Developments and Issues Related to Human Papilloma Virus (HPV) and Cancer
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Developments and Issues Related to Human Papilloma Virus (HPV) and Cancer

Human papilloma virus (HPV) is well known as a causative agent of cervical cancer and genital warts. But fewer people are aware that HPV also causes throat cancer, and skin cancer. HPV vaccination may be an important tactic in the prevention of all of these conditions.

Human papilloma virus (HPV), is a category of viruses of which more than seventy subtypes are known. Most people have heard of HPV, because the media have spent a good deal of time discussing the issue of mandatory vaccination against the virus. The discussion in the news is well-deserved. Each year, approximately 6.2 million people are infected with (HPV). Usually, the virus is cleared by the immune system, before any disease can develop. However, because of the high rate of infection, HPV-associated disease is all-too common around the world. Each year 11,000 new cases of invasive cervical cancer are diagnosed in the United States, leading to approximately 4,000 deaths. The rate would be much higher, were it not for the advent of the the Papanicolaou test (Pap smear), used to screen for precancerous conditions since the 1930s. Since Pap smears and HPV vaccinations are hot topics, even if you have no background in medicine, it is likely that you are aware of HPV as an agent that causes cervical cancer. What you may not know, however, is that HPV also is involved in cancers of the throat and the skin.

HPV and Cervical Cancer

Actually, not all of the subtypes of HPV are known to be involved in the pathological process leading to cancer and precancerous conditions of the cervix. Of the HPV subtypes linked to cervical cancer, four types are most important. These are  HPV-6b, HPV-11, HPV-16, and HPV-18, the latter two being the most dangerous for women, because they are found in a high percentage (60-80%) of the high-grade lesions that lead cancer if not removed, and 90% of the cancers that invade from the cervix to other parts of the body. Although less important in the development of cervical cancer, subtypes 6b and 11 cause genital warts. Thus, one of the two vaccines licensed by the Food and Drug Administration (FDA) to prevent the spread of HPV in the United States, Gardasil, works against HPV types 6b and 11 as well as types 16 and 18. Since genital warts affects males as well as females, the Advisory Committee on Immunization Practices (ACIP) of the Center for Disease Control (CDC) has recommended this vaccine for both sexes. The other licensed vaccine, Cervarix, is recommended for females. These recommendations, however, may change eventually, since studies in recent years have revealed that HPV causes disease not only in the genitals but elsewhere in the body.

Arguments For and Against Mandatory HPV Vaccination

In Texas, Executive Order 4 mandated HPV vaccination for 6th grade girls. While this was overturned by the Texas legislature, Virginia and the District of Columbia now require HPV vaccination with Gardasil or Cervarix for girls from age 11. Parents are allowed to opt out, however, and in the case of Virginia without submission of signed waivers. Thus, in Virginia, the state public health department has no way to know for certain how many girls actually receive the vaccine. Currently, legislation seeking mandatory vaccination for girls, but not boys, is pending in several other states.

Opponents of mandatory HPV vaccination for girls note the success of secondary prevention of cervical cancer, namely early detection by PAP smear. When detected early, however, the pre-cancerous condition must be treated, often by procedures such as loop electrosurgical excision (LEEP), cryotherapy, laser therapy, or conization. This has implications in patient well-being, making primary prevention (preventing the disease process from beginning in the first place) more attractive.

Those favoring mandatory vaccination for girls but opposing it for boys cite low benefit/cost ratios, but this assumes most girls actually get the vaccine and ignores data which suggest that males as well as females can develop HPV-associated throat cancer as a result of oral sex. Also cited by opponents of mandatory HPV vaccination are concerns that private, for-profit manufacturers influence lawmakers by inflating the need for the vaccine.

HPV and Throat Cancer

For several years, it has been known that HPV causes warts in the upper respiratory tract, a condition known as respiratory papillomatosis. Then a few years ago, a very strong association was found between HPV-16 and oropharyngeal squamous cell carcinoma (OPSCC) - throat cancer. Naturally, it was thought that HPV could be spread by way or oral sex, and this turned out to be true. A study by the National Cancer Institute (NCI) found the incidence of OPSCC to be high in people with more than twenty-five life time sex partners, but with only six or more life time oral sex partners. While it is true that smokers have a higher incidence of both cervical cancer and throat cancer, in the association between OPSCC and HPV-16 was found to be particularly high for non-smokers. This is to say that assuming you're not foolish enough to smoke, the only way you'll get throat cancer is by way of exposure to HPV, and specifically type-16 one of the types that causes cervical cancer. Based on this, it seems likely that the CDC eventually will recommend the Cervarix vaccine for males as well for females. But this is not the end of the HPV story. Recently, it was discovered that HPV also is associated with one type of skin cancer.

HPV and Skin Cancer

Earlier this month, a study was published in the British Medical Journal showing that HPV plays a causative role in the generation of squamous cell carcinoma of the skin. Though not nearly as dangerous as malignant melanoma, squamous cell carcinoma is the second most common type of skin cancer, behind basal cell carcinoma. If the term "squamous cell" sounds familiar, it may be because I mentioned it above, discussing OPSCC, a squamous cell carcinoma of the throat. Squamous cells are a subtype of a cell type known as epithelial cells. Squamous epithelial cells form linings, such as the outer layer of the skin, the lining of inner body surfaces, like the throat, and -you guessed it-the lining of the cervix; cervical cancer also is a carcinoma of squamous epithelial cells. And so, it should be no surprise that the same type of virus -HPV- causes cancers in three different body parts.

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