Statement on Human Papillomavirus and Squamous Cell Cancers of the Oropharynx
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
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.
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
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;6
4. D’Souza G, Dempsey A. The role of HPV in head and neck cancer and review of the HPV vaccine. Prev Med
2011;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;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):259-66.
7. CDC. Human
Papillomavirus–Associated Cancers — United States, 2004–2008. Morbidity and Mortality Weekly Report. April 20,
2012. 2012;61(15):258-61. Accessed October 7, 2013.
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, Schmidt BL, Jordan RC. Tongue and tonsil carcinoma: increasing trends in the US population
ages 20–44 years. Cancer 2005;103(9):1843–9.
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(32):4294–301.
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;348(6):518-27.
12. D’Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal
cancer. N Engl J Med 2007;356:1944-56.
13. Rethman MP, Carpenter W, Cohen EE, et al. Evidence-based clinical recommendations regarding screening
for oral squamous cell carcinomas. J Am Dent Assoc 2010;141(5):509-20.
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):915-24.
15. Lingen MW, Xiao W, Schmidt A, et al. Low etiologic fraction for high-risk human papillomavirus in oral
cavity squamous cell carcinomas. Oral Oncol 2013;49(1):1-8.
16. Cleveland JL, Junger ML, Saraiya M, et al. HPV and oral health. Response from Dr. Cleveland and
colleagues (letter). J Am Dent Assoc 2012:143(5):440-4.
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;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):630-2. Accessed October 7, 2013.
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. Accessed
October 7, 2013. Erratum in MMWR Morb Mortal
Wkly Rep 2010;59(36):1184. Accessed October 7, 2013
20. Fakhry C, Westra WH, Li S, 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):261-9.