[MUSIC] Welcome to Module II. HPV Risk Factors and Clinical Presentation. In Module II, this module describes risk factors associated with the transmission of HPV and the development of HPV-associated cancer. We will review how the virus is transmitted and malignant transformation. We will also explore the clinical presentation of HPV-associated throat cancer, early signs, and the clinical manifestations of advanced disease. It's important to understand that the lifetime risk of developing HPV is more than 90%. However, 90% of these infections are transient. That's to say that only 10% will remain as chronic infections and 90% will completely disappear from the host. It's the chronic infection that is the risk of carcinogenesis or the development of cancer, malignancy. Sexual intercourse is the most significant risk for developing HPV. It's the most common mode of transmission. We've seen that as sexual debut has decreased over the course of the last half century and the number of sexual partners has increased over the past half century. The rate of transmission of sexually transmitted disease, including HPV, has increased dramatically. Open mouth kissing is another way that HPV can be transmitted, but without question, the most significant and most common transmission is through oral sex. With the HIV and condom use, there's been an increase in oral sexual practices. A general change in sexual practices, not only US wide, but worldwide. As a result, a five fold increase in those who have a history of more than 5 oral sexual partners is associated with a higher risk HPV transmission. Oral sex is not the only risk factor however, and in many studies, somewhere between 8 and 40% of patients with HPV, reported having no oral sex. This is a birth cohort and it demonstrates that this is a disease not of our parents or our grandparents, but of this generation. And of even more so, the generation to follow, our children. We referred to HPV-negative throat cancer, or HPV-negative oral pharyngeal cancer, as a cancer that typically arises as a result of heavy alcohol and tobacco use. It typically occurs in older patients, usually in their 60s and 70s. And as I said, most have a greater than 20 pack year history. That means that they smoke a pack a day for more than 20 years. Pain is typically the presenting sign. Typically they present with an ulcer, as you see in this photograph in the upper right. The ulcer is often painful and can bleed. And these tumors or ulcers are firm, so they're easy to detect on physical examination. If you noticed, there's a peripheral dysplasia or field effect. You'll see in the photograph, there's a white changes along the tongue and the palette. That's because these patients, as they breath in or inhale the smoke or drink the alcohol, cause a blanketing effect across all of the lining. And if you see the cartoon down in the lower right, you'll see the red center represents the cancer. The surrounding pink area is the dysplasia. Those are precancerous cells that are destined to evolve into cancer cells. This is very specific for HPV-negative cancer. Cancer induced from tobacco and/or alcohol. And they may present at the time of presentation with a neck metastasis, where the tumor has spread from the oral cavities, as you see here, to the neck. Not always, but it's common. In contrast, HPV induced disease is much more defined. You can see the clear boarders where these lesions are on the tongue on the left or on the palette and the uvula on the right. There's a clear demarcation where the tumor starts and where the normal mucosa surrounds it. These tumors as you see here, the tonsil tumor on the right and the palette tumor on the left, are very well demarcated. You can see that there's no white changes along the palette or the tongue. And as a result, we refer to this as a focal disease. A disease that occurs where you see the tumor and not in the peripheral regions. In fact, if you biopsy the peripheral regions and do molecular analysis, you'll find that those cells are completely normal. The biology and clinical presentations unique. This tumors, unlike HPV-negative tumors, arise in the palatine and the lingual tonsils almost exclusively. The HPV targets the reticulated epithelium, a special type of epithelium in the tonsil that occurs at the base of tongue and the palatine tonsils. The typical patient profile who presents with HPV-associated disease is a married man who in the past has participated in casual sex. And has had inconsistent use of barrier protection during vaginal and oral sex. And who may have had a history of non-HPV related infection. HPV-associated cancer is very different from HPV-negative cancer. These cancers are not associated with epithelial dysplasia as we discussed. They are lobular in their growth pattern, as you can see in this photograph. They typically are very well defined. They tend to demonstrate well demarcated borders and they're permeated with lymphocytes. Very basaloid as you in the histologic picture in the upper hand right. They're also referred to as poorly differentiated. In most HPV-negative cancers, poorly differentiated cancer refers to an aggressive type of cancer. However, in this particular cancer, it's often considered a misnomer and poorly differentiated tumors that are HPV-positive are not associated with any worse prognosis. You see from the animation on the lower left where we discussed cancer occurring in the center red and a peripheral dysplasia, or precancerous lesions around it. That's not the case in HPV-positive disease. In HPV-positive disease, this is a focal disease on the far right. The biology is somewhat interesting and somewhat fascinating because typically, the virus integrates deep within the crypt of the tonsil, at the very base. That means the superficial aspect, which is denoted here by the circle, can often be negative in biopsy. But the virus and the cancer begins deep within the crypts, as you see here on the pink arrow. The tumor begins deep within the crypt and tends to burgeon out towards the surface. As a result, unlike HPV-negative cancer, HPV-positive disease often is soft, fleshy, difficult to determine or diagnose on palpation or finger examination. And if you biopsy the surface, as you see in the circle, you could get normal mucosa. As a result in the diagnosis of this disease, we typically recommend removing the lymphoid tissue on black or in one piece. And that's usually done either through a lingual tonsillectomy or a tonsillectomy in the standard approach. More recent work shows that the burden of oral oncogenic HPV infection is substantially higher in men than women. This is due to the fact that men, on average, have a higher number of lifetime sexual partners as compared to women. A NHANES study, published by Dr. Gillison and colleagues, recently found that the prevalence of oral oncogenic HPV, the HPV that causes cancer, was three times higher in men when compared to women. Consistent with this higher risk of HPV-positive oropharyngeal cancer in men in the US population. Why are men more susceptible to chronic HPV infection than women? Well, men are generally more susceptible than women to parasitic, bacterial, and viral infections due to a weaker immune response, to both natural infection and vaccination. There's a lower rate of seroconversion following genital HPV infection in men compared to women. And men may exhibit a lower antibody titer upon seroconversion when compared with women. Overall and generally speaking, men do not mount the same robust immune response that women do to vaccination or disease. As a result, it's believed that men become weakened in their immunity to fight off this disease which is why cancer, it is believed, is more common in the male population. Summary of Module II. HPV is a common viral illness that afflicts nearly 90% of people. HPV is commonly transmitted through oral sex but this is not the only means of transmission. Chronic HPV infection can lead to oropharyngeal cancer. And men are more commonly able to develop HPV-associated throat cancer than woman. It's about nine to one. And finally, clinical presentation may include a large tender tonsil or more commonly, a foreign body sensation when swallowing. And it's not uncommon that these patients will present with a neck mass. Remember that 90% of the patients that present with this disease present with neck metastasis, stage three disease. Thank you for joining us for Module II. There will be a short quiz to follow where you can test your knowledge on this disease and Module III will focus on disease management, treatment. Thank you. [MUSIC]
