[SOUND] Welcome to this discussion on HPV-related Oral and Throat cancer: What You Need to Know. This discussion will be broken down into four modules. The first module is HPV-associated Throat Cancer: An Epidemic. The second module is Risk Factors and Clinical Presentation. The third module is Management of HPV-associated Cancer. And finally, the fourth module is dedicated to prevention, vaccination, and what's on the horizon. Module 1, HPV-associated Throat Cancer: An Epidemic, this module describes the nature of Human Papillomavirus, referred to as HPV, and the effect of viral infection. The module explains the emerging epidemic and its impact on the development of throat cancer. The module concludes with the current state of population awareness and the impact that erroneous information can have on the spread of disease and the risk of malignancy. HPV, Human Papillomavirus, is a group of somewhere between 100 and 200 different viruses that's spread through sexual contact. In a minority of people, the virus can lead to the development of cervical cancer in women and throat cancer in men and women. In this animation, you can see on the far left HPV viral DNA as it enters into the cell and then into the host nucleus. The viral DNA can then exist either as an integrated form, where it integrates into the host's DNA or in an episomal form in a lower panel. In both cases, the DNA is then transcribed into messenger RNA and eventually a protein, E6 and or E7. Both of these proteins act to block cell death, or apoptosis, which is a form of programmed cell death. When this is blocked, unfortunately, this leads to cellular division that's uncontrolled. And when this happens, we lead to cellular transformation that leads to unrestricted cancer or unrestricted cell growth. These cells begin to grow at an uncontrollable rate. They produce enzymes and those enzymes can break into blood vessels and lymphatics and spread throughout the system. That's essentially how metastases develop. Going back to this animation, it's very important to understand how we make the diagnosis of HPV within a cell and relate it to the disease process. There are essentially two ways that this is done. The first is through PCR or polymerase chain reaction. This is an assessment of the messenger RNA products and is the most sensitive and the most specific way to determine if a cell has been invaded by HPV virus. The second approach is through immunohistochemistry, which assesses protein, and in this case, the E6, E7 protein. We stain the cells or stain the slides for P16. This is an excellent way to determine if a cell has been infected by HPV. It can be very sensitive, but is not very specific. What I mean by that is, you can have cancers of the head and neck or other regions that are positive for P16. But that doesn't necessarily mean that they have been infected by HPV. The only way to know that is to use the PCR analysis, the polymerase chain reaction. That is the most sensitive and most specific way to make the diagnosis. In a 2011 publication, you can see here in yellow that there's been a slow decline in the rate and prevalence of cervical cancer in women as a result of HPV. But alarming, has been the increase, as you can see this rise in oral oropharyngeal and throat cancer, and in particular, this rise has been largely in young men. This sharp curve upward denotes an epidemic. In the same article in 2011, it was suggested that by 2025, cervical cancer would be surpassed in prevalence by throat cancer in men. Recent data seems to suggest that it may be before 2005 that this crossing pattern occurs. This is not a new virus. In fact, dating back to 1841, Italian physicians noted that there was a higher rate of cervical dysplasia, warts, and even cervical cancer in women who were prostitutes, as opposed to nuns and virgins. So this virus has been present and has been noted in the medical literature for many, many years, but clearly, something has changed. The work by Harold Zur Hausen in 1976 that eventually led to the Nobel Prize demonstrated that HPV virus infects cells and can lead to cervical cancer in women. In this particular model, Dr. Zur Hausen was able to demonstrate that through sexual contact, HPV was transmitted and infected the transitional zone between the cervix and the uterus and led to cervical cancer. It's now recognized that this is essentially 99% of all cervical cancers. HPV exists in several different types. 60% of those types are cutaneous, they lead to warts, common warts that exist on the skin. They're not cancerous, and they're not pre-cancerous. The 40% that remain are broken down into the low risk group, which are typically types 6 and 11. These lead to diseases, such as cervical dysplasia, genital warts, and respiratory papillomatosis. You can see in this photograph here, these are papillomas on the true vocal cords that are a result of the low risk type 6 and 11. Generally speaking, these types do not lead to malignancy. In contrast, there is a high risk type, HPV 16 and 18, these are the types that were most commonly associated with cervical cancer, anogenital cancer, and for the purposes of this discussion, oropharyngeal and throat cancer. Back in 1985, it was noted that in the United States, the number of cases of throat cancer that were related to HPV-infection was approximately 40%. In places like UK, Australia, and Sweden, the numbers were below 30%. Just 20 years later, there's been a rise in the number of cases of oropharyngeal and throat cancer that had been related to HPV, as high as 80% of the United States and 93% in Sweden. Today in 2016, those numbers are well above 80 to 90% in most countries. When we talk about relative risk, we're talking about the risk of developing a disease as a result of an exposure. An example of this is if you drink alcohol, the risk of developing throat cancer is approximately 5.5 times that of the normal who doesn't drink alcohol. If you smoke tobacco, that risk rises to 19.5. And if you smoke and drink together, these are synergistic, leading to a relative risk of 56.5. To give you an idea how virulent and the effect of the HPV-associated diseases, a patient who has been chronically infected with active HPV infection, it has been estimated that their risk of developing cancer is roughly 230 times. What about population awareness? What do we know, and what does the population know? Well, in 2006, the Food and Drug Administration approved the HPV vaccine. Unfortunately, less than 30% of women are currently being vaccinated. And there are significant gaps in the knowledge of this disease and the effects of this disease. In a recent study, 95% of women and 80% of men knew that there was a vaccine against cervical cancer, but only half of the women and a quarter of the men had even heard of HPV. Similarly, female college students reported a very high level of awareness of HPV. But there were significant misconceptions that existed. In a statewide survey of 17,000 women in California, less than half of the respondents could correctly answer three or more HPV knowledge questions. More than a third reported that men could not contract HPV, this is false. And over 40% believe that HPV and HIV have similar effects on the human body, this is also false. Men display a significantly poorer knowledge about HPV than women, especially concerning the long term consequences and modes of HPV transmission. Why is education important? Well, it's incredibly important because those who report confusion or lack of knowledge are often less compliant with follow up treatment. And they are less compliant and less likely to disclose their HPV status to their partners. So what can we do? These observations warrant a counseling paradigm in which healthcare providers play a critical role in providing accurate information about HPV and HPV-associated diseases. This is important that not only the population be aware of the cause and the implications of this disease, but also pediatricians, obstetricians, and gynecologists. Otolaryngologists and general medical physicians should be aware of the nature of this disease, its causes of transmission and the downstream effects and disease that are caused by this virus. Summery of Module I, HPV is the only known cause of cervical cancer in women. HPV is associated with an epidemic of throat cancers in men, and to a lesser degree, in women. Active HPV infection can present in many different ways. And finally, there's significant misconceptions regarding HPV infection and its association with cancer. This concludes Module I. There'll be a short quiz, so that you can test your knowledge regarding the things we've discussed today in Module I. In Module II, we'll focus on diagnosis and the identification of this disease. [SOUND]
