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CancerLynx - we prowl the net
May 5, 2008

Human Papilloma Virus - HPV
Robert A. Wascher, MD, FACS

Human Papilloma Virus (HPV) Infection, PAP Smear Results & Cervical Cancer
Human Papilloma Virus (HPV) Infection & Oral Cancer

Human Papilloma Virus (HPV) Infection, PAP Smear Results & Cervical Cancer
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An estimated 11,000 women will be diagnosed with cancer of the cervix in the United States in 2008, and almost 4,000 will die of the disease. The majority of cervical cancer cases, by far, are thought to result from chronic infection with certain strains of human papilloma virus (HPV) that are known to induce cancer. These high-risk strains of HPV are commonly spread though sexual contact and, increasingly, these oncogenic HPV strains are being linked to a variety of cancers in both men and women (see next article, below). Recently, the FDA has approved a new vaccine against HPV (Gardasil®), and other vaccines against HPV are in the pipeline as well. However, once a woman (or man) becomes infected with HPV, the vaccine is no longer effective or helpful.

For most women, annual screening for cervical cancer includes a Pap smear, named after Dr. Georgios N. Papanikolaou, the Greek-American physician who originally developed the test. During a woman's routine annual pelvic examination, a thin layer of superficial cells are scraped off of the cervix and examined under the microscope. In a few hospitals, the cells are also routinely tested for the presence of oncogenic HPV infection. However, in most hospitals, if the cervical cells appear normal under the microscope, then the costly DNA testing for oncogenic HPV infection is omitted. A new study, just reported in the current issue of the Annals of Internal Medicine, evaluated nearly 10,000 women at 26 clinical facilities, in 6 cities, in the United States by including DNA testing for oncogenic HPV infections of the cervix in addition to performing a Pap smear. The results of the DNA tests for HPV infection were then correlated with the findings of the Pap smear tests.

Overall, nearly 1 in 4 (23%) of the women participating in this trial had DNA evidence of chronic infection of the cervix with one or more high-risk strains of the HPV. Women 14 to 19 years of age were most commonly found to be infected with these strains of HPV, while women 50 and older were least likely to be infected. Among women younger than 30 years of age with an abnormal Pap smear, a whopping 53% had DNA evidence of chronic cervical infection with oncogenic HPV strains, while 9% of women 30 years of age and older who had a normal Pap smear had DNA evidence of high-risk HPV infection.

The findings of this study have several important implications, the two most important of which are improving prevention of cervical cancer, and improving screening for this disease. With the recent availability of a vaccine that appears to be more than 90% protective against cervical HPV infection in women, there is finally an effective method of preventing infection with the oncogenic strains of the HPV virus (of course, taking appropriate measures to avoid unprotected sexual contact should always be used, when appropriate).

Secondly, the results of this test show that even among women who are already above the age range considered to be at greatest risk of infection with high risk HPV and who have a normal Pap smear, nearly 1 in 10 are already likely to be infected with cancer-causing strains of HPV. This finding strongly suggests that Pap smears alone are missing a significant number of cases of chronic oncogenic HPV infection. Based upon the results of this study, it may be the case that we will have to reassess our current screening guidelines for cervical cancer.

Human Papilloma Virus (HPV) Infection & Oral Cancer
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The vast majority of oral cancers are diagnosed in patients (and mostly men) who are heavy drinkers and smokers. However, approximately 20% of oral cancers diagnosed today occur in patients who have never smoked. HPV, a family of viruses that are easily passed between people during sexual contact, has previously been implicated in these particular cases of oral cancer (the same oncogenic strains of HPV that are known to cause cervical cancer also appear to cause oral cancer as well). A new study in the journal Carcinogenesis provides important further insight into the association of HPV with oral cancer, especially among non-smokers.

In this study, 186 patients newly diagnosed with squamous cell cancer of the oropharynx and 342 cancer-free control patients were compared. All patients participating in this study underwent a blood test for the HPV strain most commonly associated with both cervical and oral cancers (HPV-16). Overall, having a positive blood test for HPV-16 was almost 6 times more common among the patients diagnosed with oral cavity cancers. When the researchers looked at just the non-smokers in both groups of patients, the association between HPV-16 and oral cancer was even more striking: oral cancer was a whopping 14 times more frequent among the non-smoking patients in presence of HPV-16 infection.

An additional part of this research study looked at variations in a very important cancer suppressor gene, p53. Patients with a specific variation (polymorphism) in the p53 gene and with evidence of HPV-16 infection were 9 times more likely to have oral cancer. However, among non-smoking patients with evidence of HPV-16 infection and the codon 72 polymorphism in the p53 gene, there was a nearly 23-fold increase in the likelihood of having oral cancer, which is an incredibly high level of increased risk for any disease.

The results of this study confirm other recent data suggesting that oncogenic strains of HPV are significantly involved in causing many cases of oral cancers, especially in non-smokers; and that certain naturally occurring variations in important tumor suppressor genes may further magnify the risk of developing this cancer in the presence of chronic HPV infection. The findings of this study, and others like it, have also added further weight to the argument that boys and young men should also be considered for vaccination against HPV, rather than the current guidelines which recommend its use for girls and young women, only.

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