glycogen and Papillomavirus-Infections

Reinterpretation of the Wartburg effect leads to understanding aerobic glycolysis as a process that provides considerable amount of molecular precursors for the production of lipids, nucleotides and amino acids that are necessary for continuous growth and rapid proliferation characteristic for cancer cells. Human papilloma virus (HPV) is a number one cause of cervical carcinoma with 99% of the cervical cancer patients being HPV positive. This tight link between HPV and cancer raises the question if and how HPV impact cells to reprogram their metabolism? Focusing on early phase proteins E1, E2, E5, E6 and E7 we demonstrate that HPV activates plethora of metabolic pathways and directly influences enzymes of the glycolysis pathway to promote the Warburg effect by increasing glucose uptake, activating glycolysis and pentose phosphate pathway, increasing the level of lactate dehydrogenase A synthesis and inhibiting β-oxidation. Our considerations lead to conclusion that HPV is substantially involved in metabolic cell reprogramming toward neoplastic phenotype and its metabolic activity is the fundamental reason of its oncogenicity.

Topics: Female; Glycogen; Humans; Lipid Metabolism; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus E7 Proteins; Papillomavirus Infections; Uterine Cervical Neoplasms

The authors noted a significant increase in the diagnosis of atypical squamous cells of undetermined significance (ASCUS) in premenopausal women using oral contraceptive pills (OCP) (9%) versus women not on OCP (4%) using ThinPrep Pap smears (P = 0.02). The purpose of this study was to correlate these morphologic changes with human papillomavirus (HPV) DNA detection by in situ hybridization and clinical follow-up.. Eighty-four ThinPrep Pap smears diagnosed as ASCUS or ASCUS favor low-grade squamous intraepithelial lesions (LGSIL) in young women receiving OCP were studied by HPV in situ hybridization. This information was correlated with colposcopic follow-up and AutoCyte Pap smear results. The authors also studied 80 ThinPreps from young women with a Pap smear diagnosis of unequivocal LGSIL where there was a corresponding biopsy (positive controls) and 40 ThinPreps diagnosed as within normal limits and that rescreened as such (negative controls).. The detection rate of HPV DNA by in situ hybridization was 33% (28 of 84) in ASCUS cases versus 90% (72 of 80) for cases of unequivocal LGSIL. A blinded review of the 29 ASCUS Pap smears performed by AutoCyte showed that 66% (19 of 29) were diagnosed as within normal limits. The majority of the cervical biopsies in the women with ASCUS by ThinPrep Pap smears were negative for dysplasia (29 of 39 [74%]) whereas 71 of 80 biopsies (88%) showed dysplasia in women with Pap smears diagnosed as unequivocal LGSIL. The periodic acid-Schiff (PAS) stain demonstrated that many of the cells with halos in the ThinPrep Pap smears that mimicked LGSIL contained glycogen.. The ThinPrep induces changes that mimic LGSIL in young women on OCP. These artifacts may reflect pressure-induced alteration of glycogen. PAS analysis and, more directly, HPV testing by in situ hybridization can help differentiate this mimicking from actual LGSILs.

Topics: Adolescent; Adult; Artifacts; Contraceptives, Oral; DNA, Viral; False Positive Reactions; Female; Glycogen; Humans; In Situ Hybridization; Papanicolaou Test; Papillomaviridae; Papillomavirus Infections; Precancerous Conditions; Premenopause; Retrospective Studies; Tumor Virus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears