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ADA Council on Scientific Affairs

The rising incidence of oropharyngeal cancer, specifically oropharyngeal squamous cell carcinoma (OSCC) associated with human papillomavirus (HPV), is a significant concern for the health care community. Over the past quarter-century, HPV infection has become firmly established as an etiologic risk factor for cancers of the oropharynx, specifically those of the tonsils and the base of the tongue.1-6 Based on data from U.S. cancer registries, an estimated 63 percent of oropharyngeal cancers each year—or over 11,000 cases—are associated with HPV infection.7,8

The vast majority (~85 to 90%) of HPV-positive oropharyngeal cancers are associated with HPV-16 and HPV-18, two high-risk, HPV types that are commonly associated with cervical cancer and other anogenital cancers.2,5-8 A recent study showed a 225 percent increase in HPV-positive oropharyngeal cancers during 1988 through 2004, compared to a 50 percent decrease of HPV-negative cancers over the same time period.10 The authors added that if the rise in incidence continues at its present pace, the incidence of oropharyngeal cancers among males will overtake that of cervical cancers by the year 2020.10

HPV infection does not appear to be a significant risk factor for cancer of the anterior two-thirds of the tongue or remaining sites in the oral cavity.13,15 HPV-positive squamous cell carcinomas have been identified in the oral cavity, although their occurrence is relatively low (estimated at 5.9% in one study of over 400 oral cancers).15

Researchers have identified more than 100 types of HPV,11 including some that are known to infect mucosal surfaces. These give rise to an array of cutaneous or mucosal epithelial lesions, mostly benign hyperplasias such as warts or papillomas. According to one analysis of U.S. cancer incidence data, the proportion of oropharyngeal cancers arising from sites typically associated with HPV significantly increased from 1973 to 2004, particularly in white males aged 40 to 59 years.1 Studies have also demonstrated that the incidence of HPV-associated oropharyngeal cancers is four times higher among men than women,7 higher among younger adults,3 and among persons with a higher lifetime number of sex partners (vaginal and oral).5,9 Although some studies have suggested that oral HPV infection can occur through oral sex or other sexual behaviors, others have not.16

Risk factors for oral and oropharyngeal cancers have typically been older age (median age 62 years at diagnosis) and the use of tobacco and excessive alcohol consumption.1,10,11 However, based on the available evidence, HPV infection is now considered a validated risk factor for OSCC in both men and women, even in the absence of smoking and alcohol consumption.10,17 Given this emerging evidence, it has been suggested that use of prophylactic HPV vaccines directed against HPV-16 and HPV-18 infection may reduce OSCC incidence. Currently, the commercially available HPV vaccines are FDA-approved for the prevention of HPV-associated cancers of the cervical, vulvar, vaginal and anal mucosa.18,19

Dentists are formally trained to perform thorough intra- and extra-oral soft tissue examinations, identify suspicious oral lesions, and perform or refer patients for scalpel/punch biopsies to determine a definitive diagnosis. The Council encourages clinicians to provide adult patients with thorough hard-tissue and soft-tissue examinations, including lymph node examination, following completion of the patient’s health history and risk assessment.13,14 Early detection of oropharyngeal cancer significantly increases the five-year survival rate.10 Although cancers of the oropharynx are difficult to visualize and are diagnosed at later stages than those of the oral cavity, persons with HPV-positive oropharyngeal cancers have a lower risk of dying or having recurrence than those with HPV-negative cancers.20 The patient’s health history, particularly any verbal or written indication of initially suggestive symptoms, such as persistent sore throat, dysphagia, hoarseness, ear pain, enlarged lymph nodes or weight loss, should be carefully evaluated as part of the full clinical assessment and head and neck examination. Patients with initially suggestive symptoms should also be referred for medical evaluation and follow-up. In addition, dentists should continue to provide advice and guidance to their patients regarding the known risks for oral and oropharyngeal cancers from smoking and heavy alcohol consumption.

The ADA Council on Scientific Affairs encourages dentists to educate themselves and their patients about the relationship between HPV and oropharyngeal cancer, especially the growing prevalence of these cancers in younger non-smokers and non-drinkers. Further research is required to improve understanding of the natural history of oral HPV infection, transmission risks, screening/testing, and the predictive value of a positive HPV test for the subsequent development of oropharyngeal cancer. Studies are also needed to investigate the efficacy of these vaccines for the prevention of HPV-associated oropharyngeal cancers. The ADA will continue to provide guidance to the dental profession about HPV-associated oropharyngeal cancer, promote early oropharyngeal cancer detection, and expand public awareness of the oncogenic potential of some HPV infections.

References

1. Chaturvedi AK, Engels EA, Anderson WF, Gillison MF. Incidence trends for human papillomavirus–related and –unrelated oral squamous cell carcinomas in the United States. J Clin Oncol 2008;26:612-9.

2. Dayyani F, Etzel CJ, Liu M et al. Meta-analysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC). Head Neck Oncol 2010;2:15.

3. Chaturvedi AK. Epidemiology and clinical aspects of HPV in head and neck cancers. Head Neck Pathol. 2012 Jul;6 Suppl 1:S16-24.

4. D’Souza G, Dempsey A. The role of HPV in head and neck cancer and review of the HPV vaccine. Prev Med 2011 2011 Oct;53 Suppl 1:S5-S11.

5. Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005 Feb; 14(2):467-75

6. Hobbs CG, Sterne JA, Bailey M, Heyderman RS, Birchall MA, Thomas SJ. Human papillomavirus and head and neck cancer: a systematic review and meta-analysis. Clin Otolaryngol 2006;31(4):259-266.

7. CDC. Human Papillomavirus–Associated Cancers — United States, 2004–2008. Morbidity and Mortality Weekly Report. April 20, 2012. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6115a2.htm?s_cid=mm6115a2_w”.

8. Gillison ML, Chaturvedi AK, Lowy DR. HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women. Cancer 2008;113(10 suppl):3036–46.

9. Shiboski CH et al. Tongue and tonsil carcinoma: increasing trends in the US population ages 20–44 years. Cancer;103:1843–1849.

10. Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011; 29: 4294–4230.

11. Munoz N, Bosch FX, de Sanjose S, et al; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003 Feb 6;348(6):518-27.

12. D’Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 2007;356:1944-56.

13. Rethman MP et al. Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas. JADA 2010;141(5):509-520.

14. Cleveland JL, Junger ML, Saraiya M, et al. The connection between human papillomavirus and oropharyngeal squamous cell carcinomas. Implications for dentistry. J Am Dent Ass 2011;142(8):915-924.

15. Lingen MW, Xiao W, Schmidt A, Jiang B, Pickard R, Kreinbrink P, Perez-Ordonez B, Jordan RC, Gillison ML. Low etiologic fraction for high-risk human papillomavirus in oral cavity squamous cell carcinomas. Oral Oncol 2012 July 27; [epub ahead of print].

16. HPV and oral health. Response from Dr. Cleveland and colleagues (letter). Cleveland JL, Junger ML, Saraiya M, Markowitz LE, Dunne EF, Epstein JB. J Am Dent Assoc 2012:143(5):440-442.

17. Ryerson AB, Peters ES, Coughlin SS et al. Burden of potentially human papillomavirus-associated cancers of the oropharynx and oral cavity in the US, 1998-2003. Cancer 2008 Nov 15;113(10 Suppl): 2901-9.

18. CDC. FDA Licensure of Quadrivalent Human Papillomavirus Vaccine (HPV4, Gardasil) for Use in Males and Guidance from the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2010;59(20):630-632.

19. CDC. FDA Licensure of Bivalent Human Papillomavirus Vaccine (HPV2, Cervarix) for Use in Females and Updated HPV Vaccination Recommendations from the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2010;59(20):626-629.

20. Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 2008;100(4):261-269.  

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Updated January 2013