“A serious safety issue that should not be swept under the regulatory carpet,” Professor Joe Cummins.
When the Human Papilloma Virus (HPV) vaccine Gardasil was recently found to be contaminated with DNA, the US Food and Drug Administration (FDA) lost no time in declaring that the DNA was not a contaminant but a harmless by-product of vaccine production. I disagree; that extraneous DNA is potentially harmful. It should also be noted that the safety and efficacy of HPV vaccines have been controversial from the start (see [1] The HPV Vaccine Controversy and other articles in the series, SiS 41).
The Virus
HPV establishes productive infections only in keratinocytes of the skin or mucous membranes. While the majority of the known HPV types cause no symptoms in most people, some types can cause warts (verrucae), while others can lead to cancers of the cervix, vulva, vagina, penis, oropharynx and anus.
Recently, HPV has been linked to an increased risk of cardiovascular disease. In addition, HPV 16 and 18 infections are strongly associated with an increased risk of developing throat cancer. Worldwide in 2002, an estimated 561 200 new cancer cases (5.2 %) were attributable to HPV, making HPV one of the most important infectious causes of cancer, and cervical cancer is the second most common cancer in women worldwide. In 2008, there were an estimated 529 000 new cases of cervical cancer and 274 000 deaths; more than 85 % of the deaths in developing countries, where it accounts for 13 % of all female cancers [2].
The Viral Genome
The HPV genome consists of 8 genes coding for proteins and a non-protein-coding region with regulatory genes. The genes are distinguished as early and late functioning in virus development. The early genes include those involved in virus replication and transcription along with the oncogenes for cancer development. The late genes encode the two structural proteins L1 and L2 of the virus capsid. HPV infects the basal cells of the cervical epithelium when it is damaged in some way. The viral genome becomes established in the basal cells as an episome (an independently replicating nuclear micro-chromosome). The episome replicates in tandem with the chromosomes of the cell and forms virus particles. The complete virus particles are in the outermost cells of the epithelium and the viruses are spread as the cells slough off from the epithelium. Some virus proteins function as oncoproteins, transforming the epithelial cells to a precancerous state. HPV infection is necessary but not sufficient for cancer formation, however. In high grade lesions and cancer, an episome is integrated into the cell chromosome. Integration disrupts a viral transcription regulatory protein that controls the production of the cancer proteins, leading to their continual and enhanced production [3] (Recombinant Cervical Cancer Vaccines, SiS 29). HPV integration into human chromosomes is non-random; with integration hot spots in chromosome regions homologous to the oncogene E5 of HPV or the structural protein L2 [4]. Women with cervical cancer have been found with viral chromosomes integrated completely or partially as chromosome fragments, or as independent episomes. Partially integrated HPV was most prevalent in women with cancer while complete virus integration was about half as frequent and the episomal form rare. The cancer- causing integration breaks the HPV chromosome at the E1/E2 region, causing a loss of that region. This in turn results in loss of control of the cancer genes E6 and E7. The E7 cancer gene produces a protein that inactivates the retinoblastoma gene – a cancer suppressor gene – of the host cell, thereby promoting cancer [5]. (Retinoblastoma is an inherited cancer of the eye caused by loss of the retinoblastoma gene.) The main lesson is that fragmentation or breakage of the HPV DNA is an important factor in cancer progression of the host cell.
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Mindanoiha says
September 15, 2012 at 1:00 pmExcellent article. However, I beg to differ on one point: In the section for HPV Vaccines it is stated “They are prophylactic, that is, they prevent cervical cancer but do not cure existing infections”.
It has not yet been shown that the HPV vaccines prevent cervical cancer.