COURSE TITLE: Human Papillomavirus

COURSE DESCRIPTION This continuing education course is designed especially for health care professionals, but the information is crucial for all sexually active individuals particularly women. It discusses the human papillomavirus (HPV) as a sexually transmitted disease and its role in causing genital warts and cancer in women and, more uncommonly, men. Fortunately, there are things that can be done to minimize and even prevent HPV infection and the risk of cancer. With the availability of a HPV vaccine, the risk of HPV- related cancer in women could be substantially reduced, if not eliminated. Rev 2.0 Feb 2009 1

COURSE TITLE: Human Papillomavirus Authors: Emily Bertrand University of South Florida Tampa, FL Lucia Johnson, MA Ed, CLS(NCA), MT(ASCP)SBB Director of Continuing Education National Center for Competency Testing Number of Clock Hours Credit: 2.0 Course # 1221507 P.A.C.E. Approved: Yes X No Upon completion of this continuing education module, the professional should be able to: 1. Define HPV. 2. Describe the breadth of HPV infection in the United States. 3. State the number of people who are diagnosed with HPV each year. 4. State the number of women (U.S.) diagnosed with cervical cancer each year. 5. State the number of women (U.S.) who die from cervical cancer. 6. Explain the types of transmission of HPV and the populations at risk. 7. State the HPV types, by number, that are associated with cervical cancer. 8. State the HPV types, by number, that are associated with genital warts. 9. Describe symptoms, tests, and treatments for HPV. 10. Describe methods of prevention of HPV and their limitations. 11. Describe the two-step approach to decreasing cervical cancer in women. 12. Describe current thoughts on the Gardasil vaccine, and possible mandates. Disclaimer The writers for NCCT continuing education courses attempt to provide factual information based on literature review and current professional practice. However, NCCT does not guarantee that the information contained in the continuing education courses is free from all errors and omissions. 2

INTRODUCTION Human papillomavirus (HPV) is a group of more than 100 different types of viruses that cause papillomas, genital warts, cancer of the cervix, and rarely, cancer of the penis and anus. Papillomas are benign growths, also called warts, that are most often found on the hands, feet, and face. Papillomas are transmitted by casual skin-to-skin contact or by environmental means such as use of communal showers, swimming pools, or by sharing footwear. More than 30 types of HPV are sexually transmitted. Most individuals infected with sexually transmitted HPV will not have any symptoms. However, some sexually transmitted HPV infections may cause cancer of the cervix, vulva, vagina, anus, or penis. This CE course will focus on the sexually transmitted types of HPV. WHAT IS THE IMPORTANCE OF HPV IN THE UNITED STATES? Studies report that approximately 20 million people in the United States are currently infected with sexually transmitted HPV and more than 6 million people are diagnosed each year. Data estimates that 70% of women are exposed to the virus sometime during their lives and over 50% of sexually active men in the United States will have HPV at some time in their lives. Not everyone will show signs and symptoms of disease and HPV can unknowingly be transmitted to sex partners. According to a study conducted by Eileen Dunne, MD, MPH, and reported in the February 2007 issue of the Journal of the American Medical Association, about 14,000 women in the United States are diagnosed with cervical cancer each year, and more than 3,900 women die each year from the disease. Dunne also states that there is a 24.5% prevalence of HPV among females 14 to 19 years old and a 44.8% prevalence of HPV among females 20 to 24 years old. While uncommon, anal and penile cancer in men has also been associated with HPV infection. The American Cancer Society (ACS) estimates that annually 1,500 men will be diagnosed with penile cancer and 1,900 with anal cancer in the United States. It is estimated that approximately 980 men will die from these two types of cancer. Every year, an estimated $1.6 billion is spent on treating the symptoms of HPV infection in the United States. In addition, the annual costs of cervical cancer screening programs (Pap smears) are estimated to be between $5 billion - $6 billion. For these reasons, HPV is an important health care issue. It is not only vital that health care professionals should know about it, it is vital that all sexually active individuals have knowledge about HPV in order to protect themselves and those they love. While HPV infection is the leading cause of cervical cancer, it is not the cause of all cervical cancers. In addition, not everyone infected with HPV will develop cervical cancer. 3

HOW IS HPV TRANSMITTED? HPV can be transmitted through sexual intercourse, oral sex, anal sex, or any skin-toskin genital contact and rubbing. Fifteen types of HPV are considered high risk for causing cancer, and HPV-16 and HPV-18 have been specifically associated with cervical cancer. Thirty other types of HPV, typically HPV-6 and HPV-11, cause genital warts. Infections may fluctuate between asymptomatic and symptomatic, and duration may range from a few weeks to years. The types of HPV that cause genital warts are not the same as the types that can cause cervical, anal, or penile cancer. However, because a person can be infected with more than one type of HPV, the presence of genital warts does not rule out the possibility that he/she is also infected with a high-risk type of HPV. WHAT ARE THE SYMPTOMS OF HPV? According to Martin, signs and symptoms of HPV infection may include any or all of the following: Dry, painless, cauliflower-like warts located in or around the genitalia or anus Genital sores located in or around the genitalia or anus Increased moisture in the area of the warts Chronic itching in or around the genitalia or anus Increased vaginal discharge Abnormal vaginal/penile/anal discharge or bleeding, and/or Abnormal Pap smear WHO IS AT RISK FOR HPV INFECTION? Anyone who engages in sexual, genital contact with an infected person is at risk for contracting a form of genital HPV. Since most types are reported to be without symptoms, and others have delayed signs of symptoms, HPV is easily spread, infecting about 6 million Americans with new cases each year. Individuals are more likely to get HPV if they have: Sex at an early age Many sex partners and/or A sex partner who has had many partners In the United States, the risk for anal cancer is 17 times higher among gay and bisexual men than among heterosexual men. Penile cancer is more common in uncircumcised men regardless of sexual orientation. 4

Sexually transmitted HPV also causes 25% of cancers of the mouth and upper throat. Engaging in oral sex with an HPV-infected partner may increase the risk of developing this type of cancer. Approximately fifty percent of sexually active males and females become infected at some point in life, including women without a history of intercourse. Although rare, an HPV infected pregnant woman can also transmit the virus to her infant during vaginal childbirth. HOW CAN RISK FOR HPV INFECTION BE REDUCED? Safer sex practices are very important to reduce the risk of HPV. Taking the following precautions may help to minimize the chances of contracting HPV: Abstinence Mutual monogamy Limiting sexual partners and Avoiding sexual activity with promiscuous partners Taking precautions during sexual contact can help, but it is important to recognize that the skin surfaces not covered by male or female condoms during contact can still transmit HPV. In addition, there is some evidence that the virus can be transmitted by fomite transmission. A fomite is any object such as a towel, tissue, or utensil that is capable of harboring or transmitting a disease agent. After exposure or contact with a genital wart, it is recommended that hands be washed immediately to avoid spreading the virus. It is also recommended to keep the wart dry and avoid scratching the area to prevent spreading the virus. If an individual suspects he/she has genital warts, the individual should stop having sexual contact and seek immediate treatment. HOW IS HPV INFECTION DIAGNOSED? Genital warts Genital warts are generally diagnosed by a visual inspection from a healthcare provider. The healthcare provider may use a magnifying lens to identify small warts. Some healthcare providers may choose to wash the genital area with acetic acid (vinegar). This causes the warts to turn white, making them more easily seen. However, this procedure is not specific for genital warts as normal bumps and tissue may also turn white. Biopsies are usually not necessary to diagnose genital warts but a biopsy may be performed if the suspected wart is discolored or unusual looking. There are no blood tests currently available to diagnose an individual for HPV. 5

HPV Related Cancer Women HPV cervical infection is typically detected with a Pap smear that demonstrates abnormal changes in the cells of the cervix. Cervical cells infected with HPV show characteristic features when stained and observed microscopically. As the Pap smear is not 100% sensitive or specific for the detection of HPV related cancer, additional tests are required to confirm a HPV infection. For the confirmatory test, cells are scraped from the cervix and undergo an HPV DNA test. This test can confirm the presence of HPV and identify the high risk HPV types associated with the development of cervical cancer. If an HPV infection persists in cervical cells, the Pap smear abnormalities may become more severe, indicating the presence of either pre-cancer or cancer. Pap smear changes are graded on a specific scale and the higher the grade, the more serious the disease. Men There are no currently available tests used for early detection of HPV related cancer in men. Biopsies of abnormal areas of the penis, scrotum, or anus can be obtained for microscopic evaluation. Some medical experts recommend that men who are at increased risk for anal cancer have routine Pap tests on cells scraped from the anus to identify the presence of abnormal cells. At this time, however, the Centers for Disease Control and Prevention (CDC) do not recommend routine anal cancer screening. HOW IS HPV TREATED? Genital warts Genital warts may go away on their own, stay unchanged, or increase in size and number. The primary goal of treating genital warts is cosmetic. Many treatments are available for genital warts and evidence does not indicate that one treatment is better than another. Treatments include: Antiviral creams Chemical treatment (usually with acids) Surgical excision (removal) Freezing with liquid nitrogen Laser treatment of the papillomas Antiviral therapy, e.g. interferon Problems with treatments can include abdominal cramping, pelvic discomfort, foul smelling vaginal discharge, bleeding, allergic reactions, inflammation of the cervical tissue, and raw or painful skin reactions. Unfortunately, HPV still lives in the cells of the individual even after these procedures, but with any of these processes, the recurrence of outbreaks generally becomes less common. 6

HPV Related Cancer Cervix The treatment options for cervical cancer depend primarily on how advanced the cancer is (i.e., the stage of the cancer). Surgical treatment options are listed below. The treatment options become more extensive as the severity of the cancer increases. Cryosurgery: cervical cancer cells are killed by freezing Laser surgery: laser beam is used to burn off cervical cancer cells Cone biopsy: removal of a cone-shaped piece of cervical tissue Simple hysterectomy: the uterus only is removed Radical hysterectomy and pelvic lymph node dissection: the uterus, vagina, fallopian tubes, ovaries, and pelvic lymph nodes are removed Pelvic exenteration: a radical hysterectomy is performed and the bladder, rectum, and portions of the colon are removed Depending on the severity of the cancer, radiation therapy and/or chemotherapy may be given prior to or after surgery. Penis Early stages of penile cancer can be treated by surgical removal of the cancerous lesion and use of a chemotherapy cream such as 5-FU. Mohs surgery (microscopically guided removal of only the cancerous layers of skin) and laser surgery are generally the surgical techniques of choice. Radiation therapy is recommended for early stages of penile cancer. As the stages of penile cancer become more advanced, surgery that is more extensive is required. The surgery may include partial or complete removal of the penis, testicles, scrotum, and pelvic lymph nodes. The effectiveness of using chemotherapy or chemotherapy with radiation therapy in the advanced stages of penile cancer is under investigation. Anus Early stages of anal cancer can be treated by surgical removal of the cancerous lesion. If the removal of the lesion involves the rectal sphincter, radiation and chemotherapy are recommended. If cancer remains after radiation and chemotherapy, surgery that is more radical may be needed. It may become necessary to remove pelvic lymph nodes and portions of the colon. If significant amounts of the colon are removed, a colostomy will be required. 7

CAN HPV BE PREVENTED? Some types of HPV can be prevented. The Food and Drug Administration (FDA) has recently approved the Gardasil vaccine (marketed by Merck) to protect young women at ages 12 to 26 from the human papillomavirus. Although the vaccine has been shown to be 100% effective in preventing certain types of HPV, not all types can be prevented. The Gardasil vaccine is projected to protect women from contracting 70% of cancercausing forms of the virus and 90% of forms causing genital warts. The Gardasil vaccine includes purified inactive proteins from HPV types 6, 11, 16, and 18. These four types are major causes of cervical cancer and genital warts. It is important, however, that women understand that the vaccination is not a substitute for having annual Pap smears, as the vaccine does not prevent other types of cervical disease, other types of HPV infection, other sexually transmitted diseases (STDs), or other types of cancer. GlaxoSmithKline is seeking FDA approval of their vaccine, known as Cervarix. This vaccine targets HPV types 16 and 18, which cause the majority of cervical cancer and anal cancer in men and women. WHAT ARE CURRENT RECOMMENDATIONS FOR HPV? It is clear that the human papillomavirus has become an increasing threat to society, particularly to females from the ages of 14 to 24. Of the 20 million Americans currently infected, more than 14,000 women will be diagnosed with resultant cervical cancer each year, and nearly 4,000 will die from the disease. In addition, nearly 6 million more will be newly diagnosed with HPV each year, making it the most common sexually transmitted infection in the United States. Current prevention efforts must be continued, the public must be educated about the significance of HPV, and the vaccine must be affordable and available to young women at an early age. Although HPV infections by themselves are generally self-limiting, persistent infection is a primary cause of cervical cancer, and many believe that its connection to cervical cancer should be addressed using a two-step approach. Both approaches are necessary to prevent and/or reduce the damage that HPV can cause. (1) The first step involves limiting exposure to HPV, or if exposed, preventing infection. Lifelong monogamy and the use of condoms would limit exposure, and HPV vaccination would prevent infection if exposed. (2) The second step includes continued cervical testing (such as PAP smears), HPV screening, and removal of HPV-infected pre-cancerous lesions. 8

Both men and women should be educated about HPV, and it should be a part of any discussion about sexually transmitted diseases in schools or in the health community. Lifelong monogamy and the use of condoms are already recommended practices to limit exposure to all sexually transmitted infections, including HPV and HIV (Human Immunodeficiency Virus), but it is naïve to believe this will be sufficient. It will be crucial to add the HPV vaccination to the arsenal of weapons. People will need to be educated about the vaccination. Vaccine study data demonstrated that females with no prior sexual partner were most likely to benefit from the HPV vaccination, as females with even a single partner already had an incidence of HPV infection of more than 14%. Surveillance data indicated that routine vaccination of females at age 11 or 12 would provide immunization before exposure, while extending protection during the early teenage years. This approach was also supported by evidence that higher antibody titers were achieved if vaccines were administered at younger ages. Based on approved statistical analysis, if the HPV vaccine is just 75-90% effective among 12-year-old females, the lifetime risk of cervical cancer could be reduced by 20% to 66%. Although the importance of vaccination is apparent, there may be a few obstacles to overcome to gain 100% compliance. The immunization requires a series of three injections over a six-month period. There are a few reported side effects, including pain, swelling, itching, and redness at the site of injection and occasionally fever. Difficulty breathing is a rare but serious side effect. The vaccine is costly, as it is expected to exceed $350 per person. The efficacy of the vaccine is not yet known in males. The vaccine is currently recommended only for females, who would still need to continue with PAP screening until more data is collected. This places what some may consider an unfair share of the burden and cost of prevention on women alone. Men will eventually need to be vaccinated to eradicate the disease as they can be carriers of HPV. Studies are in process to determine the effectiveness of vaccinating boys. As always, men and women who are concerned about the spread of HPV should contact qualified health care providers for their advice. Because new tests and treatments are developed every day, physicians should be a primary contact for information about HPV and other sexually transmitted diseases. 9

References Cancer Reference Information: Frequently Asked Questions About Human Papilloma Virus. www.cancer.org/docroot/cri/content/cri_2_6x_faq_hpv_vaccines.asp Center for Disease Control. HPV Diseases and Conditions. www.cdc.gov/diseasesconditions Detailed Treatment Options Penile And Anal Cancer by Stage. www.cancer.org/docroot/cri/content/cri_2_4_4x_treatment_options_by_stage HPV Background Information. American Social Health Association. www.ashastd.org HPV Research: Information on HPV. H. Lee Moffitt Cancer Center and Research Institute. moffitt.org/site.aspx?spid=912c3ac36cfe437593e74b84a4759a81 Bauer, Heidi M., & Ault, Kevin. Human Papillomavirus: Current Prevalence and Future Protection. Journal of the American Venereal Disease Association, 33(8), 509-511. Dunne, Eileen F. Prevalence of HPV Infection Among Females in the United States. Journal of the American Medical Association, 297(8), 813-819. Edlin, G., & Golanty, E. (2007). Health & Wellness. Sudbury: Jones and Bartlett Publishers. Gardner, Amy. Drugmaker Assists In Pushing for Mandate for HPV Vaccination. www.washingtonpost.com/wpdyn/content/article/2007/02/10/ar2007021001279.html Gross, G., Pfister, H. Role of human papillomavirus in penile cancer, penile Intraepithelial squamous cell neoplasia and in genital warts. Medical Microbial Immunology, 193, 35-44. Martin, Eva. Human Papillomavirus Infections in Females. www.health.discovery.com/encyclopedias/illnesses.html?article=2029 Merck and Co. Gardasil. Merck and Co. 1-2. Severson et al. Human papillomavirus infections: Epidemiology, Pathogenesis and therapy. Journal of Cutaneous Medicine and Surgery, 5(1), 43-60. Zimmerman, Richard Kent. HPV Vaccine and its Recommendations, 2007. The Journal of Family Practice, 56(2), S1-S5. 10

TEST QUESTIONS Human Papillomavirus Course 1221507 Directions: Before taking this test, read the instructions on how to correctly complete the answer sheet. Select the response that best completes each sentence or answers each question from the information presented in the module. If you are having great difficulty answering a question, go to www.ncctinc.com and select CE/Renewals, then select CE Update to see if course content and/or a test question have been revised. 1. Which one of the following is NOT associated with HPV infection? a. cervical cancer b. genital warts c. gonorrhea d. papillomas 2. Approximately how many people in the United States are currently infected with HPV? a. 10 million b. 15 million c. 20 million d. 25 million 3. Approximately how many people in the United States are newly diagnosed with HPV each year? a. 3 million b. 6 million c. 9 million d. 12 million 4. Which one of the following is NOT associated with sexual transmission of HPV? a. Genital skin-to-skin contact b. Kissing c. Oral or anal sex d. Sexual intercourse 5. Which two types of HPV are most associated with cervical cancer? a. HPV-6 and HPV-11 b. HPV-6 and HPV-18 c. HPV-16 and HPV-18 d. HPV-18 and HPV-21 11

6. What is the most obvious symptom of HPV infection? a. Bleeding b. Fever c. Itching d. Warts 7. Which of the following individuals would be at LEAST risk for becoming infected with HPV? a. Male and female who had a monogamous sexual relationship for 25 years b. Female who began having sexual relations with numerous men at age 15 c. Female who has sexual relations with a promiscuous man d. Male homosexual and has had sexual relations with many men 8. Which one of the following practices reduces the risk of being infected with HPV? a. Becoming sexually active at a young age b. Being promiscuous c. Practicing mutual monogamy d. Occasionally using condoms 9. Which one of the following is FALSE regarding genital warts? a. Acetic acid may help to identify b. Blood tests needed for diagnosis c. Easily identified by physical appearance d. A biopsy is not always needed for diagnosis 10. HPV cervical infection is typically detected by what technique? a. Biopsy b. Gram stain c. Pap smear d. Surgery 11. Which one of the following would be a treatment for genital warts? a. Chemotherapy b. Freezing with liquid nitrogen c. Radiation d. Radical hysterectomy 12

12. The recommended treatment for a woman with a very advanced stage of cervical cancer is. a. interferon b. cryosurgery c. laser surgery d. pelvic exenteration 13. Treatment for early stages of HPV-related penile cancer includes all of the following EXCEPT. a. complete removal of the penis b. Mohs microscopic guided surgery c. use of radiation therapy d. use of 5-FU chemotherapy cream 14. The Gardasil vaccine provides immunity to which two types of HPV that cause genital warts? a. HPV-6 and HPV-11 b. HPV-6 and HPV-18 c. HPV-16 and HPV-18 d. HPV-18 and HPV-21 15. The Gardasil vaccine is projected to protect women from contracting % of the cancer-causing forms of HPV? a. 30 b. 50 c. 70 d. 90 16. Which of the following is the most common sexually transmitted disease in the United States? a. Chlamydia b. Herpes c. HIV d. HPV 17. Which of the following is NOT considered an obstacle to the use and efficacy of the Gardasil vaccine? a. Availability of vaccine b. Cost of vaccine c. Given only to females d. Three doses in six months 13

18. Which of the following would be the best population to target for a widespread immunization program, to maximize benefits over time? a. Females with multiple sexual partners b. Late adolescent or early teenaged girls c. Post-menopausal females d. Women seeking marriage licenses *end of test* 14