Human Papillomavirus

By Daria L. Zucchi, MBS 2020, Geisinger Commonwealth School of Medicine
Mentor: Darina Lazarova, PhD

Back in high school, I remember sitting in my mandatory health class alongside my peers dreading the lesson of the week. Sexually-transmitted infections. While I was interested in learning about the infections themselves, there was a degree of discomfort that arose when the gym teacher stood in front of a giggling audience as they attempted to discuss genital warts. My father is a registered nurse, so any questions that would come to my mind during the class would be relayed to him for clarification. As a healthcare professional, he was able to explain these infections to me in a way that he knew I understood. Granted, I was passionate about science as it was, but it was a privilege to have him as a resource to ensure that I understood the severity of some of these infections. Especially Human Papillomavirus (HPV). 

HPV is the most common sexually transmitted infection in the United States, impacting both men and women despite the virus’ association with cervical cancers. In high school health classes, it was taught that HPV causes genital warts. However, the infection is not confined to the genital area. This is because the virus spreads through skin-to-skin contact or skin-mucosa contact. This means that an HPV infection can occur in the oral tissues like the mouth, throat, nose, lips, and salivary glands following oral sex. When these oral infections are considered, the possibility of an oral cancer diagnosis down the road is something to consider. Surprisingly, middle-aged white men are actually the most-impacted population in the United States for oral cancers that came from an HPV infection. In the U.S. alone, as of 2004, oral cancers that developed from an HPV infection has reached 70% of total oral cancer diagnoses. Even more disturbing is the fact that the incidence of HPV-associated oral cancer diagnoses has been increasing by 5% every year. If that wasn’t bad enough, most people who have an HPV infection will be completely unaware, and won’t show symptoms until up to a decade later. This makes HPV able to spread under the radar between sexual partners without either of them knowing. 

So, how does HPV spread without anyone knowing? Wouldn’t our immune systems notice and rid our bodies of the infection? The answers to these questions lie in the life cycle of the virus itself. Following contact with an infected person, HPV enters the layer of cells in the mouth, called epithelium, where it searches for an immature cell to infect. These immature cells are usually at the base of the epithelium and these cells are still rapidly dividing as they mature into cells that “know” their function. HPV uses proteins on their surface, called L1 and L2, to bind to a receptor on the immature cell surface and enter the cell. There, the virus "dumps" its DNA into the cell, where it is packaged in a structure called a vesicle and delivered to the nucleus of the cell, where the host’s DNA is. Once there, HPV stealthily blocks anything in the cell that is used to detect any invaders, and this allows the HPV DNA to divide with the host cell. As the infected immature cell divides, its progeny spreads throughout the layers of epithelium until it eventually matures. When the cell matures, the HPV within it springs into action, using the resources inside the cell to replicate its DNA as much as possible before bursting out as new, fully-formed viruses. In order to accomplish this, HPV needs the cell to grow as much as possible. Normally, when a cell grows too much molecules called tumor suppressors will detect the abnormal growth and stop the cell from growing to allow time for the problem to be corrected. If it cannot be corrected, the tumor suppressors tell the cell that it needs to self-destruct to prevent cancer from forming. HPV doesn’t "want" the tumor suppressors to detect the abnormal growth that they need to replicate, so HPV targets these suppressors and prevents them from functioning entirely. Without those suppressors there is nothing to regulate how much the infected cell is growing, and this is where cancer can rear its ugly head. 

Despite the controversy that surrounds them, vaccines are the strongest tool that we currently have against HPV infections. The most-current vaccine protects against nine types of HPV that have a high potential of causing cancer. Compared to other vaccines, the HPV is the one that parents seem to hesitate the most about due to many misconceptions and personal fears. The fact that the virus can spread so far and wide without most people knowing about it, along with the high probability of cancer development after being infected, make the HPV vaccine crucial for pre-teens to receive.