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1 2013 course four self-study course The Ohio State University College of Dentistry is a recognized provider for ADA CERP credit. ADA CERP is a service of the American Dental Association to assist dental professionals in identifying quality providers of continuing dental education. ADA CERP does not approve or endorse individual courses or instructors, nor does it imply acceptance of credit house by boards of dentistry. Concerns or complaints about a CE provider may be directed to the provider or to ADA CERP at The Ohio State University College of Dentistry is approved by the Ohio State Dental Board as a permanent sponsor of continuing dental education contact us p h o n e t o l l f r e e f a x e - m a i l smsosu@osu.edu w e b sterilization ABOUT this COURSE READ the MATERIALS. Read and review the course materials. COMPLETE the TEST. Answer the eight question test. A total of 6/8 questions must be answered correctly for credit. SUBMIT the ANSWER FORM ONLINE. You MUST submit your answers ONLINE at: RECORD or PRINT THE CONFIRMATION ID This unique ID is displayed upon successful submission of your answer form. ABOUT your FREE CE TWO CREDIT HOURS are issued for successful completion of this selfstudy course for the OSDB biennium totals. CERTIFICATE of COMPLETION is used to document your CE credit and is mailed to your office. ALLOW 2 WEEKS for processing and mailing of your certificate. FREQUENTLY asked QUESTIONS Q: Who can earn FREE CE credits? A: EVERYONE - All dental professionals in your office may earn free CE credits. Each person must read the course materials and submit an online answer form independently. Q: What if I did not receive a confirmation ID? A: Once you have fully completed your answer form and click submit you will be directed to a page with a unique confirmation ID. Q: Where can I find my SMS number? A: Your SMS number can be found in the upper right hand corner of your monthly reports, or, imprinted on the back of your test envelopes. The SMS number is the account number for your office only, and, is the same for everyone in the office. Q: How often are these courses available? A: FOUR TIMES PER YEAR (8 CE credits). Page 1

2 2013 course four HUMAN PAPILLOMAVIRUS Dental health professionals encounter HPV derived processes on a daily basis. There are more than 40 types of HPV that can infect the genital areas as well as the mouth and throat. The objective is to equip dental health professionals with the basic knowledge of the infection, its clinical manifestations, diagnostic procedures, prevention and management. written by amber kiyani, dds edited by rachel flad, bs karen k. daw, mba, cecm INTRODUCTION Human papillomavirus (HPV) is a DNA virus that has the ability to infect epithelial cells of the skin and mucous membranes. More than one hundred types of the virus have been identified. Each type has a unique genetic sequence of the outer capsule. Most forms of HPV are recognized to infect the mucosa and are classified as high risk or low risk viruses based on their ability or inability to cause cancers. High risk HPV is associated with almost all forms of cervical cancers, 50% of vulvar cancers, 65% of vaginal cancers, 35% of penile cancers, 95% of anal cancers and 60% of oropharyngeal cancers. Low risk human papillomaviruses are common, harmless, non-cancerous, and, are primarily responsible for inducing benign papillomas and warts. HPV infects the basal layer of the epithelium. For most people, the infection is asymptomatic and resolves spontaneously. However, in a small percentage of people, the virus may persist causing warts, papillomas and, in rare cases, cancers. HPV can be transmitted through sexual contact, non-sexual human contact, saliva, breast milk or, very rarely, though vertical transmission. Approximately 79 million Americans are currently infected with HPV and about 14 million people become infected each year. Anogenital HPV Warts in Oral Cavity Source: Paul A. Volberding, MD, University of California in San Francisco is the most common sexually transmitted disease in the U.S. at present, with over 20 million people currently infected and increasing by 6.2 million infections every year. 64% of sexually active females between the ages of are affected. Over 30 types of HPV have been identified in the mouth. Most lesions produced by the virus are benign and of little significance. While HPV has been identified in a significant number of oral cancers, there is doubt about the significance of its role in the pathogenesis. According to the Centers of Disease Control and Prevention, about 8,400 people in the United States are diagnosed with oropharyngeal cancers that may have been caused by HPV. These cancers are three times more common in men than women. Page 2

3 SQUAMOUS PAPILLOMA Squamous papilloma is a benign papillary process of the oral cavity that is linked to HPV. It is one of the more common lesions of the oral mucosa and is attributed to low risk HPV subtypes 6 and 11. Squamous papillomas have low virulence and infectivity. The incubation period for the virus can be up to 12 months before any visible signs of infection are seen. The lesions are seen in both men and women with an equal frequency. The lesions can be identified in individuals of any age group. Tongue, lips and soft palate are commonly involved. The lesions appear as small, solitary, painless papules or nodules with finger-like projections that may appear either pink or white in the oral cavity. Their bases may either be pedunculated (growing off of a stem) or sessile (attached directly). The lesions may grow up to 3.0 cm in rare instances. Although the lesions are benign and have no reports of malignant transformation, conservative surgical excision is the recommended form of treatment to rule out lesions of significance mimicking this benign process. The excised tissue must be submitted for histologic examination. VERRUCA VULGARIS (COMMON WART) Verruca vulgaris is a common cutaneous epithelial process of the skin that is rarely seen in the oral cavity. It is associated with virus subtypes 2, 4, 6, and 40. Because the lesions are highly infectious, the transmission of the virus to the oral cavity is usually by self-inoculation. While the lesions are seen across all age groups, they are most commonly encountered in young children. Fingers, arms and feet are common sites of cutaneous infection. In the oral cavity, lips, labial mucosa and the tongue are frequent sites of involvement. The oral lesions appear as painless, white nodules with rough Verruca Vulgaris papillary projections. Verruca vulgaris grows rather quickly until a final size is attained. The lesions are usually small and may have a pedunculated or a sessile base. It is not unusual to have cutaneous warts simultaneously. Source: Dr. Carl Allen, The Ohio State University College of Dentistry Conservative excision is the treatment of choice for oral lesions. Cutaneous warts may resolve spontaneously, however, persistent warts may require excision, removal by cryotherapy or keratolytic agents. Oral lesions must be submitted for histopathology. This helps in attaining a definitive diagnosis and rules out presence of more significant pathology. CONDYLOMA ACUMINATUM Condyloma acuminatum, also known as venereal wart or anogental wart, is primarily acquired through sexual contact and accounts for over 20% of all sexually transmitted infections. Low risk human papillomavirus types 2, 6, 11, 53, and 54 are commonly found in these lesions. High risk types 16, 18, and 31 may also be identified less frequently. The prevalence of condylomas appears to be higher in immuno-compromised individuals such as those with HIV. Please refer to the section HPV in Patients with HIV, beginning on page 6, for more details. Page 3

4 HECK S DISEASE (MULTIFOCAL EPITHELIAL HYPERPLASIA): Multifocal epithelial hyperplasia is a HPV-derived epithelial process. Human papillomavirus types 13 and 32 are linked to this condition. DEMOGRAPHICS: It is seen more commonly in Native Americans and Inuit. It is usually seen in children, and females appear to be more affected than males. Condyloma Acuminatum Oral infection may result through oral sexual practices and, in rare instances, through vertical transmission. The incubation period for the virus is between 1 to 3 months. The lesions are seen most frequently on the labial mucosa, soft palate and lingual frenum. They appear as pink, exophytic, (outward growing) masses with sessile bases and short, blunted papillary projections. Multiple lesions may be present at one time, usually in the form of clusters. The lesions are usually much larger than a papilloma and may attain sizes as large as 3 cm. DIAGNOSIS: A biopsy of the lesion and submission of the excised specimen is necessary in order to confirm diagnosis. While the histopathologic features are quite distinct, a definitive diagnosis cannot be made until HPV testing is performed. Source: Dr. Carl Allen, The Ohio State University College of Dentistry The lesions are usually surgically excised or laser ablated. CONDYLOMA ACUMINATUM IN CHILDREN: It is important to note that condyloma acuminatum is a sexually transmitted disease. Presence of this lesion in a child is indicative of sexual abuse and needs to be reported to the authorities. The report should only be made once the diagnosis is confirmed by histopathology since some sessile squamous papillomas may show resemblance to this process. The lesions associated with Heck s disease characteristically appear as small, round papules arranged in clusters that imparts a cobblestone appearance to the mucosa. Sometimes a papillary architecture may be noted. The papules are symptomatic. Labial, buccal and lingual mucosa are commonly involved. The lesions may also be seen less frequently on the gingiva, palate and tonsils. In rare instances, conjunctival involvement has also been reported. Most of the patients with this condition undergo spontaneous regression. For persistent lesions and cosmetic purposes, surgical removal, laser ablation or cryotherapy can be employed. LARYNGEAL PAPILLOMATOSIS Laryngeal papillomatosis is an extremely rare condition attributed to human papillomavirus types 6 and 11. Papillomas develop in the larynx over a period of time. If the condition is not treated in a timely manner, obstruction of the airway may result in death. Recurrent lesions are common and the condition requires long term follow-up with multiple surgical procedures. It is currently not understood why only a small percentage of people exposed to HPV types 6 and 11 develop this condition. Vertical transmission is listed as a potential source of transmission of the virus. Most of the people affected by the condition are children. Difficulty in breathing, swallowing and inability to make sounds should raise alarm and warrant further investigation. Page 4

5 In adults, laryngeal papillomatosis may present itself as voice changes. Difficulty breathing is usually not seen in adults. DIAGNOSIS: Laryngoscopy is performed by an otolaryngologist to view the area. If laryngeal papillomatosis is suspected, an endoscopic or open biopsy is performed and sent for histopathologic evaluation to establish a definitive diagnosis. The biopsy specimen is tested for presence of low risk HPV. Conservative excision or laser ablation of the papillomas is necessary to ensure a clear airway. Laser is preferred over conventional surgery because it prevents scarring and damage to the tissue. Periodic procedures are usually necessary because of the recurrent nature of this disease. Antiviral drugs have been used to treat this condition. The efficacy of these antivirals is however unclear. They appear to slow down the process of papilloma formation but they are unable to provide complete resolution of the condition. HUMAN PAPILLOMAVIRUS AND DENTAL DISEASE A recent research study from the University of Texas reported an increased incidence of dental disease in patients who were at risk for acquiring oral HPV infection. The oral health status of about 3,500 patients who were positive for low or high risk HPV was evaluated on the basis of four parameters including self ranking of oral health, presence of periodontal disease, use of mouthwash to treat a dental problem in the past week and the number of missing teeth. An appropriate age and sex matched control population was also evaluated. A higher prevalence of oral disease was seen in individuals who were HPV-positive compared to a control population. The study also noted a higher prevalence of HPV in men, individuals who smoked, and those who have had multiple oral sexual partners. OROPHARYNGEAL CANCER Oropharynx is made up of the base of tongue, soft palate, tonsils and the walls of pharynx. Oropharyngeal cancers can sometimes be a human papillomavirus derived process. It is estimated that about 63% of oropharyngeal cancers are HPV-related. High risk HPV type 16 and 18 is linked to the development 90% of these lesions. TRANSMISSION: The virus is usually transmitted through sexual contact. Oral sexual practices allow transmission of the organisms from the anogenital area to the oral cavity where the virus gains access to the mucosa through a site of injury. The virus then makes its way to the basal cell layer of the epithelium. Patients with multiple sexual partners are at a higher risk for oropharyngeal cancers. Immunosuppression or iatrogenic exposures predispose an individual to acquiring HPV. Interestingly, while tobacco is not involved in the oncogenic process, its proinflammatory and immunosuppressive effects may present with a higher risk of infection and persistence. Papilloma on Lingual Frenum Source: Dr. Carl Allen, The Ohio State University College of Dentistry The incubation period of the virus can be up to several years. Certain studies have reported that it may take up to 15 years to develop this form of cancer. EPIDEMIOLOGY: Oral human papillomavirus can be found in up to 7% of sexually active individuals. About 75% of the infected individuals are males. However, only 1% of these people harbor HPV type 16, most of which are young Caucasian males. Page 5

6 Oropharyngeal cancer can present as persistent pain in the throat, painful swallowing, voice changes, neck lump and unexplained weight loss. Less frequently, ear pain, sternal lump, pain behind the sternum and a persistent cough is noted. DIAGNOSIS: A thorough clinical examination is performed by an otolaryngologist that includes an endoscopic evaluation. If an obvious mass is visualized during the endoscopic exam, biopsies are performed and sent for histopathological examination. Once the diagnosis of oropharyngeal cancer is made, the tissue is sent for testing for high risk types of human papillomavirus. A positive result will influence the course of treatment. PREVENTION: Dental dams and condoms help prevent infection with the virus. A vaccine is now available that may provide protection against high risk strains of human papillomavirus, however the efficacy of this vaccine against oropharyngeal cancers is still undetermined. It is discussed in more detail in the section on Prevention on page 7. Early diagnosis is the key to successful treatment. The cancer is treated with by surgery followed by radiation or radiation alone. The disease appears to have a good prognosis and longer survival rates. It has an extremely low rate of occurrence. NON-HPV OROPHARYNGEAL CANCER: About 40% of oropharyngeal cancers are not associated with high risk human papillomavirus. These types of cancers are linked to: 1. Use of tobacco products 2. Excessive alcohol intake 3. Genetic factors 4. Epstein-Barr Virus The presentation, diagnosis and treatment of the disease are very similar to HPV-related cancers. The prognosis for these cancers depends on the extent of disease and is generally worse than HPV-related oropharyngeal carcinomas. Rate of recurrence is high, so regular follow-ups are necessary in these patients. DENTAL PROFESSIONALS AND OROPHARYNGEAL CANCERS Dental health professionals see patients at regular 6-month intervals. This puts them in a unique position to monitor any abnormal growths in the oral cavity and the oropharyngeal area. This is why it is necessary to perform a comprehensive oral examination that includes palpation of the neck and visualization of the oropharynx. Dental health professional are not required to diagnose the oropharyngeal pathology, they are simply expected to note any asymmetric enlargements. The enlargements identified during the oral exam require further evaluation by an otolaryngologist. ORAL CANCER AND HPV The most common type of cancer in the oral cavity is squamous cell carcinoma. Like non-hpv forms of oropharyngeal cancer, tobacco related products, alcohol and genetic mutations are the major etiology for the development of these lesions. The prevalence of HPV in squamous cell carcinomas is low. It is estimated that about 5% of the oral cavity cancers may harbor high risk types of HPV, with some studies claiming rates as high as 35% available. The role of the virus in the oncogenic process is unknown and the popular opinion is that the virus is just a secondary occupant in the area. In rare instances, extension of HPV-related oropharyngeal cancers may be seen in the oral cavity. Such lesions are usually seen at the posterior aspect of the tongue and the soft palate may also be involved. A biopsy with a characteristic histopathologic appearance and a positive HPV probe will warrant further investigation by an otolaryngologist. An endoscopic examination will be required to locate the primary lesion in the oropharynx. Management has already been discussed in the section on oropharyngeal cancers. HPV IN HIV PATIENTS Patients with HIV are at a higher risk for acquiring HPV infections. The increased frequency of warty lesions in HIV patients is linked to the use of antiretrovirals. It is speculated that the use of these drugs generates an altered immune response Page 6

7 against the latent virus that leads to its activation and production of epithelial changes. The arguments used in favor of this theory are the constantly rising rates of cervical and anal cancers in patients with HIV since the introduction of Highly Active AntiRetroviral Therapy (HAART). The HPV-associated warts are commonly seen in the anogenital areas, but oral involvement may also occur. HPV strains linked to these lesions include common types 2,,4, 6 and 11, and less frequent types 7 and 32. The oral lesions seen in patients with HIV appear as condyloma acuminatum; multiple, irregularly surfaced, white or pink plaques. Labial and buccal mucosa, tongue and gingiva are common sites of involvement. Excision is usually the preferred form of treatment because it allows for histopathologic evaluation of the tissue. Laser ablation may also be used. The excised specimen requires HPV probing in order to establish definitive diagnosis. Since cancers are a concern in patients with HIV and these lesions tend to exhibit some degree of dysplasia, close clinical follow-up is usually mandatory in these patients. DIAGNOSING ORAL HPV Diagnosis of HPV is not a simple process. While several commercial tests are available for use in the market, the efficacy of these tests is still undetermined. In 2010, OraDNA labs introduced a non-invasive and easy to use salivary test called OraRisk HPV. The patient swishes and gargles a saline solution for about 30 seconds and expectorates in a tube. The specimen is then shipped to the lab to complete the testing process. The virus is detected using a PCR technique. The final report includes information about the types Oral HPV in an HIV-Positive Patient Source: Centers for Disease Control and Prevention of HPV identified and the level of risk of associated with each of the types. Positive results do not mean that the infection will persist. For most individuals, the virus is cleared out from the system within 2 years. Since most HPV infections are asymptomatic, clinical examination provides no assistance. According to a study carried out by the International Agency of Research and the National Cancer Institute, antibodies to human papillomavirus type 16 were identified in 35% of blood specimens taken from individuals up to 12 years before they developed oropharyngeal cancers. It is expected that in the future, detection of these antibodies may be used as a screening tool or a risk factor for oropharyngeal cancers. VACCINE: PREVENTION The HPV vaccine provides protection against high risk strains; type 16 and 18. It can protect an individual from most forms of HPV-related cancers and genital warts. It s marketed under the tradenames Gardasil and Cervarix. It is delivered as a three-dose regimen over a 6-month period at 0, 2 and 6 months. Only a completed regimen will provide effective protection against the virus. Studies have shown that the protective antibodies remain in the bloodstream for over 5 years. Though the HPV vaccine provides protection against anogenital disease and cancers, its role in protection against oropharyngeal cancers is still unknown. The World Health Organization has recommended vaccination of young women between the ages 9 and 26 to protect against cervical cancer. Studies have shown that women up to the age of 45 can safely receive this vaccine. Since the vaccine is directed against two strains of the virus only, the women are still advised to have regular pap smears. The vaccine has been approved by the FDA for use in males between the ages 9 and 26 as well. It can protect against genital warts, anal cancers, and penile cancers. The efficacy of the vaccine for people with HIV is currently undetermined. Since this group is at a significant risk with high risk HPV types, studies are underway to determine the effectiveness. Page 7

8 The vaccine is not recommended for people who are sensitive to yeast, have an ongoing serious illness and pregnant women. It is only linked to minor side effects such as fainting, pain, swelling to the area, headache and nausea. However, there have been occasional reports of death, permanent disability, hypersensitivity reactions and thromboembolism. While private insurance companies are reluctant to pay for the vaccine (the cost is over $360) federal and state insurances are liable to provide complete coverage. CONDOMS: Condoms may lower the risk of HPV transmission. Since male condoms still allow for some contact, they provide less protection than female condoms. Continued use of condoms can limit the spread of infection to other sites. It can also allow for swifter clearance of infection. DENTAL DAMS: Dental dams are barrier devices that provide protection against sexually transmitted infections such as HPV and HIV. They are recommended for individuals that engage in oral sex practices and if used consistently, can significantly reduce the possibility of infection. MICROBICIDES: Certain antimicrobial chemicals can provide protection against the organism if applied to the genitals before intimate contact. These products are inexpensive but are still currently undergoing clinical trials. Michael Douglas CONCLUSION Source: A few important points to keep in mind: 1. Human papillomavirus is the most common sexual transmitted infection in the United States. 2. More than 120 types of HPV have been identified but only a few have been linked with cancers. 3. Most of the lesions associated with HPV are common, harmless and non-cancerous. 4. Over 60% of oropharyngeal cancers have been linked to HPV but the link between oral cancers and HPV is still undetermined. 5. The HPV vaccine provides protection against anogenital disease and cancers, however, its role in protection against oropharyngeal cancers is still unknown. MICHAEL DOUGLAS AND HUMAN PAPILLOMAVIRUS In 2010, human papillomavirus came under spotlight when Michael Douglas, an American television and movie producer and actor, announced that he had been diagnosed with throat cancer caused by the virus. He was treated with radiation and chemotherapy. In October 2013, Douglas announced that he had been diagnosed with tongue cancer, rather than throat cancer. The decision to initially not reveal the true diagnosis was made by Douglas and his doctor to protect his career. The 68 year old is now actively involved in spreading awareness about sexually transmitted viruses. ORIGINATING FROM PAKISTAN, DR. KIYANI WENT TO RIPHAH UNIVERSITY FOR THEIR 5-YEAR DENTAL SCHOOL PROGRAM. GRADUATING WITH A 4.0 GPA, SHE CAME TO THE OHIO STATE UNIVERSITY IN ORDER TO FURTHER HER STUDIES FOCUSING ON ORAL AND MAXILLOFACIAL PATHOLOGY. SHE PLANS TO TAKE THE INFORMATION SHE LEARNS BACK TO PAKISTAN FOR BOTH DIAGNOSTIC AND TEACHING PURPOSES. HER CURRENT RESEARCH STUDIES AS A FELLOW AT OSU INVOLVE EVALUATING THE ORAL CHANGES ASSOCIATED WITH GASTROINTESTINAL DISEASES. DR. AMBER KIYANI CAN BE CONTACTED AT: KIYANI.1@OSU.EDU Page 8

9 post-test instructions - answer each question ONLINE - press submit - record your confirmation id - deadline is November 22, 2013 High risk types of human papillomavirus have been linked to cervical, vulvar, anal, penile and oropharyngeal cancers. 1 T F SUBMIT 2 T F HIV patients are at a higher risk of acquiring HPV infections. Difficulty in breathing, swallowing, and inability to make sounds are signs of squamous papilloma in children. 3 ONLINE T F 4 T F Condyloma acuminatum is a sexually transmitted infection, and when confirmed in young children, requires alerting the authorities. SUBMIT 5 T F multiple sexual partners. ONLINE 6 T F 7 T F 8 T F Dental health professionals are expected to diagnose oropharyngeal cancers. According to a recent study, a higher prevalence of HPV was found in men, individuals who smoked, and those who had There are over 40 types of HPV that can infect the genital areas, as well as the mouth and throat. The HPV vaccine provides effective protection against oropharyngeal cancers. d i r e c t o r john r. kalmar, dmd, phd kalmar.7@osu.edu a s s i s t a n t d i r e c t o r karen k. daw, mba, cecm daw.37@osu.edu channel coordinator rachel flad, bs flad.4@osu.edu Page 9

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