During the past 17 years 73 genotypes of human pathogenic papillomaviruses (HPV) have been identified. Most of them are found in benign proliferations; however, several have been discovered in malignant tumors. Specifically, cancer of the cervix, other anogenital cancers, but also some cancers of the skin, the oral and nasal cavity, and the rare periungual carcinomas have been linked to specific HPV infections. The pathogenesis of cancer of the cervix has been particularly well studied. Specific viral genes (E6 and E7) of high risk HPVs (types 16, 18, and others) act as oncogenes. Their expression emerges as necessary but not sufficient factors for malignant conversion. Besides stimulating cell proliferation, they are responsible for the genetic instability of the infected cells. Their transcriptional and functional activity is regulated by host cell genes. Mutational modifications of the latter appear to be required for malignant progression.
The role of human papillomavirus (HPV) in the aetiology of in situ and invasive carcinoma of the genital tract is well established. In the rare disorder epidermodysplasia verrucifor-mis (EV), in which patients develop extensive warts of unusual types and multiple cutaneous squamous cancers on light-exposed skin, current evidence suggests a probable role for a specific group of EV HPVs in the carcinogenic process. Determination of the possible role of HPV in the aetiology of non-melanoma skin cancers (NMSCs), which occur frequently in immunosuppressed organ allograft recipients, has been limited, until recently, by the lack of availability of a sensitive detection system for a wide range of cutaneous HPV types. We have used a combination of 2 sets of PCR primers to examine 68 benign and malignant tumours collected over a 12-year period from 25 renal allograft recipients. Cloning and sequencing of the PCR products were carried out to distinguish HPV DNA from cellular sequences. A combination of these techniques revealed HPV DNA in all viral warts, 65% of keratoses, 91% of intra-epidermal cancers and 91% of invasive squamous cancers. Both cutaneous and EV HPV types were detected, including 18 novel types. In 4 patients with multiple cancers, the most prevalent types were in the EV group: HPV 20, 23, 38 and 2 novel types, DL40 and DL267 (related to HPV 10 and 38, respectively). These 5 HPV types were present in a total of 73% of all malignant lesions tested. The technique described represents a reliable method of HPV DNA detection in NMSC. The EV group of HPVs predominate in the cancers, but the multiplicity of HPV types detected with double infection in some lesions suggests virus/virus in addition to virus/host interaction in the carcinogenic process. Int. The most frequently occurring cancer in Caucasians is non-melanoma carcinoma of the skin (Preston and Stern, 1992). Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) develop mainly on sun-exposed sites (Frost and Green, 1994), BCC outnumbering SCC by a ratio of 5:1 in immunocompetent populations. Organ allograft recipients commonly develop multiple skin lesions, such as warts, keratoacanthomas and keratoses, with progression to in situ or invasive SCCs, which occur mainly on sun-exposed sites (Penn, 1991). Patients with epidermodysplasia verruciformis (EV) also have a predisposition for extensive viral warts and non-melanoma skin cancers (NMSCs), especially SCC (Orth, 1987). In these tumours, a specific group of closely related papillomaviruses, thus far not commonly found in the general population, has been identified (Jablonska and Majewski, 1994). Human papillomavirus (HPV) 5 and HPV 8 DNA usually are found in those sun-exposed lesions which progress to carcinomas (Orth et al., 1979). A possible role for EV and other HPV types in the carcinogenic process in organ allograft recipients has been investigated over the past 12 years, but results have shown an enormous variation in the frequency and type of HPV DNA detected depending on the method employ...
The in silico analyses of 109 replication-competent genomic DNA sequences isolated from cow milk and its products (97 in the bovine meat and milk factors 2 group – BMMF2, and additional 4 in BMMF1) seems to place these in a specific class of infectious agents spanning between bacterial plasmid and circular ssDNA viruses. Satellite-type small plasmids with partial homology to larger genomes, were also isolated in both groups. A member of the BMMF1 group H1MBS.1 was recovered in a distinctly modified form from colon tissue by laser microdissection. Although the evolutionary origin is unknown, it draws the attention to the existence of a hitherto unrecognized, broad spectrum of potential pathogens. Indirect hints to the origin and structure of our isolates, as well as to their replicative behaviour, result from parallels drawn to the Hepatitis deltavirus genome structure and replication.
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