Viruses and Cancer: What’s the Link?

History as teacher
At the University of Pittsburgh School of Pharmacy, one of the major historical links between viruses and cancer hits very close to home (yes, we sometimes do feel as if we live in Salk hall).The Salk inactivated polio vaccine, which was hugely successful in preventing polio, was found to be contaminated with Simian Virus 40 (SV40) several years after it had already been administered to millions of Americans.The further observation that SV40, a “monkey virus” which infected the rhesus kidney cells in which the vaccine was produced, caused transformation of several nonhuman cell lines into cancerous cells caused great alarm and led to intense study of the link between cancer and the virus, and the possible ramifications of exposure.While the jury is still out (and most likely is out for good[1]) on whether or not this contamination led to an increased rate of cancer in exposed individuals, scientists’ intense scrutiny of the virus contributed to the discovery of one of the archetypical tumor suppressors, the retinoblastoma (Rb) protein. The SV40 viral protein dubbed “large T antigen” inactivates Rb, thereby mitigating its critical role in cell cycle regulation.Loss of Rb-mediated cell cycle control can lead to enhanced proliferation and, when combined with additional cumulative genetic or epigenetic changes, can lead to overt cancer.While issues of infectivity and transmissibility may hamper SV40’s contribution to the development of human cancers, the role of HPV in causing human cervical cancer has been established with much more certainty.Interestingly, HPV also encodes a viral protein named E7 which inactivates the Rb tumor suppressor and gives infected cells a growth advantage, ultimately leading to cervical cancer in a fraction of infected individuals. Thus, while a vaccine to “prevent all cancers,” may be unrealistic at this point in time, when we consider the multitude of ways cancers emerge in the human body, it can be appreciated that we have been able to develop several vaccines against specific, known etiologic agents.
For discussion
A detailed counseling session on the importance of mitigation of Rb tumor suppressor function in the biology of cervical cancer would not be an effective way to convince a teenage girl to receive the vaccine; however, we do feel that an appreciation of some key historical events leading to the discovery of the Rb tumor suppressor and the molecular link between HPV and cervical cancer is valuable information for all pharmacists.Other than discussing molecular biology, what strategies would you, as a pharmacist, employ to convince women to receive the HPV vaccine?
On another note, contamination of the polio vaccine led to a great deal of negative press about the safety of vaccinations.In more recent times, worries about safety ranging from autism to Guillain-Barré Syndrome have caused patients and their caregivers to refuse vaccination.How would you try to convince these patients that the benefits of vaccination outweigh the potential risks?
[1] Fisher SG, Weber L, Carbone M. Cancer risk associated with simian virus 40 contaminated polio vaccine. Anticancer Res. 1999;19(3B):2173-80.





