene: codes for group antigen.
indicate the involvement of transmissible biologic agents in ii) pol gene: codes for polymerase enzyme.
their development, chiefly viruses. Other biologic agents iii) env gene: codes fro envelope protein.
implicated in carcinogenesis are as follows: Primary viral infections are majority of the common viral
Parasites. Schistosoma haematobium infection of the urinary infections in which the infection lasts for a few days to a few
bladder is associated with high incidence of squamous cell weeks and produce clinical manifestations. Primary viral
carcinoma of the urinary bladder in some parts of the world infections are generally cleared by body’s innate immunity
such as in Egypt. Clonorchis sinensis, the liver fluke, lives in and specific immune responses. Subsequently, an
the hepatic duct and is implicated in causation of immunocompetent host is generally immune to the disease
cholangiocarcinoma. or reinfection by the same virus. However, body’s immune
Fungus. Aspergillus flavus grows in stored grains and system is not effective against surface colonization or deep
liberates aflatoxin; its human consumption, especially by infection or persistence of viral infection.
those with HBV infection, is associated with development of Persistence of viral infection or latent infection in some
hepatocellular carcinoma. viruses may occur by acquiring mutations in viruses which
Bacteria. Helicobacter pylori, a gram-positive spiral-shaped resist immune attack by the host, or virus per se induces
micro-organism, colonises the gastric mucosa and has been immunosuppression in the host such as HIV.
found in cases of chronic gastritis and peptic ulcer; its
prolonged infection may lead to gastric lymphoma and Viral Oncogenesis: General Aspects
gastric carcinoma, this subject is discussed in detail in
Chapter 20. In general, persistence of DNA or RNA viruses may induce
mutation in the target host cell, although persistence of viral
However, the role of viruses in the causation of cancer is
General Pathology and Basic Techniques
more significant. Therefore, biologic carcinogenesis is largely infection alone is not sufficient for oncogenesis but is one
step in the multistep process of cancer development.
viral carcinogenesis, described below.
Generally, RNA viruses have very high mutation rate (e.g.
HIV, HCV) than DNA viruses. Mechanisms as to how specific
VIRAL CARCINOGENESIS
DNA and RNA viruses cause mutation in the host cell are
It has been estimated that about 20% of all cancers worldwide varied, but in general persistence of DNA or RNA viral
are due to persistent virus infection. The association of infection causes activation of growth-promoting pathways
oncogenic viruses with neoplasia was first observed by an or inhibition of tumour-suppressor products in the infected
Italian physician Sanarelli in 1889 who noted association cells. Thus, such virus-infected host cells after having
between myxomatosis of rabbits with poxvirus. The undergone genetic changes enter cell cycle and produce next
contagious nature of the common human wart was first progeny of transformed cells which have characteristics of
established in 1907. Since then, a number of viruses capable autonomous growth and survival completing their role as
of inducing tumours (oncogenic viruses) in experimental oncogenic viruses.
animals, and some implicated in humans, have been General mode of oncogenesis by each group of DNA and
identified. RNA oncogenic viruses is briefly considered below:
1. Mode of DNA viral oncogenesis. Host cells infected by
Oncogenic Viral Infections: General Aspects DNA oncogenic viruses may have one of the following 2
Most of the common viral infections (including oncogenic results (Fig. 8.25):
viruses) can be transmitted by one of the 3 routes: i) Replication. The virus may replicate in the host cell with
i) Horizontal transmission. Commonly, viral infection passes consequent lysis of the infected cell and release of virions.
from one to another by direct contact, by ingestion of ii) Integration. The viral DNA may integrate into the host
contaminated water or food, or by inhalation as occurs in cell DNA.
most contagious diseases. Most of these infections begin on The latter event (integration) results in inducing mutation
the epithelial surfaces, spread into deeper tissues, and then and thus neoplastic transformation of the host cell, while the
through haematogenous or lymphatic or neural route former (replication) brings about cell death but no neoplastic
disseminate to other sites in the body. transformation. A feature essential for host cell trans-
ii) By parenteral route such by inoculation as happens in some formation is the expression of virus-specific T-(transforming
viruses by inter-human spread and from animals and insects protein) antigens immediately after infection of the host cell
to humans. by DNA oncogenic virus (discussed later).