In a recent article in the Journal of the American Dental Association, a study of the literacy of dentists on the topic of oral cancer risk factors, specifically the human papilloma virus, indicated a need for improvement in the knowledge base among dentists about oral cancer risk factors and in how to handle such discussions with patients. 

As someone who was somewhat of a pioneer in the field of adjunctive screening technologies and a strong advocate for early recognition of suspicious tissue changes and early intervention as key components of improving the outcomes of oral cancer, this author was “all over this HPV thing” when it was first identified as a risk factor for oropharyngeal cancer. The fact has remained for nearly a decade that dentists need more information and require better tools to share that information with patients; however, there are significant challenges that must be overcome.

There is first a need to understand the common risk factors that are well-known for oral cancer - specifically squamous cell carcinoma, which is the most common form of cancer discovered in the oral cavity. Classically, the typical oral cancer patient is a male who is older than 50, who smokes and consumes alcohol heavily and frequently. In fact, it has been suggested that tobacco use in combination with alcohol - but not so much independently - accounts for approximately 75 percent of all oral cancer. Poor oral hygiene lack of regular dental care and the presence of chronic infections like herpes simplex virus, candidiasis, lichen planus and various forms of the human papilloma virus present additional classic risk factors for oral cancer.

It is important to note that these statistics deal with oral cancer, which is anterior to the anterior tonsillar pillar and includes the anterior two-thirds of the tongue, the hard palate and the floor of the mouth. Oropharyngeal cancer - which is often lumped into the “oral cancer” category and involves the tissues posterior to the anterior tonsillar pillars and the soft palate (Figure 1) - requires an endoscopic evaluation by an otolaryngologist and, therefore, may fall outside the scope of general dentistry.

oropharynx oral cancer risk
Figure 1. The oropharynx begins at the soft palate and anterior tonsillar pillars and extends to the epiglottis, including the posterior third of the tongue and portions of the nasopharynx.(Image accessed 1/29/2018: https://d2ebzu6go672f3.cloudfront.net/media/content/images/cr/205051.jpg)

While papillomas and condylomas can and do occur in the oral cavity and may be associated with dysplasia that can progress to squamous cell carcinoma, oral cavity lesions typically are caused by the non-oncogenic varieties of the human papilloma virus, 6 and 11. (Figure 2)  

oral cancer hpv risks
Figure 2. An oropharyngeal papilloma (condyloma based on reported history of sexual practices) caused by HPV-6 is highlighted in yellow. An area of moderate epithelial dysplasia is identified in blue, which was not genotyped. (Both lesions were biopsied.)

HPV 16 and 18 have been identified as the primary types implicated in cervical and oropharyngeal cancer, but the other oncogenic types that have been identified to date are 31, 33, 45, 52 and 58. Unfortunately, their clinical appearance is unknown and often involves tonsillar crypts and lymphoid tissues that are not easily identifiable by routine clinical examination unless pain, induration, or loss of function has developed. At this point, immediate referral to an otolaryngologist is imperative because the prognosis of oropharyngeal cancer is time dependent. Oncogenic HPV lesions are typically unassociated with epithelial dysplasia.

It has been proposed that open discussions about HPV and its relationship with oral cancer should be a routine activity in the general dental practice as a prudent preventive measure.i,While this is noble and ethical in this author’s opinion, it appears currently to be outside of social norms for dentists to be having discussions about oral sex practices with patients. It may even prove to be extremely offensive to many patients. This may be a significant reason why most dentists who have been interviewed on this topic do not discuss this topic with their patients routinely.i 

As an example, there is at least one case where a dentist had his life personally threatened by a father of an adolescent female who presented with a papilloma in her oropharynx, and an appropriate professional discussion occurred between the clinician, the patient and the patient's mother about possible causes of the lesion.viii  The implication that his daughter would be sexually active at her age was beyond the limits of comprehension by the father; however, the possibility of sexual abuse had to be ruled out. 

In fact, the patient was evaluated and managed by an otolaryngologist, who confirmed the original finding. While the care given was appropriate and timely intervention occurred, it was clear that an alternative approach to the process was necessary that would have still achieved the goal of intervention without the social drama and negative experience for all concerned.

Possibly a more socially acceptable approach to the HPV dilemma in the dental practice would be to parallel that which is typically used regarding herpes labialis. It is well-known that cold sores are a viral infection resulting from close contact with an infected individual and that nearly everyone is exposed to the virus at some point in their life. Discussions occur when a patient presents with an active lesion about preventing spreading the virus through contact through self and others, but seldom is it necessary or even appropriate to discuss how the patient actually got the virus unless the patient asks for an explanation. 

Who would benefit from telling the patient that they likely got the virus from a parent or sibling, and how would it affect the treatment plan? The fact is that they have the virus, and it needs to be managed.

This author has opted to adapt this approach to HPV as well, except that now it is possible to incorporate some basic education into the medical history interview with patient and parent. A simple question about HPV vaccines on the medical history form that is routinely asked of everyone easily opens the door for discussion, when appropriate, in a professional manner.

For example, having a single yes/no question on the form with a date of the vaccination will enable the dentist to enter a discussion about the general benefits of an inoculation, just like a question about cold sores enables the dentist to discuss expectations regarding dental care during active lesions for the protection of the dental staff and the patient and appropriate treatment strategies.

Just as in the case of the herpes virus, it is still essential that the clinician understands how HPV is acquired, spread and functions in histological modification so that if the patient or parent asks, the clinician can provide educated answers; therefore, a basic review of the HPV family is important.

It is important to understand that the oropharynx is comprised of similar tissue to that of the cervix. Therefore, it is reasonable to extrapolate much of the information known about HPV from gynecological research to oral HPV, including the information about vaccines. 

Essentially, like all viruses, HPV infects susceptible host cells - in this case, via contact with infected bodily fluids or contact of lesions with susceptible mucosa. The virus then enters the host cells and then goes into the nuclei of each infected cell to hijack the normal genetic expression of the cell. The oncogenic varieties of HPV specifically transform the epithelial cells in the genital and upper respiratory tracts. The genetic mutations inactivate normal tumor-suppressing protein synthesis and form oncoproteins that stimulate mitosis and proliferation of the host cells and shut down normal cell regulation, such as apoptosis (cell death). In fact, this same process mimics the normal cancerous process, except that there is an external living entity (the virus itself) rather than a carcinogen.ii 

The risk factors for oral cancer now need to be modified by adding the risk factors for HPV infection. v  (Table 1.)  It seems that alcohol use remains a risk factor, especially if it is consumed concomitantly with smoking; however, it is interesting that smoking alone may slow the progress of HPV-related cancers. Marijuana use tends to correlate with higher HPV incidence, but this may be due to risky social practices more than the drug itself. However, risky sexual practices create the highest risk factor for HPV infection, including a proportionate risk increase for the number of lifetime sexual partners, the age of first sexual experience with a partner, and unsafe sexual practices - including the use of prophylactics, which have not been proven to be effective against the transmission of HPV. 

The fact that the younger age of sexual contact with a partner, along with the increased risk per sexual partner in the course of a lifetime, create a significant public health concern because of exponential transmission through vicarious exposure. In other words, if an individual who has never been sexually active participates with a partner who has been exposed to three other partners, then the individual potentially now has equivalently been exposed to four partners since HPV can be carried without symptoms.

This cycle continues and increases the need for a vaccine against this potentially deadly disease, because it is nearly impossible to change the behaviors of society entirely, even with diligent training, counseling and phenomenal healthcare. Therefore, there is risk of an epidemic.

oral and hpv dental cancer risk factors

There are currently three vaccines available for oncogenic HPVs, two of which are FDA-approved for males as well as females, and one of which was recently discontinued in the United States. Gardasil and Gardasil 9 are indicated for boys and girls starting at age 9. Cervarix, which was discontinued due to poor demand, was typically only used for girls and offered minimal coverage.

 All of the vaccines protect against the high-risk types 16 and 18; Gardasil also protects against condylomas caused by 6 and 11; Gardasil 9 protects against five other oncogenic types (31, 33, 45, 52 and 58). There is also evidence that those who are vaccinated against these specific oncogenic strains may be less likely to become infected with other strains of HPV as well, through cross-protection.

While no serious side effects have been validated from these vaccines, there are multiple reports and unjustified claims against HPV vaccines, as is seen with all vaccines. In fact, reports against Gardasil, the oldest of such vaccines, have been scrutinized and evaluated carefully in the United States by the Centers for Disease Control and the Food and Drug Administration and by healthcare agencies in Sweden and Denmark, none of which have been able to prove a link to untoward events from the vaccine. Risks of the vaccine include injuries sustained in falls from fainting during and immediately after the vaccine and possible blood clots when the patient is taking birth control pills. In general, other risk factors are common to all other vaccines.iv

In addition to vaccines, salivary diagnostics may show promise going forward. For example, the OraRisk® salivary test is available to test for the presence of HPV in saliva. The challenge is that in healthy individuals, most HPV infections are completely cleared within two years of infection. There is currently no evidence-based protocol that gives guidance or direction as to how a positive result should be managed. While the test is a good test in that it does test for the presence of HPV, it has questionable value when there is no clarity as to how to manage a positive result. 

Furthermore, since HPV infections can be cleared in as little as 90 days in healthy individuals,ii it is impossible to determine if repeated positive saliva tests are a result of persistent infections or reinfection from the same infected partner.  The discussions that must occur for informed consent and disclosure of positive findings can create significant social stress and disharmony for the partners involved without a clear resolve. Vaccines are only protective against oncogenic HPV strains if given before the first infection,iv and there are currently no medications that justifiably can be prescribed to manage an asymptomatic HPV infection.

The former Secretary General of the United Nations, Ban Ki-Moon, once said that the spread of diseases like HPV is “…a public health emergency in slow motion.” In fact, it has been recognized worldwide that approximately one in five cancers may be linked to infectious diseases like HPV, which poses a threat " ... on every nation’s health, economy and national security.” Clearly there is a need for dentists to become familiar with the risk factors for oral cancer and oropharyngeal cancer and to take a preventive role in management.

This can likely best be accomplished at this time by encouraging and supporting research efforts in the fight against cancer, being aware of the risk factors, generally increasing awareness of the risk factors through community education and general discussions with patients during medical history review, and by encouraging timely vaccinations as a matter of public health.

Kevin D. Huff, DDS, MAGD, is a Visiting Faculty member at Spear Education and a Spear Digest contributing author.  He has published many articles on the topic of ethical oral cancer screening strategies and lectured on this topic extensively around the United States and Canada. Links to several of his articles can be found at www.doctorhuff.net/articles.htm.

References

I. Vazquez-Otero, C., et al. Assessing dentists’ human papillomavirus–related health literacy for oropharyngeal cancer prevention. The Journal of the American Dental Association.  2018.  149(1), 9-17. doi:10.1016/j.adaj.2017.08.021

II. Kahn, M., & Huff, K. (2008, October 3-4). Embracing Technology to Save Lives: A Review of Oral Cancer Screening Techniques and New Technologies. Lecture presented at the Ohio Academy of General Dentistry MasterTrack Course at The Ohio State University., Columbus, OH.

III. Truelove, E., et al. Narrow band (light) imaging of oral mucosa in routine dental patients. Part I: assessment of value in detection of mucosal changes.  General Dentistry.  July/August, 2011.  281-289.

IV. Human Papillomavirus (HPV) Vaccines. (n.d.). Retrieved January 29, 2018, from https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-vaccine-fact-sheet#q5

V. Kahn M.  The emerging role of human papillomavirus in oropharyngeal squamous cell carcinoma.  Compendium of Continuing Education in Dentistry.  2011:32(Spec Iss 2):1-7.

VI. Solomon L.  Potentially Malignant Lesions of the Oral Cavity.  Compendium of Continuing Education in Dentistry.  2011:32(Spec Iss 2):9-13.

VII. (n.d.). Retrieved January 29, 2018, from https://www.medscape.com/viewarticle/870853

VIII. Human Papillomavirus (HPV). (n.d.). Retrieved January 29, 2018, from https://www.webmd.com/hw-popup/human-papillomavirus-hpv

IX. ​​Huff, K. (2011, November 27). Ethical Considerations and Decision-Making Methodology for Integrating Oral Mucosal Screening. Greater New York Dental Meeting. Lecture presented at Greater New York Dental Meeting in Jacob K. Javitz Convention Center, Manhattan, NY.

X. Blumenthal SB.  Non-Communicable Diseases (NCDs): The Costs of Omission from the MDGs  [Millennium Development Goals] Results in a September UN Summit. Huffington Post.  http://www.huffingtonpost.com/susan-blumenthal/chronic-disease-development_b_950414.html.  September 7, 2011.  

 

Comments

Andrew C.
February 4th, 2018
Excellent, Should we be recommending any preventive treatment for patients in there 20's-40's beside safety. What about the fact it lays dormant for up to 20 years only to become active later in life with devastating effects
Kevin H.
February 4th, 2018
Thanks for the question, Andy. The vaccine is indicated until I believe age 26, but the ideal time is before any exposure at all. Merck did a study where they found that a significant number of cohorts identified sexual activity as early as 9 years old, which is why the vaccine is recommended starting at age 9. Our best defense currently is through awareness of HPV as an STD with oral ramifications and prevention through vaccination and education of the public at large. You are correct in that exposure can happen early in life, even through exposure coming through the birth canal, and not be expressed phenotypically until later in life. However, currently there is no cure or treatment in the absence of symptoms. Not having a solution to the problem is another challenge with salivary diagnostics in this situation. If we knew what to do with a positive test, it would be very good practice to routinely use it.
Kevin H.
February 4th, 2018
It looks like the yellow and blue highlight circles in the figure did not transfer from the manuscript. The condyloma is the large raised lesson at about the 11:00 position above the metal mirror handle. Thee dusplasia is farther to the patient's right, just left of the uvula area. It is a slightly lighter punk ovoid area relative to the surrounding tissue.