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Most national prophylactic HPV vaccination programs started in approximately 2008, with either the bivalent Cervarix HPV16/18 or quadrivalent Gardasil (HPV6/11/16/18) vaccines, which were then followed by introduction of the nonavalent Gardasil 9 (HPV6/11/16/18/ 31/33/45/52/58) vaccine from 2015. Since that time, these products have demonstrated their ability to prevent infection with vaccine-covered HPV types and subsequent development of HPV-related cervical and genital pathologies. The data indicate that vaccination of young girls prior to sexual debut is more effective than vaccination of older HPV+ve women. Although some studies have shown a decline in the prevalence of vaccine-covered HPV types, there are national and regional differences in overall vaccine efficacy. Furthermore, several recently published studies show an increase in the prevalence of non-vaccine-covered HPV types in vaccinated populations, which is indicative of HPV type-replacement. It is also notable that vaccine-related changes in HPV type prevalence spread between vaccinated and unvaccinated women at the same geographical location—presumably via sexual transmission. In conclusion, it is not yet clear what effect dissemination of vaccine-associated changes in HPV type prevalence will have on vaccine efficacy and cervical pathology, particularly in mixed populations of vaccinated and unvaccinated women. However, it is very clear these observations do underscore the need for long-term continuation of cervical screening combined with regular reassessment of testing practices. [ABSTRACT FROM AUTHOR]

Regulation of CDK4 activity by a novel CDK4-binding protein, p34(super.SEI-1), is discussed. The p16(super.INK4a) tumor suppressor works against cyclin-dependent kinases, CDK6 and CDK4. The novel gene SEI-1, the product of which seems to work against the function of p16(super.INK4a), has been isolated.

The oncogenic retrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is endemic in some countries although its prevalence and relationship with other sexually transmitted infections in Sub-Saharan Africa is largely unknown. A novel endpoint PCR method was used to analyse the prevalence of HTLV-1 proviral DNA in genomic DNA extracted from liquid based cytology (LBC) cervical smears and invasive cervical carcinomas (ICCs) obtained from human immunodeficiency virus-positive (HIV+ve) and HIV-negative (HIV-ve) Kenyan women. Patient sociodemographic details were recorded by structured questionnaire and these data analysed with respect to HIV status, human papillomavirus (HPV) type (Papilocheck®) and cytology. This showed 22/113 (19.5%) of LBC’s from HIV+ve patients were positive for HTLV-1 compared to 4/111 (3.6%) of those from HIV-ve women (p = 0.0002; odds ratio (OR) = 6.42 (2.07–26.56)). Only 1/37 (2.7%) of HIV+ve and none of the 44 HIV-ve ICC samples were positive for HTLV-1. There was also a significant correlation between HTLV-1 infection, numbers of sexual partners (p < 0.05) and smoking (p < 0.01). Using this unique method, these data suggest an unexpectedly high prevalence of HTLV-1 DNA in HIV+ve women in this geographical location. However, the low level of HTLV-1 detected in HIV+ve ICC samples was unexpected and the reasons for this are unclear. [ABSTRACT FROM AUTHOR]

Background: XMRV (xenotropic murine leukaemia virus-related virus) is a gammaretrovirus first discovered in human prostate carcinomas and later linked to chronic fatigue syndrome (CFS). Emerging conflicting data and lack of reproducibility of results within the scientific community has now led to the association of XMRV with CFS being discounted. Indeed the case for an involvement with any human disease has been questioned with the suggestion that XMRV is a laboratory generated recombinant virus. The fact that not all published positive findings can be easily explained as contamination artefacts coupled with the observation that XMRV may have a sexually transmitted mode of infectivity and can be infectious for primates, where it preferential resides in cells of the reproductive tract, prompted us to look for evidence of XMRV in the cervical cells of a cohort of Kenyan women both with and without pre-existing HIV/HPV infections. Results: Using a highly sensitive and selective triplex PCR approach we analysed DNA from the liquid based cytology (LBC) cervical smears of 224 Kenyan women. There was no evidence of XMRV expression in any of the sample population irrespective of HPV and/or HIV status. Conclusions: The data presented show no indication of XMRV infection in any of the cervical samples screened in this study. Approximately 50% of the women were HIV positive but this did not influence the findings signifying that XMRV does not act as an opportunistic infection in this cohort nor is it related to HPV status. Our results therefore support the findings that XMRV is confined to the laboratory and does not currently represent an infectious agent for humans, with a cautionary adage that such potential zoonotic viruses should be carefully monitored in the future. [ABSTRACT FROM AUTHOR]

It has been shown that the HIV protease inhibitors indinavir and lopinavir may have activity against the human papilloma virus (HPV) type 16 inhibiting HPV E6-mediated proteasomal degradation of p53 in cultured cervical carcinoma cells. However, their mode and site of action is unknown. HPV-negative C33A cervical carcinoma cells and the same cells stably transfected with E6 (C33AE6) were exposed to indinavir and lopinavir at concentrations of 1 mM and 30 μM, respectively. The intracellular distribution of metabolites and metabolic changes induced by these treatments were investigated by Raman microspectroscopic imaging combined with the analysis of cell fractionation products by liquid chromatography-mass spectrometry (LC-MS). A uniform cellular distribution of proteins was found in drug-treated cells irrespective of cell type. Indinavir was observed to co-localise with nucleic acid in the nucleus, but only in E6 expressing cells. Principal components analysis (PCA) score maps generated on the full Raman hypercube and the corresponding PCA loadings plots revealed that the majority of metabolic variations influenced by the drug exposure within the cells were associated with changes in nucleic acids. Analysis of cell fractionation products by LC-MS confirmed that the level of indinavir in nuclear extracts was approximately eight-fold greater than in the cytoplasm. These data demonstrate that indinavir undergoes enhanced nuclear accumulation in E6-expressing cells, which suggests that this is the most likely site of action for this compound against HPV. [ABSTRACT FROM AUTHOR]

Examines the role of CD105 in preventing apoptosis in hypoxic endothelial cells. Increase in the membrane-bound and secreted CD105 protein levels; Elevation of the mRNA and promoter activity; Assessment of the ownregulation of Bcl-Xl and Mcl-1.