Genital HPV Types Research Articles

Molecular diagnosis of genital HPV DNA types by polymerase chain reaction and sensitivity-standardized filter in situ hybridization in randomly sampled cohorts of Singapore women

Infection of the cervix uteri with various types of human papillomaviruses is generally considered a necessary factor in the etiology of cancer of the cervix uteri. In many human populations throughout the world, approximately 90% of cervical carcinomas are found to harbour HPV genomes, as judged by Southern blot hybridization, while only a few percent of the cervical smears of asymptomatic individuals contain viral DNA, as assessed by filter in situ hybridization. To obtain corresponding epidemiological data from Singapore, we analysed two groups of 740 and 130 individuals by filter in situ hybridization, and found 4·1% and 6·9% of them to be HPV positive, with HPV 16 and HPV 31 being the predominant types. In consideration of the limitations of filter in situ hybridization, namely low sensitivity and a tendency to suggest false positives due to contaminants, including blood, we analysed the cervical smears of two further groups of 52 and 50 individuals by the polymerase chain reaction for infection by HPV 16 and HPV 18 respectively. With this test, 61% and 14% of the cervical smears proved to be HPV 16 and HPV 18 DNA positive respectively. We conclude that in Singapore, if not worldwide, the majority of the population the population is infected by genital HPV types, suggesting that factors other than HPV infection are ultimately rate-limiting in cervical carcinogenesis.

Analysis of human papillomavirus type 16 open reading frame E7 immortalizing function in rat embryo fibroblast cells

The E7 open reading frame of human papillomavirus type 16 (HPV-16) encodes a protein that can immortalize primary rat cells, cooperate with the ras oncoprotein to transform low passage rat cells and transform established rodent cells to anchorage independence. The immortalizing and cooperation functions have been investigated using a series of point mutations that introduce single amino acid changes into the E7 protein in two distinct regions. Certain mutations altering amino acids conserved between the E7 protein of genital HPV types, the adenovirus E1a protein and simian virus 40 large T antigen abolished the ability of the E7 protein to immortalize or cooperate with ras in a focus forming assay. Mutations in a consensus sequence for a casein kinase II recognition site, which is also shared by E1a and large T, reduced immortalizing activity, but did not affect the ability to cooperate with ras. Single mutations disrupting cysteine motifs, which form putative zinc-binding sites in the second region, reduced the activity of the E7 protein, whereas double mutants, in which neither of the cysteine motifs remained intact, showed no or very low activity. The activity of the mutants in immortalization and cooperation assays was essentially the same as their transforming activities in NIH 3T3 cells. This indicates that these three functions of E7 map to overlapping domains which cannot be separated by these mutations in the region of E1a/large T homology or the cysteine motifs.

Clinical Manifestations and Natural History of Genital Human Papillomavirus Infection

Over the past decade, the ever-increasing volume of evidence implicating HPV types in genital neoplasia has stimulated much research interest into all aspects of the biology of this interesting group of viruses. This has led to the identification of an ever-increasing heterogeneity of HPV types. It is not surprising, therefore, that the clinical profile of disease associated with genital HPV types is much broader than previously recognized. Knowledge of this clinical spectrum is mandatory to the understanding of the possible role of specific HPV types in human carcinogenesis.