by Vincent RacanielloThursday, September 01, 2011 at 06:45 AM EDT
This article was written for extracredit by a student in my virology course.
Human papillomavirus (HPV) infection is the most common sexually transmitteddisease in the United States, and as of yet, there is no cure. however, thereis a vaccine to prevent infection by certain strains. Recent research mayencourage not just the young women of the world, but also the men, to rush totheir doctors for this vaccine. As the advertisements for Gardasil have taughtmany of us, certain strains of HPV are responsible for the majority of cervicalcancer cases. Now research is uncovering HPV as a major factor in several oralcancers as well. while men may have thought there was no need to get vaccinatedagainst HPV before, this new information may change things.
Human papillomavirus infects epithelial cells of skin and mucous membranes.Through skin abrasions caused by injury or sexual contact, the virus gainsaccess to the basal layer of the epithelial tissue, which is the lowest layerof the skin. HPV is a DNA virus that replicates in the epithelium at theprimary site of infection. Noncancerous strains, which cause papillomas (warts)or even no apparent symptoms, replicate in the basal epithelial cells. Theviral genome does not integrate into the host genome of the cell it infects,but instead replicates autonomously in a dividing cell. the productivity ofviral replication depends on the stage of cell differentiation. As the infectedcell moves to the upper level of the epithelium and begins to differentiate,viral replication becomes more productive. Replication producing highconcentrations of viral genomes and the assembly of new virus particles(virions) is restricted to the outer epithelial cells, which are fullydifferentiated and no longer divide.
In cancers caused by viral infection, the virus must transform the infectedcell, changing its growth properties and allowing for progression to cancer. Intransformed cells, the viral genome has integrated into the host genome. Whenthe viral DNA is integrated into the cellular genome, the viral mRNA that isthen transcribed can contain cellular DNA sequences and is subsequently morestable than sequences transcribed from a nonintegrated viral genome. Becausethe mRNA transcripts are more stable, viral proteins, specifically proteins E6and E7, are present in higher concentrations than in cells where the viralgenome is not integrated. These viral proteins E6 and E7 interfere with thecell cycle by restricting the activity of the cellular tumor suppressorproteins p53 and Rb. Specifically, E6 blocks apoptosis (programmed cell death)by inducing degradation of p53. In an uninfected cell, proteins Rb and p53sense DNA damage and prevent the cell cycle from progressing further. ProteinE7 binds Rb proteins, allowing the cell replication cycle to progress so thevirus can replicate. once a cell has been transformed, the cell replicationcycle goes unchecked and this can allow for the accumulation of mutations inthe cell’s DNA. this buildup of mutations and frequent cellular replication canlead to oncogenesis, the development of cancer. the specific strains that areassociated with these changes in epithelial tissue that can lead to cancer arestrains 16 and 18. These are the strains from which Gardasil protects anindividual, along with strains 6 and 11, which cause genital warts.
Researchers have studied oral cancers among men who are nonsmokers andnondrinkers, and discovered the presence of HPV in the biopsied tissues. Infact, some researchers are now claiming that the prevalence of HPV induced oralcancers is greater than cancers caused by both smoking and drinking combined.HPV is spread by direct skin-to-skin contact and sexual contact, and itsreplication is localized to the site of infection. Therefore, individuals whodo not engage in vaginal intercourse, but do engage in other forms of sexualcontact, such as oral sex, are still at risk for HPV infection. Virus is shedfrom the epithelial cells of the infected individual, even when the individualis asymptomatic. if an individual is orally infected with one of the high-riskstrains (either 16 or 18), the virus will replicate locally in the infectedtissue, and as described above, can cause cell transformation, leading tooncogenesis and tumor progression. because of these risks, the importance ofthis vaccine for both men and women is becoming blatantly apparent.
HockingJS, Stein A, Conway EL, Regan D, Grulich A, Law M, & Brotherton JM (2011).Head and neck cancer in Australia between 1982 and 2005 show increasingincidence of potentially HPV-associated oropharyngeal cancers. British journal of cancer, 104 (5), 886-91PMID: 21285981
This article originally appeared on virology blog.