Question:Discuss how the revelatory information regarding the numbers and hypothesized mechanisms of oropharyngeal cancer caused by human papillomavirus has changed the “face of oral cancer.”

Michael A. Kahn, DDS; William L. Balanoff, DDS, MS, FICD; Scott D. Benjamin, DDS

Dr. Kahn
For the past 20 years, many researchers and clinicians suspected that a certain percentage of oral/oropharyngeal cancers were caused by a viral infection, and the main putative organism was human papillomavirus (HPV), a double-stranded DNA virus with a propensity to invade basal cells in areas of epithelial lining transition. During the past 2 years, several studies have strongly suggested that there are two distinct pathways for the development of oropharyngeal carcinoma - one is driven predominantly by the carcinogenic effects of tobacco and/or alcohol and the other by HPV-induced genomic instability. Although there still is not absolute proof of causality, there is little doubt now that HPV, particularly HPV type 16 (and to a lesser degree type 18), is strongly associated with oropharyngeal carcinoma among people without the established risk factors of tobacco and alcohol use. Recent studies have shown that 20% to 23% of the approximately 31,000 annual cases of oral/oropharyngeal carcinoma in the United States each year are associated with HPV infection. This subset of carcinomas tends to occur in younger males, and they have shown enhanced susceptibility to radiation and/or chemoradiation therapy.

Current data strongly suggest that oral HPV infection is sexually acquired. For example, in one recent study,¹ the association with oropharyngeal carcinoma increased significantly (3 to 8 times) with the number of vaginal-sex partners or oral-sex partners, and the rate was markedly elevated among patients with a high lifetime number of such partners. Investigators have pointed out that other routes of transmission, such as direct mouth-to-mouth (skin and saliva) contact, cannot be ruled out. Public health implications are underscored by the annual increases in the incidence of tonsillar and base of tongue cancers in the United States since 1973, with the increase likely due to widespread oral sexual practices among adolescents. It will be interesting to see if widespread adoption of HPV vaccination (eg, Gardasil® quadravalent vaccine) in preteenaged girls (and hopefully soon approved for boys), will result in a reduction of this type of oral cancer in the next generation of young adult Americans.

Reference
1. D’Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356(19):1944-1956.

Dr. Balanoff
With a forecasted rise in the incidence of HPV-related oral cancers, it is imperative that dentists as well, as hygienists, re-evaluate their examination procedures used during routine oral cancer examinations. HPV-related oral cancers not only necessitate a change in conventional thinking with regard to carcinogenesis, but they also constitute a change in conventional high-risk lesion locations.

Tobacco and chronic alcohol consumption are well-recognized risk factors for oral cavity and oropharyngeal cancers and, historically, 95% of cases occur after the age of 45 with a median age of 64 years.² With the increase in incidence in HPV-related cancers there now appears to be a paradigm shift in conventional statistics. It has been demonstrated that patients presenting with HPV type 16 strains of oropharyngeal cancer (the most oncogenic strain for these cancers and accounting for more than 90% of cases of HPV-positive squamous-cell carcinomas of the head and neck)³ are markedly younger than the typical oral cancer patient.⁴ To further confound the diagnosis of these cancers, there appears to be a rising incidence in tonsillar and base of the tongue cancers. It is believed that HPV cancers of the oropharynx may present as completely separate entities when compared with conventional oral squamous cell carcinomas, due, in part, to younger patient incidence, presentation of dysplasia, cancers independent of conventional risk behaviors, and better overall treatment outcomes.

The conventional head and neck examination remains the community standard for the detection of frank cancer and mucosal changes that may harbor pathology. It is imperative, and in my opinion is the standard of care, that practitioners exercise diligence and employ the use of a screening adjunct (eg, ViziLite® Plus [Zila Pharmaceuticals, Phoenix, AZ], Velscope [LED Dental Inc, White Rock BC, Canada]) when performing oral examinations. Not offering screening to a patient is, in my opinion, a gross disservice to the patient and the dental profession. Great care must be taken to inspect the tonsillar pillars and base of the tongue with the use of transillumination to maximize visualization. The emergence of HPV type 16 as an oral carcinogen necessitates greater care in the office.

References
1. Centers for Disease Control. Oral cancer background papers. www.cdc.gov/oralHealth/pdfs/chapter1.pdf . Accessed December 2, 2008.

2. Herrero R, Castellsagué X, Pawlita M, et al. Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study. J Natl Cancer Inst. 2003;95: 1772-1783.

3. Gillison ML. Human papillomavirus-related diseases: oropharynx cancers and potential implications for adolescent HPV vaccination. J Adolesc Health. 2008;43(4 Suppl): S52-S60.

Dr. Benjamin
Traditionally, the patients who were thought to have an elevated risk for developing oral cancer were those who smoked, regularly used alcohol, or were over 50 years of age. When all of these factors were combined, the patient was considered to be at an even higher risk. However, in recent years, we are seeing an alarming change in the incidence and demographics associated with this disease and its progression.

Paradoxically, although tobacco is undeniably one of the major etiological agents for oral cancer, it is not the tobacco-associated potential lesions that appear to have the highest risk of malignant transformation, but those that were previously thought to be idiopathic.

In the last 3 decades, there has been a 5-fold increase in the occurrence of oral and pharyngeal cancer in patients under the age of 40; and many of those affected are not positive for traditional risk factors. This definitely raises the question of what has changed and why? In addition, between 2006 and 2007, there was an overall increase of more than 10% in the occurrence of oral cancer, which is even more alarming. Especially when you consider that the use of tobacco in North America has been steadily declining.

Recent studies in the New England Journal of Medicine and other journals are strongly suggesting a link between sexual activity, HPV, and oral cancer. A 2002 Centers for Disease Control survey on sexual activity in teenagers demonstrated that over 25% of 15-year-olds and 75% of 19-year-olds had already engaged both in intercourse and oral sexual activities. When you combine all of this information it definitely invites the question of “what adult patient is not at risk?” More importantly, it very strongly suggests the need for regular thorough and enhanced oral mucosal evaluations on all adult patients, especially those who were not deemed at high risk in the past, as they are the “new face of oral cancer.”

About the Authors

Michael A. Kahn, DDS, is a professor and chairman in the Department of Oral and Maxillofacial Pathology at Tufts University School of Dental Medicine. William L. Balanoff, DDS, MS, FICD, practices implant surgery and cosmetic dental reconstruction at Smile Perfect, Fort Lauderdale, FL. Scott D. Benjamin, DDS, is on the ADA Standards Committee on Dental Products and Informatics.