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Sex Ed:
What Every Dentist Must Know About HPV

By Eric K. Curtis, DDS, MAGD
Featured in AGD Impact, June 2010

Here’s what I know about oral cancer: It can make dentists whisper—especially if it is connected to sex. I recently had lunch with a group of dentists, and our casual conversation about basketball scores and underwater mortgages gradually drifted to shop talk about bonding agents and impression materials. Eventually, the discussion turned to a seminar someone had attended about oral cancer. Out of curiosity, I asked what everyone knew about human papillomavirus (HPV). The talk stopped. Although together we represented approximately 200 years of clinical practice—hardboiled, practical experience—no one at the table wanted to say what everyone was thinking: HPV is transmitted through sex. And it can cause oral cancer, sometimes in very young people.

One of my colleagues cleared his throat. “Kids today, are, you know, more active,” he murmured.
Another one lowered his voice and whispered, “More cancer is happening because kids don’t think that oral sex is really sex.”
“What do you think about the vaccine?” I asked.
“Vaccine?” someone else said. “That’s off my radar.”

The oral sex-cancer connection
On March 26, 2010, The Daily Telegraph (Telegraph), a newspaper from the United Kingdom, announced in public what my dentist friends understand in private, that “a rise in mouth cancer may be due to sexually transmitted disease.” The Telegraph’s journalistic revelation was hardly new. The title of a May 2007 article in TIME, for example, warned, “Oral Sex Can Add to HPV Cancer Risk.” The Telegraph article, however, identified not just a connection but a trend. It reported a 50 percent increase in the incidence of oral cancers in the last 20 years that appear to be HPV-related. The Telegraph article referred to a March 2010 report published in the British Medical Journal (BMJ), titled “Oropharyngeal Carcinoma Related to Human Papillomavirus.” The report cited a Swedish study that showed that in the 1970s, 23.3 percent of oral cancers were HPV-related—a proportion that rose to 93 percent by 2006. The report also cited a United States study which found that approximately 60 to 80 percent of recent oral cancer biopsies were HPV-positive—10 years ago, only 40 percent of such biopsies were HPV-positive. The BMJ report also suggested that HPV can be transmitted through oral sex.

Cancer, of course, is an intricate, complicated disease. Sequencing the human genome has revealed cancer to be a disease of the DNA—an affliction of the genes. The 33,000 genes that are present in identical form in each of our cells—and estimates of each body’s total cell count range from 10 to 75 trillion—are active in different, constantly changing combinations.

Forty years ago, cancer seemed simple. People thought that if something made cells divide too fast, then the cure lay in finding that something and turning it off. “When Richard Nixon declared war on cancer in 1971, he had no way of knowing that the fight would turn into medicine’s own Vietnam,” wrote Jennifer Kahn in the August 2003 issue of Wired. The world came to realize that cancer is a combination of nature and nurture, inheritance and environment. According to the American Cancer Society’s website (www.cancer.org), only 5–10 percent of all cancers are inherited. This means that nearly all of the DNA damage—also known as mutations—that leads to cancer is due to environmental factors.

In an October 2009 report in Compendium of Continuing Education in Dentistry, Nelson L. Rhodus, DMD, MPH, explains: “The etiology of oral cancers appears multifactorial, involving long-term exposure to carcinogenic substances, as well as alterations in host immunity and metabolism, angiogenesis, exposure to chronic inflammation, and possibly other factors that accumulate gradually in a genetically susceptible individual.” Carcinogens include irradiation, hormones, foods, chemicals, and physical irritants. Tobacco, of course, has long been known to be a major culprit in oral cancers. In fact, the Oral Cancer Foundation notes that tobacco and alcohol interact synergistically to increase each other’s adverse effects. As researchers continue to investigate the causes of cancer, it can be assumed that almost anything can prod the DNA into unleashing a cancerous response.

According to a report in the February 2008 Journal of Clinical Oncology, oral squamous cell carcinomas (OSCCs), which arise from the mucosa of the mouth and oropharynx, are the eighth most common cancer among men and the 14th most common among women in the United States. Approximately 75 percent of all OSCCs can be attributed to tobacco and alcohol consumption. HPV-linked carcinomas have recently been identified as a subset of OSCCs, especially those appearing in such areas of the oropharynx as the base of the tongue and the tonsils. The report reinforces the trend that the BMJ warns about: Patients with HPV-positive OSCCs are, on average, three to five years younger than patients with other OSCCs, and they are less likely to have a history of alcohol or tobacco use. While the incidence of oral cancers among Americans in general has decreased, probably due to reduced tobacco use, certain kinds of oropharyngeal cancer have increased, especially among younger populations.

Common denominators
According to the Centers for Disease Control and Prevention (CDC), there are more than 100 related HPVs. Of those, more than 40 can infect the genital areas, as well as the mouth and throat, of both males and females. HPV is primarily transferred by skin-to-skin contact and may enter the host through a miniscule cut or abrasion. Risk factors for HPV transmission involve the number of sexual partners (the more partners, the more likely an infection), age and gender (genital HPV infections are most commonly diagnosed in sexually active girls and women under age 25), and immune system health (HIV infection or immunosuppressant drugs may increase the risk of contracting HPV). The most significant risk factor is young age.

HPV is now the most common sexually transmitted infection in the United States. According to the CDC, approximately 20 million Americans are currently infected with HPV, which often manifests as genital warts. Each year, six million people are infected with HPV. In fact, the infection is so common that at least half of sexually active males and females will contract it at some point in their lives. But most people who have HPV are not even aware of the infection and do not develop symptoms or health problems. In 90 percent of the cases, the body’s immune system clears HPV within two years. However, even though most HPV infections do not lead to cancer, a few do.

In the article “The Human Papillomavirus, the Vaccines, and Oral and Oropharyngeal Squamous Cell Carcinoma: What Every Dentist Should Know” (General Dentistry, May/June 2007), James J. Closmann, DDS, points out that while the association between high-risk HPV strains and OSCCs was initially overlooked, the medical literature is now teeming with studies demonstrating the link. “Many carcinomas are related to HPV,” adds Dr. Rhodus, “and HPV will increase the severity of oral cancer and lead to a poorer prognosis.” Echoing the report in the Journal of Clinical Oncology, Dr. Rhodus notes that most HPV-related oral cancers seem to occur on the base of the tongue and the tonsils.

A shot against cancer
Recently developed vaccines can protect both females and males against some of the most common kinds of HPV. In June 2006, the U.S. Food and Drug Administration (FDA) approved GARDASIL® (human papillomavirus quadrivalent [types 6, 11, 16, and 18] vaccine, recombinant), made by Merck, for the prevention of cervical cancer caused by the two HPV strains that are responsible for 70 percent of cervical cancer cases. In October 2009, the FDA approved Cervarix® (human papillomavirus bivalent [types 16 and 18] vaccine, recombinant), made by GlaxoSmithKline. GARDASIL is a quadrivalent vaccine, meaning it also confers immunity against two additional HPV strains that cause 90 percent of genital warts. Cervarix is a bivalent vaccine, aimed only at the two cervical cancer-associated HPV strains. Both vaccines report a nearly 100 percent efficacy rate for the targeted strains. Furthermore, both are thought to affect OSCCs as well as aerodigestive tract papillomas and anogenital carcinomas. The vaccines are administered in a series of three injections. All three doses are necessary for the best protection. The vaccines are prophylactic, not therapeutic, and are most effective when administered before a person’s first sexual contact.

The introduction of HPV vaccines has elicited intense debate (see the sidebar, “The Great Vaccine Debate,” on page 17). The vaccines were initially recommended for 11- and 12-year-old girls and older females through age 26 who did not get all of the shots when they were younger; however, the vaccines can be given to girls as young as age 9. The suggestion that not only girls but young women should receive a vaccine has been debated because, as a March 2010 article in The Vancouver Sun indicates, Pap smears can “catch cervical cancer before it even develops.”

GARDASIL was approved by the FDA in 2009 for use in boys and young men ages 9 to 26 to help protect against 90 percent of genital warts cases. According to the website Medical News Today (www.medicalnewstoday.com), HPV causes approximately 7,500 cancers, 1,000 cancer deaths, and at least 250,000 new infections in males every year. The Washington Post reported that vaccinating males against HPV also could prevent its transmission to their sexual partners. However, it might be more difficult to persuade parents to vaccinate boys than it is to persuade them to vaccinate girls because males are not at risk for cervical cancer.
It also might be difficult to convince experts of the need to vaccinate males. Agreement on administering the vaccines to men and boys is not unanimous. Biomedical researchers seem to be torn, with some advocating the shots for boys and others hesitating.

In any case, vaccine use for the prevention of oral cancer is still officially off-label. “I strongly believe that HPV vaccines will improve the prognosis and decrease the incidence of HPV-associated oral cancer,” says Dr. Rhodus. But he points out that the American Cancer Society and the CDC have declined to comment about the benefit of the vaccines, which are currently FDA-approved only for cervical cancer. “It may take five or six years,” Dr. Rhodus says, “for researchers to feel confident recommending the vaccines for oral and oropharyngeal malignancies.”

In the September/October 2008 issue of General Dentistry, John C. Comisi, DDS, FAGD, wrote about discovering an HPV-induced squamous papilloma during a study using an adjunctive oral cancer screening device. “Personally, I think it makes sense to vaccinate both male and female populations,” he says, “especially in light of the rather casual approach to sexual contact, oral and otherwise, by the younger generations.”

The dentist’s new dynamic
According to the Oral Cancer Foundation, more than 34,000 Americans will be diagnosed with oral or oropharyngeal cancer this year, only half of whom will be alive in five years. Oral cancer is typically hard to diagnose because it is not noticed by patients in its early stages. These days, the war against cancer is waged on three major fronts: cancer classification, drug development, and early detection. The recognition of HPV-related oral cancer encompasses all three.

In the future, some pundits predict that dentists will be geneticists. Right now, though, dentists should also be public health advocates. “The role of dental health care professionals with respect to HPV involves not only recognition but also education,” says Eugene L. Antenucci, DDS, FAGD. “Dentists are in a unique position to educate their patients, both adolescent and adult, regarding sexually transmitted diseases such as HPV, along with providing recommendations for vaccination against HPV,” he says. According to Dr. Antenucci, dentistry has, for the most part, ignored the discussion of HPV vaccines. “Although the vaccine is commercially available, it is my impression that the dental profession has not been adequately informed regarding its availability, its efficacy, and the potential side effects.”

According to eMedTV (www.emedtv.com), a health information website, side effects of the HPV vaccine may include pain, swelling, and redness at the injection site, fever, malaise, headache, weakness, dizziness, nausea, and coughing. Even toothache was reported as a side effect in approximately 1 percent of GARDASIL recipients. While unusual side effects and serious adverse affects are reported to be extremely low, 32 people have died after getting the vaccine, although the exact cause of death is unclear.

For dentists, preparation and vigilance are crucial for the prevention of any oral cancer. “Although the HPV that I discovered was not one of the types currently suspected as being aggressive,” Dr. Comisi says, “we don’t know if these squamous papillomas won’t be seen in the future as a precursor to more aggressive lesions.” For updated information, Dr. Comisi recommends visiting the Oral Cancer Foundation website (www.oralcancerfoundation.org) and viewing its YouTube video (www.youtube.com/user/oralcancerfoundation). Aimed at teens and young adults, the video candidly discusses HPV and oral cancer and reinforces the importance of having a dentist routinely screen for oral cancer.

Complete oral examination
Dr. Antenucci recommends a thorough head and neck examination at every dental exam (see the sidebar, “Components of an Oral Cancer Examination,” on page 18). He says, “The most basic role of any dentist is to be fully aware of what is ‘normal’ and to at least refer a patient for evaluation of findings that are suspicious.”
Dr. Antenucci describes how HPV can manifest itself in the mouth on oral mucosal tissue. “The lesions appear as raised and whitish, or ‘oral warts,’” he says. “They are contagious. Dentists should be able to recognize these lesions as an HPV infection. Treatment involves excision with a laser, a scalpel, or cryosurgery.”

In addition to visual observation, radiographs, and 3-D cone beam imaging, many dentists enhance their ability to diagnose pathology using light-based screening technology that fluoresces the tissue to disclose pathologic changes (see the sidebar, “Oral Cancer Clinical Diagnostic Aids,” on page 18). Says Dr. Antenucci, “These are adjuncts, however, with the baseline being a knowledge of what is normal, a basic knowledge of pathology, a systematic approach toward screening, and a means of dealing with suspicious findings—either referral or biopsy.”

In conjunction with a complete head and neck examination using a white operatory light and headlamp, Dr. Comisi says, “I use the VELscope® on all patients 18 years and older at each recare visit. I believe it is currently the best way to thoroughly screen for possible lesions.”

Further considerations
Just as oral cancer screening is more complicated than an isolated “look-see,” the HPV prevention issue is more complex than a single vaccine. Of the 100 HPV strains, at least 15 are oncogenic. The vaccines, however, prevent only a few strains. In an August 2009 Journal of the American Medical Association editorial, Charlotte Haug, MD, PhD, raises philosophical questions regarding the current strategies for addressing HPV infection: “When do physicians know enough about the beneficial effects of a new medical intervention to start recommending or start using it? When is the available information about harmful adverse effects sufficient to conclude that the risks outweigh potential benefits?” Any decision about treating HPV is not only about absolute risk, she argues, but the relationship between potential risks and benefits. “It is impossible to tell either who will get cancer in 20 years or what long-term effects people will experience from the vaccine,” she wrote.
Although mode of transmission of HPV to the oral cavity is less understood and less defined at this time, researchers believe that American’s changing behaviors in tobacco and alcohol use and sexual practices may be indicative of the specific mechanisms responsible for the origination of cancers at particular locations. In the meantime, public education is of vital importance. The connection between HPV and oral cancer must be communicated to all patients and all health care professionals. Regular oral cancer screenings are something that every dentist can do.

Eric K. Curtis, DDS, MA, MAGD, is an adjunct associate professor at University of the Pacific. Dr. Curtis holds a certificate in professional writing from the University of Arizona and is certified by the Board of Editors in the life sciences. He maintains a private general dental practice in Safford, Ariz. To comment on this article, send an e-mail to impact@agd.org.

THE GREAT VACCINE DEBATE
Vaccines traditionally have been controversial, especially regarding the morality, ethics, effectiveness, and safety of using them. Here are some of the reasons that people have concerns about using HPV vaccines:

Some religious groups frown on medical interventions.
A small number of educational groups are concerned about a possible link to autism.
People tend to resist forced compliance, such as the 2007 executive order from the governor of Texas mandating a HPV vaccine for all 11- and 12-year-old girls.
Some parents insist that their kids—especially young children—don’t need a vaccine that protects against a sexually transmitted disease, even though statistics contradict this belief.
The vaccines feel “too new” to some people, prompting questions about safety (although they are FDA-approved, no long-term studies are available) and duration (no one knows how long their protection will last).
Some fear that the vaccines will promote promiscuity due to fewer deterrents to having sex.



COMPONENTS OF AN ORAL CANCER EXAMINATION
A good oral examination requires an adequate light source, protective gloves, gauze squares, and a mouth mirror.
1. Extraoral examination
• Inspect the head and neck (including the back of the neck).
• Bimanually palpate the lymph nodes and salivary glands.
• Closely inspect the face (including the external ears) for skin lesions.
2. Lips
• Inspect and palpate the outer surfaces of the lip and vermillion border.
• Inspect and bidigitally palpate the inner labial mucosa (upper and lower).
3. Buccal mucosa
• Inspect and palpate the inner cheek lining.
4. Alveolar ridge and gingiva
• Inspect the maxillary/mandibular gingiva and alveolar ridges on both the buccal and lingual sides.
5. Tongue
• Inspect the dorsal surface of the protruded tongue.
• Inspect the ventral surface of the lifted tongue.
• Grasping the tongue with a piece of gauze and gently pulling it to each side, inspect the lateral borders of the tongue from its tip to the posterior lingual tonsil region.
• Palpate the tongue.
6. Floor of mouth
• Bimanually inspect and palpate the floor of the mouth.
7. Hard palate
• Inspect and palpate the hard palate.
• Palpate for any lumps.
8. Soft palate and oropharynx
• Gently depress the patient’s tongue with a mouth mirror and inspect the soft palate, tonsillar pillars, and oropharynx.

Source: National Guideline Clearinghouse™

ORAL CANCER CLINICAL DIAGNOSTIC AIDS
Biopsy is considered the gold standard for oral pathology diagnosis. Although a 2008 review of adjunctive screening procedures in the Journal of the American Dental Association concludes that the jury is still out as to whether their use actually results in higher numbers of oral cancers diagnosed or diminished oral cancer mortality and morbidity, these additional measures may augment soft tissue oral examinations and possibly expedite a biopsy.

Chemoluminescence—When soft tissue is conditioned with 1% acetic acid and inspected under a fluorescent light, a suspicious lesion, particularly at its hard-to-read borders, may appear to glow white.

Toluidine blue—This inexpensive metachromatic thiazine dye, also known as tolonium chloride, binds to DNA to achieve a vital nuclear stain marking high-risk lesions. While the National Institute of Dental and Craniofacial Research notes that toluidine blue often misses low- or moderate-grade precancerous lesions manifesting late alterations in cell structure, the dye accurately stains most cancerous lesions. Nelson L. Rhodus, DMD, MPH, director of the Division of Oral Medicine, University of Minnesota School of Dentistry, reports that several studies show that chemoluminescence followed by toluidine blue staining assists in early recognition of oral cancer and effectively speeds up biopsy, diagnosis, and treatment. John C. Comisi, DDS, FAGD, warns that such a combined approach may yield only limited compliance since the various solutions needed to identify a lesion with this technique are often objectionable to patients.

Direct optical fluorescence—This technology reportedly facilitates direct visualization of tissue fluorescence and the changes in fluorescence that can result when abnormal tissue is present. When examined under a light-emitting device such as the VELscope® or Identafi® 3000, healthy tissue normally glows (the blue VELscope light produces a green fluorescence, while the violet Identafi 3000 light produces a blue fluorescence), while dysplastic tissue may show a loss of fluorescence and appear dark.


DETECTING ORAL CANCER
Warning signs
• Leukoplakia (white lesions) or erythroplakia (red lesions)*
• A lump or thickening in the oral soft tissues
• Soreness or feeling that something is caught in the throat
• Difficulty chewing or swallowing
• Ear pain
• Difficulty moving the jaw or tongue
• Hoarseness
• Numbness of the tongue or other areas of the mouth
• Swelling of the jaw that causes dentures to fit poorly or become uncomfortable

If the above problems persist for more than two weeks, a thorough clinical examination and laboratory tests should be performed, as necessary, to obtain a definitive diagnosis. If a diagnosis cannot be obtained, referral to the appropriate specialist is indicated.

*Any white or red lesion that does not resolve in two weeks should be considered for referral to obtain a definitive diagnosis.

Risk factors
• Tobacco or alcohol use (combining tobacco and alcohol poses a much greater risk than using either substance alone)
• Human papillomavirus infection
• Sunlight exposure (lip cancer)
• Age
• Gender (oral cancer strikes men twice as often as it does women)
• Race (oral cancer occurs more frequently in African Americans than it does in Caucasians)

The dentist’s role
• Examine your patients at each visit using the head and neck examination.
• Take a history of your patients’ alcohol and tobacco use.
• Inform your patients of the association between tobacco use, alcohol use, and oral cancer.
• Follow up to make sure a definitive diagnosis is obtained on any possible signs/symptoms of oral cancer.
• Patients with oral lesions or neck masses should be referred for evaluation and biopsy and then for evaluation of the entire upper aerodigestive tract to stage the extent of disease and for detection of extraoral metastasis cancers.

Source: “Detecting Oral Cancer: A Guide for Dentists,” National Institutes of Health National Institute of Dental Research; National Institute of Dental and Craniofacial Research

MANAGING RISK
• Carefully review the patient’s medical history to note any predisposing factors.
• Perform a comprehensive oral evaluation that includes careful intraoral and extraoral examinations.
• Review oral radiographic images to note any possible abnormalities in the dentition and bones of the patient.
• Document each area carefully and clearly in the patient’s permanent record. Make sure to note abnormalities and record normal areas as well. Failure to do so can be used as evidence that the examination was not performed.
• For abnormalities, schedule the patient for a re-evaluation or properly refer the patient.
• If cancer is present, extract compromised teeth before radiation therapy to reduce the risk of developing osteoradionecrosis. (Note: Extractions after radiation treatments can result in severe consequences if not handled properly. Interface between the oncology group and the dentists who follow the patient for the subsequent post-treatment period is essential.)
• Record in the patient’s medical history that he or she has undergone such medical treatment.

Source: “Risk Management Considerations for Oral Cancer” (JADA, November 2005)
AGD Impact, June 2010



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