Genital human papillomavirus infection and genotype prevalence among Albanian women: a cross-sectional study.

"High risk" HPV types have different geographical distribution and evidence suggests their respective prevalence may vary in different areas and regions. An accurate description of high-risk HPV circulation is a key feature for the rational design of prevention and screening campaigns. A cross-sectional, virological study was conducted on adult Albanian women living either in the Tirana area or in the Duress prefecture. Clinical and gynecological evaluations were performed according to current standard criteria. HPV detection and typing were carried out by a combined MY09/MY11 and GP5+/GP6+ PCR followed by direct sequencing of generated amplicons. Virological data were obtained from 402 out of 452 patients enrolled between January 2004 and December 2007. Sixty-one patients (15.1% of the cohort) were found to be infected with a genital HPV. As expected, viral prevalence was higher among women younger than 30 years of age (25.2%) in comparison to those aged 30 or older (13.6%). HPV 16 was found to be the most frequent type (41% of cases), followed by HPV 53 (7.2%), HPV 31 (5.8%), and HPV 18 (4.3%). HPV 81 and HPV 84 were the most prevalent low-risk types detected with prevalences of 11.6% and 5.8%, respectively. No differences were noted in any type-specific prevalence between young and mature women. The circulation of HPV types is far more complex than assumed generally. Detailed knowledge of HPV type circulating patterns in specific local geographical areas is essential for appropriate implementation of screening, prevention, and surveillance campaigns.

Expression of human papilloma virus type 16 E5 protein in amelanotic melanoma cells regulates endo-cellular pH and restores tyrosinase activity.

BACKGROUND: Melanin synthesis, the elective trait of melanocytes, is regulated by tyrosinase activity. In tyrosinase-positive amelanotic melanomas this rate limiting enzyme is inactive because of acidic endo-melanosomal pH. The E5 oncogene of the Human Papillomavirus Type 16 is a small transmembrane protein with a weak transforming activity and a role during the early steps of viral infections. E5 has been shown to interact with 16 kDa subunit C of the trans-membrane Vacuolar ATPase proton pump ultimately resulting in its functional suppressions. However, the cellular effects of such an interaction are still under debate. With this work we intended to explore whether the HPV16 E5 oncoprotein does indeed interact with the vacuolar ATPase proton pump once expressed in intact human cells and whether this interaction has functional consequences on cell metabolism and phenotype. METHODS: The expression of the HPV16-E5 oncoproteins was induced in two Tyrosinase-positive amelanotic melanomas (the cell lines FRM and M14) by a retroviral expression construct. Modulation of the intracellular pH was measured with Acridine orange and fluorescence microscopy. Expression of tyrosinase and its activity was followed by RT-PCR, Western Blot and enzyme assay. The anchorage-independence growth and the metabolic activity of E5 expressing cells were also monitored. RESULTS: We provide evidence that in the E5 expressing cells interaction between E5 and V-ATPase determines an increase of endo-cellular pH. The cellular alkalinisation in turn leads to the post-translational activation of tyrosinase, melanin synthesis and phenotype modulation. These effects are associated with an increased activation of tyrosine analogue anti-blastic drugs. CONCLUSION: Once expressed within intact human cells the HPV16-E5 oncoprotein does actually interact with the vacuolar V-ATPase proton pump and this interaction induces a number of functional effects. In amelanotic melanomas these effects can modulate the cell phenotype and can induce a higher sensitivity to tyrosine related anti-blastic drugs.