ISSUES Cervical squamous cell carcinomas, adenocarcinomas and their precursors are caused by the human papillomavirus (HPV). Although HPV appears to be essential to the transformation of these epithelial cells, it is not sufficient, and a variety of cofactors and molecular events must take place between when an HPV infection occurs and a cervical cancer or its precursor develops. This review examines the data supporting these contentions, briefly outlines the molecular events that occur, considers the epidemiology and natural history of the disease, and details the implications of using HPV detection and typing in both clinical management and population-based screening programs. CONSENSUS POSITION 1. Based on the available molecular, clinical and epidemiologic data, a subset of HPVs are unequivocally the etiologic agents for cervical cancers and their precursors. 2. Different mucosotropic HPVs have varying neoplastic potential. However, the great majority of cervical HPVs have oncogenic potential. Since oncogenic HPV-induced epithelial transformation to a high grade lesion or cancer is rare relative to the rate of infection, the term high risk is discouraged. 3. HPV's interaction with host cells has two principal biologic consequences: a) All anogenital HPVs induce low grade squamous lesions, which are the morphologic correlate of a productive infection. b) Rarely, HPVs induce a proliferative epithelial phenotype that pathologists recognize as a high grade lesion and that is the proximate cytohistologic precursor of invasive cervical carcinoma. 4. HPV biology and issues of practical clinical management should be reflected in the classification systems used for cytologic and histologic diagnosis. ONGOING ISSUES The molecular identification of HPVs (HPV testing) potentially may be very useful for primary screening or secondary triage of patients with certain lesions. However, the technology available to the practicing clinician is still evolving. Optimization of type spectrum, sensitivity, specificity and ease of use is under development. Data regarding these factors as well as a clear cost benefit analysis are sparse or pending in several large trials. Until such data are available, caution in clinical implementation of HPV testing is warranted.

Human papillomavirus. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

Biochemical studies on adenovirus multiplication

Herpesvirus saimiri (H. saimiri) is a ubiquitous agent of squirrel monkeys (Saimiri sciureus), a primate species native to the South American rain forests. The virus can easily be isolated from blood and tissue-culture cells of most healthy squirrel monkeys, and there is no evidence so far that H. saimiri is pathogenic in its natural host. After the first report on isolation of H. saimiri from primary kidney-cell cultures by Melendez et al. (1968) from the New England Primate Research Center, the virus was regarded as a harmless indigenous agent of squirrel monkeys. The interest in this virus arose from the observation that H. saimiri is extremely oncogenic in a number of other primate species that are presumably not infected under usual wildlife conditions (Melendez et al., 1969b). Marmoset monkeys of the genus Saguinus consistently develop malignant tumors of the lymphatic system, usually within 2 months of infection. The ability to induce neoplastic disease rapidly and reproducibly has made this system attractive for investigation of the biological, immunological, and molecular parameters of Cell transformation and tumor induction.

Herpesvirus saimiri and Herpesvirus ateles

Excerpt During the past 2 decades extraordinary advances have occurred in our understanding of the biology of normal cells. Dramatic progress has been made in defining the "molecular pathology" of ...

Metabolic Effects of Intracellular Infections in Man

A naturally-occurring cutaneous papilloma is commonly present on wild hares captured in states bordering the Mississippi River.25* 40, 41 This epithelial tumor became interesting to many investigators following the discovery in 1933 by Shope41 of its virus etiology and the demonstration by Rous and 34 and others’j, 24, 48 that the benign virus-induced growth may terminate in an epidermoid carcinoma. A wide variety of investigations of this tumor and its etiological agent resulted. Our interest in this disease and in the causative virus has been continuous since June, 1934.46-54 Since then, we have kept in our rabbit colony more than 1700 wild cottontail and domestic rabbits with papillomatosis. Our cumulative data and comparative studies51* j2, b4 reflect a wide experience that has confirmed and extended work previously reported. It is the purpose of the present paper to summarize these findings! and the reported experiences of other investigators in an attempt to understand two phenomena of fundamental importance: (a) the role of Shope’s papilloma virus in the papilloma-tocarcinoma sequence and (b) the biological phenomenon that results during the virus papilloma-to-carcinoma sequence in the disappearance, or “masking,” of the causative virus in papillomas of domestic rabbits and in cancers of domestic rabbits and wild hares.

The pathogenesis of the rabbit papilloma-to-carcinoma sequence.

The effect of poliomyelitis virus type I (Mahoney strain) on the phosphorus metabolism of the HeLa cell.

Summary Neoplasms developed in rabbits which were infected in utero as readily as in mature animals. Thus, fetal domestic rabbits (genus Oryctolagus) were found fully susceptible to infection by papilloma virus, as manifested after birth by the papilloma-to-carcinoma sequence. The immaturity of the host was without any remarkable alterative effect in this sequence. Since the observation that cancer developed in five of six animals within 7 months of birth makes it apparent that the time required in immature rabbits for the papilloma-to-carcinoma sequence to eventuate in cancer is probably shorter than in adult rabbits, it is more than suggestive that the provocative carcinogenic effect of papilloma virus results from the initial host cell-virus relationship and that it is not significantly conditioned by the age of the host.

https://cancerres.aacrjournals.org/content/canres/11/9/737.full.pdf

The Virus-induced Papilloma-to-Carcinoma Sequence: IV. Carcinomas in Domestic Rabbits Infected while in Utero

Herpesvirus saimiri: Viability in Four Species of Hematophagous Insects and Attempted Insect Transmission to Marmosets

Summary
In experiments in which cockroaches, Periplaneta americana, were fed a single meal containing a member of the Coxsackie group of viruses, the results proved that the test roaches excreted daily over a period of as many as 15 days sufficient virus to paralyze and kill test mice. Control experiments and other tests showed that the lethal effect was due to infection by the Coxsackie virus and not from extraneous bacterial or viral infection.
The significance of these experiments in relation to the natural transmission and dissemination of the Coxsackie group of viruses remains to be determined.

The cockroach as an experimental vector of Coxsackie virus.

SummaryIn experiments in which cockroaches, Periplaneta americana, were fed a single meal containing the virus of mouse encephalomyelitis, GD VII strain, proof was obtained that the test cockroaches daily over a period of as many as 7 days excreted sufficient virus to kill test mice. Control experiments showed that the lethal effect was from infection by the virus of mouse encephalomyelitis, GD VII strain, and not from extraneous bacterial or viral infection.

Robert G. Fischer

Papers

The effect of poliomyelitis virus type I (Mahoney strain) on the phosphorus metabolism of the HeLa cell.

The Virus-induced Papilloma-to-Carcinoma Sequence: IV. Carcinomas in Domestic Rabbits Infected while in Utero

Herpesvirus saimiri: Viability in Four Species of Hematophagous Insects and Attempted Insect Transmission to Marmosets

The cockroach as an experimental vector of Coxsackie virus.

The cockroach as an experimental vector of the virus of spontaneous mouse encephalomyelitis (Theiler).